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  • Principal Controversies in Vaccine Safety in the United States
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-12
    DeStefano F, Bodenstab H, Offit P.

    Concerns about vaccine safety can lead to decreased acceptance of vaccines and resurgence of vaccine-preventable diseases. We summarize the key evidence on some of the main current vaccine safety controversies in the United States, including: 1) MMR vaccine and autism; 2) thimerosal, a mercury-based vaccine preservative, and the risk of neurodevelopmental disorders; 3) vaccine-induced Guillain-Barré Syndrome (GBS); 4) vaccine-induced autoimmune diseases; 5) safety of HPV vaccine; 6) aluminum adjuvant-induced autoimmune diseases and other disorders; and 7) too many vaccines given early in life predisposing children to health and developmental problems. A possible small increased risk of GBS following influenza vaccination has been identified, but the magnitude of the increase is less than the risk of GBS following influenza infection. Otherwise, the biological and epidemiologic evidence does not support any of the reviewed vaccine safety concerns.

    更新日期:2019-02-14
  • Transmission-blocking effects of primaquine and methylene blue suggest P. falciparum gametocyte sterilisation rather than effects on sex ratio
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-12
    Bradley J, Soumaré H, Mahamar , et al.

    Gametocyte density and sex-ratio can predict the proportion of mosquitoes that become infected after feeding on blood of patients receiving non-gametocytocidal drugs. Because primaquine and methylene blue sterilize gametocytes before affecting their density and sex-ratio, mosquito feeding experiments are required to demonstrate their early transmission-blocking effects.

    更新日期:2019-02-14
  • Impact of rotavirus vaccine introduction in children less than 2 years of age presenting for medical care with diarrhea in rural Matlab, Bangladesh
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-12
    Schwartz L, Zaman K, Yunus M, et al.

    BackgroundFollowing the conclusion of a Rotarix vaccine (HRV) cluster-randomized controlled trial (CRT) in Matlab, Bangladesh, HRV was included in Matlab’s routine immunization program. We describe the population-level impact of programmatic rotavirus vaccination in Bangladesh in children <2 years of ageMethodsInterrupted time series were used to estimate the impact of HRVintroduction. Diarrheal surveillance collected between 2000 and 2014 within the two service delivery areas (icddr,b service area [ISA] and government service area [GSA]) of the Matlab Health and Demographic Surveillance System administered by icddr,b was used. Age-group specific incidence rates were calculated for both rotavirus-positive (RV+) and rotavirus-negative (RV-) diarrhea of any severity presenting to the hospital. Two models were used to assess impact within each service area: Model 1 used the pre-vaccine time period in all villages (HRV- and control-only) and Model 2 combined the pre-vaccine time period and the CRT time period using outcomes from control-only villages. ResultsBoth models demonstrated a downward trend in RV+ diarrheal incidence in the ISA villages during 3.5 years of routine HRV use, though only Model 2 was statistically significant. Significant impact of HRV on RV+ diarrhea incidence in GSA villages was not observed in either model. Differences in population-level impact between the two delivery areas may be due to varied rotavirus vaccine coverage and presentation rate to the hospital.ConclusionsThis study provides initial evidence of the population-level impact of rotavirus vaccines in children <2 years of age in Matlab, Bangladesh. Further studies of rotavirus vaccine impact after nationwide introduction in Bangladesh are needed.

    更新日期:2019-02-14
  • Glycocalyx Breakdown is Associated with Severe Disease and Fatal Outcome in Plasmodium falciparum Malaria
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-12
    Yeo T, Weinberg J, Lampah D, et al.

    BackgroundInteractions between the endothelium and infected erythrocytes, microvascular dysfunction and parasite sequestration play major roles in the pathogenesis of severe falciparum malaria. The glycocalyx is a carbohydrate-rich layer lining the endothelium mediating NO production and vascular homeostasis. The role of the glycocalyx in falciparum malaria and the association with disease severity is not known.MethodsWe prospectively enrolled Indonesian inpatients (≥18 years old) with severe (SM) or moderately-severe (MSM) falciparum malaria and healthy controls (HCs). Glycocalyx breakdown products were measured in enrolment samples of urine (glycosaminoglycans; dimethylmethylene blue [GAG-DMMB] and liquid chromatography-tandem mass spectrometry [GAG-MS] assays) and plasma (syndecan-1; ELISA), and related to vascular NO bioavailability (reactive hyperemia-peripheral arterial tonometry).ResultsA total of 129 subjects (SM=43, MSM=57, HC=29) were recruited. Syndecan-1 (µg/ml), GAG-DMMB and GAG-MS (g/mol creatinine) were increased in SM [median (range) 332.4 (85-3-1913), 3.16 (0.04-27.9) and 4.73 (2.02-27.13)] compared to MSM [99.1 (19.9-767.6), 1.28 (0.03-9.3) and 4.44 (1.19-13.87)], and HCs [48.9 (32.3-88.3), 0.11 (0.02-1.9) and 2.55 (0.73-10.19)]; P<0.001. In SM, GAG-DMMB and GAG-MS were increased in non-survivors (n=3) [median (IQR): 6.72 (3.80-27.87) and 12.15 (7.88-17.20)] compared to survivors n=39 [(3.10 (0.46-4.5) and 4.64 (2.02-15.20)]; P=0.03. Glycocalyx degradation was associated with parasite biomass in MSM (r=0.31, P=0.03 [syndecan-1]; r=0.48 [GAG-DMMB] and r=0.43 [GAG-MS], P<0.001), and SM patients (r=0.29, P=0.04, r=0.47; P=0.002 and r=0.33, P=0.04), and inversely associated with endothelial NO bioavailability.ConclusionsIncreased endothelial glycocalyx breakdown is associated with impaired vascular NO, severe disease and fatal outcome in adults with falciparum malaria, likely contributing to pathogenesis.

    更新日期:2019-02-14
  • Prevalence, Predictors, and Successful Treatment Outcomes of Xpert MTB/RIF–identified Rifampicin-resistant Tuberculosis in Post-conflict Eastern Democratic Republic of the Congo, 2012–2017: A Retrospective Province-Wide Cohort Study
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-13
    Bulabula A, Nelson J, Musafiri E, et al.

    BackgroundMultidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program.Methods of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death.ResultsOf 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P = .06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71).ConclusionsFavorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes.

    更新日期:2019-02-14
  • The Association of Antibiotic Stewardship With Fluoroquinolone Prescribing in Michigan Hospitals: A Multi-hospital Cohort Study
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-13
    Vaughn V, Gandhi T, Conlon A, et al.

    BackgroundFluoroquinolones increase the risk of Clostridioides difficile infection and antibiotic resistance. Hospitals often use pre-prescription approval or prospective audit and feedback to target fluoroquinolone prescribing. Whether these strategies impact aggregate fluoroquinolone use is unknown.MethodsThis study is a 48-hospital, retrospective cohort of general-care, medical patients hospitalized with pneumonia or positive urine culture between December 2015–September 2017. Hospitals were surveyed on their use of pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing during hospitalization (fluoroquinolone stewardship). After controlling for hospital clustering and patient factors, aggregate (inpatient and post-discharge) fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) exposure was compared between hospitals with and without fluoroquinolone stewardship.ResultsThere were 11 748 patients (6820 pneumonia; 4928 positive urine culture) included at 48 hospitals. All hospitals responded to the survey: 29.2% (14/48) reported using pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing. After adjustment, fluoroquinolone stewardship was associated with fewer patients receiving a fluoroquinolone (37.1% vs 48.2%; P = .01) and fewer fluoroquinolone treatment days per 1000 patients (2282 vs 3096 days/1000 patients; P = .01), driven by lower inpatient prescribing. However, most (66.6%) fluoroquinolone treatment days occurred after discharge, and hospitals with fluoroquinolone stewardship had twice as many new fluoroquinolone starts after discharge as hospitals without (15.6% vs 8.4%; P = .003).ConclusionsHospital-based stewardship interventions targeting fluoroquinolone prescribing were associated with less fluoroquinolone prescribing during hospitalization, but not at discharge. To limit aggregate fluoroquinolone exposure, stewardship programs should target both inpatient and discharge prescribing.

    更新日期:2019-02-14
  • Influenza Vaccine Effectiveness Against Hospitalization in Fully and Partially Vaccinated Children in Israel; 2015-16, 2016-17, and 2017-18
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-11
    Segaloff H, Leventer-Roberts M, Riesel D, et al.

    Background Influenza vaccine effectiveness (VE) varies by season, circulating influenza strain, age, and geographic location. There have been few studies of influenza VE among hospitalized children, particularly in Europe and the Middle East. Methods We estimated VE against influenza hospitalization among children six months to eight years at Clalit Health Services hospitals in Israel in the 2015-16, 2016-17, and 2017-18 influenza seasons using the test-negative design. Estimates were computed for full and partial vaccination. Results We included 326 influenza-positive cases and 2821 influenza-negative controls (140 cases and 971 controls from 2015-16, 36 cases and 1069 controls from 2016-17, and 150 cases and 781 controls from 2017-18). Over all seasons, VE was 53.9% for full vaccination (95% CI:(38.6,68.3)), and 25.6% for partial vaccination (95% CI:(-3, 47)). In 2015-16, most viruses were influenza A(H1N1) and vaccine lineage-mismatched influenza B/Victoria; VE for fully vaccinated children was statistically significant for influenza A (80.7%, 95% CI:(40.3,96.1)) but not B (23.0%, 95% CI:(-38.5, 59.4)). During 2016-17, influenza A(H3N2) predominated, and VE was (70.8%, 95% CI:(17.4, 92.4)). In 2017-18, influenza A(H3N2), H1N1 and lineage-mismatched influenza B/Yamagata co-circulated; VE was statistically significant for influenza B (63.0% 95% CI: (24.2,83.7)), but not A (46.3%, 95% CI:(-7.2, 75.3)). Conclusions Influenza vaccine was effective in preventing hospitalizations among fully vaccinated Israeli children over three influenza seasons, but not among partially vaccinated children. There was cross-lineage protection in a season where the vaccine contained B/Victoria and the circulating strain was B/Yamagata, but not in a season with the opposite vaccine-circulating strain distribution.

