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  • Syndromic Panel-Based Testing in Clinical Microbiology [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-11-15
    Poornima Ramanan, Alexandra L. Bryson, Matthew J. Binnicker, Bobbi S. Pritt, Robin Patel

    The recent development of commercial panel-based molecular diagnostics for the rapid detection of pathogens in positive blood culture bottles, respiratory specimens, stool, and cerebrospinal fluid has resulted in a paradigm shift in clinical microbiology and clinical practice. This review focuses on U.S. Food and Drug Administration (FDA)-approved/cleared multiplex molecular panels with more than five targets designed to assist in the diagnosis of bloodstream, respiratory tract, gastrointestinal, or central nervous system infections. While these panel-based assays have the clear advantages of a rapid turnaround time and the detection of a large number of microorganisms and promise to improve health care, they present certain challenges, including cost and the definition of ideal test utilization strategies (i.e., optimal ordering) and test interpretation.

    更新日期:2017-11-15
  • Candida auris: a Review of the Literature [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-11-15
    Anna Jeffery-Smith, Surabhi K. Taori, Silke Schelenz, Katie Jeffery, Elizabeth M. Johnson, Andrew Borman, Candida auris Incident Management Team, Rohini Manuel, Colin S. Brown

    The emerging pathogen Candida auris has been associated with nosocomial outbreaks on five continents. Genetic analysis indicates the simultaneous emergence of separate clades of this organism in different geographical locations. Invasive infection and colonization have been detected predominantly in patients in high-dependency settings and have garnered attention due to variable antifungal resistance profiles and transmission within units instituting a range of infection prevention and control measures. Issues with the identification of C. auris using both phenotypic and molecular techniques have raised concerns about detecting the true scale of the problem. This review considers the literature available on C. auris and highlights the key unknowns, which will provide direction for further work in this field.

    更新日期:2017-11-15
  • Laboratory Diagnosis of Parasites from the Gastrointestinal Tract [Practical Guidance For Clinical Microbiology]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-11-15
    Lynne S. Garcia, Michael Arrowood, Evelyne Kokoskin, Graeme P. Paltridge, Dylan R. Pillai, Gary W. Procop, Norbert Ryan, Robyn Y. Shimizu, Govinda Visvesvara

    This Practical Guidance for Clinical Microbiology document on the laboratory diagnosis of parasites from the gastrointestinal tract provides practical information for the recovery and identification of relevant human parasites. The document is based on a comprehensive literature review and expert consensus on relevant diagnostic methods. However, it does not include didactic information on human parasite life cycles, organism morphology, clinical disease, pathogenesis, treatment, or epidemiology and prevention. As greater emphasis is placed on neglected tropical diseases, it becomes highly probable that patients with gastrointestinal parasitic infections will become more widely recognized in areas where parasites are endemic and not endemic. Generally, these methods are nonautomated and require extensive bench experience for accurate performance and interpretation.

    更新日期:2017-11-15
  • Human Parechovirus: an Increasingly Recognized Cause of Sepsis-Like Illness in Young Infants [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-11-15
    Laudi Olijve, Lance Jennings, Tony Walls

    Human parechovirus (HPeV) is increasingly being recognized as a potentially severe viral infection in neonates and young infants. HPeV belongs to the family Picornaviridae and is currently divided into 19 genotypes. HPeV-1 is the most prevalent genotype and most commonly causes gastrointestinal and respiratory disease. HPeV-3 is clinically the most important genotype due to its association with severe disease in younger infants, which may partly be explained by its distinct virological properties. In young infants, the typical clinical presentation includes fever, severe irritability, and rash, often leading to descriptions of “hot, red, angry babies.” Infants with severe central nervous system (CNS) infections are at an increased risk of long-term sequelae. Considering the importance of HPeV as a cause of severe viral infections in young infants, we recommend that molecular diagnostic techniques for early detection be included in the standard practice for the investigation of sepsis-like illnesses and CNS infections in this age group.

