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  • Impact of BD Kiestra™ InoqulA™ streaking patterns on colony isolation and turnaround time of methicillin-resistant Staphylococcus aureus and carbapenem-resistant Enterobacterales surveillance samples
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2020-01-11
    Cheng Wan Rong Carmen; Ong Chiou Horng; Chan Su Gin Douglas

    Objective The objective of this study is to determine if using alternative streaking patterns on the BD Kiestra™ InoqulA™ can impact colony isolation and improve turnaround time (TAT) of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacterales (CRE) screening samples. Method A total of 1571 positive MRSA screening samples were studied of which 755 screening plates were streaked by the standard pattern (4-Quadrant uniform S200) and 816 plates were streaked by an alternative pattern (Zigzag 3.5–1 S200). A total of 424 CRE positive screening samples were studied of which 211 screening plates were streaked by the standard pattern (Zigzag 2.5–1 inoc S200) and 213 plates were streaked by an alternative customised pattern (NTFGH Zigzag 3.5-1 vertstreak s200). Results There was a reduction in the number of MRSA screening plates with insufficient isolated colonies for confirmatory testing from 75 (9.9%) when using the standard pattern to 18 (2.2%) plates when using the alternative streaking pattern. MRSA cases with a TAT above 36 hours also reduced significantly from 144 (19.1%) to 20 (2.4%). The number of CRE screening plates with insufficient colonies for same-day confirmatory testing reduced from 16 (7.6%) when using the standard pattern to 2 (1.1%) plates when using the alternative customised pattern. CRE cases with a TAT above 36 hours also reduced from 16 (7.6%) to 7 (3.3%). Conclusion The change in streaking patterns resulted in more plates with sufficient isolated colonies, reduced man-hours and materials required to perform subculture of mixed colonies, and overall improvements in TAT.

  • Influenza increases invasive meningococcal disease risk in temperate countries
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2020-01-11
    Angela Salomon; Isha Berry; Ashleigh R. Tuite; Steven Drews; Todd Hatchette; Frances Jamieson; Caroline Johnson; Jeff Kwong; Bruno Lina; Jose Lojo; Anne Mosnier; Victoria Ng; Philippe Vanhems; David N. Fisman

    Objectives Invasive meningococcal disease (IMD) is a severe bacterial infection that displays wintertime seasonality in temperate countries. Mechanisms driving seasonality are poorly understood and may include environmental conditions and/or respiratory virus infections. We evaluated the contribution of influenza and environmental conditions to IMD risk, using standardized methodology, across multiple geographical regions. Methods We evaluated 3,276 IMD cases occurring between January 1999 and December 2011 in 11 jurisdictions in Australia, Canada, France and The United States. Effects of environmental exposures, and normalized weekly influenza activity, on IMD risk were evaluated using a case-crossover design. Meta-analytic methods were used to evaluate homogeneity of effects and to identify sources of between-region heterogeneity. Results After adjustment for environmental factors, elevated influenza activity at a two-week lag was associated with increased IMD risk (adjusted OR per standard deviation increase 1.29, 95% CI: 1.04-1.59). This increase was homogeneous across jurisdictions studied. By contrast, although associations between environmental exposures and IMD were identified in individual jurisdictions, none were generalizable. Conclusions Using a self-matched design that adjusts for both co-seasonality and case characteristics, we find that surges in influenza activity result in an acute increase in population-level IMD risk. This effect is seen across diverse geographic regions in North America, France, and Australia. The impact of influenza infection on downstream meningococcal risk should be considered a potential benefit of influenza immunization programs.

  • Community-acquired bacterial meningitis in adults: in-hospital prognosis, long term disability and determinants of outcome in a multicentre prospective cohort
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2020-01-10
    Sarah Tubiana; Emmanuelle Varon; Charlotte Biron; Marie-Cecile Ploy; Bruno Mourvillier; Muhamed-Kheir Taha; Mathieu Revest; Claire Poyart; Guillaume Martin-Blondel; Marc Lecuit; Eric Cua; Blandine Pasquet; Marie Preau; Bruno Hoen; Xavier Duval

    Objectives To identify factors associated with unfavorable in-hospital outcome (death or disability) in adults with community-acquired bacterial meningitis (CABM). Methods In a prospective multicenter cohort study (COMBAT; February 2013-July 2015), all consecutive cases of CABM in the 69 participating centers in France were enrolled and followed up for 12 months. Factors associated with unfavorable outcome were identified by logistic regression and long-term disability analyzed. Results Among the 533 enrolled patients, (S. pneumoniae 53.8% (280/520 isolates identified), N. meningitidis 21.3% (111/520), others 24.9% (129/520)), case fatality rate was 16.9% (90/533) and unfavorable outcome occurred in 45.0% (225/500). Factors independently associated with unfavorable outcome were: age > 70 years (aOR=4.64; 95%CI [1.93-11.15]), male gender (aOR=2.11; [1.25-3.57]), chronic renal failure (aOR=6.65; [1.57-28.12]), purpura fulminans (aOR=4.37; [1.38-13.81]), localized neurological signs (aOR=3.72; [2.29-6.05]), disseminated intravascular coagulation (aOR=3.19; [1.16-8.79]), cerebrospinal fluid (CSF) white-cell count < 1500 cells/μL (aOR=2.40; [1.42-4.03]), CSF glucose concentration (0.1-2.5g/L: aOR=1.92; [1.01-3.67]; <0.1g/L: aOR=2.24; [1.01-4.97]), elevated CSF protein concentration (aOR=1.09; [1.03-1.17]), time interval between hospitalization and lumbar puncture > 1 day (aOR=2.94; [1.32-6.54]), and S. pneumoniae meningitis (aOR=4.99; [1.98-12.56]), or meningitis other than N. meningitidis (aOR=4.54; [1.68-12.27]). At twelve months, 26.7% (74/277) had hearing loss, 32.8% (87/265) depressive symptoms, 31.0% (86/277) persistent headache, and 53.4% had a Physical HRQL (142/266) < 25th percentile of the distribution of the score in the general French population (p<0.0001). Conclusions The burden of CABM (death, disability, depression, impaired quality of life, and hearing loss) is high. Identification of cases from the first symptoms may improve prognosis. ClinicalTrial Gov identification number: NCT01730690.

  • Candida blankii: an emerging yeast in an outbreak of fungemia in neonates in Delhi, India
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2020-01-09
    Anuradha Chowdhary; J. Benjamin Stielow; Gargi Upadhaya; Pradeep K. Singh; Ashutosh Singh; Jacques F. Meis

    Objective Outbreaks of fungal sepsis due to emerging and rare multidrug resistant Candida species are increasingly reported in healthcare settings. We report an outbreak of fungemia due to the rare multidrug-resistant yeast Candida blankii in an Indian neonatal unit. Material and Methods Blood cultures grew C. blankii in nine neonates in the NICU of a multispecialty hospital, Delhi during a period of seven months. Isolates were identified by ITS and D1/D2 region sequencing. Antifungal susceptibility testing was performed by M27-A3 CLSI broth microdilution. To determine genetic relatedness among C. blankii isolates we undertook amplified fragment length polymorphism analysis and DNA sequencing using the Illumina NextSeq500 platform. Results C. blankii fungemia occurred at 2-3 postnatal days in nine LBW/VLBW neonates. All neonates were treated with fluconazole and four of nine patients died, resulting in a case fatality rate of 45%. C. blankii was misidentified or not identified by automated identification systems. Fluconazole had higher MICs (GM-MIC, 8 μg/ml) than the other azoles. Also, anidulafungin (GM-MIC, 2 μg/ml) had high MICs. Genome sequencing confirmed transmission of genetically mostly indistinguishable strains. The C. blankii genome showed an altered 1,3-beta-D-glucan synthase protein and several larger deletions in the echinocandin target FKS1 gene suggesting potential for development of antifungal resistance. Conclusions The study emphasizes the emergence of a rare and uncommon yeast C. blankii, with reduced susceptibility to one or more antifungal agents, in nosocomial fungemia. Genomic insights of this rare yeast are reported using whole genome sequencing typing.

  • It takes two to tango: two Aeromonas isolates combine virulence and multidrug resistance in flap infection following leech therapy
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2020-01-09
    Olivier Barraud; Alexandre Robert; Lucie Laval; Raymond Ruimy; David Morquin; Laurent Boyer; Brigitte Lamy

    Most leech infections are caused by an obligate bacterial symbiont of the crop of leeches, Aeromonas sp. Here, we describe a flap infection following leech therapy mediated by two Aeromonas veronii isolates that presented complementary and synergistic features in terms of virulence and antimicrobial drug resistance. One strain was multidrug resistant and harboured an ESBL-encoding blaVEB-1 gene embedded within a class 1 integron. This is the first report that a bacterial mixture including an ESBL Aeromonas may have worsened the course of a flap infection following leech therapy.

  • The incidence and seasonal variation of necrotizing fasciitis in Korea: a nationwide cross-sectional study
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2020-01-09
    Hee Kyoung Choi; GiHyeon Seo; Euna Han

    Objectives NF is a rare but fatal disease, and there is no known annual incidence of NF in Korea. The aim of this study was to investigate the incidence and seasonal variation of necrotizing fasciitis (NF) in Korea. Methods We analyzed claims from the nationwide Korean Health Insurance Review and Assessment Service database. Patients who were hospitalized with an NF diagnosis code and received surgical intervention were classified as NF cases. Poisson regression models were used to assess the relationships of incidence rates with year, age, and sex. A multivariate Poisson regression model was used to investigate variations in monthly NF incidence trends. Results From 2012 to 2017, the overall average annual NF incidence rate was found to be 0.86 per 100,000 population. NF incidence increased with age and was 2.5-times higher among males across all age groups. Two-thirds of cases occurred among patients with diabetes. The peak NF incidence occurred during the summer. Multivariate Poisson regression modeling using national meteorological variables suggested that mean temperatures and number of NF cases in the previous month were associated with the number of NF cases in the current month. Conclusions Clinicians should consider NF when encountering an elderly male with diabetes in the summer.

  • Bone and joint infections of the hand
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2020-01-07
    Parham Sendi; Alexandre Kaempfen; Ilker Uçkay; Rahel Meier
  • Age distribution of human papillomavirus infection and neutralizing antibodies in healthy Chinese women aged 18-45 years enrolled in a clinical trial
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2020-01-03
    Lihui Wei; Yingying Su; Yuemei Hu; Rongcheng Li; Wen Chen; Qinjing Pan; Xun Zhang; Fanghui Zhao; Yuqian Zhao; Qing Li; Ying Hong; Chao Zhao; Mingqiang Li; Wenyu Liu; Caihong Li; Dongping Guo; Lidong Ke; Bizhen Lin; Ningshao Xia

    Objectives Data from clinical trials of human papillomavirus (HPV) vaccines showed that women naïve (negative for both type-specific antibodies and DNA) to vaccine types would derive benefit from vaccination; therefore, an understanding of the proportion of naïve women in different age groups is important for developing HPV vaccination strategies. Methods From November 2012 to April 2013, a total of 7372 healthy women aged 18-45 years were recruited at five provinces in China. Cervical specimens and serum samples were collected for each woman at entry. Cervical specimens were first tested by the HPV DNA enzyme immunoassay method; if positive, the specimens were then tested by reverse hybridization line probe assay and HPV-16 and HPV-18 specific polymerase chain reactions. Neutralizing antibodies against HPV-16 or HPV-18 were tested with a pseudovirion-based neutralization assay. Results The overall prevalence of high-risk HPV DNA was 14.8% (1088/7367, 95% CI: 14.0, 15.6), and the seroprevalence of neutralizing antibodies against HPV-16 and HPV-18 was 12.6% (925/7367) and 4.9% (364/7367), respectively. In younger women (18-26 years) and middle-aged women (27-45 years), 83.8% (3116/3719) and 81.4% (2968/3648) were naïve to both HPV-16 and HPV-18 (both neutralizing antibodies and DNA were negative), respectively. In addition, 98.5% (3664/3719) and 98.0% (3575/3648) of the younger or middle-aged women were naïve to at least one HPV type (HPV-16 or HPV-18). Conclusions This study revealed that the majority of Chinese women aged 18-26 years and 27-45 years were naïve to both HPV-16 and HPV-18 and would thus derive full benefit from bivalent HPV vaccination.

  • Environmental shedding of toxigenic Clostridioides difficile by asymptomatic carriers: A prospective observational study
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2020-01-03
    Mayan Gilboa; Esther Houri Levi; Carmit Cohen; Ilana Tal; Carmit Rubin; Olga Feld-Simon; Adi Brom; Yehudit Eden- Friedman; Shoshi Segal; Galia Rahav; Gili Regev-Yochay

    Objectives To compare the burden of environmental shedding of toxigenic C. difficile among asymptomatic carriers, C. difficile infected (CDI) patients and non-carriers, in an inpatient non-epidemic setting. Methods C. difficile carriage was determined by positive toxin-B PCR from rectal swabs of asymptomatic patients. Active CDI was defined as a positive 2-step EIA/PCR test in patients with >3 unformed stools/24 hours. C. difficile environmental contamination was assessed by obtaining specimens from 10 sites in the patients' rooms. Toxigenic strains were identified by PCR. We created a contamination scale to define the overall level of room contamination that ranged from clean to heavy contamination. Results 117 rooms were screened; 70 rooms inhabited by C. difficile carriers, 30 rooms by active CDI patients and 17 rooms by non C. difficile -carriers (Control). In the carrier rooms 29 (41%) had more than residual contamination, from which 17 (24%) were heavily contaminated. In the CDI rooms 12 (40%) had more than residual contamination from which 3 (10%) were heavily contaminated, while in the control rooms, one room (6%) had more than residual contamination and none were heavily contaminated. In a multivariate analysis, the contamination score of rooms inhabited by carriers did not differ from rooms of CDI patients, yet both were significantly more contaminated than those of none carriers OR 12.23 and 11.16 (95%CI:1.5-99.96 P=0.0195, and 1.19-104.49 p=0.035), respectively. Conclusion Here we show that C. difficile carriers' rooms are as contaminated as those of patients with active CDI and significantly more than those of non-carriers.