    更新日期:2019-02-13
  • The SHIELD Orange County Project –Multi Drug-Resistant Organism (MDRO) Prevalence in 21 Nursing Homes and Long Term Acute Care Facilities in Southern California
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-11
    McKinnell J, Singh R, Miller L, et al.

    Background Multidrug-resistant organisms (MDROs) spread between hospitals, nursing homes (NH), and long-term acute care facilities (LTACs) via patient transfers. SHIELD OC is a regional public health collaborative involving decolonization at 38 healthcare facilities selected based upon their high degree of patient sharing. We report baseline MDRO prevalence in 21 NH/LTACs Methods A random sample of 50 adults for 21 NH/LTACs (18 NHs, 3 LTACs) were screened for methicillin-resistant Staphylococcus aureus(MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum beta-lactamase producing organisms (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE) using nares, skin (axilla/groin), and peri-rectal swabs. Facility and resident characteristics associated with MDRO carriage were assessed using multivariable models clustering by person and facility. Results Prevalence of MDROs was 65% in NHs and 80% in LTACs. The most common MDROs in NHs were MRSA (42%) and ESBL (34%); in LTACs they were VRE (55%) and ESBL (38%). CRE prevalence was higher in facilities that manage ventilated LTAC patients and NH residents (8% vs. <1%, p<0.001). MDRO status was known for 18% of NH residents and 49% of LTAC patients. MDRO colonized adults commonly harbored additional MDROs (54% MDRO+ NH residents and 62% MDRO+ LTACs patients). History of MRSA [OR=1.7 C.I. (1.2, 2.4),p=0.004], VRE [OR=2.1 C.I.(1.2, 3.8),p=0.01], ESBL [OR=1.6 C.I.(1.1, 2.3),p=0.03] and diabetes [OR=1.3 C.I.(1.0, 1.7),p=0.03] were associated with any MDRO carriage. Conclusions The majority of NH residents and LTACs patients harbor MDROs. MDRO status is frequently unknown to the facility. The high MDRO prevalence highlights the need for prevention efforts in NH/LTACs as part of regional efforts to control MDRO spread.

    更新日期:2019-02-13
  • Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus bacteremia – Nationwide Estimates of 30-day Readmission, In-hospital Mortality, Length of Stay, and Cost in the US
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-11
    Inagaki K, Lucar J, Blackshear C, et al.

    Background Information on outcomes of methicillin-susceptible and -resistant S. aureus (MSSA and MRSA, respectively) bacteremia, particularly readmission is scarce, and require further research to inform optimal patient care. Methods We performed a retrospective analysis using the 2014 Nationwide Readmissions Database, capturing 49.3% of US hospitalizations. We identified MSSA and MRSA bacteremia using International Classification of Diseases, Ninth Revision, Clinical Modification among patients aged ≥18 years. Thirty-day readmission, mortality, length of stay and costs were assessed using Cox proportional hazards regression, logistic regression, Poisson regression, and generalized linear model with gamma distribution and log link, respectively. Results Of 92089 (standard error, SE: 1905) patients with S. aureus bacteremia, 48.5% (SE: 0.4%) had MRSA bacteremia. Thirty-day readmission rate was 22% (SE: 0.3) overall with no difference between MRSA and MSSA, but MRSA bacteremia had more readmission for bacteremia recurrence (hazard ratio: 1.17 [95% confidence interval, CI: 1.02-1.35]), higher in-hospital mortality (odds ratio: 1.15 [95%CI: 1.07-1.22]), and longer hospitalization (incidence rate ratio: 1.08 [95%CI: 1.06-1.11]). Readmission with bacteremia recurrence was particularly more common among patients with endocarditis, immunocompromising comorbidities, and drug abuse. The cost of readmission was $12425 (SE: 174) /case overall, and $19186 (SE: 623) in those with bacteremia recurrence. Conclusions Thirty-day readmission after S. aureus bacteremia is common and costly. MRSA bacteremia is associated with readmission for bacteremia recurrence, increased mortality, and longer hospitalization. Efforts should continue to optimize patient care, particularly for those with risk factors, to decrease readmission and associated morbidity and mortality in patients with S. aureus bacteremia.

    更新日期:2019-02-13
  • Birth Cohort Studies Assessing Norovirus Infection and Immunity in Young Children: A Review
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-12
    Cannon J, Lopman B, Payne D, et al.

    Globally, noroviruses are among the foremost causes of acute diarrheal disease, yet there are many unanswered questions on norovirus immunity, particularly following natural infection in young children during the first 2 years of life when the disease burden is highest. We conducted a literature review on birth cohort studies assessing norovirus infections in children from birth to early childhood. Data on infection, immunity, and risk factors are summarized from 10 community-based birth cohort studies conducted in low- and middle-income countries. Up to 90% of children experienced atleast one norovirus infection and up to 70% experienced norovirus-associated diarrhea, most often affecting children 6 months of age and older. Data from these studies help to fill critical knowledge gaps for vaccine development, yet study design and methodological differences limit comparison between studies, particularly for immunity and risk factors for disease. Considerations for conducting future birth cohort studies on norovirus are discussed.

    更新日期:2019-02-13
  • Clinical Spectrum of Primaquine-induced Hemolysis in G6PD Deficiency: A Nine-Year Hospitalization-Based Study from the Brazilian Amazon
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-11
    Brito-Sousa J, Santos T, Avalos S, et al.

    Despite G6PDd prevalence of 5% in the Amazon, primaquine is administered without G6PD screening. This is an important cause of hospitalization among Plasmodium vivax-infected individuals, leading to life-threatening anemia and acute renal failure across endemic areas. In Manaus, the frequency of primaquine-induced hemolysis was 85.2 cases per 100.000 primaquine users.

    更新日期:2019-02-13
  • Ensuring Antibiotic Development, Equitable Availability, and Responsible Use of Effective Antibiotics: Recommendations for Multisectoral Action
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-09

    The following error appeared in the corrected proof publication of this article [Monnier A.A., Schouten, J., Tebano, G., et al. Ensuring Antibiotic Development, Equitable Availability, and Responsible Use of Effective Antibiotics: Recommendations for Multisectoral Action. Clin Infect Dis https://doi.org/10.1093/cid/ciy824

    更新日期:2019-02-11
  • Erratum
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-09

    An error appeared in the initial publication of this article [Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Infect Dis https://doi.org/10.1093/cid/ciy866]. This article was originally published with the two following errors:

    更新日期:2019-02-11
  • Erratum
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-06

    An error appeared in the 1 January 2011 issue of the journal [Rubinstein E, Lalani T, Corey GR, et al. Telavancin versus Vancomycin for Hospital-Acquired Pneumonia due to Gram-positive Pathogens. Clin Infect Dis 2011; 52(1):31–40. https://doi.org/10.1093/cid/ciq031]. In line 6 of column 2 of Table 5, the current number of microbiologically evaluable patients with monomicrobial Staphylococcus aureus treated with telavancin is reported as 85. The correct number should be 89 due to miscounting multiple samples with the same organism. Table 5 column 2 line 6, “Telavancin, % (proportion) of patients: Monomicrobial S. aureus – Vancomycin MIC ≥1 µg/mL” should read “83.1 (74/89).”

    更新日期:2019-02-07
  • Clinical and Microbiologic Variables Predictive of Orthopedic Complications Following S. aureus Acute Hematogenous Osteoarticular Infections in Children
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-07
    McNeil J, Vallejo J, Kok E, et al.

    BackgroundStaphylococcus aureus is the most common cause of acute hematogenous osteoarticular infections (AHOAIs) in children. The risk factors for the development of orthopedic complications (OC) after AHOAI are poorly understood. We sought to describe clinical and microbiologic variables present on the index admission which may predict OC in S. aureus AHOAI.MethodsS. aureus AHOAI cases were identified from 2011-2017 at Texas Children’s Hospital and reviewed for the development of OC. OC included chronic osteomyelitis, growth arrest, avascular necrosis, chronic dislocation and pathologic fracture. All S. aureus isolates were characterized by PFGE and agr group.Results286 cases were examined of which 27 patients (9.4%) developed OC. Patients who developed OC more often had infection with an agr group III organism (p=0.04), bacteremia (p=0.04), delayed source control (p<0.001), ≥2 surgical procedures (p<0.001), ICU admission (p=0.09) and fever > 4 days after admission (p=0.008). There was no association with OC and patient age, methicillin-resistance, or choice/route of antibiotics. In multivariable analyses of OC, infection with agr group III S. aureus, prolonged fever, and delayed source control remained statistically significant. ConclusionsOC develop following S. aureus AHOAI in 9.4% of cases. Although the development of OC is likely multifactorial, agr group III organisms, prolonged fever and delayed source control are independently associated with OC. While nonspecific, these findings suggest that such patients may warrant especially cautious clinical follow-up to identify sequelae early. Moreover, early aggressive surgical source control may be beneficial in children with S. aureus AHOAI.

