Clinical Microbiology Reviews[JOURNAL]
Sun
200 papers
Companions in antimicrobial resistance: examining transmission of common antimicrobial-resistant organisms between people and their dogs, cats, and horses.
Caddey B, Fisher S, Barkema HW … +1 more , Nobrega DB
Clin Microbiol Rev · 2025 Mar · PMID 39853095 · Full text
SUMMARYNumerous questions persist regarding the role of companion animals as potential reservoirs of antimicrobial-resistant organisms that can infect humans. While relative antimicrobial usage in companion animals is lo...
SUMMARYNumerous questions persist regarding the role of companion animals as potential reservoirs of antimicrobial-resistant organisms that can infect humans. While relative antimicrobial usage in companion animals is lower than that in humans, certain antimicrobial-resistant pathogens have comparable colonization rates in companion animals and their human counterparts, which inevitably raises questions regarding potential antimicrobial resistance (AMR) transmission. Furthermore, the close contact between pets and their owners, as well as pets, veterinary professionals, and the veterinary clinic environment, provides ample opportunity for zoonotic transmission of antimicrobial-resistant pathogens. Here we summarize what is known about the transmission of AMR and select antimicrobial-resistant organisms between companion animals (primarily dogs, cats, and horses) and humans. We also describe the global distribution of selected antimicrobial-resistant organisms in companion animals. The impact of interspecies AMR transmission within households and veterinary care settings is critically reviewed and discussed in the context of methicillin-resistant staphylococci, extended-spectrum β-lactamase and carbapenemase-producing bacteria. Key research areas are emphasized within established global action plans on AMR, offering valuable insights for shaping future research and surveillance initiatives.
Extracutaneous sporotrichosis.
Ramírez-Soto MC
Clin Microbiol Rev · 2025 Mar · PMID 39807894 · Full text
SUMMARYSporotrichosis is a subacute-to-chronic infection endemic to tropical and subtropical regions. It usually involves subcutaneous tissue but can occasionally cause extracutaneous infections, especially in hyperendem...
SUMMARYSporotrichosis is a subacute-to-chronic infection endemic to tropical and subtropical regions. It usually involves subcutaneous tissue but can occasionally cause extracutaneous infections, especially in hyperendemic areas. Extracutaneous infections are classified based on the anatomic location of the lesion and the route of infection (primary or multifocal). The clinical forms are as follows: (i) pulmonary (primary or multifocal); (ii) osteoarticular (primary or multifocal); (iii) ocular (ocular adnexal lesions including eyelid lesions, conjunctivitis and dacryocystitis, and intraocular infections); (iv) central nervous system; and (v) mucosal (primary or disseminated). Multifocal clinical presentations are observed mainly in immunocompromised individuals. The diagnosis must be confirmed in the laboratory by mycological examination of the clinical samples. Itraconazole and amphotericin B are the most commonly used antifungal agents for treating pulmonary, osteoarticular, ocular, and mucosal forms. Treatment may include surgical excision of the initial lesions in pulmonary and osteoarticular forms. The treatment of neurological involvement is far from optimal and is associated with a high mortality rate despite long treatment periods.
The endothelium at the interface between tissues and in the bloodstream.
Speziale P, Foster TJ, Arciola CR
Clin Microbiol Rev · 2025 Mar · PMID 39807893 · Full text
SUMMARY is a major human pathogen. It can cause many types of infections, in particular bacteremia, which frequently leads to infective endocarditis, osteomyelitis, sepsis, and other debilitating diseases. The developmen...
SUMMARY is a major human pathogen. It can cause many types of infections, in particular bacteremia, which frequently leads to infective endocarditis, osteomyelitis, sepsis, and other debilitating diseases. The development of secondary infections is based on the bacterium's ability to associate with endothelial cells lining blood vessels. The success of endothelial colonization and infection by relies on its ability to express a wide array of cell wall-anchored and secreted virulence factors. Establishment of endothelial infection by the pathogen is a multistep process involving adhesion, invasion, extravasation, and dissemination of the bacterium into surrounding tissues. The process is dependent on the type of endothelium in different organs (tissues) and pathogenetic potential of the individual strains. In this review, we report an update on the organization of the endothelium in the vessels, the structure and function of the virulence factors of S. , and the several aspects of bacteria-endothelial cell interactions. After these sections, we will discuss recent advances in understanding the specific mechanisms of infections that develop in the heart, bone and joints, lung, and brain. Finally, we describe how neutrophils bind to endothelial cells, migrate to the site of infection to kill bacteria in the tissues, and how staphylococci counteract neutrophils' actions. Knowledge of the molecular details of -endothelial cell interactions will promote the development of new therapeutic strategies and tools to combat this formidable pathogen.