  • An update on Toscana virus distribution, genetics, medical and diagnostic aspects
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2020-01-02
    Nazli Ayhan; Remi N. Charrel

    Background Toscana virus is an arbovirus transmitted by sand flies within the Mediterranean area where it can cause febrile illness and neuroinvasive infections during the seasonal circulation period of the vector. Although it is an important cause of meningitis and encephalitis, it remains a neglected virus with limited published data as demonstrated by less than 250 peer-reviewed articles since the 1970's. Objectives The last review article on Toscana virus was published in 2012. The aim was to compile peer-reviewed articles in order to provide an updated review highlighting recent findings to complement previous review articles. Sources PubMed database was searched using the "Toscana virus" keyword from 2010 to present. A total of 152 articles were retrieved and identified studies were assessed for novel information on virus genetics, and geographic and medical aspects compared with existing knowledge reported in previous review articles. Content Studies addressing medical, veterinary and entomological aspects have provided evidence that Toscana virus is present in North Africa, in the Balkan Peninsula, and in most of the Mediterranean islands. Beside the two previously recognized genetic lineages, a novel evolutionary lineage has been identified in the Balkan Peninsula. Co-circulation of two genetic lineages has been demonstrated in France, in Turkey and in Croatia. In addition to meningitis and meningo-encephalitis that have been reported for forty years, various neuroinvasive forms have been recently reported such as Guillain-Barré syndrome, hydrocephalus, myositis, fasciitis, polymyeloradiculopathy, deafness, facial paralysis. Implication Because it is endemic in countries bordering the Mediterranean, physicians should include Toscana virus in the differential diagnosis of patients presenting with febrile illness and/or neurological manifestations.

  • 5-Nitroimidazole refractory giardiasis is common in Matanzas, Cuba and effectively treated by secnidazole plus high-dose mebendazole or quinacrine: a prospective observational cohort study
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2020-01-01
    Roberto Cañete; Amuri L. Noda; Maylin Rodríguez; Katia Brito; Elaine Herrera; Poul-Erik Kofoed; Johan Ursing

    Objective To evaluate the effectiveness and tolerability of secnidazole combined with high-dose mebendazole for treatment of 5-nitroimidazole resistant giardiasis. Method Adults with microscopically verified Giardia intestinalis monoinfection attending a secondary level hospital in Matanzas City, Cuba were prospectively included into a cohort. A recently introduced treatment ladder consisting of metronidazole as first line, followed by secnidazole, tinidazole, secnidazole plus mebendazole and quinacrine as 2nd to 5th line treatment was used. Adverse events and treatment success were determined by questioning and microscopy on concentrated stool samples, respectively on days 3, 5 and 7 after end of treatment. If G. intestinalis were detected on day 3, 5 or 7 the infection was classified as refractory and no further microscopy was done. Results 456 patients were included. Metronidazole, 500 mg three times daily for 5 days, cured 248/456 (54%) patients. A single two gram secnidazole dose as second line treatment cured 50/208 (24%) patients. A single two gram tinidazole dose as third line treatment cured 43/158 (27%) patients. Three rounds of 5-nitroimidazole therapy thus cured 341/456 (75%) patients. Secnidazole plus mebendazole (200 mg every 8 hours for 3 days) cured 100/115 (87%) of nitroimidazole refractory infections. Quinacrine cured the remaining 15 patients. All treatments were well tolerated. Conclusions 5-Nitroimidazole refractory giardiasis was common indicating that an alternative first line treatment may be needed. Retreatment of metronidazole refractory giardiasis with an alternative 5-nitroimidazole was suboptimal indicating cross-resistance. Mebendazole plus secnidazole were well tolerated and effective for the treatment of 5-nitroimidazole refractory G. intestinalis infection in this setting.

  • Seroprevalence of Aspergillus IgG and disease prevalence of chronic pulmonary aspergillosis in a country with intermediate burden of tuberculosis: a prospective observational study
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2020-01-01
    Meng-Rui Lee; Hung-Ling Huang; Lun-Che Chen; Han-Ching Yang; Jen-Chung Ko; Meng-Hsuan Cheng; Inn-Wen Chong; Li-Na Lee; Jann-Yuan Wang; George Dimopoulos

    Objectives Chronic pulmonary aspergillosis (CPA) is an emerging global disease with tuberculosis (TB) being the most important risk factor. Epidemiologic data on the seroprevalence of Aspergillus IgG and prevalence of CPA in different areas, especially in country with intermediate burden of TB, are lacking. Methods We prospectively recruited healthy volunteers, TB close contacts, active TB patients and participants with old pulmonary TB in Taiwan during 2012-2019. We measured serum Aspergillus fumigatus and niger-specific IgG levels and assessed if the participants were having CPA. Results A total of 1242 participants (including 200 healthy volunteers, 326 TB close contacts, 524 active TB patients and 192 old TB cases) were recruited. Using 27 mgA/L as cut-off level, the seropositive rate of A. fumigatus-specific IgG was 33.0% (66/200), 37.7% (123/326), 26.5% (139/524) and 43.2% (83/192) among the four groups, respectively. In multivariate logistic regression, pulmonary cavitation (OR: 1.73 [1.07-2.80]), female sex (OR: 1.49 [1.14-1.95]), old TB (OR: 1.59 [1.05-2.42]) were independent risk factors for Aspergillus IgG positivity. One (0.2%) active TB patient and 4 (2.1%) old TB people developed CPA. Correlation between A. fumigatus and A. niger-specific IgG was high (Spearman correlation coefficient: 0.942). Conclusions Geographic variation in Aspergillus IgG seroprevalence and CPA prevalence exists. A universal cut-off value for Aspergillus IgG may not exist. In areas and populations in which background Aspergillus IgG level is unknown, Aspergillus IgG may be better used as a test of exclusion for CPA using pre-specified cut-off level.

  • Necrotizing skin and soft-tissue infections in the intensive care unit
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-07-05
    M. Peetermans; N. de Prost; C. Eckmann; A. Norrby-Teglund; S. Skrede; J.J. De Waele

    Background Necrotizing skin and soft-tissue infections (NSTI) are rare but potentially life-threatening and disabling infections that often require intensive care unit admission. Objectives To review all aspects of care for a critically ill individual with NSTI. Sources Literature search using Medline and Cochrane library, multidisciplinary panel of experts. Content The initial presentation of a patient with NSTI can be misleading, as features of severe systemic toxicity can obscure sometimes less impressive skin findings. The infection can spread rapidly, and delayed surgery worsens prognosis, hence there is a limited role for additional imaging in the critically ill patient. Also, the utility of clinical scores is contested. Prompt surgery with aggressive debridement of necrotic tissue is required for source control and allows for microbiological sampling. Also, prompt administration of broad-spectrum antimicrobial therapy is warranted, with the addition of clindamycin for its effect on toxin production, both in empirical therapy, and in targeted therapy for monomicrobial group A streptococcal and clostridial NSTI. The role of immunoglobulins and hyperbaric oxygen therapy remains controversial. Implications Close collaboration between intensive care, surgery, microbiology and infectious diseases, and centralization of care is fundamental in the approach to the severely ill patient with NSTI. As many aspects of management of these rare infections are supported by low-quality data only, multicentre trials are urgently needed.

  • Management of infected pancreatic necrosis in the intensive care unit: a narrative review
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-06-22
    D.R.J. Wolbrink; E. Kolwijck; J. Ten Oever; K.D. Horvath; S.A.W. Bouwense; J.A. Schouten

    Background Severe acute pancreatitis is marked by organ failure and (peri)pancreatic necrosis with local complications such as infected necrosis. Infection of these necrotic collections together with organ failure remain the major causes of admission to an intensive care unit (ICU) in acute pancreatitis. Appropriate treatment of infected necrosis is essential to reduce morbidity and mortality. Overall knowledge of the treatment options within a multidisciplinary team—with special attention to the appropriate use of antimicrobial therapy and invasive treatment techniques for source control—is essential in the treatment of this complex disease. Objectives To address the current state of microbiological diagnosis, antimicrobial treatment, and source control for infected pancreatic necrosis in the ICU. Sources A literature search was performed using the Medline and Cochrane libraries for articles subsequent to 2003 using the keywords: infected necrosis, pancreatitis, intensive care medicine, treatment, diagnosis and antibiotic(s). Content This narrative review provides an overview of key elements of diagnosis and treatment of infected pancreatic necrosis in the ICU. Implications In pancreatic necrosis it is essential to continuously (re)evaluate the indication for antimicrobial treatment and invasive source control. Invasive diagnostics (e.g. through fine-needle aspiration, FNA), preferably prior to the start of broad-spectrum antimicrobial therapy, is advocated. Antimicrobial stewardship principles apply: paying attention to altered pharmacokinetics in the critically ill, de-escalation of broad-spectrum therapy once cultures become available, and early withdrawal of antibiotics once source control has been established. This is important to prevent the development of antimicrobial resistance, especially in a group of patients who may require repeated courses of antibiotics during the prolonged course of their illness.

  • Mediastinitis in the intensive care unit patient: a narrative review
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-07-12
    B. Pastene; N. Cassir; J. Tankel; S. Einav; P.-E. Fournier; P. Thomas; M. Leone

    Background Mediastinitis is a rare but severe infection, defined as an inflammation of the connective tissues and structures within the mediastinum. Due to its proximity to vital structures, mediastinitis represents a highly morbid pathological process associated with a high risk of mortality. In most cases mediastinitis requires treatment in the intensive care unit. Objectives To highlight to the reader the clinical features of mediastinitis, to attempt to define each clinical scenario, to describe the responsible pathogens and finally to depict both the medical and surgical treatments. Sources We performed a literature search of the PubMed and Cochrane libraries, limited for articles published between January 2003 and December 2018, reporting on acute mediastinitis. Content The term covers different entities of different aetiologies including deep sternal wound infection related to sternotomy; oesophageal perforation or anastomosis leakage; and finally descending necrotizing mediastinitis, often secondary to oropharyngeal abscess. The responsible pathogens and therefore subsequent management depends on the underlying aetiology. Empirical antimicrobial therapy should cover the suspected microorganisms while surgery and supportive measures should aim to reduce the inoculum of pathogens by providing adequate drainage and debridement. Implications Literature concerning mediastinitis in the intensive care unit is relatively scarce. We have collated the evidence and reviewed the different causes and treatment options of acute mediastinitis with a particular focus on microbiological epidemiology. Future research in larger cohorts is needed to better understand the treatment of this difficult disease.

  • When not to start antibiotics: avoiding antibiotic overuse in the intensive care unit
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-07-12
    K.J. Denny; J. De Wale; K.B. Laupland; P.N.A. Harris; J. Lipman

    Background Most intensive care unit (ICU) patients receive broad-spectrum antibiotics. While lifesaving in some, in others these treatments may be unnecessary and place patients at risk of antibiotic-associated harms. Objectives To review the literature exploring how we diagnose infection in patients in the ICU and address the safety and utility of a ‘watchful waiting’ approach to antibiotic initiation with selected patients in the ICU. Sources A semi-structured search of PubMed and Cochrane Library databases for articles published in English during the past 15 years was conducted. Content Distinguishing infection from non-infectious mimics in ICU patients is uniquely challenging. At present, we do not have access to a rapid point-of-care test that reliably differentiates between individuals who need antibiotics and those who do not. A small number of studies have attempted to compare early aggressive versus conservative antimicrobial strategies in the ICU. However, this body of literature is small and not robust enough to guide practice. Implications This issue will not likely be resolved until there are diagnostic tests that rapidly and reliably identify the presence or absence of infection in the ICU population. In the meantime, prospective trials that identify clinical situations wherein it is safe to delay or withhold antibiotic initiation in the ICU until the presence of an infection is proven are warranted.