    更新日期:2019-02-07
  • Naïve CD4+ T Cells Harbor a Large Inducible Reservoir of Latent, Replication-Competent HIV-1
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-07
    Zerbato J, McMahon D, Sobolewski M, et al.

    BackgroundThe latent HIV-1 reservoir represents a major barrier to a cure. Based on the levels of HIV-1 DNA in naïve (TN) versus resting memory CD4+ T cells, it is widely hypothesized that the latent reservoir resides primarily within memory cells. Here, we compared virus production from TN and central memory (TCM) CD4+ T cells isolated from HIV-1-infected individuals on suppressive therapy.MethodsCD4+ TN and TCM cells were purified from the blood of seven HIV-1-infected individuals on suppressive therapy for ≥ 5 years. Real-time PCR was used to quantify total HIV-1 DNA, and extracellular virion-associated HIV-1 RNA or viral outgrowth assays were used to assess latency reversal following treatment with anti-CD3/CD28 mAbs, phytohaemagglutinin/interleukin-2, phorbol 12-myristate 13-acetate/ionomycin, prostratin, panobinostat, or romidepsin. ResultsHIV-1 DNA was significantly higher in TCM compared to TN cells (2,179 versus 684 copies/10 6 cells, respectively). Following exposure to anti-CD3/CD28 mAbs, virion-associated HIV-1 RNA levels were similar between TCM and TN cells (15,135 versus 18,290 copies/mL, respectively). In 4/7 donors, virus production was higher for TN cells independent of the latency reversing agent used. Replication-competent virus was recovered from both TN and TCM cells. ConclusionsAlthough the frequency of HIV-1 infection is lower in TN compared to TCM cells, as much, if not more, virus is produced from the TN population after exposure to latency reversing agents. This finding suggests that quantifying HIV-1 DNA alone may not predict the size of the inducible latent reservoir, and that TN cells may be an important reservoir of latent HIV-1.

    更新日期:2019-02-07
  • Potential for Erosion of Efficacy in Non-Inferiority Trials of Decreasing Duration of Antibiotic Therapy
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-06
    MacFadden D, Hanage W.

    non-inferiority trialsstudy designstewardshipantibiotic duration

    更新日期:2019-02-06
  • Outcomes of Resistance-guided Sequential Treatment of Mycoplasma genitalium Infections: A Prospective Evaluation
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-06-05
    Read T, Fairley C, Murray G, et al.

    Background Rising macrolide and quinolone resistance in Mycoplasma genitalium necessitate new treatment approaches. We evaluated outcomes of sequential antimicrobial therapy for M. genitalium guided by a macrolide-resistance assay. Methods In mid-2016, Melbourne Sexual Health Centre switched from azithromycin to doxycycline (100 mg twice daily for 7 days) for nongonococcal urethritis, cervicitis, and proctitis. Cases were tested for M. genitalium and macrolide-resistance mutations (MRMs) by polymerase chain reaction. Directly after doxycycline, MRM-negative infections received 2.5 g azithromycin (1 g, then 500 mg daily for 3 days), and MRM-positive infections received sitafloxacin (100 mg twice daily for 7 days). Assessment of test of cure and reinfection risk occurred 14–90 days after the second antibiotic. Results Of 244 evaluable M. genitalium infections (52 women, 68 heterosexual men, 124 men who have sex with men) diagnosed from 20 June 2016 to 15 May 2017, MRMs were detected in 167 (68.4% [95% confidence interval {CI}, 62.2%–74.2%]). Treatment with doxycycline decreased bacterial load by a mean 2.60 log10 (n = 56; P < .0001). Microbiologic cure occurred in 73 of 77 MRM-negative infections (94.8% [95% CI, 87.2%–98.6%]) and in 154 of 167 MRM-positive infections (92.2% [95% CI, 87.1%–95.8%]). Selection of macrolide resistance occurred in only 2 of 76 (2.6% [95% CI, .3%–9.2%]) macrolide-susceptible infections. Conclusions In the context of high levels of antimicrobial resistance, switching from azithromycin to doxycycline for presumptive treatment of M. genitalium, followed by resistance-guided therapy, cured ≥92% of infections, with infrequent selection of macrolide resistance.

    更新日期:2019-02-05
  • Immediate Versus Deferred Switching From a Boosted Protease Inhibitor–based Regimen to a Dolutegravir-based Regimen in Virologically Suppressed Patients With High Cardiovascular Risk or Age ≥50 Years: Final 96-Week Results of the NEAT022 Study
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-06-14
    Gatell J, Assoumou L, Moyle G, et al.

    Background Both immediate and deferred switching from a ritonavir-boosted protease inhibitor (PI/r)–based regimen to a dolutegravir (DTG)–based regimen may improve lipid profile. Methods European Network for AIDS Treatment 022 Study (NEAT022) is a European, open-label, randomized trial. Human immunodeficiency virus (HIV)–infected adults aged ≥50 years or with a Framingham score ≥10% were eligible if HIV RNA was <50 copies/mL. Patients were randomized to switch from PI/r to DTG immediately (DTG-I) or to deferred switch at week 48 (DTG-D). Week 96 endpoints were proportion of patients with HIV RNA <50 copies/mL, percentage change of lipid fractions, and adverse events (AEs). Results Four hundred fifteen patients were randomized: 205 to DTG-I and 210 DTG-D. The primary objective of noninferiority at week 48 was met. At week 96, treatment success rate was 92.2% in the DTG-I arm and 87% in the DTG-D arm (difference, 5.2% [95% confidence interval, –.6% to 11%]). There were 5 virological failures in the DTG-I arm and 5 (1 while on PI/r and 4 after switching to DTG) in the DTG-D arm without selection of resistance mutations. There was no significant difference in terms of grade 3 or 4 AEs or treatment-modifying AEs. Total cholesterol and other lipid fractions (except high-density lipoprotein) significantly (P < .001) improved both after immediate and deferred switching to DTG overall and regardless of baseline PI/r strata. Conclusions Both immediate and deferred switching from a PI/r to a DTG regimen in virologically suppressed HIV-infected patients ≥50 years old or with a Framingham score ≥10% was highly efficacious and well tolerated, and improved the lipid profile. Clinical Trials Registration NCT02098837 and EudraCT: 2013-003704-39.

    更新日期:2019-02-05
  • Long-term Risk of Hemorrhagic Stroke in Patients With Infective Endocarditis: A Danish Nationwide Cohort Study
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-06-16
    Klein C, Gørtz S, Wohlfahrt J, et al.

    Background The present study aimed to investigate the long-term risk of hemorrhagic stroke (HS) in patients with infective endocarditis (IE). Methods Using a register-based nationwide cohort of 9 million Danes, we performed propensity score matching between patients with left-sided IE from 1977 to mid-2015 and IE-free individuals (1:10). Follow-up started 1 year after the IE diagnosis. Hazard ratios (HRs) for HS in patients with IE compared with the matched cohort were estimated using Cox regression. Results During follow-up of 5735 patients with left-sided IE from 1 year after IE diagnosis and up to 37.5 years (median, 6.3 years), 103 cases of HS were observed. Compared with the matched cohort, patients with IE had a higher long-term risk of HS (HR, 1.47; 95% confidence interval, 1.20–1.80; P < .001). The risk of HS was particularly increased in patients within the lowest propensity score quartile (HR, 2.60; 95% confidence interval, 1.89–3.58). Mediation analyses suggested that the increased HS risk could be explained by an indirect effect of mechanical heart valve insertion, atrial fibrillation, or treatment with anticoagulants. The cumulative risk of HS 30 years after start of follow-up was 3.0% in patients with IE. Conclusions IE does not directly increase the long-term risk of HS. The apparent excess risk of HS in patients with previous IE was explained by mediating factors, including mechanical heart valve insertion, atrial fibrillation, and anticoagulation medication.

    更新日期:2019-02-05
  • Cessation of Cigarette Smoking and the Impact on Cancer Incidence in Human Immunodeficiency Virus–infected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-06-14
    Shepherd L, Ryom L, Law M, et al.

    Background Cancers are a major source of morbidity and mortality for human immunodeficiency virus (HIV)–infected persons, but the clinical benefits of smoking cessation are unknown. Methods Participants were followed from 1 January 2004 until first cancer diagnosis, death, or 1 February 2016. Smoking status was defined as ex-smoker, current smoker, and never smoker. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression, adjusting for demographic and clinical factors. Results In total 35442 persons from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study contributed 309803 person-years of follow-up. At baseline, 49% were current smokers, 21% were ex-smokers, and 30% had never smoked. Incidence of all cancers combined (n = 2183) was highest <1 year after smoking cessation compared to never smokers (aIRR, 1.66 [95% confidence interval {CI}, 1.37–2.02]) and not significantly different from never smokers 1–1.9 years after cessation. Lung cancer incidence (n = 271) was elevated <1 year after cessation (aIRR, 19.08 [95% CI, 8.10–44.95]) and remained 8-fold higher 5 years after smoking cessation (aIRR, 8.69 [95% CI, 3.40–22.18]). Incidence of other smoking-related cancers (n = 622) was elevated in the first year after cessation (aIRR, 2.06 [95% CI, 1.42–2.99]) and declined to a level similar to nonsmokers thereafter. Conclusions Lung cancer incidence in HIV-infected individuals remained elevated >5 years after smoking cessation. Deterring uptake of smoking and smoking cessation efforts should be prioritised to reduce future cancer risk.