    更新日期:2017-11-15
  • Molecular Tools for the Detection and Deduction of Azole Antifungal Drug Resistance Phenotypes in Aspergillus Species [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-09-13
    Anna Dudakova, Birgit Spiess, Marut Tangwattanachuleeporn, Christoph Sasse, Dieter Buchheidt, Michael Weig, Uwe Groß, Oliver Bader

    The incidence of azole resistance in Aspergillus species has increased over the past years, most importantly for Aspergillus fumigatus. This is partially attributable to the global spread of only a few resistance alleles through the environment. Secondary resistance is a significant clinical concern, as invasive aspergillosis with drug-susceptible strains is already difficult to treat, and exclusion of azole-based antifungals from prophylaxis or first-line treatment of invasive aspergillosis in high-risk patients would dramatically limit drug choices, thus increasing mortality rates for immunocompromised patients. Management options for invasive aspergillosis caused by azole-resistant A. fumigatus strains were recently reevaluated by an international expert panel, which concluded that drug resistance testing of cultured isolates is highly indicated when antifungal therapy is intended. In geographical regions with a high environmental prevalence of azole-resistant strains, initial therapy should be guided by such analyses. More environmental and clinical screening studies are therefore needed to generate the local epidemiologic data if such measures are to be implemented on a sound basis. Here we propose a first workflow for evaluating isolates from screening studies, and we compile the MIC values correlating with individual amino acid substitutions in the products of cyp51 genes for interpretation of DNA sequencing data, especially in the absence of cultured isolates.

    更新日期:2017-09-13
  • The Role of BAFF System Molecules in Host Response to Pathogens [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-08-30
    Jiro Sakai, Mustafa Akkoyunlu

    The two ligands B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) and the three receptors BAFF receptor (BAFF-R), transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA) are members of the “BAFF system molecules.” BAFF system molecules are primarily involved in B cell homeostasis. The relevance of BAFF system molecules in host responses to microbial assaults has been investigated in clinical studies and in mice deficient for each of these molecules. Many microbial products modulate the expression of these molecules. Data from clinical studies suggest a correlation between increased expression levels of BAFF system molecules and elevated B cell responses. Depending on the pathogen, heightened B cell responses may strengthen the host response or promote susceptibility. Whereas pathogen-mediated increases in the expression levels of the ligands and/or the receptors appear to promote microbial clearance, certain pathogens have evolved to ablate B cell responses by suppressing the expression of TACI and/or BAFF-R on B cells. Other than its well-established role in B cell responses, the TACI-mediated activation of macrophages is also implicated in resistance to intracellular pathogens. An improved understanding of the role that BAFF system molecules play in infection may assist in devising novel strategies for vaccine development.

    更新日期:2017-08-30
  • Whole-Genome Sequencing of Bacterial Pathogens: the Future of Nosocomial Outbreak Analysis [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-08-30
    Scott Quainoo, Jordy P. M. Coolen, Sacha A. F. T. van Hijum, Martijn A. Huynen, Willem J. G. Melchers, Willem van Schaik, Heiman F. L. Wertheim

    Outbreaks of multidrug-resistant bacteria present a frequent threat to vulnerable patient populations in hospitals around the world. Intensive care unit (ICU) patients are particularly susceptible to nosocomial infections due to indwelling devices such as intravascular catheters, drains, and intratracheal tubes for mechanical ventilation. The increased vulnerability of infected ICU patients demonstrates the importance of effective outbreak management protocols to be in place. Understanding the transmission of pathogens via genotyping methods is an important tool for outbreak management. Recently, whole-genome sequencing (WGS) of pathogens has become more accessible and affordable as a tool for genotyping. Analysis of the entire pathogen genome via WGS could provide unprecedented resolution in discriminating even highly related lineages of bacteria and revolutionize outbreak analysis in hospitals. Nevertheless, clinicians have long been hesitant to implement WGS in outbreak analyses due to the expensive and cumbersome nature of early sequencing platforms. Recent improvements in sequencing technologies and analysis tools have rapidly increased the output and analysis speed as well as reduced the overall costs of WGS. In this review, we assess the feasibility of WGS technologies and bioinformatics analysis tools for nosocomial outbreak analyses and provide a comparison to conventional outbreak analysis workflows. Moreover, we review advantages and limitations of sequencing technologies and analysis tools and present a real-world example of the implementation of WGS for antimicrobial resistance analysis. We aimed to provide health care professionals with a guide to WGS outbreak analysis that highlights its benefits for hospitals and assists in the transition from conventional to WGS-based outbreak analysis.

    更新日期:2017-08-30
  • Intrinsic Maturational Neonatal Immune Deficiencies and Susceptibility to Group B Streptococcus Infection [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-08-16
    Michelle L. Korir, Shannon D. Manning, H. Dele Davies

    Although a normal member of the gastrointestinal and vaginal microbiota, group B Streptococcus (GBS) can also occasionally be the cause of highly invasive neonatal disease and is an emerging pathogen in both elderly and immunocompromised adults. Neonatal GBS infections are typically transmitted from mother to baby either in utero or during passage through the birth canal and can lead to pneumonia, sepsis, and meningitis within the first few months of life. Compared to the adult immune system, the neonatal immune system has a number of deficiencies, making neonates more susceptible to infection. Recognition of GBS by the host immune system triggers an inflammatory response to clear the pathogen. However, GBS has developed several mechanisms to evade the host immune response. A comprehensive understanding of this interplay between GBS and the host immune system will aid in the development of new preventative measures and therapeutics.