  • Unconventional diagnostic tests for Lyme borreliosis: a systematic review
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-07-12
    A. Raffetin; A. Saunier; K. Bouiller; P. Caraux-Paz; C. Eldin; S. Gallien; R. Jouenne; A. Belkacem; J. Salomon; O. Patey; E. Talagrand-Reboul; B. Jaulhac; A. Grillon

    Background Lyme borreliosis (LB) diagnosis currently relies mainly on serological tests and sometimes PCR or culture. However, other biological assays are being developed to try to improve Borrelia-infection diagnosis and/or monitoring. Objectives To analyse available data on these unconventional LB diagnostic assays through a systematic literature review. Methods We searched PubMed and Cochrane Library databases according to the PRISMA-DTA method and the Cochrane Handbook for Systematic Reviews of Interventions. We analysed controlled and uncontrolled studies (published 1983–2018) on biological tests for adults to diagnose LB according to the European Study Group for Lyme Borreliosis or the Infectious Diseases Society of America definitions, or identify strongly suspected LB. Two independent readers evaluated study eligibility and extracted data from relevant study reports; a third reader analysed full texts of papers to resolve disagreements. The quality of each included study was assessed with the QUADAS-2 evaluation scale. Results Forty studies were included: two meta-analyses, 25 prospective controlled studies, five prospective uncontrolled studies, six retrospective controlled studies and two case reports. These biological tests assessed can be classified as: (i) proven to be effective at diagnosing LB and already in use (CXCL-13 for neuroborreliosis), but not enough to be standardized; (ii) not yet used routinely, requiring further clinical evaluation (CCL-19, OspA and interferon-α); (iii) uncertain LB diagnostic efficacy because of controversial results and/or poor methodological quality of studies evaluating them (lymphocyte transformation test, interferon-γ, ELISPOT); (iv) unacceptably low sensitivity and/or specificity (CD57+ natural killer cells and rapid diagnostic tests); and (v) possible only for research purposes (microscopy and xenodiagnoses). Discussion QUADAS-2 quality assessment demonstrated high risk of bias in 25/40 studies and uncertainty regarding applicability for 32/40, showing that in addition to PCR and serology, several other LB diagnostic assays have been developed but their sensitivities and specificities are heterogeneous and/or under-evaluated or unassessed. More studies are warranted to evaluate their performance parameters. The development of active infection biomarkers would greatly advance LB diagnosis and monitoring.

  • Evaluation of early clinical failure criteria for gram-negative bloodstream infections
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-31
    H. Rac; A.P. Gould; P.B. Bookstaver; J.A. Justo; J. Kohn; M.N. Al-Hasan

    Objectives The aim was the development of early clinical failure criteria (ECFC) to predict unfavourable outcomes in patients with Gram-negative bloodstream infections (GN-BSI). Methods Adults with community-onset GN-BSI who survived hospitalization for ≥72 hr at Prisma Health-Midlands hospitals in Columbia, SC, USA from January 1, 2010 to June 30, 2015 were identified. Multivariable logistic regression was used to examine the association between clinical variables between 72 and 96 hr after GN-BSI and unfavourable outcomes (28-day mortality or hospital length of stay >14 days from GN-BSI onset). Results Among 766 patients, 225 (29%) had unfavourable outcomes. After adjustments for Charlson Comorbidity Index and appropriateness of empirical antimicrobial therapy in multivariable model, predictors of unfavourable outcomes included systolic blood pressure <100 mmHg or vasopressor use (adjusted odds ratio (aOR) 1.8, 95% confidence interval (CI) 1.2–2.9), heart rate >100 beats/minute (aOR 1.7, 95% CI 1.1–2.5), respiratory rate ≥22 breaths/minute or mechanical ventilation (aOR 2.1, 95% CI 1.4–3.3), altered mental status (aOR 4.5, 95% CI 2.8–7.1), and white blood cell count >12 000/mm3 (aOR 2.7, 95% CI 1.8–4.1) between 72 and 96 hr after index GN-BSI. Area under receiver operating characteristic curve of ECFC model in predicting unfavourable outcomes was 0.77 (0.84 and 0.71 in predicting 28-day mortality and prolonged hospitalization, respectively). Conclusions Risk of 28-day mortality or prolonged hospitalization can be estimated between 72 and 96 hr after GN-BSI using ECFC. These criteria may have clinical utility in management of GN-BSI and may improve methodology of future investigations assessing response to antimicrobial therapy based on a standard evidence-based definition of early clinical failure.

  • Dynamic transmission models and economic evaluations of pneumococcal conjugate vaccines: a quality appraisal and limitations
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-02
    A. Løchen; R.M. Anderson

    Background Of over 90 serotypes of Streptococcus pneumoniae, only seven were included in the first pneumococcal conjugate vaccine (PCV). While PCV reduced the disease incidence, in part because of a herd immunity effect, a replacement effect was observed whereby disease was increasingly caused by serotypes not included in the vaccine. Dynamic transmission models can account for these effects to describe post-vaccination scenarios, whereas economic evaluations can enable decision-makers to compare vaccines of increasing valency for implementation. Aim The aim of this review was to examine epidemiological and economic models and their assumptions for their potential contributions to future research and immunisation policy. Sources Pubmed, Scopus, Ovid, ISI Web of Knowledge, Centre of Reviews and Dissemination (CRD) databases were searched. Content Twenty-three dynamic transmission models and 21 economic models were retrieved and reviewed. Published models employed various templates, revealing several key uncertainties regarding the biology and epidemiology of pneumococcal infection. While models suggested that PCVs will reduce the burden of disease, the extent to which they are predicted to do so depended on various assumptions regarding features of pneumococcal infection and epidemiology that governed PCV cost-effectiveness as well. Such features include the duration of protection and competitive interactions between serotypes, which are unclear at present, but which directly relate to herd immunity and serotype replacement. Implications Economic evaluations are not typically based on transmission dynamic models and hence omit indirect herd immunity effects. The two tools could be used in conjunction to inform decision-makers on vaccine implementation, but so far there have been few attempts to build economic evaluations on transmission dynamic models, and none in this field. Future directions for research could include studies to evaluate key parameters for the models involving herd immunity, serotype competition and the natural history of infection.

  • Estimating the association between antibiotic exposure and colonization with extended-spectrum β-lactamase-producing Gram-negative bacteria using machine learning methods: a multicentre, prospective cohort study
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-23
    E. Tacconelli; A. Górska; G. De Angelis; C. Lammens; G. Restuccia; J. Schrenzel; D.H. Huson; B. Carević; L. Preoţescu; Y. Carmeli; M. Kazma; T. Spanu; E. Carrara; S. Malhotra-Kumar; B.P. Gladstone

    Objectives The aim of the study was to measure the impact of antibiotic exposure on the acquisition of colonization with extended-spectrum β-lactamase-producing Gram-negative bacteria (ESBL-GNB) accounting for individual- and group-level confounding using machine-learning methods. Methods Patients hospitalized between September 2010 and June 2013 at six medical and six surgical wards in Italy, Serbia and Romania were screened for ESBL-GNB at hospital admission, discharge, antibiotic start, and after 3, 7, 15 and 30 days. Primary outcomes were the incidence rate and predictive factors of new ESBL-GNB colonization. Random forest algorithm was used to rank antibiotics according to the risk of selection of ESBL-GNB colonization in patients not colonized before starting antibiotics. Results We screened 10 034 patients collecting 28 322 rectal swab samples. New ESBL-GNB colonization incidence with and without antibiotic treatment was 22/1000 and 9/1000 exposure-days, respectively. In the adjusted regression analyses, antibiotic exposure (hazard ratio (HR) 2.38; 95% CI 1.29–4.40), age 60–69 years (HR 1.19; 95% CI 1.05–1.34), and spring season (HR 1.25; 95% CI 1.14–1.38) were independently associated with new colonization. Monotherapy ranked higher als combination therapy in promoting ESBL-GNB colonization. Among monotherapy, cephalosporins ranked first followed by tetracycline (second), macrolide (fourth) and cotrimoxazole (seventh). Overall the ranking of cephalosporins was lower when used in combination. Among combinations not including cephalosporins, quinolones plus carbapenems ranked highest (eighth). Among sequential therapies, quinolones ranked highest (tenth) when prescribed within 30 days of therapy with cephalosporins. Conclusions Impact of antibiotics on selecting ESBL-GNB at intestinal level varies if used in monotherapy or combination and according to previous antibiotic exposure. These finding should be explored in future clinical trials on antibiotic stewardship interventions. Clinical Trial registration NCT01208519.

  • 更新日期:2019-12-31
  • Incidence and mortality of brain abscess in Denmark: a nationwide population-based study
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-31
    J. Bodilsen; M. Dalager-Pedersen; D. van de Beek; M.C. Brouwer; H. Nielsen

    Objectives To examine the incidence and mortality of brain abscesses. Methods We accessed nationwide population-based medical registries to obtain data for patients with first-time brain abscesses in Denmark from 1982 through 2016. Annual age- and sex-standardized incidence rates with 95% confidence intervals were calculated and compared by direct standardization. We used Cox regression to compute mortality rate ratios adjusted for age and year groups, sex and Charlson comorbidity index score. Results We identified 1384 patients (37% female). The overall standardized incidence rate of brain abscess was 0.76 per 100 000 person-years (95% confidence interval 0.70–0.81). The incidence rates gradually increased from 0.60 during 1982–88 to 0.90 per 100 000 person-years during 2010–16, yielding an incidence rate ratio of 1.50 (95% confidence interval 1.26–1.79). This increase in incidence was most pronounced in the proportions of brain abscess patients >40 years of age and those with immuno-compromise. The 1-year mortality declined from 29% during 1982–88 to 20% during 2010–16, yielding an adjusted mortality rate ratio of 0.44 (95% confidence interval 0.31–0.63). Risk factors for death were advanced age, Charlson comorbidity index >0, immuno-compromised status and congenital heart disease. Conclusions The incidence of brain abscess in Denmark is low but increasing, especially in the elderly, along with an increasing proportion of brain abscess patients with immuno-compromise. The prognosis has improved during the last decades, but mortality remains high. Risk factors for death in our study were advanced age, presence of comorbidity, immuno-compromised status and congenital heart disease.

  • Quadrivalent versus trivalent influenza vaccine: clinical outcomes in two influenza seasons, historical cohort study
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-17
    D. Shasha; L. Valinsky; F. Hershkowitz Sikron; A. Glatman-Freedman; M. Mandelboim; A. Toledano; Y. Paran; R. Ben-Ami; D. Goldman

    Objectives The quadrivalent influenza vaccine (QIV) contains two influenza B antigens (one of each B lineage), while the trivalent vaccine (TIV) contains solely one. As a result, a mismatch between the circulating B lineage and the lineage in the TIV occurs frequently. We aimed to compare the frequency of clinically significant outcomes in a large cohort of vaccinees receiving either TIV or QIV. Methods Historical cohort study of all inactivated influenza vaccinees (aged 3 years and older) in a Health Maintenance Organization insuring 1.2 million individuals, over two influenza seasons in which both vaccines were provided non-selectively. Primary outcome was hospital admissions during the influenza season. Multivariate analysis was performed using logistic regression to adjust for relevant covariates. Results Our cohort included 150 518 and 168 296 vaccinees in the first (S1) and second season (S2), respectively. The two influenza seasons were characterized by high Influenza B activity. Of those vaccinated with QIV, 2074 of 49 726 (4.2%) and 6563 of 121 741 (5.4%) were hospitalized compared with 7378 of 100 792 (7.3%) and 3372 of 46 555 (7.2%) of those vaccinated with TIV (S1 and S2, respectively). After multivariate analysis adjusting for several covariates (gender, age, socioeconomic status, chronic morbidity, timing of vaccination), compared with TIV recipients, QIV vaccinees had lower odds for hospitalization (OR = 0.92, 95% CI 0.87–0.98 and OR = 0.89, 95% CI 0.85–0.93) or emergency department visit (OR = 0.91, 95% CI 0.87–0.95 and OR = 0.84, 95% CI 0.81–0.87) in S1 and S2, respectively (p < 0.001). Lower odds of mortality and influenza-like illness were also observed in S2 (OR = 0.61, 95% CI 0.50–0.75 and OR = 0.92, 95% CI 0.90–0.95, respectively). Conclusions In seasons with relatively high influenza B activity, QIV appeared more protective than TIV in Israel.

  • Association of a single nucleotide polymorphism in the ubxn6 gene with long-term non-progression phenotype in HIV-positive individuals
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-31
    F. Díez-Fuertes; H.E. De La Torre-Tarazona; E. Calonge; M. Pernas; M. Bermejo; J. García-Pérez; A. Álvarez; L. Capa; F. García-García; M. Saumoy; M. Riera; A. Boland-Auge; C. López-Galíndez; M. Lathrop; J. Dopazo; A. Sakuntabhai; J. Alcamí
  • Performance evaluation of different strategies based on microscopy techniques, rapid diagnostic test and molecular loop-mediated isothermal amplification assay for the diagnosis of imported malaria
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-31
    E. Charpentier; E. Benichou; A. Pagès; P. Chauvin; J. Fillaux; A. Valentin; H. Guegan; E. Guemas; A.-S. Salabert; C. Armengol; S. Menard; S. Cassaing; A. Berry; X. Iriart

    Objectives Malaria is one of most common tropical diseases encountered in travellers and migrants. It requires an urgent and reliable diagnosis considering its potential severity. In this study, performance of five diagnostic assays were evaluated in a nonendemic region and compared prospectively to quantitative PCR (qPCR). Methods A prospective study was conducted at Toulouse Hospital from August 2017 to January 2018 and included all patients with initial Plasmodium screening. Thin and thick blood smears (TnS, TkS), quantitative buffy coat (QBC), rapid diagnostic tests (RDTs) and commercial loop-mediated isothermal amplification (LAMP) were independently performed on each blood sample and compared to our qPCR reference standard. Results The study encompassed 331 patients, mainly returning from Africa. qPCR detected 73 Plasmodium-positive samples (including 58 falciparum). Individually, LAMP had a 97.3% (71/73) sensitivity, far ahead of TnS (84.9%, 62/73), TkS (86.3%, 63/73), QBC (86.3%, 63/73) and RDT (86.3%, 63/73). RDT demonstrated a high sensitivity for falciparum (98.3%, 57/58) but missed all ovale, malariae and knowlesi infections. Specificity was excellent for all techniques (99.6–100%). The most sensitive diagnosis strategies were TnS + RDT (95.9%, 70/73), TnS + LAMP (97.3%, 71/73) and TnS + RDT + LAMP (100%, 73/73), about 10% higher than strategies using exclusively microscopy, TkS + TnS (87.7%, 64/73) or QBC + TnS (87.7%, 64/73). TnS remains necessary for Plasmodium species identification and quantification. Adding sequentially TnS only on LAMP-positive samples did not decrease TnS + LAMP strategy sensitivity. Conclusions In nonendemic countries, the currently recommended microscopy-based strategies seem unsatisfactory for malaria diagnosis considering RDT and LAMP performance, two rapid and sensitive assays that require limited training.