    更新日期:2019-02-05
  • Preexposure Intradermal Rabies Vaccination: A Noninferiority Trial in Healthy Adults on Shortening the Vaccination Schedule From 28 to 7 Days
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-06-25
    Soentjens P, Andries P, Aerssens A, et al.

    Background The existing 4-week preexposure rabies vaccination schedule is costly and often not practicable. Shorter effective schedules would result in wider acceptance. Methods We conducted a noninferiority trial in 500 healthy adults comparing the safety and immunogenicity of a 2-visit (days 0 and 7) intradermal (ID) primary vaccination (2 doses of 0.1 mL ID of the human diploid cell culture rabies vaccine [HDCV] at days 0 and 7) vs a standard 3-visit schedule (single dose of 0.1 mL ID at days 0, 7, and 28). One year to 3 years after primary vaccination, a single booster dose of 0.1 mL ID of HDCV was given to evaluate the anamnestic rabies antibody response. The primary endpoint for immunogenicity was the percentage of subjects with an adequate antibody level >0.5 IU/mL 7 days after the booster injection. The safety endpoint was the proportion of participants developing adverse reactions following the primary vaccination and/or booster dose. Results All subjects in both study groups possessed a rabies antibody titer >0.5 IU/mL on day 7 following the booster dose. Following the booster dose, subjects exposed to the double-dose 2-visit ID schedule had a geometric mean titer of 37 IU/mL, compared with 25 IU/mL for the single-dose 3-visit schedule (P < .001). Local reactions at the injection site following primary vaccination were mild and transient. Conclusions In healthy adults, ID administration of a double dose of 0.1 mL of HDCV over 2 visits (days 0 and 7) was safe and not inferior to the single-dose 3-visit schedule. Clinical Trials Registration NCT01388985, EudraCT 2011-001612-62.

    更新日期:2019-02-05
  • Community-based Malaria Screening and Treatment for Pregnant Women Receiving Standard Intermittent Preventive Treatment With Sulfadoxine-Pyrimethamine: A Multicenter (The Gambia, Burkina Faso, and Benin) Cluster-randomized Controlled Trial
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-06-29
    , Scott S, D’Alessandro U, et al.

    Background We investigated whether adding community scheduled malaria screening and treatment (CSST) with artemether-lumefantrine by community health workers (CHWs) to standard intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) would improve maternal and infant health. Methods In this 2-arm cluster-randomized, controlled trial, villages in Burkina Faso, The Gambia, and Benin were randomized to receive CSST plus IPTp-SP or IPTp-SP alone. CHWs in the intervention arm performed monthly CSST during pregnancy. At each contact, filter paper and blood slides were collected, and at delivery, a placental biopsy was collected. Primary and secondary endpoints were the prevalence of placental malaria, maternal anemia, maternal peripheral infection, low birth weight, antenatal clinic (ANC) attendance, and IPTp-SP coverage. Results Malaria infection was detected at least once for 3.8% women in The Gambia, 16.9% in Benin, and 31.6% in Burkina Faso. There was no difference between study arms in terms of placenta malaria after adjusting for birth season, parity, and IPTp-SP doses (adjusted odds ratio, 1.06 [95% confidence interval, .78–1.44]; P = .72). No difference between the study arms was found for peripheral maternal infection, anemia, and adverse pregnancy outcomes. ANC attendance was significantly higher in the intervention arm in Burkina Faso but not in The Gambia and Benin. Increasing number of IPTp-SP doses was associated with a significantly lower risk of placenta malaria, anemia at delivery, and low birth weight. Conclusions Adding CSST to existing IPTp-SP strategies did not reduce malaria in pregnancy. Increasing the number of IPTp-SP doses given during pregnancy is a priority. Clinical Trials Registration NCT01941264; ISRCTN37259296.

    更新日期:2019-02-05
  • Accuracy and Operational Characteristics of Xpert Human Immunodeficiency Virus Point-of-Care Testing at Birth and Until Week 6 in Human Immunodeficiency Virus–exposed Neonates in Tanzania
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-06-29
    Sabi I, Mahiga H, Mgaya J, et al.

    Background Point-of-care (PoC) systems for early infant diagnosis (EID) may improve timely infant human immunodeficiency virus (HIV) management. Experiences within African public health settings are limited. Methods We evaluated the accuracy and operational feasibility of the Xpert HIV-1 Qual for PoC-EID testing, using fresh blood and dried blood spots (DBS) samples at obstetric health facilities in Tanzania at birth and at postpartum weeks 1, 2, 3, and 6 in HIV-exposed infants. Test results were confirmed using TaqMan DBS HIV-deoxyribonucleic acid and/or plasma HIV-ribonucleic acid (RNA) testing. Results At week 6, 15 (2.5%) out of 614 infants were diagnosed with HIV; 10 (66.7%) of them at birth (median HIV-RNA 4570 copies/mL). At birth, the Xpert-PoC and Xpert-DBS were 100% sensitive (95% confidence intervals: PoC, 69.2–100%; DBS, 66.4–100%) and 100% specific (PoC, 92.1–100%; DBS, 88.4–100%). By week 3, 5 infants with intra/postpartum HIV-infection (median HIV-RNA 1 160 000 copies/mL) were all correctly diagnosed by Xpert. In 2 cases, Xpert-PoC testing correctly identified HIV-infection when DBS tests (Xpert and TaqMan) were negative, suggesting a greater sensitivity. In 2 infants with confirmed HIV at birth, all tests were negative at week 6, possibly because of viral suppression under nevirapine prophylaxis. Problems were reported in 183/2736 (6.7%) of Xpert-PoC tests, mostly related to power cuts (57.9%). Conclusions We demonstrated excellent Xpert HIV-1 Qual performance and good operational feasibility for PoC-EID testing at obstetric health facilities. Week 6 sensitivity issues were possibly related to nevirapine prophylaxis, supporting additional birth PoC-EID testing to avoid underdiagnosis. Clinical Trials Registration NCT02545296

    更新日期:2019-02-05
  • Temporal Dynamics and Risk Factors for Bloodstream Infection With Extended-spectrum β-Lactamase–producing Bacteria in Previously-colonized Individuals: National Population-based Cohort Study
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-06-29
    Isendahl J, Giske C, Hammar U, et al.

    Background Little is known of the long-term risks of bloodstream infection (BSI) with extended spectrum β-lactamase–producing Enterobacteriaceae (EPE) in previously-colonized individuals. We investigated EPE-BSI risks and associated risk factors during 6 years following EPE colonization. Methods We performed a population-based cohort study in Sweden using national health registers. Subjects were followed from their first EPE finding in feces (n = 5513) or urine (n = 17189). The effects of co-morbidity, sociodemography, and outpatient antibiotic dispensation on EPE-BSI risks were assessed. The EPE-BSI risks were compared to those of 45161 matched population–based reference subjects. Results The cumulative 6-year EPE-BSI incidences were 3.8%, 1.6%, and 0.02% in the urine, feces, and reference cohorts, respectively. The incidences decreased exponentially during the first 6–12 months. Among EPE-exposed subjects, urological disorders were associated with the highest adjusted cause–specific hazard ratio (aCSHR) for subsequent EPE-BSIs (3.40, 95% confidence interval 2.47–4.69). The aCSHRs were between 1.62–2.20 for male sex, immunosuppression, diabetes, malignancy, lung disease, baseline urine source, and Klebsiella pneumoniae, compared to the Escherichia coli baseline sample. Antibiotics with selective activity against gram-negative bacilli—but mostly not EPE (trimethoprim-sulfamethoxazole, fluoroquinolones, oral cephalosporins, and penicillins with extended spectrums)—and pivmecillinam were associated with doubled EPE BSI risk during the 3 months after antibiotic dispensation in EPE-colonized subjects. Conclusions EPE in urine or feces is a substantial risk factor for subsequent EPE-BSIs, but the risk declines rapidly during the first year after detection. In EPE-colonized individuals, specific risk factors can be used to identify subgroups for targeted interventions, such as eradication therapy.

    更新日期:2019-02-05
  • Assessment of Human-to-Human Transmissibility of Avian Influenza A(H7N9) Virus Across 5 Waves by Analyzing Clusters of Case Patients in Mainland China, 2013–2017
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-06-29
    Wang X, Wu P, Pei Y, et al.