    更新日期:2017-08-16
  • Impact of Childhood Malnutrition on Host Defense and Infection [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-08-02
    Marwa K. Ibrahim, Mara Zambruni, Christopher L. Melby, Peter C. Melby

    The global impact of childhood malnutrition is staggering. The synergism between malnutrition and infection contributes substantially to childhood morbidity and mortality. Anthropometric indicators of malnutrition are associated with the increased risk and severity of infections caused by many pathogens, including viruses, bacteria, protozoa, and helminths. Since childhood malnutrition commonly involves the inadequate intake of protein and calories, with superimposed micronutrient deficiencies, the causal factors involved in impaired host defense are usually not defined. This review focuses on literature related to impaired host defense and the risk of infection in primary childhood malnutrition. Particular attention is given to longitudinal and prospective cohort human studies and studies of experimental animal models that address causal, mechanistic relationships between malnutrition and host defense. Protein and micronutrient deficiencies impact the hematopoietic and lymphoid organs and compromise both innate and adaptive immune functions. Malnutrition-related changes in intestinal microbiota contribute to growth faltering and dysregulated inflammation and immune function. Although substantial progress has been made in understanding the malnutrition-infection synergism, critical gaps in our understanding remain. We highlight the need for mechanistic studies that can lead to targeted interventions to improve host defense and reduce the morbidity and mortality of infectious diseases in this vulnerable population.

    更新日期:2017-08-02
  • The Role of Antibiotics in Modulating Virulence in Staphylococcus aureus [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-07-19
    Elisabeth Hodille, Warren Rose, Binh An Diep, Sylvain Goutelle, Gerard Lina, Oana Dumitrescu

    Staphylococcus aureus is often involved in severe infections, in which the effects of bacterial virulence factors have great importance. Antistaphylococcal regimens should take into account the different effects of antibacterial agents on the expression of virulence factors and on the host's immune response. A PubMed literature search was performed to select relevant articles on the effects of antibiotics on staphylococcal toxin production and on the host immune response. Information was sorted according to the methods used for data acquisition (bacterial strains, growth models, and antibiotic concentrations) and the assays used for readout generation. The reported mechanisms underlying S. aureus virulence modulation by antibiotics were reviewed. The relevance of in vitro observations is discussed in relation to animal model data and to clinical evidence extracted from case reports and recommendations on the management of toxin-related staphylococcal diseases. Most in vitro data point to a decreased level of virulence expression upon treatment with ribosomally active antibiotics (linezolid and clindamycin), while cell wall-active antibiotics (beta-lactams) mainly increase exotoxin production. In vivo studies confirmed the suppressive effect of clindamycin and linezolid on virulence expression, supporting their utilization as a valuable management strategy to improve patient outcomes in cases of toxin-associated staphylococcal disease.

    更新日期:2017-07-20
  • Two Tales of Cytauxzoon felis Infections in Domestic Cats [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-06-21
    Jin-Lei Wang, Ting-Ting Li, Guo-Hua Liu, Xing-Quan Zhu, Chaoqun Yao

    Cytauxzoonosis is an emerging infectious disease that affects wild felids as well as the domestic cat; it is caused by the apicomplexan protozoan parasites belonging to the genus Cytauxzoon. Cytauxzoon felis is the species of major concern, whose transmission occurs via the bite of an infected tick. Cytauxzoonosis of the domestic cat has historically been considered uniformly fatal, with a short course of illness, and most domestic cats die within 9 to 15 days postinfection. However, increasing evidence of domestic cats surviving C. felis infection suggests the existence of different strains with various levels of pathogenicity. Although wild felids are considered natural reservoirs for this parasite, a number of studies suggest that domestic cats that have survived nonlethal infections may serve as an additional reservoir. The current article comprehensively reviews the parasite and its life cycle, geographic distribution, genetic variability, and pathogenesis, as well as host immunology and the diagnosis, treatment, and prevention of infection in the domestic cat. This information should provide a basis for better understanding the parasite as well as the pathogenesis of the disease.