  • A prospective prediction tool for understanding Crimean–Congo haemorrhagic fever dynamics in Turkey
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-24
    Ç. Ak; Ö. Ergönül; M. Gönen

    Objectives We aimed to develop a prospective prediction tool on Crimean–Congo haemorrhagic fever (CCHF) to identify geographic regions at risk. The tool could support public health decision-makers in implementation of an effective control strategy in a timely manner. Methods We used monthly surveillance data between 2004 and 2015 to predict case counts between 2016 and 2017 prospectively. The Turkish nationwide surveillance data set collected by the Ministry of Health contained 10 411 confirmed CCHF cases. We collected potential explanatory covariates about climate, land use, and animal and human populations at risk to capture spatiotemporal transmission dynamics. We developed a structured Gaussian process algorithm and prospectively tested this tool predicting the future year's cases given past years' cases. Results We predicted the annual cases in 2016 and 2017 as 438 and 341, whereas the observed cases were 432 and 343, respectively. Pearson's correlation coefficient and normalized root mean squared error values for 2016 and 2017 predictions were (0.83; 0.58) and (0.87; 0.52), respectively. The most important covariates were found to be the number of settlements with fewer than 25 000 inhabitants, latitude, longitude and potential evapotranspiration (evaporation and transpiration). Conclusions Main driving factors of CCHF dynamics were human population at risk in rural areas, geographical dependency and climate effect on ticks. Our model was able to prospectively predict the numbers of CCHF cases. Our proof-of-concept study also provided insight for understanding possible mechanisms of infectious diseases and found important directions for practice and policy to combat against emerging infectious diseases.

  • EUCAST disc diffusion criteria for the detection of mecA-Mediated β-lactam resistance in Staphylococcus pseudintermedius: oxacillin versus cefoxitin
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-17
    R. Skov; A. Varga; E. Matuschek; J. Åhman; D. Bemis; B. Bengtsson; M. Sunde; R. Humphries; L. Westblade; L. Guardabassi; G. Kahlmeter

    Objectives Until recently, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommended the cefoxitin disc to screen for mecA-mediated β-lactam resistance in Staphylococcus pseudintermedius. A recent study indicated that cefoxitin was inferior to oxacillin in this respect. We have re-evaluated cefoxitin and oxacillin discs for screening for methicillin resistance in S. pseudintermedius. Methods We included 224 animal and human S. pseudintermedius isolates from Europe (n = 108) and North America (n = 116), of which 109 were mecA-positive. Disc diffusion was performed per EUCAST recommendations using 30-μg cefoxitin and 1-μg oxacillin discs from three manufacturers and Mueller–Hinton agar from two manufacturers. Results Cefoxitin inhibition zones ranged from 6 to 33 mm for mecA-positive S. pseudintermedius (MRSP) and from 29 to 41 mm for mecA-negative S. pseudintermedius (MSSP). The corresponding oxacillin zone intervals were 6–20 mm and 19–30 mm. For cefoxitin 16% (95% CI 14.8–18.0%) of the isolates were in the area where positive and negative results overlapped. For oxacillin the corresponding number was 2% (1.6–2.9%). For oxacillin a breakpoint of susceptible (S) ≥ 20 mm and resistant (R) <20 mm resulted in only 0.4% and 1.1% very major error and major error rates respectively. Conclusions This investigation confirms that the 1-μg oxacillin disc predicts mecA-mediated methicillin resistance in S. pseudintermedius better than the 30-μg cefoxitin disc. For a 1-μg oxacillin disc we propose that 20 mm should be used as cut off for resistance, i.e. isolates with a zone diameter <20 mm are resistant to all β-lactam antibiotics except those with activity against methicillin-resistant staphylococci.

  • Characterization of fungal microbiota on normal ocular surface of humans
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-23
    Y. Wang; H. Chen; T. Xia; Y. Huang

    Objectives Our objective was to characterize the fungal microbiota on normal ocular surface of humans with the culture-based method and high-throughput sequencing approach. Methods A total of 45 adults were recruited from an urban community, and 90 conjunctival swabs were obtained, one from each eye of each participant. One of the two swabs from each participant was randomly chosen and allocated to internal transcribed spacer (ITS) sequencing, and the other was subjected to conventional fungal cultivation. Results Four filamentous fungi were isolated from the 45 samples using the culture-based method, Penicillium citrinum, Aspergillus niger, Phialophora and Trichoderma. In the other 45 samples, 18 samples were positive for PCR amplification and sent for subsequent ITS sequencing. A total of 518 703 valid reads were generated and assigned into 467 operational taxonomic units. Overall, 4 phyla and 94 genera were identified. Two phyla, Basidiomycota (78.67%) and Ascomycota (19.54%), and five genera, Malassezia (74.65%), Rhodotorula (1.93%), Davidiella (1.89%), Aspergillus (1.25%) and Alternaria (0.61%), which accounted for >80% of the fungal microbiome and presented in >80% of the individuals tested, constituted the possible ‘core fungal taxa’ on normal ocular surface. Conclusions The fungal microbiome on normal ocular surface of humans was identified using the high-throughput sequencing method, providing a basis for further investigations on the potential role of the fungal microbiota in ocular health and disease.

  • Diagnostic challenges of central nervous system infection: extensive multiplex panels versus stepwise guided approach
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-12-31
    P. Vetter; M. Schibler; J.L. Herrmann; D. Boutolleau

    Background Cerebrospinal fluid (CSF) testing is a key component for the diagnosis of central nervous system (CNS) infections. Current meningitis and encephalitis management guidelines agree on the need for CSF molecular testing in combination with other direct and indirect biological testing, both in CSF and blood. Multiplex molecular tests have been developed to reduce turnaround times and facilitate the diagnostic approach. Objectives We aim to discuss the role of multiplex molecular panels in the management of CNS infections. Sources The MEDLINE database and the grey literature have been searched for relevant articles. Content New molecular multiplex panels are being developed to simultaneously detect a large array of neuropathogens in CSF. While one of these assays has been FDA-approved, extensive analytical and clinical validation is still missing, and suboptimal performance related issues have been raised. Its use has been associated with decreased costs and reduced length of hospital stay and antiviral therapy administration in retrospective, industry-sponsored studies. The pros and cons of this multiplex syndromic approach are discussed in this narrative review. Implications Molecular multiplex CNS infection diagnosis panels have been developed and present several attractive features, including ease of use and low turnaround time. However, suboptimal analytical performances render these tests difficult to use without additional confirmatory tests. Such panels are not comprehensive nor adapted to all situations, depending on the epidemiological or clinical context. Overall, available data in the literature currently do not support the use of a multiplex PCR panel in clinical routine as a ‘stand-alone’ molecular assay. Except in restricted laboratory capacity settings where such easy-to-use multiplex panels offer the diagnostic means that would otherwise be not available, the stepwise testing approach remains a more rational option. Serological testing both in blood and CSF should not be neglected, since it represents essential complementary tools regarding some neuropathogens.

  • Comparative efficacy and safety of lock solutions for the prevention of catheter-related complications including infectious and bleeding events in adult hemodialysis patients: a systematic review and network meta-analysis
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-12-16
    Kaixiang Sheng; Ping Zhang; Jiawei Li; Jun Cheng; Yongchun He; Maristela Böhlke; Jianghua Chen

    Background Central venous catheters are used extensively as temporary or permanent vascular access for hemodialysis patients. Catheter-related bloodstream infections are the main complication of central venous catheters and increase morbidity and mortality in hemodialysis patients. Objectives To assess the most appropriate lock solution for central venous catheters to prevent catheter-related bloodstream infections and other complications. Data sources Medline, Embase, and Cochrane Central Register of Controlled Trials from the date of their inception to August 2018. The reference lists of eligible studies and relevant reviews were also checked. Study eligibility criteria and participants: Randomized controlled trials (RCTs) comparing different lock solutions for the prevention of central venous catheters related infectious and bleeding complications for adult dialysis patients. Interventions Lock solutions for hemodialysis catheters. Methods The primary outcomes were catheter-related bloodstream infections and bleeding events. The secondary outcomes were catheter malfunction, exit-site infection, and all-cause mortality. We estimated summary risk ratios (RRs) using pairwise and network meta-analysis. We assessed the risk of bias of individual studies with the Cochrane risk of bias tool. Results 49 trials (7020 patients) were included for this study. Compared with heparin 5000U/ml, antibiotic locks (antibiotics with trisodium citrate (TSC), ethylenediamine tetraacetic acid (EDTA), heparin 5000U/ml, low-dose heparin, or urokinase) and ethanol locks were more effective in preventing catheter-related bloodstream infections. Antimicrobial agents plus low-dose heparin (500-2500 U/ml), TSC and low-dose heparin locks had lower risk of bleeding events than heparin 5000 U/ml. No lock solution reduced rates of catheter malfunction and all-cause mortality compared with heparin 5000 U/ml. In summary, antibiotics plus low-dose heparin was ranked as the best lock solution. The overall results were not materially changed in sensitivity analyses. Conclusions Taking into account both efficacy and safety, antibiotics plus low-dose heparin (500-2500 U/ml) may be the preferred lock solution.

  • Invasive infections with Fusobacterium necrophorum including Lemierre’s syndrome – An eight-year Swedish nationwide retrospective study
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-12-14
    David Nygren; Karin Holm

    Objectives We aimed to evaluate the nationwide incidence and a potential increase of invasive infections with F. necrophorum. Secondly, we aimed to describe epidemiology, clinical characteristics and outcomes for the different presentations; i.e. Lemierre’s syndrome (LS), invasive head and neck-infection without LS and invasive non-head and neck-infection. Methods A retrospective multicentric population-based study of all invasive infections with F. necrophorum diagnosed in Sweden from 2010-17 with six months of follow-up was performed through reviews of medical records. Invasive infections were defined and identified by a positive blood culture or sequencing of 16S rDNA, targeted PCR or culture from normally sterile sites. Incidence calculations were performed, including comparisons between 2010-13 and 2014-17, age groups and clinical presentations. Patient and infection characteristics, treatment and clinical outcomes were analyzed. Results Invasive infections with F. necrophorum were diagnosed in 300 cases in Sweden 2010-17. The incidence increased from 2.9 to 5.0 cases/million/year from 2010-13 to 2014-17 (p=0.001). 104/300 (35%) patients developed LS, 102/300 (34%) invasive head and neck-infection without LS and 94/300 (31%) invasive non-head and neck-infection. The median age was 20, 25 and 64 years, respectively. Among patients with LS 72/96 (75%) had thrombocytopenia on admission, 86/104 (83%) had sepsis, 19/104 (18%) developed septic shock and 45/104 (43%) needed intensive care. 30-day mortality in LS was 2/104 (2%). Conclusion We describe an increased incidence of invasive infections with F. necrophorum in Sweden and highlight its full spectrum of invasive clinical presentations. LS, in particular, causes considerable morbidity in young and previously healthy patients.

  • Tick-borne encephalitis virus vaccination breakthrough infections in Germany - A retrospective analysis from 2001-2018
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-12-13
    Gerhard Dobler; Klaus Kaier; Philip Hehn; Merle M. Böhmer; Teresa M. Kreusch; Johannes P. Borde

    Objectives There are only few data available regarding the clinical course of tick-borne encephalitis virus (TBEV) vaccination breakthrough infections. The published studies suggest, that vaccination breakthrough infections may have a more severe course than native TBEV infection in unvaccinated individuals - potentially due to antibody dependent enhancement. Here we report a large analysis of vaccination breakthrough infections. Methods This retrospective analysis was based on a national surveillance dataset spanning the years 2001–2018. Variables reflecting disease severity, like “CNS symptoms”, “myelitis”, “fatal outcome” and “hospitalization” were analyzed beside general epidemiological variables. Cases were categorized as “unvaccinated” or “ever vaccinated”, the latter category including cases with at least one dose of a TBEV vaccine. Results 6,073 notified TBEV infection cases were included in our analysis. Sufficient data on vaccination status were available for 95.1% of patients (5,777/6,073) - of these, 5,298 presented with a native infection. 334 (334/5,777) cases developed an infection despite having been vaccinated at least once. Comparing unvaccinated patients to those with at least one vaccination, we find an OR 2.73, [95% CI 0.79 to 9.50] regarding the variable fatal outcome, however not reaching statistical significance. Analyzing the clinical variables “CNS symptoms” and “myelitis”, there is no difference between these groups ((OR 0.86, [95% CI 0.68 to 1.08]) and (OR 1.30, [95% CI 0.74 to 2.27]) respectively). Patients who were vaccinated and had an assumed protection at symptom onset (n=100) had a higher risk for the development of myelitic symptoms (OR 2.21, [95% CI 1.01 to 4.86]) than unvaccinated patients. Conclusion Our findings could neither verify that vaccination breakthrough infections might cause a more severe disease than native infections nor prove a clear antibody dependent enhancement phenomenon. It remains unclear whether the increased myelitis risk in a subgroup of vaccinated patients is a true effect or confounded.