    Background The 2016–17 epidemic of human infections with avian influenza A(H7N9) virus was alarming, due to the surge in reported cases across a wide geographic area and the emergence of highly-pathogenic A(H7N9) viruses. Our study aimed to assess whether the human-to-human transmission risk of A(H7N9) virus has changed across the 5 waves since 2013. Methods Data on human cases and clusters of A(H7N9) virus infection were collected from the World Health Organization, open access national and provincial reports, informal online sources, and published literature. We compared the epidemiological characteristics of sporadic and cluster cases, estimated the relative risk (RR) of infection in blood relatives and non–blood relatives, and estimated the bounds on the effective reproductive number (Re) across waves from 2013 through September 2017. Results We identified 40 human clusters of A(H7N9) virus infection, with a median cluster size of 2 (range 2–3). The overall RR of infection in blood relatives versus non–blood relatives was 1.65 (95% confidence interval [CI]: 0.88, 3.09), and was not significantly different across waves (χ2 = 2.66, P = .617). The upper limit of Re for A(H7N9) virus was 0.12 (95% CI: 0.10, 0.14) and was not significantly different across waves (χ2 = 1.52, P = .822). Conclusions The small cluster size and low Re suggest that human-to-human transmissibility of A(H7N9) virus has not changed over time and remains limited to date. Continuous assessment of A(H7N9) virus infections and human case clusters is of crucial importance for public health.

    更新日期:2019-02-05
  • Epidemiology of Meningococcal Disease Outbreaks in the United States, 2009–2013
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-06-30
    Mbaeyi S, Blain A, Whaley M, et al.

    Background Although the incidence of meningococcal disease is low in the United States, outbreaks remain a serious public health concern. In this evaluation, we identify and describe outbreaks of meningococcal disease. Methods A retrospective review of all meningococcal disease cases reported from 1 January 2009 to 31 December 2013 was performed by state health departments and the Centers for Disease Control and Prevention to identify meningococcal disease outbreaks. An outbreak was defined as ≥2 primary cases of the same serogroup within <3 months in an organization, or a ≥2-fold increase in disease rates in a community. Results From 2009 to 2013, a total of 3686 cases of meningococcal disease were reported in the United States. Among these, 180 primary cases (4.9%) occurred as part of 36 outbreaks (17 organization-based and 19 community-based). Serogroup B accounted for 8 (47.1%) of the organization-based outbreaks, including 6 of 8 university outbreaks. Serogroup C accounted for 10 (52.6%) of the community-based outbreaks, including both of 2 outbreaks identified among men who have sex with men. Organization- and community-based outbreaks differed in predominant serogroup, age distribution of cases, and clinical syndrome. Among 33 outbreaks with known information, a vaccination and/or expanded chemoprophylaxis campaign was conducted in 16 (48.5%). Conclusions Outbreak-associated cases account for approximately 5% of all meningococcal disease cases in the United States. Serogroup B is the primary cause of organization-based outbreaks, with the majority of university outbreaks due to serogroup B, and serogroup C is the primary cause of community-based outbreaks.

    更新日期:2019-02-05
  • Autologous Adoptive T-cell Therapy for Recurrent or Drug-resistant Cytomegalovirus Complications in Solid Organ Transplant Recipients: A Single-arm Open-label Phase I Clinical Trial
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-07-05
    Smith C, Beagley L, Rehan S, et al.

    Background Opportunistic infections including cytomegalovirus (CMV) are a major cause of morbidity and mortality in solid organ transplant (SOT) recipients. The recurrent and protracted use of antiviral drugs with eventual emergence of drug resistance represents a significant constraint to therapy. Although adoptive T-cell therapy has been successfully used in hematopoietic stem cell transplant recipients, its extension to the SOT setting poses a considerable challenge because of the inhibitory effects of immunosuppressive drugs on the virus-specific T-cell response in vivo and the perceived risk of graft rejection. Methods In this prospective study, 22 SOT recipients (13 renal and 8 lung and 1 heart transplants) with recurrent or ganciclovir-resistant CMV infection were recruited, and 13 of them were treated with in vitro–expanded autologous CMV-specific T cells. These patients were monitored for safety, clinical symptoms, and immune reconstitution. Results Autologous CMV-specific T-cell manufacture was attempted for 21 patients, and was successful in 20. The use of this adoptive immunotherapy was associated with no therapy-related serious adverse events. Eleven (84%) of the 13 treated patients showed improvement in symptoms, including complete resolution or reduction in DNAemia and CMV-associated end-organ disease and/or the cessation or reduced use of antiviral drugs. Furthermore, four of these patients showed coincident increased frequency of CMV-specific T cells in peripheral blood after completion of T-cell therapy. Conclusions The data presented here demonstrate for the first time the clinical safety of CMV-specific adoptive T-cell therapy and its potential therapeutic benefit for SOT recipients with recurrent and/or drug-resistant CMV infection or disease. Clinical Trials Registration ACTRN12613000981729.

    更新日期:2019-02-05
  • Rapid Rebound of a Preexisting CXCR4-tropic Human Immunodeficiency Virus Variant After Allogeneic Transplantation With CCR5 Δ32 Homozygous Stem Cells
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-07-18
    Verheyen J, Thielen A, Lübke N, et al.

    Allogeneic stem cell transplantation (alloSCT) of homozygous CCR5 Δ32 stem cells once resulted in the cure of human immunodeficiency virus (HIV) infection. We have recently reported a viral breakthrough in a similar setting. Here, we demonstrate that the rapid rebound after alloSCT was related to a highly replicative CXCR4-tropic HIV variant, which could already be detected before alloSCT.

    更新日期:2019-02-05
  • Impact of Routine Cryptococcal Antigen Screening and Targeted Preemptive Fluconazole Therapy in Antiretroviral-naive Human Immunodeficiency Virus–infected Adults With CD4 Cell Counts <100/μL: A Systematic Review and Meta-analysis
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-07-18
    Temfack E, Bigna J, Luma H, et al.

    Cryptococcal antigen (CrAg) screening and targeted preemptive fluconazole in antiretroviral-naive human immunodeficiency virus–infected adults with CD4 cell counts <100/μL seems promising as a strategy to reduce the burden of cryptococcal meningitis (CM). We searched MEDLINE, EMBASE, and Web of Science and used random-effect meta-analysis to assess the prevalence of blood CrAg positivity (31 studies; 35644 participants) and asymptomatic CM in CrAg-positive participants and the incidence of CM and the all-cause mortality rate in screened participants. The pooled prevalence of blood CrAg-positivity was 6% (95% confidence interval [CI], 5%–7%), and the prevalence of asymptomatic CM in CrAg-positive participants was 33% (95% CI, 21%–45%). The incidence of CM was 21.4% (95% CI, 11.6%–34.4%) without preemptive fluconazole and 5.7% (95% CI, 3.0%–9.7%) with preemptive fluconazole therapy initiated at 800 mg/d. In CrAg-positive participants, postscreening lumbar puncture before initiating preemptive fluconazole at 800 mg/d further reduced the incidence of CM to null and showed some survival benefits. However, the all-cause mortality rate remained significantly higher in CrAg-positive than in CrAg-negative participants (risk ratio, 2.2; 95% CI, 1.7–2.9; P < .001).

    更新日期:2019-02-05
  • A Tale of Two Healthcare-associated Infections: Clostridium difficile Coinfection Among Patients With Candidemia
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-07-27
    Tsay S, Williams S, Benedict K, et al.

    Candidemia and Clostridium difficile infection (CDI) are important healthcare-associated infections that share certain risk factors. We sought to describe candidemia-CDI coinfection using population-based surveillance data. We found that nearly 1 in 10 patients with candidemia had CDI coinfection.

    更新日期:2019-02-05
  • Bezlotoxumab
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-07-18
    Johnson S, Gerding D.

    Clostridium difficile infection (CDI) is mediated by actions of toxin A and toxin B. Fully human monoclonal antibodies directed against the binding domains of these toxins were developed. Despite preclinical studies suggesting efficacy for the anti–toxin A monoclonal, actoxumab, the anti–toxin B monoclonal, bezlotoxumab, alone was shown to be effective in clinical trials. Intravenous infusion of bezlotoxumab at a 10 mg/kg dosage as adjunctive treatment reduced the risk of recurrent CDI over placebo for adult patients at increased risk for CDI recurrence in 2 large randomized, double-blind trials. Significant benefit was noted for patients with 1 or more of the following predefined risks: age >65 years, history of CDI, immunocompromise, severe CDI. Overall, bezlotoxumab appeared to be safe; however, an unexplained increased risk of heart failure was noted for patients with underlying congestive heart failure. Further refinement of who would benefit most and when best to administer bezlotoxumab is warranted.

    更新日期:2019-02-05
  • Methicillin-resistant Staphylococcus aureus Colonization and Pre- and Post-hospital Discharge Infection Risk
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-08-11
    Nelson R, Evans M, Simbartl L, et al.

    Background The Department of Veterans Affairs implemented an active surveillance program for methicillin-resistant Staphylococcus aureus (MRSA) in 2007 in which acute care inpatients are tested for MRSA carriage on admission, unit-to-unit transfer, and discharge. Using these data, we followed patients longitudinally to estimate the difference in infection rates for those who were not colonized, those who were colonized on admission (importers), and those who acquired MRSA during their stay. We examined MRSA infections that occurred prior to discharge and at 30, 90, 180, and 365 days after discharge. Methods We constructed a dataset of 985626 first admissions from January 2008 through December 2015 who had surveillance tests performed for MRSA carriage. We performed multivariable Cox proportional hazards and logistic regression models to examine the relationship between MRSA colonization status and infection. Results The MRSA infection rate across the predischarge and 180-day postdischarge time period was 5.5% in importers and 7.0% in acquirers without a direct admission to the intensive care unit (ICU) and 11.4% in importers and 11.7% in acquirers who were admitted directly to the ICU. The predischarge hazard ratio for MRSA infection was 29.6 (95% confidence interval [CI], 26.5–32.9) for importers and 28.8 (95% CI, 23.5–35.3) for acquirers compared to those not colonized. Fully 63.9% of all MRSA pre- and postdischarge infections among importers and 61.2% among acquirers occurred within 180 days after discharge. Conclusions MRSA colonization significantly increases the risk of subsequent MRSA infection. In addition, a substantial proportion of MRSA infections occur after discharge from the hospital.