Transforming the chemotherapy of human African trypanosomiasis.
Barrett MP
Clin Microbiol Rev · 2025 Mar · PMID 39772631 · Full text
SUMMARYPrior to 2019, when the orally available drug fexinidazole began its clinical use, the treatment of human African trypanosomiasis (HAT) was complex and unsatisfactory for many reasons. Two sub-species of the para...
SUMMARYPrior to 2019, when the orally available drug fexinidazole began its clinical use, the treatment of human African trypanosomiasis (HAT) was complex and unsatisfactory for many reasons. Two sub-species of the parasite are responsible for HAT, namely the rhodesiense form found in East and Southern Africa and the gambiense form found in Central and West Africa. Diseases caused by both forms manifest in two stages: stage 1 before and stage 2 after central nervous system involvement. Prior to 2019, different drugs were required for each of the two parasite sub-species at each stage. Gambiense disease required pentamidine or nifurtimox-eflornithine combination therapy, while for rhodesiense disease, suramin or melarsoprol was given for stages 1 and 2, respectively. These drugs all suffered complications including protracted administration regimens involving multiple injections with drug-induced adverse effects common. Today, a single drug, fexinidazole, can be given orally in most cases for both diseases at either stage. Another compound, acoziborole, effective in both stages 1 and 2 gambiense disease with a single dosing is anticipated to become available within a few years. Moreover, the recent engagement of multilateral organizations in seeking other compounds that could be used in HAT therapy has also been successful, and a rich vein of new trypanocides has been discovered. Here, the clinical use, modes of action, and resistance risks for drugs used against HAT are discussed.
Henipaviruses: epidemiology, ecology, disease, and the development of vaccines and therapeutics.
Spengler JR, Lo MK, Welch SR … +1 more , Spiropoulou CF
Clin Microbiol Rev · 2025 Mar · PMID 39714175 · Full text
SUMMARYHenipaviruses were first identified 30 years ago and have since been associated with over 30 outbreaks of disease in humans. Highly pathogenic henipaviruses include Hendra virus (HeV) and Nipah virus (NiV), classi...
SUMMARYHenipaviruses were first identified 30 years ago and have since been associated with over 30 outbreaks of disease in humans. Highly pathogenic henipaviruses include Hendra virus (HeV) and Nipah virus (NiV), classified as biosafety level 4 pathogens. In addition, NiV has been listed as a priority pathogen by the World Health Organization (WHO), the Coalition for Epidemic Preparedness Innovations (CEPI), and the UK Vaccines Research and Development Network (UKVN). Here, we re-examine epidemiological, ecological, clinical, and pathobiological studies of HeV and NiV to provide a comprehensive guide of the current knowledge and application to identify and evaluate countermeasures. We also discuss therapeutic and vaccine development efforts. Furthermore, with case identification, prevention, and treatment in mind, we highlight limitations in research and recognize gaps necessitating additional studies.
Rapid and accurate testing for urinary tract infection: new clothes for the emperor.
Moreland RB, Brubaker L, Tinawi L … +1 more , Wolfe AJ
Clin Microbiol Rev · 2025 Mar · PMID 39641639 · Full text
SUMMARYUrinary tract infection (UTI) is among the most common infections in clinical practice. In some cases, if left untreated, it can lead to pyelonephritis and urosepsis. In other cases, UTI resolves without treatment...
SUMMARYUrinary tract infection (UTI) is among the most common infections in clinical practice. In some cases, if left untreated, it can lead to pyelonephritis and urosepsis. In other cases, UTI resolves without treatment. Clinical diagnosis is typically based on patient symptoms and/or urinalysis, including urine dipsticks. The standard urine culture method is sometimes employed to identify the suspected urinary pathogen (uropathogen) and/or guide antimicrobial choice, but results are rarely available before 24 h. The standard urine culture method also misses fastidious, anaerobic, and slow-growing uropathogens and rarely reports polymicrobial infections. The unexplained combination of negative urine cultures with persistent urinary tract symptoms is distressing to both patients and clinicians. Given the broad appreciation of the advantages provided by rapid testing (e.g., for COVID-19 or influenza A), a rapid, accurate diagnostic test is needed to deliver timely treatment to patients seeking care for UTI that optimizes antibiotic stewardship. Herein, we discuss progress being made toward an accessible, timely (i.e., within hours), accurate assay with results that are clinically useful for the treating clinician within the timeframe of the infection (i.e., the growth rate of the pathogen(s)). New and emerging uropathogens often overlooked by current diagnostic techniques are also reviewed.
Group B streptococcal infections in pregnancy and early life.