  • Mandatory surveillance and outbreaks reporting of the WHO priority pathogens for research & Discovery of new antibiotics in European countries
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-12-05
    Nithya Babu Rajendran, Nico T. Mutters, Giuseppe Marasca, Michela Conti, Frangiscos Sifakis, Cuong Vuong, Andreas Voss, Jesús Rodriguez Baño, Evelina Tacconelli

    Objectives In 2017 World Health Organization (WHO) published a global priority list of 12 antibiotic-resistant bacteria (ARB) in urgent need of new antibiotics. We aimed to identify and assess publicly-accessible mandatory surveillance systems and outbreaks reporting for these pathogens in the 28 European Union and 4 European Free Trade Association member states. Methods Compulsory reporting was mapped by reviewing national documents without applying language restrictions and through experts consultation. Information on surveillance targets, indicators, metrics, and dissemination modalities were extracted and a qualitative assessment performed for open access systems only. Results 21 countries (66%) had a mandate to survey at least one among the 12 WHO priority pathogens; 15 provided access to surveillance frameworks. These systems covered most frequently carbapenem-resistant Enterobacteriales (12; 38%), methicillin-resistant Staphylococcus aureus (12; 38%), and vancomycin-resistant enterococci (8; 25%). None of the European countries required reporting of resistance in Salmonella, Campylobacter, Helicobacter pylori, and Neisseria gonorrhoeae. High heterogeneity was observed in data collection, reporting, and dissemination among countries with clinical outcomes and risk factors being reported in less than half (22% and 25%). Only 6 countries (19%) implemented mandatory surveillance of outbreaks due to at least one WHO priority pathogen. Conclusions Our review shows that despite the increasing burden of ARB on the European population, only a very few countries implemented mandatory surveillance and outbreak reporting of the WHO priority pathogens. International efforts are needed to define the effectiveness of implementing mandatory reporting of these pathogens and assess their role in reducing the spread of ARB in healthcare and community settings.

  • Oral amoxicillin and amoxicillin-clavulanate: properties, indications, and usage
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-12-04
    Angela Huttner, Julia Bielicki, Michelle N. Clements, Niels Frimodt-Møller, Anouk E. Muller, Jean-Pierre Paccaud, Johan W. Mouton

    Background Amoxicillin has been in use since the 1970s; it is the most widely used penicillin both alone and in combination with the beta-lactamase clavulanic acid. Objectives In this narrative review, we re-examine the properties of oral amoxicillin and clavulanic acid and provide guidance on their use, with emphasis on the preferred use of amoxicillin alone. Sources Published medical literature (MEDLINE database via Pubmed) Content While amoxicillin and clavulanic acid have similar half-lives, clavulanic acid is more protein-bound and even less heat-stable than amoxicillin, with primarily hepatic metabolism. It is also more strongly associated with gastrointestinal side effects, including Clostridium difficile infection, and thus, in oral combination formulations, limits the maximum daily dose of amoxicillin that can be given. The first ratio for an amoxicillin-clavulanic acid combination was set at 4:1 due to clavulanic acid’s high affinity for beta-lactamases; ratios of 2:1, 7:1, 14:1 and 16:1 are currently available in various regions. Comparative effectiveness data for the different ratios are scarce. Amoxicillin-clavulanic acid is often used as empiric therapy for many of the World Health Organisation’s Priority Infectious Syndromes in adults and children, leading to extensive consumption, when some of these syndromes could be handled with a delayed-antibiotic-prescription approach or amoxicillin alone. Implications Using available epidemiologic and pharmacokinetic data, we provide guidance on indications for amoxicillin versus amoxicillin-clavulanic acid and on optimal oral administration, including choice of combination ratio. More data are needed, particularly on heat stability, pharmacodynamic effects and emergence of resistance in “real-world” clinical settings.

  • A multicenter observational study on the epidemiology, risk factors, management and outcomes of mucormycosis in India
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-12-04
    Atul Patel, Harsimran Kaur, Immaculata Xess, Joy S. Michael, Jayanthi Savio, Shivaprakash Rudramurthy, Rakesh Singh, Prakash Shastri, Pamidimukkala Umabala, Raman Sardana, Anupama Kindo, Malini Rajinder Capoor, Sangeetha Mohan, Valliappan Muthu, Ritesh Agarwal, Arunaloke Chakrabarti

    Objectives To describe the epidemiology, management, and outcome of subjects with mucormycosis; and, to evaluate the risk factors associated with mortality. Methods We conducted a prospective observational study involving consecutive subjects with proven mucormycosis across 12 centers from India. The demographic profile, microbiology, predisposing factors, management, and 90-day mortality were recorded; risk factors for mortality were analyzed. Results We included 465 subjects. Rhino-orbital mucormycosis was the most common (315/465, 67.7%) presentation followed by pulmonary (62/465, 13.3%), cutaneous (49/465, 10.5%), and others. The predisposing factors included diabetes mellitus (342/465, 73.5%), malignancy (42/465, 9.0%), transplant (36/465, 7.7%), and others. Rhizopus species (231/290, 79.7%) were the most common followed by Apophysomyces variabilis (23/290, 7.9%), and several rare Mucorales. Surgical treatment was performed in 62.2% (289/465) of the subjects. Amphotericin B was the primary therapy in 81.9% (381/465), while posaconazole was used as combination therapy in 53 (11.4%) subjects. Antifungal therapy was inappropriate in 7.6% (30/394) of the subjects. The 90-day mortality rate was 52% (242/465). On multivariate analysis, disseminated and rhino-orbital (with cerebral extension) mucormycosis, shorter duration of symptoms, shorter duration of antifungal therapy, and treatment with amphotericin B deoxycholate (vs. liposomal) were independent risk factors of mortality. A combined medical and surgical management was associated with a better survival. Conclusions Diabetes mellitus was the dominant predisposing factor in all forms of mucormycosis. Combined surgical and medical management was associated with better outcomes. Several gaps surfaced in the management of mucormycosis. The rarer Mucorales identified in the study warrant further evaluation.

  • Differentiation between Streptococcus pneumoniae and other viridans group streptococci by Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS)
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-12-04
    Rachid Y. Yahiaoui, Wil H. Goessens, Ellen E. Stobberingh, Annelies Verbon

    Objectives MALDI-TOF MS is becoming the method of choice for bacterial identification. However, correct identification by MALDI-TOF of closely related microorganisms such as viridans streptococci is still cumbersome especially in the identification of S. pneumoniae. By making use of additional spectra peaks for S. pneumoniae and other VGS. We re-identified viridans streptococci which had been identified and characterized by molecular and phenotypic techniques by MALDI-TOF. Methods VGS isolates (n=579), 496 S. pneumoniae and 83 non-S. pneumoniae were analysed using MALDI-TOF MS and the sensitivity and specificity of MALDI-TOF MS was assessed. Hereafter, Mass spectra analysis was performed. Presumptive identification of proteins represented by discriminatory peaks was performed by molecular weight matching and the corresponding nucleotides sequences against different protein databases. Results Using the Bruker reference library, 495 of 496 S. pneumoniae isolates were identified as S. pneumoniae and 1 isolate was identified as non-S. pneumoniae. Of the 83 non-S. pneumoniae isolates, 37 were correctly identified as non-S. pneumoniae, and 46 isolates as S. pneumoniae. The sensitivity of the MALDI-TOF MS was 99.8% (95% CI 98.9-100) and the specificity was 44.6% (95% CI 33.7-55.9). Eight spectra peaks were mostly present in one category (S. pneumoniae or other VGS) and absent in the other category and inversely. Two spectra peaks of these (m/z 3420 and 3436) were selected by logistic regression to generate three identification profiles. These profiles could differentiate between S. pneumoniae and other VGS with high sensitivity and specificity (99.4% and 98.8%, respectively). Conclusions Spectral peaks analysis based identification is a powerful tool to differentiate S. pneumoniae from other VGS species with high specificity and sensitivity and is a useful method for pneumococcal identification in carriage studies. More research is needed to further confirm our findings. Extrapolation of these results to clinical strains need to be deeply investigated.

  • Assessment of trimethoprim-sulfamethoxazole susceptibility testing methods for fastidious Haemophilus spp.
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-12-04
    Yanik Sierra, Fe Tubau, Aida González-Díaz, Anna Carrera-Salinas, Javier Moleres, Paula Bajanca-Lavado, Junkal Garmendia, MaÁngeles Domínguez, Carmen Ardanuy, Sara Martí

    Objectives To compare the determinants of trimethoprim-sulfamethoxazole (SXT) resistance with established susceptibility values for fastidious Haemophilus spp., in order to provide recommendations for optimal SXT measurement. Methods We collected 50 strains each of Haemophilus influenzae and Haemophilus parainfluenzae at Bellvitge University Hospital. SXT susceptibility was tested by microdilution, E-test, and disc diffusion using both Mueller-Hinton Fastidious (MH-F) and Haemophilus Test Medium (HTM) following EUCAST and CLSI criteria respectively. Mutations in folA, folP and additional determinants of resistance were identified in whole-genome sequenced isolates. Results Strains presented generally higher rates of SXT resistance when grown on HTM than on MH-F, independent of the methodology used (average MIC 2.6-fold higher in H. influenzae and 1.2-fold higher in H. parainfluenzae). The main resistance-related determinants were as follows: I95L and F154S/V in folA; 3 and 15 base pair insertions and substitutions in folP; acquisition of sul genes; and FolA overproduction potentially linked to mutations in -35 and -10 promoter motifs. Of note, 2 of 19 H. influenzae strains (10.5%) and 9 of 33 H. parainfluenzae strains (27.3%) with mutations and assigned as resistant by microdilution were inaccurately considered susceptible by disc diffusion. This misinterpretation was resolved by raising the clinical resistance breakpoint of the EUCAST guidelines to ≤30 mm. Conclusions Given the routine use of disc diffusion, a significant number of strains could potentially be miscategorised as susceptible to SXT despite having resistance-related mutations. A simple modification to the current clinical resistance breakpoint given by the EUCAST guideline for MH-F ensures correct interpretation and correlation with the gold-standard method of microdilution.

  • High-volume culture and quantitative real-rime PCR for the detection of Aspergillus in sputum
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-12-04
    Paschalis Vergidis, Caroline B. Moore, Lily Novak-Frazer, Riina Richardson, Adam Walker, David W. Denning, Malcolm D. Richardson

    Objectives Sputum culture is an insensitive method for the diagnosis of pulmonary aspergillosis. Growth of the organism allows identification of the causative species and susceptibility testing, both of which can inform treatment choices. The current practice is to culture an aliquot of diluted sputum. We assessed the value of culturing large volumes of unprocessed sputum, a method that we have termed high-volume culture (HVC). Methods Specimens were processed by conventional culture (using an aliquot of homogenized, diluted sputum on Sabouraud agar at 37°C and 45°C for up to 5 days) and HVC (using undiluted sputum on Sabouraud agar at 30°C for up to 14 days). A separate specimen was tested by quantitative real-time PCR (qPCR). Antifungal susceptibility testing was performed by the EUCAST standard. Results We obtained sputum specimens from 229 patients with the following conditions: Chronic pulmonary aspergillosis (66.8%, 153/229), allergic bronchopulmonary aspergillosis (25.3%, 58/229) and Aspergillus bronchitis (7.9%, 18/229). Patients with invasive pulmonary aspergillosis were not included. The positivity rate of conventional culture was 15.7% (36/229,95% CI: 11.6-21.0%) and that of HVC was 54.2% (124/229, 95% CI: 47.7-60.5%) (p<0.001). The higher positivity rate of HVC was demonstrated regardless of administration of antifungal treatment. qPCR had an overall positivity rate of 49.2% (65/132, 95% CI: 40.9-57.7%), comparable to that of HVC. Conclusion Detection of Aspergillus spp. in sputum is greatly enhanced by HVC. HVC allows for detection of azole-resistant isolates that would have been missed by conventional culture. This method can be performed in any microbiology laboratory without the need for additional equipment.