    更新日期:2019-02-05
  • The Proof Is in the Patient: Hepatitis C Virus Microelimination in the Swiss Human Immunodeficiency Virus Cohort Study
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-08-13
    Sulkowski M.

    (See the Major Article by Braun et al on pages 561-8 and Major article by Braun et al on pages 569-76.)

    更新日期:2019-02-05
  • High Cure Rates With Grazoprevir-Elbasvir With or Without Ribavirin Guided by Genotypic Resistance Testing Among Human Immunodeficiency Virus/Hepatitis C Virus–coinfected Men Who Have Sex With Men
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-08-13
    Braun D, Hampel B, Kouyos R, et al.

    Background This study was performed to investigate the efficacy and safety of grazoprevir-elbasvir guided by baseline resistance-associated substitutions (RASs) in the Swiss HCVree Trial. Methods We performed hepatitis C virus (HCV) RNA screening among all men who have sex with men (MSM) enrolled in the Swiss HIV Cohort Study. Individuals with replicating HCV genotype 1 or 4 infection were eligible for grazoprevir-elbasvir treatment. Genotype 1a–infected individuals with baseline RASs and genotype 4–infected individuals with prior failure of HCV treatment received 16 weeks of grazoprevir-elbasvir combined with ribavirin. All other individuals received 12 weeks of grazoprevir-elbasvir alone. Patients reporting unprotected sex with occasional partners were offered a HCV risk reduction–oriented behavioral intervention. Results We screened 3722 MSM and identified 177 (4.8%) with replicating infection. A total of 122 individuals (3.3%) were eligible for study treatment. Six of 76 patients infected with genotype 1a (7.3%) harbored baseline RASs. Sustained virological response after 12 weeks of follow-up was achieved in 121 patients (99%), including all with genotype 1a infection. Overall, 8 serious adverse events occurred, none of which was related to the study drug. Seventy-five percent of eligible MSM participated in the risk counseling program. Conclusions Grazoprevir-elbasvir for 12 or 16 weeks, with or without ribavirin, achieved high cure rates and had an excellent safety profile. Unique to other studies, the treatment duration was guided by the presence of baseline RASs among genotype 1a–infected individuals, and the treatment phase was accompanied by an HCV risk reduction–oriented behavioral intervention. This successful population-wide treatment approach lays the groundwork to achieve HCV elimination in coinfected MSM. Clinical Trials Registration NCT02785666

    更新日期:2019-02-05
  • High Number of Potential Transmitters Revealed in a Population-based Systematic Hepatitis C Virus RNA Screening Among Human Immunodeficiency Virus-infected Men Who Have Sex With Men
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-08-13
    Braun D, Hampel B, Martin E, et al.

    Background The proportion of undiagnosed hepatitis C virus (HCV) infections in high-risk populations, such as human immunodeficiency virus (HIV)–infected men who have sex with men (MSM) is unclear. Identification of potential HCV transmitters is important to reach World Health Organization HCV elimination targets. Methods Between October 2015 and May 2016, we performed a systematic HCV RNA–based screening among HIV-infected MSM participating in the Swiss HIV Cohort Study (SHCS). HCV antibodies were measured from all HCV RNA–positive samples. Results Of 4257 MSM recorded in the SHCS database, we screened 3722 (87%) by HCV polymerase chain reaction, and 177 (4.8%) harbored a replicating HCV infection. We identified 24 individuals (14%) with incident HCV infection; one-third of them had a negative HCV antibody result at the time of HCV RNA positivity. In a multivariable model, elevated liver enzyme values (odds ratio, 14.52; 95% confidence interval, 9.92–21.26), unprotected sex with occasional partners (2.01; 1.36–2.98), intravenous drug use (7.13; 4.36–11.64), noninjectable drug use (1.94; 1.3–2.88), and previous syphilis diagnosis (2.56; 1.74–3.76) were associated with HCV RNA positivity. Conclusions A systematic HCV RNA–based screening among HIV-infected MSM revealed a high number of potential transmitters. A substantial subpopulation of MSM had incident infection, one-third of whom had a negative HCV antibody test result at the time of the HCV RNA positivity. These data reveal that one-time RNA testing of a high-risk population for HCV RNA might identify more infected persons than routine testing for HCV antibodies and liver enzymes. Clinical Trials Registration NCT02785666

    更新日期:2019-02-05
  • Plea for Standardized Reporting and Justification of Propensity Score Methods
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-08-22
    Roth J, Juchler F, Widmer A, et al.

    To the Editor—Propensity score methods are increasingly being used to control for confounding by indication in observational studies when random assignment may not be feasible. In this context, adjustment for baseline differences between study groups by propensity score methods are often more practical and statistically more efficient compared to techniques such as multivariable regression or stratification [1]. Unlike conventional adjustment methods that use a limited number of covariate factors, propensity score methods may allow the integration of a larger number of covariables and can reduce confounding effects to make internally valid estimates of the relationship between an exposure (eg, treatment duration) and an outcome (eg, mortality) [1].

    更新日期:2019-02-05
  • Frequency of Positive Enzyme Immunoassay for Toxin in Stool of Asymptomatic Carriers of Clostridium difficile
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-08-22
    Wong Y, Gonzalez-Orta M, Saldana C, et al.

    To the Editor—The recent article by Pollack et al [1] highlights an underappreciated issue related to Clostridium difficile infection (CDI) multistep testing algorithms that include stool toxin testing. While it is acknowledged that negative toxin assays in patients with positive screening tests for C. difficile require clinical evaluation to distinguish asymptomatic carriage from CDI with a negative toxin test, positive toxin assays are generally interpreted as an indicator of CDI requiring treatment [2, 3]. However, asymptomatic carriers of toxigenic C. difficile may also have detectable toxin in stool. Using cell cytotoxicity neutralization assays (CCNA), toxin has been detected in stool of 16%–79% of asymptomatic carriers [4–8], and toxin is often detectable in stool after CDI treatment [9]. The report by Pollack et al [1] demonstrating frequent detection of toxin in asymptomatic carriers using an ultrasensitive assay further reinforces concern that positive toxin assays may not be a reliable indicator of CDI, particularly in settings where inappropriate testing is common.

    更新日期:2019-02-05
  • Concurrent Seroprevalence of Antibodies to Toxoplasma gondii and Toxocara Species in the United States, 2011–2014
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-08-23
    Liu E, Elder E, Rivera H, et al.

    To the Editor—We report supplemental findings incorporating Toxoplasma gondii serology results from our study of risk factors for Toxocara seropositivity in the United States [1] using stored serum samples collected from the National Health and Nutrition Examination Survey (NHANES), 2011–2014. Whereas T. gondii is a protozoan parasite and Toxocara is an intestinal nematode, both share ingestion of contaminated soil as means of exposure in humans. Both parasites can contaminate soil when environmentally resistant T. gondii oocysts or Toxocara cati eggs are shed in the feces of infected cats [2, 3].

    更新日期:2019-02-05
  • A 44-Year-Old Female With Overwhelming Sepsis
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-08-27
    Seligman S, Bolze A, Boisson B, et al.

    sepsisaspleniaRPSA geneHowell-Jolly bodiesStreptococcus pneumonia

    更新日期:2019-02-05
  • First Human Case of Metacestode Infection Caused by Versteria sp. in a Kidney Transplant Recipient
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-09-13
    Barkati S, Gottstein B, Müller N, et al.

    Cestodes are emerging agents of severe opportunistic infections among immunocompromised patients. We describe the first case of human infection, with the recently-proposed genus Versteria causing an invasive, tumor-like hepatic infection with regional and distant extension in a 53-year-old female kidney transplant recipient from Atlantic Canada.

    更新日期:2019-02-05
  • Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus–1 Infection: Week 48 Results of the DRIVE-AHEAD Trial
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-08-31
    Orkin C, Squires K, Molina J, et al.

    Background Doravirine (DOR), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)-1 and the most common NNRTI-resistant variants, and has a favorable and unique in vitro resistance profile. Methods DRIVE-AHEAD is a phase 3, double-blind, non-inferiority trial. Antiretroviral treatment–naive adults with ≥1000 HIV-1 RNA copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg, lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300 mg (EFV/FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 48 (Food and Drug Administration snapshot approach; non-inferiority margin 10%). Results Of the 734 participants randomized, 728 were treated (364 per group) and included in the analyses. At week 48, 84.3% (307/364) of DOR/3TC/TDF recipients and 80.8% (294/364) of EFV/FTC/TDF recipients achieved <50 HIV-1 RNA copies/mL (difference 3.5%, 95% CI, -2.0, 9.0). DOR/3TC/TDF recipients had significantly lower rates of dizziness (8.8% vs 37.1%), sleep disorders/disturbances (12.1% vs 25.2%), and altered sensorium (4.4% vs 8.2%) than EFV/FTC/TDF recipients. Mean changes in fasting low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) (-3.83 vs +13.26 mg/dL) were significantly different between DOR/3TC/TDF and EFV/FTC/TDF (−1.6 vs +8.7 mg/dL and −3.8 vs +13.3 mg/dL, respectively). Conclusions In HIV-1 treatment-naive adults, DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non–HDL-C compared with EFV/FTC/TDF. Clinical Trials Registration NCT02403674

    更新日期:2019-02-05
  • Cost-effectiveness and Cost-utility of the Adherence Improving Self-management Strategy in Human Immunodeficiency Virus Care: A Trial-based Economic Evaluation
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-09-14
    Wijnen B, Oberjé E, Evers S, et al.