Manuel G, Twentyman J, Noble K … +5 more , Eastman AJ, Aronoff DM, Seepersaud R, Rajagopal L, Adams Waldorf KM
Clin Microbiol Rev · 2025 Mar · PMID 39584819 · Full text
SUMMARYBacterial infections with Group B (GBS) are an important cause of adverse outcomes in pregnant individuals, neonates, and infants. GBS is a common commensal in the genitourinary and gastrointestinal tracts and ca...
SUMMARYBacterial infections with Group B (GBS) are an important cause of adverse outcomes in pregnant individuals, neonates, and infants. GBS is a common commensal in the genitourinary and gastrointestinal tracts and can be detected in the vagina of approximately 20% of women globally. GBS can infect the fetus either during pregnancy or vaginal delivery resulting in preterm birth, stillbirth, or early-onset neonatal disease (EOD) in the first week of life. The mother can also become infected with GBS leading to postpartum endometritis, and rarely, maternal sepsis. An invasive GBS infection of the neonate may present after the first week of life (late-onset disease, LOD) through transmission from caregivers, breast milk, and other sources. Invasive GBS infections in neonates can result in sepsis, pneumonia, meningitis, neurodevelopmental impairment, death, and lifelong disability. A policy of routine screening for GBS rectovaginal colonization in well-resourced countries can trigger the administration of intrapartum antibiotic prophylaxis (IAP) when prenatal testing is positive, which drastically reduces rates of EOD. However, many countries do not routinely screen pregnant women for GBS colonization but may administer IAP in cases with a high risk of EOD. IAP does not reduce rates of LOD. A global vaccination campaign is needed to reduce the significant burden of invasive GBS disease that remains among infants and pregnant individuals. In this narrative review, we provide a comprehensive overview of the global impact of GBS colonization and infection, virulence factors and pathogenesis, and current and future prophylactics and therapeutics.
The challenges of difficult-to-treat infections.
Richards GA, Perovic O, Brink AJ
Clin Microbiol Rev · 2024 Dec · PMID 39555919 · Full text
SUMMARYInfections due to spp. are among the most difficult to treat. Most are resistant to standard antibiotics, and there is difficulty in distinguishing colonizers from pathogens. This mini-review examines the availab...
SUMMARYInfections due to spp. are among the most difficult to treat. Most are resistant to standard antibiotics, and there is difficulty in distinguishing colonizers from pathogens. This mini-review examines the available antibiotics that exhibit activity against these organisms and provides guidance as to which cultures are relevant and how to treat active infections. Antibiograms describing resistance mechanisms and the minimum inhibitory concentration (MIC) are essential to determine which agent or combination of agents should be used after confirmation of infection, utilizing clinical parameters and biomarkers such as procalcitonin. Directed therapy should be prompt as despite its reputation as a colonizer, the attributable mortality is high. However, although combination therapy is advised, no specific combination has definite evidence of superiority.
Laboratory detection of carbapenemases among Gram-negative organisms.
Simner PJ, Pitout JDD, Dingle TC
Clin Microbiol Rev · 2024 Dec · PMID 39545731 · Full text
SUMMARYThe carbapenems remain some of the most effective options available for treating patients with serious infections due to Gram-negative bacteria. Carbapenemases are enzymes that hydrolyze carbapenems and are the pr...
SUMMARYThe carbapenems remain some of the most effective options available for treating patients with serious infections due to Gram-negative bacteria. Carbapenemases are enzymes that hydrolyze carbapenems and are the primary method driving carbapenem resistance globally. Detection of carbapenemases is required for patient management, the rapid implementation of infection prevention and control (IP&C) protocols, and for epidemiologic purposes. Therefore, clinical and public health microbiology laboratories must be able to detect and report carbapenemases among predominant Gram-negative organisms from both cultured isolates and direct from clinical specimens for treatment and surveillance purposes. There is not a "one size fits all" laboratory approach for the detection of bacteria with carbapenemases, and institutions need to determine what fits best with the goals of their antimicrobial stewardship and IP&C programs. Luckily, there are several options and approaches available for clinical laboratories to choose methods that best suits their individual needs. A laboratory approach to detect carbapenemases among bacterial isolates consists of two steps, namely a screening process (, not susceptible to ertapenem, meropenem, and/or imipenem), followed by a confirmation test (, phenotypic, genotypic or proteomic methods) for the presence of a carbapenemase. Direct from specimen testing for the most common carbapenemases generally involves detection rapid, molecular approaches. The aim of this article is to provide brief overviews on Gram-negative bacteria carbapenem-resistant definitions, types of carbapenemases, global epidemiology, and then describe in detail the laboratory methods for the detection of carbapenemases among Gram-negative bacteria. We will specifically focus on the , and complex.
Animal models for exploring Chagas disease pathogenesis and supporting drug discovery.