  • Infections caused by extended-spectrum beta-lactamase-producing Enterobacterales after rectal colonisation with ESBL-producing Escherichia coli or Klebsiella pneumoniae
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-12-03
    Luisa A. Denkel, Friederike Maechler, Frank Schwab, Axel Kola, Anna Weber, Petra Gastmeier, Frieder Pfäfflin, Susanne Weber, Guido Werner, Yvonne Pfeifer, Michael Pietsch, Rasmus Leistner

    Objectives Infections due to extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) are considered infections with a high public health burden. In this study, we aimed to identify incidences of and risk factors for healthcare-associated infections (HAI) after rectal colonisation with ESBL-producing Escherichia coli (ESBL-EC) or Klebsiella pneumoniae (ESBL-KP). Methods This prospective cohort study was performed in 2014 and 2015. Patients colonised with ESBL-EC or ESBL-KP were monitored for subsequent HAI with ESBL-E, and other pathogens. In case of an ESBL-E infection, rectal and clinical isolates were compared using pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS) for ESBL-KP isolates. Proportional hazard models were applied to identify risk factors for HAI, and to analyse competing risks. Results Among all patients admitted to the hospital during the study period, 13.6% were rectally screened for third-generation cephalosporin-resistant Enterobacterales (3GCREB). 2386 rectal carriers of ESBL-EC, and 585 of ESBL-KP were included in the study. Incidence density (ID) for HAI with ESBL-E was 2.74 per 1000 patient days at risk (95%CI 2.16 – 3.43) among carriers of ESBL-EC, while it was 4.44 per 1000 patient days at risk (95%CI 3.17 – 6.04) among carriers of ESBL-KP. In contrast, ID for HAI with other pathogens was 4.36 per 1000 patient days at risk (95%CI 3.62 – 5.21) among carriers of ESBL-EC, and 5.00 per 1000 patient days at risk (95%CI 3.64 – 6.69) among carriers of ESBL-KP. Cox proportional hazard regression analyses identified colonisation with ESBL-KP (HR = 1.58, 95%CI 1.068 – 2.325) compared to ESBL-EC as independent risk factor for HAI with ESBL-E. The results were consistent over all competing risk analyses. Conclusions Clinicians should be aware of the increased risk of ESBL-E infections among patients colonised with ESBL-KP compared to ESBL-EC that might be caused by underlying diseases, higher pathogenicity of ESBL-KP and other factors.

  • Cell-free Mycobacterium tuberculosis DNA test in pleural effusion for tuberculous pleurisy: a diagnostic accuracy study
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-12-02
    Xinting Yang, Nanying Che, Hongfei Duan, Zichen Liu, Kun Li, Hua Li, Chao Guo, Qingtao Liang, Yang Yang, Yuxuan Wang, Jing Song, Weili Du, Zhang Chen, Yahong Wang, Yun Zhang, HaiBo Wang, Xiaoyou Chen

    Objectives Tuberculous pleurisy (TP) diagnosis remains difficult, with the sensitivity of Xpert MTB/RIF (Xpert) and mycobacterial culture (culture) only about 30% to 50%. We aimed to assess the diagnostic performance of a cell-free Mycobacterium tuberculosis DNA test (cf-TB) in pleural effusion for TP. Methods Adults (≥18 years) with suspected TP presenting with pleural effusion were consecutively recruited and pleural effusion specimens were prospectively collected in Beijing Chest Hospital, Beijing, China. After centrifuging pleural effusion, sediments were used for culture, Xpert and T-SPOT.TB assay, whereas supernatants were used for cf-TB and adenosine deaminase assay. The diagnostic performance was assessed against a composite reference standard. Results From June 2015 to December 2018, we prospectively evaluated 286 adults with suspected TP. One hundred twenty-two participants were classified as definite TP based on the pre-specified composite reference standard. The cf-TB produced a sensitivity of 79.5% (97/122, 95% confidence interval [CI]: 72.4 to 86.7) for definite TP, which was superior to Xpert (38.5% [29.9 to 47.2]; 47/122; P<.001) and culture (27.1% [19.2 to 34.9]; 33/122; P<.001). With pleural effusion Xpert and/or culture as the reference standard, cf-TB showed 96.6% (57/59, 95% CI: 92.0-100.0) sensitivity, which was also significantly higher than Xpert (79.7%, 95% CI: 69.4-89.9; 47/59; P=0.004) and culture (55.9%, 95% CI: 43.3-68.6; 33/59; P<.001). Conclusions The cf-TB clearly showed improved sensitivity compared with Xpert and culture. We recommend cf-TB as the first-line test for TP diagnosis.

  • Heterologous effects of vaccination and trained immunity
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-31
    I.C. Gyssens, M.G. Netea

    Vaccines are applied to large populations, but only recently has research into immunologic responses and mechanisms started to increase exponentially. Some live vaccines, such as the tuberculosis vaccine bacillus Calmette-Guérin, protect against other infections nonspecifically by eliciting complex immune responses which are not specific antibody related. These heterologous effects are explained by the concept of trained immunity. This editorial introduces five narrative reviews offering recent insights on innate and adaptive immune memory towards a variety of pathogens.

  • Trained innate immunity and resistance to Mycobacterium tuberculosis infection
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-02-23
    V.A.C.M. Koeken, A.J. Verrall, M.G. Netea, P.C. Hill, R. van Crevel

    Background Some individuals, even when heavily exposed to an infectious tuberculosis patient, develop neither active nor latent tuberculosis infection (LTBI). This ‘early clearance’ of Mycobacterium tuberculosis is associated with a history of bacillus Calmette–Guérin (BCG) vaccination. As BCG vaccination can boost innate immune responses through a process termed ‘trained immunity’, we hypothesize that BCG-induced trained innate immunity contributes to early clearance of M. tuberculosis. Objectives We describe the epidemiological evidence and biological concepts of early clearance and trained immunity, and the possible relation between these two processes through BCG vaccination. Sources Relevant data from published reports up to November 2018 were examined in the conduct of this review. Content Several observational studies and one recent randomized trial support the concept that boosting innate immunity contributes to protection against M. tuberculosis infection, with BCG vaccination providing approximately 50% protection. The molecular mechanisms mediating early clearance remain largely unknown, but we propose that trained immunity, characterized by epigenetic and metabolic reprogramming of innate immune cells such as monocytes or macrophages, is at least partially responsible for eliminating the mycobacteria and inducing early clearance. Implications Future studies should examine if BCG revaccination increases early clearance of M. tuberculosis through induction of trained immunity. Epigenetic or metabolic modulation may further boost BCG-induced trained innate immunity to promote tuberculosis prevention. New tuberculosis vaccine candidates should also be examined for their capacity to improve protection against M. tuberculosis infection and induce trained immunity.

  • Non-specific effects of BCG in protozoal infections: tegumentary leishmaniasis and malaria
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-06-15
    J.C. dos Santos, M. Vilela Teodoro Silva, F. Ribeiro-Dias, L.A.B. Joosten

    Background Leishmaniasis and malaria are major causes of illness in the poorest countries. In the absence of efficient strategies to prevent infections and to control the transmission of the parasites by insect vectors, treatment relies on drug therapy. Vaccine development continues on several fronts; however none of the candidates developed has so far been shown to provide long-lasting protection at a population level. Because the bacillus Calmette–Guérin (BCG) vaccine can induce heterologous protective effects, we hypothesize that BCG has beneficial effects in the control of tegumentary leishmaniasis (TL) and malaria. Aims In this review we describe evidence for the protective efficacy of BCG against tegumentary leishmaniasis and malaria in humans. Sources Relevant data from peer-reviewed scientific literature published on Pubmed up to January 2019 were examined. Content From experimental animal and various human studies with BCG and one recent randomized malaria trial there is evidence that BCG has beneficial effects in Leishmania spp. and Plasmodium falciparum infections. Although the precise mechanisms remain unknown, BCG can activate innate immune responses, and an increasing body of evidence demonstrates that the induction of trained innate immunity could explain its non-specific protective effects. Implications Despite many years of research to prevent and treat TL and malaria, these diseases remain a public health problem in tropical countries. Future studies are required to examine if BCG vaccination could be used as an effective treatment option.

  • Non-specific effects of BCG vaccine on viral infections
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-02
    S.J.C.F.M. Moorlag, R.J.W. Arts, R. van Crevel, M.G. Netea

    Background Some strains of Bacillus Calmette–Guérin (BCG) vaccine not only confer protection against disseminated forms of tuberculosis, but also reduce all-cause mortality by the induction of protection against infections with non-related pathogens. Objectives We review evidence for non-specific protection induced by BCG vaccination against viral infections, discuss possible mechanisms of action, and summarize implications for vaccination policies and vaccine discovery. Sources Relevant studies retrieved from PubMed and clinicaltrials.gov. Content Numerous epidemiological, clinical and immunological studies demonstrate that BCG vaccination impacts the immune response to subsequent infections, resulting in reduced morbidity and mortality. Important lines of evidence indicating that BCG protects against viral pathogens comes from experimental studies in mice showing that BCG offers protection against various DNA and RNA viruses, including herpes and influenza viruses. Recently, the effect of BCG on an experimental viral infection in humans has been demonstrated. These effects are thought to be mediated via the induction of innate immune memory and heterologous lymphocyte activation, resulting in enhanced cytokine production, macrophage activity, T-cell responses and antibody titres. Implications The discovery of innate immune memory has greatly improved our understanding of the mechanisms underlying the non-specific effects induced by BCG vaccination. However, a full understanding of the molecular mechanisms that underlie this phenomenon is still evolving. By identifying the factors that impact the non-specific effects of BCG, we will take an important step towards novel therapeutic options and vaccination strategies, which might lead to a reduction in severe morbidity and mortality associated with viral infections.

  • The impact of vaccines on heterologous adaptive immunity
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-02-20
    N.L. Messina, P. Zimmermann, N. Curtis

    Background Vaccines induce antigen-specific memory in adaptive immune cells that enables long-lived protection against the target pathogen. In addition to this, several vaccines have beneficial effects greater than protection against their target pathogen. These non-specific effects are proposed to be the result of vaccine-induced immunomodulation. In the case of bacille Calmette–Guérin (BCG) vaccine, this involves induction of innate immune memory, termed ‘trained immunity’, in monocytes and natural killer cells. Objectives This review discusses current evidence for vaccine-induced immunomodulation of adaptive immune cells and heterologous adaptive immune responses. Content The three vaccines that have been associated with changes in all-cause infant mortality: BCG, diphtheria–tetanus–pertussis (DTP) and measles-containing vaccines (MCV) alter T-cell and B-cell immunity. The majority of studies that investigated non-specific effects of these vaccines on the adaptive immune system report changes in numbers or proportions of adaptive immune cell populations. However, there is also evidence for effects of these vaccines on adaptive immune cell function and responses to heterologous stimuli. There is some evidence that, in addition to BCG, DTP and MCV, other vaccines (that have not been associated with changes in all-cause mortality) may alter adaptive immune responses to unrelated stimuli. Implications This review concludes that vaccines alter adaptive immune cell populations and heterologous immune responses. The non-specific effects differ between various vaccines and their effects on heterologous adaptive immune responses may also involve bystander activation, cross-reactivity and other as yet undefined mechanisms. This has major implications for future vaccine design and vaccination scheduling.

  • Intensive care management of influenza-associated pulmonary aspergillosis
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-16
    P. Koehler, M. Bassetti, M. Kochanek, A. Shimabukuro-Vornhagen, O.A. Cornely

    Background Severe pulmonary infections are among the most common reasons for admission to intensive care units (ICU). Within the last decade, increasing reports of severe influenza pneumonia resulting in acute respiratory distress syndrome (ARDS) complicated by Aspergillus infection were published. Objectives To provide a comprehensive review of management of influenza-associated pulmonary aspergillosis in patients with ARDS. Sources Review of the literature pertaining to severe influenza-associated pulmonary aspergillosis. PubMed database was searched for publications from the database inception to January 2019. Content In patients with lower respiratory symptoms, development of respiratory insufficiency should trigger rapid and thorough clinical evaluation, in particular in cases of suspected ARDS, including electrocardiography and echocardiography to exclude cardiac dysfunction, arrhythmias and ischaemia. Bronchoalveolar lavage should obtain lower respiratory tract samples for galactomannan assay, direct microscopy, culture, and bacterial, fungal and viral PCR. In case of positive Aspergillus testing, chest CT is the imaging modality of choice. If influenza pneumonia is diagnosed, neuraminidase inhibitors are the preferred approved drugs. When invasive aspergillosis is confirmed, first-line therapy consists of isavuconazole or voriconazole. Isavuconazole is an alternative in case of intolerance to voriconazole, drug–drug interactions, renal impairment, or if a spectrum of activity including the majority of Mucorales is desired. Primary anti-mould prophylaxis with posaconazole is recommended in haematology patients at high-risk. It may be considered in newly diagnosed influenza and ARDS, but ideally in clinical trials. Implications The rising reports of influenza-associated pulmonary aspergillosis in patients with ARDS, who are otherwise not considered at risk for fungal pneumonia demands heightened clinical awareness. Tracheobronchitis and Aspergillus in respiratory tract samples should prompt suspicion of invasive fungal infection and further work-up. The management algorithm should comprise bronchoalveolar lavage, CT imaging, sophisticated ventilator-management, rescue extracorporeal membrane oxygenation, and antifungal and antiviral therapy. To decrease the burden of influenza-related illness, vaccination is of utmost importance, specifically in patients with co-morbidities.