    Background Several promising human immunodeficiency virus (HIV) treatment adherence interventions have been identified, but data about their cost-effectiveness are lacking. This study examines the trial-based cost-effectiveness and cost-utility of the proven-effective Adherence Improving Self-Management Strategy (AIMS), from a societal perspective, with a 15-month time horizon. Methods Treatment-naive and treatment-experienced patients at risk for viral rebound were randomized to treatment as usual (TAU) or AIMS in a multicenter randomized controlled trial in the Netherlands. AIMS is a nurse-led, 1-on-1 self-management intervention incorporating feedback from electronic medication monitors, delivered during routine clinical visits. Main outcomes were costs per reduction in log10 viral load, treatment failure (2 consecutive detectable viral loads), and quality-adjusted life-years (QALYs). Results Two hundred twenty-three patients were randomized. From a societal perspective, AIMS was slightly more expensive than TAU but also more effective, resulting in an incremental cost-effectiveness ratio (ICER) of €549 per reduction in log10 viral load and €1659 per percentage decrease in treatment failure. In terms of QALYs, AIMS resulted in higher costs but more QALYs compared to TAU, which resulted in an ICER of €27759 per QALY gained. From a healthcare perspective, AIMS dominated TAU. Additional sensitivity analyses addressing key limitations of the base case analyses also suggested that AIMS dominates TAU. Conclusions Base case analyses suggests that over a period of 15 months, AIMS may be costlier, but also more effective than TAU. All additional analyses suggest that AIMS is cheaper and more effective than TAU. This trial-based economic evaluation confirms and complements a model-based economic evaluation with a lifetime horizon showing that AIMS is cost-effective. Clinical Trials Registration NCT01429142

    更新日期:2019-02-05
  • Ebola’s Curse: 2013–2016 Outbreak in West Africa
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2018-11-08
    Uhde K.

    By OldstoneMichael and OldstoneMadeleine. Elsevier, 2017. 126 pp. $89.95 (hardcover). ISBN: 9780128138885.

    更新日期:2019-02-05
  • Efficacy and Safety of IV-to-Oral Lefamulin, a Pleuromutilin Antibiotic, for Treatment of Community-Acquired Bacterial Pneumonia: The Phase 3 LEAP 1 Trial
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-04
    File T, Jr, Goldberg L, Das A, et al.

    Background Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study (NCT02559310) was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP. Methods In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin 150 mg intravenously (IV) q12h or moxifloxacin 400 mg IV q24h. After 6 doses, patients could be switched to oral study drug if prespecified improvement criteria were met. If methicillin-resistant Staphylococcus aureus was suspected, linezolid or placebo was added to moxifloxacin or lefamulin, respectively. The US FDA primary endpoint was early clinical response (ECR) 96±24 hours after the first dose of study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%). The EMA co-primary endpoints were investigator assessment of clinical response (IACR) 5-10 days after last dose of study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%). Results 551 patients were randomized (n=276 lefamulin; n=275 moxifloxacin). Lefamulin was noninferior to moxifloxacin for ECR (87.3% vs 90.2%; difference: –2.9% [95% confidence interval: –8.5, 2.8]) and IACR (mITT, 81.7% vs 84.2%; difference –2.6% [–8.9, 3.9]; CE, 86.9% vs 89.4%; difference –2.5% [–8.4, 3.4]). Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin. Conclusions Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated.

    更新日期:2019-02-05
  • Elaboration of consensus clinical endpoints to evaluate antimicrobial treatment efficacy in future HABP/VABP clinical trials
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-04
    Weiss E, Zahar J, Alder J, et al.

    Background Randomized Clinical Trials (RCTs) in Hospital-Acquired (HABP) and Ventilator-Associated Bacterial Pneumonia (VABP) are important for the evaluation of new antimicrobials. However, the heterogeneity in endpoints used in RCTs evaluating treatment of HABP/VABP may puzzle clinicians. The aim of this work was to reach a consensus on clinical endpoints to consider in future clinical trials evaluating antimicrobial treatment efficacy for HABP/VABP. Methods Twenty-six international experts from intensive care, infectious diseases and the pharmaceutical industry were polled using the Delphi method. Results The panel recommended a hierarchical composite endpoint including, by priority order, for VABP (i) survival at day 28, (ii) mechanical ventilation (MV)-free-days through day 28, and (iii) clinical cure between study days 7 and 10; and for HABP (i) survival (day 28), and (ii) clinical cure (days 7-10). Clinical cure was defined as the combination of resolution of signs and symptoms present at enrolment and improvement or lack of progression of radiological signs. More than 70% of the experts agreed to assess survival and MV-free days though day 28, and clinical cure between day 7 and day 10 after treatment initiation. Finally, the hierarchical order of endpoint components was reached after 3 Delphi rounds (72% agreement). Conclusion We provide a multinational expert consensus on separate hierarchical composite endpoints for VABP and HABP, and on a definition of clinical cure that could be considered for use in future HABP/VABP clinical trials.

    更新日期:2019-02-05
  • Early ID Outpatient Follow-up of OPAT Patients Reduces 30-Day Readmission
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-04
    Saini E, Ali M, Du P, et al.

    We conducted a pair-matched case-control study to examine the association between outpatient infectious disease follow-up and the risk of 30-day readmission in 384 patients receiving outpatient parenteral antimicrobial therapy (OPAT). We found ID outpatient follow-up within 2 weeks was associated with a lower risk of all-cause 30-day readmission (aOR=0.33, p-value=0.0001).

    更新日期:2019-02-05
  • Corrigendum
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-05

    An error appeared in the initial publication of this article [Schmitt S, MacIntyre AT, Bleasdale SC, et al. Early Infectious Diseases Specialty Intervention Is Associated With Shorter Hospital Stays and Lower Readmission Rates: A Retrospective Cohort Study. Clin Infect Dis https://doi.org/10.1093/cid/ciy494]. This article was originally published with the following error:

    更新日期:2019-02-05
  • Detection of epidemic scarlet fever group A Streptococcus in Australia
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-02-05
    Walker M, Brouwer S, Forde B, et al.

    Sentinel hospital surveillance was instituted in Australia to detect the presence of pandemic group A Streptococcus strains causing scarlet fever. Genomic and phylogenetic analyses indicated the presence of an Australian GAS emm12 scarlet fever isolate related to UK outbreak strains. National surveillance to monitor this pandemic is recommended.

    更新日期:2019-02-05
  • New FDA approvals decrease generic flucytosine costs
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-01-29
    Rajasingham R, Boulware D.

    Cryptococcal meningitisCryptococcal antigenHIVPreventionOpportunistic InfectionsFlucytosine

    更新日期:2019-01-31
  • Improved Outcomes with High-Dose Isoniazid in Multidrug-Resistant Tuberculosis Treatment in Haiti
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-01-29
    Walsh K, Vilbrun S, Souroutzidis A, et al.

    We report outcomes for a cohort of patients with multidrug-resistant tuberculosis who received high-dose isoniazid in Haiti. Patients who received high-dose isoniazid had a faster time to culture conversion and higher odds of successful outcome, despite high-level isoniazid resistance. This suggests high-dose isoniazid may have effectiveness even with phenotypic resistance.

    更新日期:2019-01-31
  • Treatment effectiveness of azithromycin and doxycycline in uncomplicated rectal and vaginal Chlamydia trachomatis infections in women: a multicentre observational study (FemCure)
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-01-28
    Dukers-Muijrers N, Wolffs P, Vries H, et al.

    Background Rectal infections with Chlamydia trachomatis (CT) are prevalent in women visiting a sexually transmitted infection (STI) outpatient clinic, but it remains unclear what the most effective treatment is. We assessed the effectiveness of doxycycline and azithromycin for the treatment of rectal and vaginal chlamydia in women. Methods This study is part of a prospective multicentre cohort study (FemCure). Treatment consisted of doxycycline (100 mg twice daily for 7 days) in rectal CT positive women, and of azithromycin (1 g single dose) in vaginal positive women who were rectally untested or rectally negative. Participants self-collected rectal and vaginal samples at enrolment (treatment timepoint) and during 4 weeks of follow-up. The endpoint was microbiological cure by a negative nucleic acid amplification test at 4 weeks. Differences between cure proportions and 95% confidence intervals (CIs) were calculated. Results We analysed 416 patients of whom 319 had both rectal and vaginal chlamydia at enrolment, 22 had rectal chlamydia only, and 75 had vaginal chlamydia only. In 341 rectal infections, microbiological cure in azithromycin treated women was 78.5% (95%CI: 72.6 to 83.7, n=164/209) and 95.5% (95%CI: 91.0 to 98.2, n=126/132) in doxycycline treated women (difference 17.0%, 95%CI: 9.6 to 24.7, p<0.001). In 394 vaginal infections, cure was 93.5% (95%CI: 90.1 to 96.1,n=246/263) in azithromycin treated women and 95.4% (95%CI: 90.9 to 98.2,n=125/131) in doxycycline treated women (difference 1.9%, 95%CI: -3.6 to 6.7,p=0.504). Conclusions The effectiveness of doxycycline is high and exceeds that of azithromycin for the treatment of rectal CT infections in women. Trial registration Clinicaltrials.gov NCT02694497.