    更新日期:2017-06-22
  • Editorial Board [Masthead]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 

    更新日期:2017-06-15
  • Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-06-07
    Deborah A. Williamson, Glen P. Carter, Benjamin P. Howden

    Bacterial skin infections represent some of the most common infectious diseases globally. Prevention and treatment of skin infections can involve application of a topical antimicrobial, which may be an antibiotic (such as mupirocin or fusidic acid) or an antiseptic (such as chlorhexidine or alcohol). However, there is limited evidence to support the widespread prophylactic or therapeutic use of topical agents. Challenges involved in the use of topical antimicrobials include increasing rates of bacterial resistance, local hypersensitivity reactions (particularly to older agents, such as bacitracin), and concerns about the indiscriminate use of antiseptics potentially coselecting for antibiotic resistance. We review the evidence for the major clinical uses of topical antibiotics and antiseptics. In addition, we review the mechanisms of action of common topical agents and define the clinical and molecular epidemiology of antimicrobial resistance in these agents. Moreover, we review the potential use of newer and emerging agents, such as retapamulin and ebselen, and discuss the role of antiseptic agents in preventing bacterial skin infections. A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future.

    更新日期:2017-06-08
  • Mycoplasma pneumoniae from the Respiratory Tract and Beyond [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-05-24
    Waites, K. B., Xiao, L., Liu, Y., Balish, M. F., Atkinson, T. P.

    SUMMARY Mycoplasma pneumoniae is an important cause of respiratory tract infections in children as well as adults that can range in severity from mild to life-threatening. Over the past several years there has been much new information published concerning infections caused by this organism. New molecular-based tests for M. pneumoniae detection are now commercially available in the United States, and advances in molecular typing systems have enhanced understanding of the epidemiology of infections. More strains have had their entire genome sequences published, providing additional insights into pathogenic mechanisms. Clinically significant acquired macrolide resistance has emerged worldwide and is now complicating treatment. In vitro susceptibility testing methods have been standardized, and several new drugs that may be effective against this organism are undergoing development. This review focuses on the many new developments that have occurred over the past several years that enhance our understanding of this microbe, which is among the smallest bacterial pathogens but one of great clinical importance.

    更新日期:2017-05-25
  • Strategies for Prevention and Treatment of Trichomonas vaginalis Infections [Reviews]
    C$L̫VxnLE$L̫Vxn (IF 19.958) Pub Date : 2017-05-24
    Bouchemal, K., Bories, C., Loiseau, P. M.

    SUMMARY The last estimated annual incidence of Trichomonas vaginalis worldwide exceeds that of chlamydia and gonorrhea combined. This critical review updates the state of the art on advances in T. vaginalis diagnostics and strategies for treatment and prevention of trichomoniasis. In particular, new data on treatment outcomes for topical administration of formulations are reviewed and discussed.

    更新日期:2017-05-25
  • Susceptibility Testing of Medically Important Parasites [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-04-26
    Genetu Bayih, A., Debnath, A., Mitre, E., Huston, C. D., Laleu, B., Leroy, D., Blasco, B., Campo, B., Wells, T. N. C., Willis, P. A., Sjö, P., Van Voorhis, W. C., Pillai, D. R.

    SUMMARY In the last 2 decades, renewed attention to neglected tropical diseases (NTDs) has spurred the development of antiparasitic agents, especially in light of emerging drug resistance. The need for new drugs has required in vitro screening methods using parasite culture. Furthermore, clinical laboratories sought to correlate in vitro susceptibility methods with treatment outcomes, most notably with malaria. Parasites with their various life cycles present greater complexity than bacteria, for which standardized susceptibility methods exist. This review catalogs the state-of-the-art methodologies used to evaluate the effects of drugs on key human parasites from the point of view of drug discovery as well as the need for laboratory methods that correlate with clinical outcomes.

    更新日期:2017-05-16
  • Toxoplasma Effectors Targeting Host Signaling and Transcription [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-04-12
    Hakimi, M.-A., Olias, P., Sibley, L. D.

    SUMMARY Early electron microscopy studies revealed the elaborate cellular features that define the unique adaptations of apicomplexan parasites. Among these were bulbous rhoptry (ROP) organelles and small, dense granules (GRAs), both of which are secreted during invasion of host cells. These early morphological studies were followed by the exploration of the cellular contents of these secretory organelles, revealing them to be comprised of highly divergent protein families with few conserved domains or predicted functions. In parallel, studies on host-pathogen interactions identified many host signaling pathways that were mysteriously altered by infection. It was only with the advent of forward and reverse genetic strategies that the connections between individual parasite effectors and the specific host pathways that they targeted finally became clear. The current repertoire of parasite effectors includes ROP kinases and pseudokinases that are secreted during invasion and that block host immune pathways. Similarly, many secretory GRA proteins alter host gene expression by activating host transcription factors, through modification of chromatin, or by inducing small noncoding RNAs. These effectors highlight novel mechanisms by which T. gondii has learned to harness host signaling to favor intracellular survival and will guide future studies designed to uncover the additional complexity of this intricate host-pathogen interaction.