  • Reporting infections in clinical trials of patients with haematological malignancies
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-14
    N. Tau, L. Shargian-Alon, S. Reich, M. Paul, A. Gafter-Gvili, D. Shepshelovich, D. Yahav

    Background Infections are common among patients treated for haematological malignancies and are associated with significant morbidity and mortality. The completeness of reporting infectious complications in randomized controlled trials (RCTs) assessing treatments for haematological malignancies is unknown. Objectives We aimed to evaluate the completeness of reporting infectious complications in RCTs assessing treatments for haematological malignancies. Data source A systematic literature search was performed in PubMed database. Study eligibility criteria and participants All primary published phase II/III RCTs between September 2016 and September 2018 evaluating treatments for haematological malignancies in adult patients were included. Intervention Reporting infectious complications. Methods A systematic review was conducted to evaluate the completeness of reporting. Study characteristics and data concerning reporting of infectious complications were collected by two independent reviewers. Quality of reporting was assessed using a modification of the CONSORT extension checklist for harms, including 15 items. Results One-hundred and seven RCTs were included. Most trials (97; 91%) provided some report on infections. Approximately half reported on each of pneumonia, sepsis and neutropenic fever; 12 trials (11%) reported on fungal infections. Only nine trials (8%) listed infections by type of pathogen (i.e. bacterial, fungal or viral) and 48 (45%) by source/type of infection (i.e. pneumonia, urinary tract infection, etc.). Most trials did not address infections in their title, abstract, introduction or discussion. Median number of items of the CONSORT modification reported was 7 points, (interquartile range (IQR) 6–9) for all included trials, with lower median for 34 acute leukaemia trials (median 6, IQR 5–8). Conclusions Most trials evaluating treatment for haematological malignancies provide some data relating to infectious complications. The reports are mostly incomplete and rarely provided in a structured presentation.

  • Digital PCR: a new technology for diagnosis of parasitic infections
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-06-18
    E. Pomari, C. Piubelli, F. Perandin, Z. Bisoffi

    Background Parasitic infections are responsible for a significant burden of disease worldwide as a result of international travel and immigration. More accurate diagnostic tools are necessary in support to parasite control and elimination programmes in endemic regions as well as for rapid case detection in non-endemic areas. Digital PCR (dPCR) is a powerful technology with recent applications in parasitology. Aims This review provides for the first time an overview of dPCR as a novel technology applied to detection of parasitic infections, and highlights the most relevant potential benefits of this assay. Sources Peer-reviewed literature pertinent to this review based on PubMed, Cochrane and Embase databases as well as laboratory experience of authors. Content Among the 86 studies retrieved, 17 used the dPCR applied to parasites belonging to protozoa (8), helminths (8) and arthropods (1) of clinical human interest. dPCR was adopted in four studies, respectively, for Plasmodium and Schistosoma japonicum. dPCR led to clear advantages over quantitative real-time PCR in P. falciparum and spp., and in S. japonicum showing higher sensitivity; and in Cryptosporidium with higher stability to inhibitors from stool. For all parasites, dPCR allows absolute quantitation without the need of a standard curve. Various dPCR platforms were used. A few critical factors need consideration: DNA load, choice of platform and reaction optimization. Implications Owing to its sensitivity and quantitative characteristics, dPCR is a potential candidate to become an appealing new method among the molecular technologies for parasite detection and quantitative analysis in the future. In general, it has more applications than genomic DNA detection only, such as quantitation in mixed infections, gene expression and mutation analysis. dPCR should be considered in malaria screening and diagnosis as a complement to routine assays and in schistosomiasis elimination programmes. Standardized strategies and further studies are needed for the integration of dPCR in routine clinical laboratory.

  • Enteropathogens in paediatric gastroenteritis: comparison of routine diagnostic and molecular methods
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-07-30
    A. Tilmanne, D. Martiny, C. Quach, M. Wautier, O. Vandenberg, P. Lepage, M. Hallin

    Objectives Studies of acute gastroenteritis (AGE) are hampered by the lack of routine diagnostic methods with good sensitivity and specificity. Molecular methods are increasingly used for clinical purposes, but the clinical significance of a positive result remains a challenge. In this study we aimed to compare results of routine diagnostic methods and molecular methods in symptomatic children and asymptomatic controls. Methods Patients presenting to the pediatric emergency departments of two university hospitals in Brussels with AGE were recruited prospectively from May 2015 to October 2016; asymptomatic controls were recruited from the same hospitals. Stool analyses were performed for all participants for common pathogenic bacteria (culture), virus (immunochromatography) and parasites (microscopy). Stools were also analysed with the Luminex Gastrointestinal Pathogen Panel, a multiplex-PCR for common enteropathogens. Results Stools from 178 patients and 165 controls were analysed. An enteropathogen was detected in 62.4% (111/178) of cases when combining the two methods (56.2% (100/178) by Luminex, 42.7% (76/178) with routine methods) and 29.1% (48/165) of controls (24.2% (40/165) by Luminex and 10.3% (17/165) by routine methods). Some pathogens were detected more often with Luminex than with routine methods, such as Salmonella (16.3% (29/178) with Luminex and 3.9% (7/178) with routine method, p < 0.05), whereas others identified by culture methods, such as Campylobacter, Shigella, Yersinia, were missed by Luminex. Conclusions Molecular tools seem attractive methods, providing high positivity and a rapid turn-around time for the diagnosis of AGE. However, high rates of positivity in both cases and controls highlight the difficulty in interpreting results. Pathogens missed by Luminex but detected by culture methods raise more questions about the true clinical interest of the technique for our patients.

  • The impact of carbapenemase-producing Enterobacteriaceae colonization on infection risk after liver transplantation: a prospective observational cohort study
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-04-27
    M. Giannella, M. Bartoletti, C. Campoli, M. Rinaldi, S. Coladonato, R. Pascale, S. Tedeschi, S. Ambretti, F. Cristini, F. Tumietto, A. Siniscalchi, V. Bertuzzo, M.C. Morelli, M. Cescon, A.D. Pinna, R. Lewis, P. Viale

    Objective To investigate the impact of colonization with carbapenemase-producing Enterobacteriaceae (CPE) on the CPE infection risk after liver transplantation (LT). Methods Prospective cohort study of all adult patients undergoing LT at our centre over an 8-year period (2010–2017). Individuals were screened for CPE colonization by rectal swabs at inclusion onto the waiting list, immediately before LT and weekly after LT until hospital discharge. Asymptomatic carriers did not receive decolonization, anti-CPE prophylaxis or pre-emptive antibiotic therapy. Participants were followed up for 1 year after LT. Results We analysed 553 individuals who underwent a first LT, 38 were colonized with CPE at LT and 104 acquired colonization after LT. CPE colonization rates at LT and acquired after LT increased significantly over the study period: incidence rate ratios (IRR) 1.21 (95% CI 1.05–1.39) and 1.17 (95% CI 1.07–1.27), respectively. Overall, 57 patients developed CPE infection within a median of 31 (interquartile range 11–115) days after LT, with an incidence of 3.05 cases per 10 000 LT-recipient-days and a non-significant increase over the study period (IRR 1.11, 95% CI 0.98–1.26). In multivariable analysis, CPE colonization at LT (hazard ratio (HR) 18.50, 95% CI 6.76–50.54) and CPE colonization acquired after LT (HR 16.89, 95% CI 6.95–41.00) were the strongest risk factors for CPE infection, along with combined transplant (HR 2.60, 95% CI 1.20–5.59), higher Model for End-Stage Liver Disease at the time of LT (HR 1.03, 95% CI 1.00–1.07), prolonged mechanical ventilation (HR 2.63, 95% CI 1.48–4.67), re-intervention (HR 2.16, 95% CI 1.21–3.84) and rejection (HR 2.81, 95% CI 1.52–5.21). Conclusions CPE colonization at LT or acquired after LT were the strongest predictors of CPE infection. Prevention strategies focused on LT candidates and recipients colonized with CPE should be investigated.

  • Microbiological changes observed over 48 weeks of treatment with inhaled liposomal ciprofloxacin in individuals with non-cystic fibrosis bronchiectasis and chronic Pseudomonas aeruginosa lung infection
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-04-26
    D.R. VanDevanter, I. Gonda, J. Dahms, D. Cipolla, A.M. Davis, J.D. Chalmers, J. Froehlich

    Objectives Non-cystic fibrosis bronchiectasis (NCFBE) with Pseudomonas aeruginosa has been associated with increased pulmonary exacerbation (PEx) and mortality risk. European Respiratory Society guidelines conditionally recommend inhaled antimicrobials for persons with NCFBE, P aeruginosa and three or more PEx/year. We report microbiological results of two randomized, 48-week placebo-controlled trials of ARD-3150 (inhaled liposomal ciprofloxacin) in individuals with NCFBE with P aeruginosa and PEx history [Lancet Respir Med 2019;7:213–26]. Methods Respiratory secretions from 582 participants receiving up to six 28-day on/off treatment cycles were analysed for sputum P. aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli densities, P. aeruginosa susceptibilities to ciprofloxacin and nine other antimicrobials, and prevalence of other bacterial opportunists. Associations between PEx risk and sputum density, antimicrobial susceptibility and opportunist prevalence changes were studied. Results Sputum P. aeruginosa density reductions from baseline after ARD-3150 treatments ranged from 1.77 (95% CI 2.13–1.40) versus 0.54 (95% CI 0.89–0.19) log10 CFU/g for placebo (second period) to 2.07 (95% CI 2.45–1.69) versus 0.70 (95% CI 1.11–0.29) log10 CFU/g for placebo (fourth period) with only modest correlation between density reduction magnitude and PEx benefit. ARD-3150 (but not placebo) treatment was associated with increased P. aeruginosa ciprofloxacin MIC but not emergence of other bacterial opportunists across the study; ciprofloxacin MIC50 increased from 0.5 to 1 mg/L, MIC90 increased from 4 to 16 mg/L. Other antimicrobial MIC were mostly unaffected. Conclusion Microbiological changes over 48 weeks of ARD-3150 treatment appear modest. Ciprofloxacin susceptibility (but not other antimicrobial susceptibility) decreases were observed that did not appear to preclude PEx risk reduction benefit.

  • Respiratory virus infection among hospitalized adult patients with or without clinically apparent respiratory infection: a prospective cohort study
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-04-18
    K.K.W. To, K.-H. Chan, J. Ho, P.K.P. Pang, D.T.Y. Ho, A.C.H. Chang, C.W. Seng, C.C.Y. Yip, V.C.C. Cheng, I.F.N. Hung, K.-Y. Yuen

    Objectives To determine the viral epidemiology and clinical characteristics of patients with and without clinically apparent respiratory tract infection. Methods This prospective cohort study was conducted during the 2018 winter influenza season. Adult patients with fever/respiratory symptoms (fever/RS group) were age- and sex-matched with patients without fever/RS (non-fever/RS group) in a 1:1 ratio. Respiratory viruses were tested using NxTAG™ Respiratory Pathogen Panel IVD, a commercially-available multiplex PCR panel. Results A total of 214 acutely hospitalized patients were included in the final analysis, consisting of 107 with fever/RS (fever/RS group), and 107 age- and sex-matched patients without fever/RS (non-fever/RS group). Respiratory viruses were detected in 34.1% (73/214) of patients, and co-infection occurred in 7.9% (17/214) of patients. The incidence of respiratory virus was higher in the fever/RS group than in the non-fever/RS group (44.9% (48/107) versus 23.4% (25/107), p 0.001). Influenza B virus, enterovirus/rhinovirus and coronaviruses were detected more frequently in the fever/RS group, whereas parainfluenza virus 4B and adenovirus were detected more frequently in the non-fever/RS group. Among the non-fever/RS group, chest discomfort was more common among patients tested positive for respiratory viruses than those without respiratory virus detected (44% (11/25) versus 22% (18/82), p 0.04). Conclusions Respiratory viruses can be frequently detected among hospitalized patients without typical features of respiratory tract infection. These patients may be a source of nosocomial outbreaks.

  • An automated smear microscopy system to diagnose tuberculosis in a high-burden setting
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-13
    Y. Tan, B. Su, X. Cai, P. Guan, X. Liu, P. Ma, H. Zhou, J. Liu, Y. Pang

    Objectives TB-EASM (Howsome, Shanghai, China), an automated system combining smear preparation, staining and microscopy in a single platform, was evaluated for tuberculosis (TB) diagnosis in a high disease-burden setting. Methods Sputum samples from individuals with pulmonary TB were processed in parallel using conventional manual smear microscopy (MS), TB-EASM, liquid culture and GeneXpert. Method sensitivity and specificity were compared with Mycobacterium tuberculosis detection by mycobacteria growth indicator tube (MGIT) and/or GeneXpert MTB/RIF. Results Of 524 samples, 496 met evaluation criteria for study inclusion. The proportion of M. tuberculosis detected by TB-EASM was 28.2% (150/496), significantly higher than for MS (111/496, 21.2%, p 0.01) and comparable to the rate for MGIT (163/496, 32.9%, p > 0.05). For 190 M. tuberculosis-positive cases identified using MGIT and/or GeneXpert MTB/RIF, the reference standard detection methods, TB-EASM detected 140 positive cases, for an overall sensitivity rate of 73.7% (140/190, 95% CI 67.4–79.9), which was significantly higher than for MS (105/190, 55.3%, 95% CI 48.2–62.3, p < 0.01). Specificities were 96.7% (296/306, 95% CI 94.7–98.7) for TB-EASM and 98.0% (300/306, 95% CI 96.5–99.6) for MS. Conclusion TB-EASM outperformed conventional MS for M. tuberculosis detection in sputum specimens.