    更新日期:2019-01-29
  • US Guideline Criteria for HIV Pre-Exposure Prophylaxis: Clinical Considerations and Caveats
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-01-28
    Calabrese S, Krakower D, Willie T, et al.

    Clinical guidelines for HIV pre-exposure prophylaxis (PrEP) developed by the US Centers for Disease Control and Prevention have been instrumental to the implementation of PrEP in medical practices throughout the country. However, the eligibility criteria contained within may inadvertently limit PrEP access for some patients. We describe key considerations and caveats surrounding these criteria: (1) promotion of a selective vs. universal approach to sexual health education involving PrEP; (2) misalignment between criteria stated in the table and text boxes; (3) problematic categorization and confounding of sexual orientation, gender identity, and risk behavior; (4) underemphasis of network/community-level drivers of HIV transmission; (5) oversimplification of serodiscordant risk; and (6) lack of clarity surrounding the relevance of condoms to PrEP eligibility. We offer concrete recommendations to address the identified issues and strengthen future iterations of the guidelines, applying these recommendations in an alternative table of “criteria.”

    更新日期:2019-01-29
  • Effectiveness of seasonal influenza vaccination of children in Senegal during a year of vaccine mismatch: a cluster-randomized trial
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-01-28
    Diallo A, Diop O, Diop D, et al.

    Background Population effects of influenza vaccination of children have not been extensively studied, especially in tropical developing countries. In rural Senegal, we assessed the total (primary objective) and indirect effectiveness of inactivated influenza vaccine, trivalent (IIV3). Methods In this double-blind, cluster-randomized trial, villages were randomly allocated (1:1) for high-coverage vaccination of children aged 6 months through 10 years with 2008-09 northern hemisphere IIV3 or inactivated polio vaccine (IPV). Vaccinees were monitored for serious adverse events. All village residents, vaccinated and unvaccinated, were monitored for signs and symptoms of influenza illness using weekly home visits and surveillance in designated clinics. The primary outcome was all laboratory-confirmed symptomatic influenza. Results Between May 23 and July 11, 2009, 20 villages were randomized, and 66.5% of age-eligible children were enrolled (3918 in IIV3 villages and 3848 in IPV villages). Follow-up continued until May 28, 2010. Four unrelated serious adverse events were identified. Among vaccinees, total effectiveness against illness caused by seasonal influenza virus (presumed all drifted A/H3N2 based on antigenic characterization data) circulating at high rates among children was 43.6% (95% CI, 18.6% to 60.9%). Indirect effectiveness against seasonal A/H3N2 was 15.4% (95% CI, −22.0% to 41.3%). Total effectiveness against illness caused by pandemic influenza virus (A/H1N1pdm09) was −52.1% (95% CI, −177.2% to 16.6%). Conclusions IIV3 provided statistically significant, moderate protection to children in Senegal against circulating pre-2010 seasonal influenza strains but not against A/H1N1pdm09 not included in the vaccine. No indirect effects were measured. Further study in low resource populations is warranted.

    更新日期:2019-01-29
  • Cost-Effectiveness of Universal Hepatitis C Virus Screening of Pregnant Women in The United States
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-01-28
    Chaillon A, Rand E, Reau N, et al.

    Background Hepatitis C Virus (HCV) chronic prevalence among pregnant women in the United States (U.S.) U.S. doubled nationally from 2009-2014 (~0.7%), yet many remain undiagnosed. Screening pregnant women is not recommended by the Society of Maternal-Fetal Medicine or the Centers for Disease Control and Prevention, despite new AASLD/IDSA guidelines recommending screening this group. We assessed the cost-effectiveness of HCV screening for pregnant women in the U.S. Methods An HCV natural history Markov model was used to evaluate the cost-effectiveness of universal HCV screening of pregnant women followed by treatment after pregnancy compared to background risk-based screening from a health care payer perspective. We assumed 0.73% HCV chronic prevalence among pregnant women based on national data. We assume no Medicaid reimbursement restrictions by fibrosis stage at baseline, but explore differing restrictions in sensitivity analyses. We assessed cost (in USD$) and health outcomes (in quality-adjusted life years, QALYs) over a lifetime horizon, using new HCV drug costs of $25,000/treatment. We assess mean incremental cost-effectiveness ratios (ICERs) under a willingness to pay threshold of $50,000/QALY gained. We additionally evaluate potential population impact. Results Universal antenatal screening was cost-effective in all treatment eligibility scenarios (mean ICER <$3,000/QALY gained). Screening remained cost-effective at 0.07% prevalence, the lowest estimated prevalence state in the U.S. (Hawaii). Screening the ~5.04 million pregnant women in 2018 could result in detection and treatment of 33,000 women based on current fibrosis restrictions. Conclusions Universal screening for HCV among pregnant women in the U.S. is cost effective and should be recommended nationally.

    更新日期:2019-01-29
  • Destination Joint Spacers, Reinfection, and Antimicrobial Suppression
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-01-28
    Valencia J, Abdel M, Virk A, et al.

    In this cohort of 51 patients managed with retained “destination spacers” after resection of infected joint prostheses, the presence of preoperative sinus drainage was significantly associated with re-infection. Chronic antimicrobial suppression after destination spacer retention did not significantly prevent re-infections.

    更新日期:2019-01-29
  • The Juncture between Clostridium difficile infection and Inflammatory Bowel Diseases
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-01-28
    Beniwal-Patel P, Stein D, Munoz-Price L.

    Clostridium difficile detection in inflammatory bowel disease (IBD) patients is a common occurrence in part due to the standard clinical practice of testing for C. difficile presence during acute IBD exacerbations. Given the clinical overlap between C. difficile infection and acute IBD exacerbations (i.e. increased frequency of loose stools, abdominal pain), it is hard to differentiate C. difficile infection versus colonization in patients with underlying IBD who test positive for C. difficile. Here we review the epidemiology, clinical presentation, risk factors, diagnosis, treatment and outcomes of IBD patients with positive C.difficiletests.

    更新日期:2019-01-29
  • Global review of the age distribution of rotavirus disease in children aged <5 years before the introduction of rotavirus vaccination
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-01-28
    Hasso-Agopsowicz M, Ladva C, Lopman B, et al.

    We sought datasets with granular age distributions of rotavirus-positive presentations among children <5 years of age, before the introduction of rotavirus vaccines. We identified 117 datasets and fit parametric age distributions to each country dataset and mortality stratum and calculated the median age, and cumulative proportion of rotavirus gastroenteritis events expected to occur at ages between birth and 5.0 years. The median age of rotavirus-positive hospital admissions was 38 weeks (inter-quartile range IQR: 25-58) in countries with very high child mortality and 65 weeks (IQR: 40-107) in countries with very low/low child mortality. In countries with very high child mortality 69% of rotavirus-positive admissions <5 years were in the first year of life, with 3% by 10 weeks, 8% by 15 weeks and 27% by 26 weeks. This information is critical for assessing the potential benefits of alternative rotavirus vaccination schedules in different countries, and for monitoring programme impact.

    更新日期:2019-01-29
  • Isolation of Nontuberculous Mycobacteria in Southeast Asian and African Human Immunodeficiency Virus–infected Children With Suspected Tuberculosis
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-01-28
    Borand L, de Lauzanne A, Nguyen N, et al.

    We enrolled 427 human immunodeficiency virus–infected children (median age, 7.3 years), 59.2% severely immunodeficient, with suspected tuberculosis in Southeast Asian and African settings. Nontuberculous mycobacteria were isolated in 46 children (10.8%); 45.7% of isolates were Mycobacterium avium complex. Southeast Asian origin, age 5–9 years, and severe immunodeficiency were independently associated with nontuberculous mycobacteria isolation.

    更新日期:2019-01-29
  • Rapid molecular tests for influenza, respiratory syncytial virus, and other respiratory viruses: a systematic review of diagnostic accuracy and clinical impact studies
    Clin. Infect. Dis. (IF 9.117) Pub Date : 2019-01-28
    Vos L, Bruning A, Reitsma J, et al.

    We systematically reviewed available evidence from EMBASE, MEDLINE and the Cochrane Library on diagnostic accuracy and clinical impact of commercially available rapid (results <3 hours) molecular diagnostics for respiratory viruses as compared to conventional molecular tests. Quality of included studies was assessed using the QUADAS-2 criteria for diagnostic test accuracy (DTA) studies, and the Cochrane Risk of Bias Assessment and ROBINS-I criteria for randomized and observational impact studies, respectively. 63 DTA reports (56 studies) were meta-analysed with a pooled sensitivity of 90.9% (95% confidence interval (CI), 88.7%-93.1%) and specificity of 96.1% (95%CI, 94.2%-97.9%) for the detection of either influenza virus (n=29), RSV (n=1), influenza virus and RSV (n=19), or a viral panel including influenza virus and RSV (n=14). The 15 included impact studies – 5 randomized – were very heterogeneous and results were therefore inconclusive. We however suggest to consider implementation of rapid diagnostics in hospital care settings. Prospero registration CRD42017057881

    更新日期:2019-01-29
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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