    更新日期:2017-05-16
  • Bacterial and Fungal Endophthalmitis [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-03-29
    Durand, M. L.

    SUMMARY Endophthalmitis is a severe eye infection that may result in permanent loss of useful vision in the affected eye. Most cases are exogenous and occur as a complication of cataract surgery, an intravitreal injection, or penetrating ocular trauma. Endogenous endophthalmitis results from hematogenous seeding of the eye by bacteria or fungi, but bacteremia or fungemia may be transient and patients may present without symptoms of systemic infection. Nearly all endophthalmitis patients present with decreased vision, and some also have eye pain. Eye examination usually reveals a hypopyon and intraocular inflammation. Diagnosis is clinical, supported by cultures of the vitreous and/or aqueous or by blood cultures in some endogenous cases. Molecular diagnostic techniques have been used in research laboratories for pathogen identification in endophthalmitis and offer the possibility of rapid diagnosis, including in culture-negative cases. Intravitreal injection of antibiotics is the most important component of treatment; some cases also benefit from surgical debridement of the vitreous by a vitrectomy. The visual outcome depends partly on the pathogen: coagulase-negative staphylococcal endophthalmitis has a better prognosis than does streptococcal endophthalmitis, for example. Endophthalmitis is a medical emergency, and prompt diagnosis and treatment are essential for saving vision.

    更新日期:2017-05-16
  • Investigating Clinical Issues by Genotyping of Medically Important Fungi: Why and How? [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-05-10
    Alanio, A., Desnos-Ollivier, M., Garcia-Hermoso, D., Bretagne, S.

    SUMMARY Genotyping studies of medically important fungi have addressed elucidation of outbreaks, nosocomial transmissions, infection routes, and genotype-phenotype correlations, of which secondary resistance has been most intensively investigated. Two methods have emerged because of their high discriminatory power and reproducibility: multilocus sequence typing (MLST) and microsatellite length polymorphism (MLP) using short tandem repeat (STR) markers. MLST relies on single-nucleotide polymorphisms within the coding regions of housekeeping genes. STR polymorphisms are based on the number of repeats of short DNA fragments, mostly outside coding regions, and thus are expected to be more polymorphic and more rapidly evolving than MLST markers. There is no consensus on a universal typing system. Either one or both of these approaches are now available for Candida spp., Aspergillus spp., Fusarium spp., Scedosporium spp., Cryptococcus neoformans, Pneumocystis jirovecii, and endemic mycoses. The choice of the method and the number of loci to be tested depend on the clinical question being addressed. Next-generation sequencing is becoming the most appropriate method for fungi with no MLP or MLST typing available. Whatever the molecular tool used, collection of clinical data (e.g., time of hospitalization and sharing of similar rooms) is mandatory for investigating outbreaks and nosocomial transmission.

    更新日期:2017-05-16
  • Bartonella Species, an Emerging Cause of Blood-Culture-Negative Endocarditis [Reviews]
    Clin. Microbiol. Rev. (IF 19.958) Pub Date : 2017-05-10
    Okaro, U., Addisu, A., Casanas, B., Anderson, B.

    SUMMARY Since the reclassification of the genus Bartonella in 1993, the number of species has grown from 1 to 45 currently designated members. Likewise, the association of different Bartonella species with human disease continues to grow, as does the range of clinical presentations associated with these bacteria. Among these, blood-culture-negative endocarditis stands out as a common, often undiagnosed, clinical presentation of infection with several different Bartonella species. The limitations of laboratory tests resulting in this underdiagnosis of Bartonella endocarditis are discussed. The varied clinical picture of Bartonella infection and a review of clinical aspects of endocarditis caused by Bartonella are presented. We also summarize the current knowledge of the molecular basis of Bartonella pathogenesis, focusing on surface adhesins in the two Bartonella species that most commonly cause endocarditis, B. henselae and B. quintana. We discuss evidence that surface adhesins are important factors for autoaggregation and biofilm formation by Bartonella species. Finally, we propose that biofilm formation is a critical step in the formation of vegetative masses during Bartonella-mediated endocarditis and represents a potential reservoir for persistence by these bacteria.

    更新日期:2017-05-16
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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