  • Multicentre study to determine the Etest epidemiological cut-off values of antifungal drugs in Candida spp. and Aspergillus fumigatus species complex
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-11
    M. Salsé, J.-P. Gangneux, S. Cassaing, L. Delhaes, A. Fekkar, D. Dupont, F. Botterel, D. Costa, N. Bourgeois, B. Bouteille, S. Houzé, E. Dannaoui, H. Guegan, E. Charpentier, F. Persat, L. Favennec, L. Lachaud, M. Sasso

    Objectives To determine the Etest-based epidemiological cut-off values (ECVs) for antifungal agents against the most frequent yeast and Aspergillus fumigatus species isolated in 12 French hospitals. Methods For each antifungal agent, the Etest MICs in yeast and A. fumigatus isolates from 12 French laboratories were retrospectively collected from 2004 to 2018. The ECVs were then calculated using the iterative statistical method with a 97.5% cut-off. Results Forty-eight Etest ECVs were determined for amphotericin B, caspofungin, micafungin, anidulafungin, fluconazole, voriconazole, posaconazole and itraconazole, after pooling and analysing the MICs of 9654 Candida albicans, 2939 Candida glabrata SC, 1458 Candida parapsilosis SC, 1148 Candida tropicalis, 575 Candida krusei, 518 Candida kefyr, 241 Candida lusitaniae, 131 Candida guilliermondii and 1526 Aspergillus fumigatus species complex isolates. These ECVs were 100% concordant (identical or within one two-fold dilution) with the previously reported Etest-based ECVs (when available), and they were concordant in 76.1% of cases with the Clinical and Laboratory Standards Institute ECVs and in 81.6% of cases with the European Committee on Antimicrobial Susceptibility Testing ECVs. Conclusions On the basis of these and other previous results, we recommend the determination of method-dependent ECVs. Etest ECVs should not be used instead of breakpoints, but may be useful to identify non-wild-type isolates with potential resistance to antifungal agents, and to indicate that an isolate may not respond as expected to the standard treatment.

  • Prevalence of human papillomavirus, human immunodeficiency virus and other sexually transmitted infections among female sex workers in Togo: a national cross-sectional survey
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-04-30
    V.M. Ferré, D.K. Ekouevi, F.A. Gbeasor-Komlanvi, G. Collin, Q. Le Hingrat, B. Tchounga, M. Salou, D. Descamps, C. Charpentier, A.C. Dagnra

    Objectives Sub-Saharan Africa is a region with high incidence of both human immunodeficiency virus (HIV) and cervical cancer. We conducted the first national study in Togo to assess prevalence of human papillomavirus (HPV), HIV and other sexually transmitted infections (STIs) among female sex workers (FSW). Methods A multicentric cross-sectional study was conducted among FSW recruited in hot spots (clubs, streets) in four Togolese cities. HPV and STIs were tested from cervical and anal swabs. HIV and syphilis were screened with rapid tests. Results In all, 310 FSW were recruited; HIV and cervical high-risk HPV (hrHPV) prevalence were 10.6% (33/310) and 32.9% (102/310), respectively. The most frequent hrHPV types were HPV58 (13.6%, 19/140), HPV35 (12.9%, 18/140), HPV31 (12.1%, 17/140) and HPV16 (10.7%, 15/140). Prevalence of hrHPV and multiple hrHPV infections showed higher rates in HIV-positive than in HIV-negative FSW (48.5% versus 31.0%, p 0.04 and 21.2% versus 9.0%, p 0.03; respectively). Prevalence of hrHPV was higher in cervical than anal swabs (34.1% versus 20.7%, p 0.0004). High-risk HPV anal infections were more frequent among HIV-positive than HIV-negative FSW (51.9% versus 17.3%, p 2 × 10−5). Concomitant anal and cervical hrHPV infections were present in 43.2% (41/95) of hrHPV-positive FSW. Overall prevalence in the cervix of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium and Trichomonas vaginalis were 4.2%, 6.1%, 5.5% and 6.5%, respectively. Conclusions This first African study on paired cervical and anal samples showed a high prevalence of genital HPV infections with a rather high rate of concomitant HPV infections but low type concordance. We report an unusual distribution of hrHPV types. These findings highlight the critical need for implementation of a national HPV vaccination strategy.

  • Isolation and culture of Methanobrevibacter smithii by co-culture with hydrogen-producing bacteria on agar plates
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-04-12
    S.I. Traore, S. Khelaifia, N. Armstrong, J.C. Lagier, D. Raoult

    Objectives Methanogenic Archaea are considered as extremely oxygen-sensitive organisms, and their culture is fastidious, requiring specific equipment. We report here conditions allowing the cultivation of Methanobrevibacter smithii in an anaerobic chamber without the addition of hydrogen. Methods We first enriched the stool sample in an anaerobic liquid medium. To cultivate M. smithii with Bacteroides thetaiotaomicron and other hydrogen-producing bacteria on solid medium in an anaerobic chamber, we divided the agar plates into two compartments and seeded each strain on each compartment. Methane production was assessed by gas chromatography, and the growing colonies were authenticated by MALDI-TOF MS. Results We successfully cultured M. smithii from a liquid culture medium inoculated with stool collected from a healthy donor in an anaerobic chamber. The isolation in pure culture permitted successful culture on agar medium by our performing a co-culture with B. thetaiotaomicron. We also successfully tested the co-cultivation of M. smithii with other known hydrogen-producing bacteria. Gas chromatographic tests showed that these strains produced hydrogen in different amounts. Agar colonies of methanogens were obtained by co-culture with these bacteria, and methane production was detected. Conclusions We propose a new approach to isolate and cultivate new strains of M. smithii by using a co-culture–based technique that can facilitate and make available the isolation of new methanogenic Archaea strains in clinical microbiology laboratories.

  • How scientists and physicians use Twitter during a medical congress
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-05-16
    M. Cevik, D.S.Y. Ong, G. Mackenzie

    Objectives During medical congresses Twitter allows discussions to disseminate beyond the congress hall and reach a wider audience. Insights into the dynamics of social media interactions during congresses, dissemination of scientific information and the determinants of a successful tweet may allow us to better understand social media's role in science communication. Methods We retrospectively extracted social media data during the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2017 and 2018 using NodeXL. We compared social media activity during these two congresses. Subsequently, we conducted in-depth analyses to identify the components of a successful tweet and multivariable analysis to assess independent factors associated with retweet activity. Results In 2018, approximately 13 000 delegates attended ECCMID, but only 591 Twitter accounts actively tweeted about the congress. Although fewer tweets were posted in 2018 compared with 2017 (4213 versus 4657, respectively), ECCMID 2018 generated a 63% increase in the total number of retweets (p < 0.001). According to multivariable logistic regression analysis, using multimedia, URL or hashtags and mentioning other Twitter account(s) were independently associated with retweet success. Mentioning of other users and use of multimedia were the only consistent predictors of retweets irrespective of the number of followers. Conclusions A substantial increase in retweet activity and a modest increase in the number of influential Twitter accounts were observed between two successive congresses. Dissemination of scientific messages is more successful when connected accounts are actively involved in social media activity, and social media posts constitute the right combination of components.

  • Association between type-specific influenza circulation and incidence of severe laboratory-confirmed cases; which subtype is the most virulent?
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-11-22
    Theodore Lytras, Anastasia Andreopoulou, Kassiani Gkolfinopoulou, Elisavet Mouratidou, Sotirios Tsiodras

    Objectives Excess population mortality during winter is most often associated with influenza A(H3N2), though susceptibility differs by age. We examined differences between influenza types/subtypes in their association with severe laboratory-confirmed cases, overall and by age group, to determine which type is the most virulent. Methods We used nine seasons of comprehensive nationwide surveillance data from Greece (2010-2011 to 2018-2019) to examine the association, separately for influenza A(H1N1)pdm09, A(H3N2) and B, between the number of laboratory-confirmed severe cases (intensive care hospitalizations or deaths) per type/subtype and the overall type-specific circulation during the season (expressed as a cumulative incidence proxy). Quasi-Poisson models with identity link were used, and multiple imputation to handle missing influenza A subtype. Results For the same level of viral circulation and across all ages, influenza A(H1N1)pdm09 was associated with twice as many intensive care hospitalizations as A(H3N2) (Rate Ratio [RR] 1.89, 95%CI 1.38–2.74) and three times more than influenza B (RR 3.27, 95%CI 2.54–4.20). Similar associations were observed for laboratory-confirmed deaths. A(H1N1)pdm09 affected adults over 40 years at similar rates, whereas A(H3N2) affected the elderly at a much higher rate than younger persons (>=65 vs 40-64 years, RR for intensive care 5.42, 95%CI 3.45–8.65, and RR for death 6.19, 95%CI 4.05–9.38). Within the 40-64 years age group, A(H1N1)pdm09 was associated with an approximately five times higher rate of severe disease compared to both A(H3N2) and B. Conclusions Influenza A(H1N1)pdm09 is associated with many more severe laboratory-confirmed cases, likely due to a more typical clinical presentation and younger patient age, leading to more testing. A(H3N2) affects older people more, with cases less often recognized and confirmed.

  • Bloodstream infections – Standard and progress in pathogen diagnostics
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-11-22
    Brigitte Lamy, Martin Sundqvist, Evgeny A. Idelevich

    Background Bloodstream infection (BSI) is a major public health burden worldwide, with high mortality. Patient outcome is critically influenced by delayed therapy, and fast and accurate pathogen diagnostics decisively improves the care of patients. During the past two decades major improvements has been made in the diagnostic performance of blood culture diagnostics through actions on pre-analysis and time-to-result. Objectives To review and discuss the literature for standard procedures and the progress in BSI pathogen diagnostics, and to propose a new mindset to reach an improved diagnostic workflow. Sources Scientific articles and reviews available through NCBI/Pubmed. Content Blood culture performance relies largely on the quality of its pre-analytical phase that is improved with educational actions monitored by using key performance indicators, and external quality assessment. Advanced blood culture systems now provide tools for an automated estimation of the bottle filling. These proved efficient to facilitate effective training for improving blood collection. On analytic aspects, rapid methods for pathogen identification, among which matrix-assisted laser desorption/ionization time of flight mass spectrometry dominates, and rapid antimicrobial susceptibility testing are reviewed. These technical developments call for improvements in all other steps, especially in pre- and post-analytic logistics to give the full reciprocation of these techniques on patient management. This aspect is summarized in the term of “microbiologistics” that covers all possible improvements in the logistic chain from sampling to report. Implications Progress in BSI pathogen diagnostics is based on a bundle approach that includes optimization of the pre-analytical parameters, rapid start of incubation, the use of rapid methods, re-organisation (e.g. 24/7, transportation service) and a close involvement of antimicrobial stewardship teams. These developments lead to define a new standard for bloodstream infection diagnostics.

  • Changing epidemiology of invasive non-typhoid Salmonella infection: a nationwide population-based registry study
    Clin. Microbiol. Infect. (IF 6.425) Pub Date : 2019-11-21
    Lapo Mughini-Gras, Roan Pijnacker, Janneke Duijster, Max Heck, Ben Wit, Kees Veldman, Eelco Franz

    Objectives Non-typhoid Salmonella (NTS) may invade beyond the intestine, causing bacteraemia, sepsis, and infection of normally sterile sites. The epidemiology of invasive NTS (iNTS) infection is under-researched. We determined trends, risk factors, serotype distribution, antimicrobial resistance (AMR), and attributable sources of iNTS infection in a high-income setting. Methods 22,837 records of culture-confirmed human salmonellosis cases and 10,008 serotyped Salmonella isolates from five putative animal reservoirs (pigs, cattle, broilers, layers, reptiles) in the Netherlands during 2005-2018 were retrieved from national surveillance registries. Risk factors for iNTS infection were identified using logistic regression analysis. Source attribution modelling was based on serotyping, prevalence, and exposure data. Results The average annual percentage of iNTS infections was 4.6% (range: 3.5-5.7%). An increase in iNTS infections was observed since 2012 (Odds Ratio [OR]: 1.09, 95% Confidence Interval [95%CI]: 1.04-1.14). Increased iNTS infection risk was associated with wintertime (OR: 1.37, 95%CI: 1.12-1.66), male sex (OR: 1.73, 95%CI: 1.51-1.99), older age (ORs: 3.27 to 16.33, depending on age groups), and living in rural areas (OR: 1.54, 95%CI: 1.23-1.93). While 52% of iNTS infections (n=950) were caused by serotypes Enteritidis and Typhimurium, those displaying the highest invasiveness relative to their occurrence were Dublin (32.9%, n=163), Panama (21.6%, n=106), and Poona (14.1%, n=71). Cattle were a larger source of iNTS than non-iNTS infections (12.2% vs. 7.6%). Lower AMR and multi-resistance rates were observed among iNTS (37.9%) than non-iNTS isolates (48.6%). Conclusions The increase in iNTS infections, which is reported also in other countries, is of public health and clinical concern. The underlying reasons seem to be multi-factorial in nature. iNTS infection risk depends more on the infecting serotypes and patient demographics, and less on the attributable reservoirs and AMR profiles.

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上海纽约大学William Glover