Khan AA, Taylor MC, Fortes Francisco A … +5 more , Jayawardhana S, Atherton RL, Olmo F, Lewis MD, Kelly JM
Clin Microbiol Rev · 2024 Dec · PMID 39545730 · Full text
Infections with the parasitic protozoan cause Chagas disease, which results in serious cardiac and/or digestive pathology in 30%-40% of individuals. However, symptomatic disease can take decades to become apparent, and...
Infections with the parasitic protozoan cause Chagas disease, which results in serious cardiac and/or digestive pathology in 30%-40% of individuals. However, symptomatic disease can take decades to become apparent, and there is a broad spectrum of possible outcomes. The complex and long-term nature of this infection places a major constraint on the scope for experimental studies in humans. Accordingly, predictive animal models have been a mainstay of Chagas disease research. The resulting data have made major contributions to our understanding of parasite biology, immune responses, and disease pathogenesis and have provided a platform that informs and facilitates the global drug discovery effort. Here, we provide an overview of available animal models and illustrate how they have had a key impact across the field.
Enriching the future of public health microbiology with hybridization bait capture.
Beaudry MS, Bhuiyan MIU, Glenn TC
Clin Microbiol Rev · 2024 Dec · PMID 39545729 · Full text
SUMMARYPublic health microbiology focuses on microorganisms and infectious agents that impact human health. For years, this field has relied on culture or molecular methods to investigate complex samples of public health...
SUMMARYPublic health microbiology focuses on microorganisms and infectious agents that impact human health. For years, this field has relied on culture or molecular methods to investigate complex samples of public health importance. However, with the increase in accuracy and decrease in sequencing cost over the last decade, there has been a transition to the use of next-generation sequencing in public health microbiology. Nevertheless, many available sequencing methods (e.g., shotgun metagenomics and amplicon sequencing) do not work well in complex sample types, require deep sequencing, or have inherent biases associated with them. Hybridization bait capture, also known as target enrichment, brings in solutions for such limitations. It is an increasingly popular technique to simultaneously characterize many thousands of genetic elements while reducing the amount of sequencing needed (thereby reducing the sequencing costs). Here, we summarize the concept of hybridization bait capture for public health, reviewing a total of 35 bait sets designed in six key topic areas for public health microbiology [i.e., antimicrobial resistance (AMR), bacteria, fungi, parasites, vectors, and viruses], and compare hybridization bait capture to previously relied upon methods. Furthermore, we provide an in-depth comparison of the three most popular bait sets designed for AMR by evaluating each of them against three major AMR databases: Comprehensive Antibiotic Resistance Database, Microbial Ecology Group Antimicrobial Resistance Database, and Pathogenicity Island Database. Thus, this article provides a review of hybridization bait capture for public health microbiologists.
American Society for Microbiology evidence-based laboratory medicine practice guidelines to reduce blood culture contamination rates: a systematic review and meta-analysis.
Sautter RL, Parrott JS, Nachamkin I … +11 more , Diel C, Tom RJ, Bobenchik AM, Bradford JY, Gilligan P, Halstead DC, LaSala PR, Mochon AB, Mortensen JE, Boyce L, Baselski V
Clin Microbiol Rev · 2024 Dec · PMID 39495314 · Full text
SUMMARYBlood cultures (BCs) are one of the critical tests used to detect bloodstream infections. BC results are not 100% specific. Interpretation of BC results is often complicated by detecting microbial contamination ra...
SUMMARYBlood cultures (BCs) are one of the critical tests used to detect bloodstream infections. BC results are not 100% specific. Interpretation of BC results is often complicated by detecting microbial contamination rather than true infection. False positives due to blood culture contamination (BCC) vary from 1% to as high as >10% of all BC results. False-positive BC results may result in patients undergoing unnecessary antimicrobial treatments, increased healthcare costs, and delay in detecting the true cause of infection or other non-infectious illness. Previous guidelines from the Clinical and Laboratory Standards Institute, College of American Pathologists, and others, based on expert opinion and surveys, promoted a limit of ≤3% as acceptable for BCC rates. However, the data supporting such recommendations are controversial. A previous systematic review of BCC examined three practices for reducing BCC rates (venipuncture, phlebotomy teams, and pre-packaged kits). Subsequently, numerous studies on different practices including using diversion devices, disinfectants, and education/training to lower BCC have been published. The goal of the current guideline is to identify beneficial intervention strategies to reduce BCC rates, including devices, practices, and education/training by providers in collaboration with the laboratory. We performed a systematic review of the literature between 2017 and 2022 using numerous databases. Of the 11,319 unique records identified, 311 articles were sought for full-text review, of which 177 were reviewed; 126 of the full-text articles were excluded based on pre-defined inclusion and exclusion criteria. Data were extracted from a total of 49 articles included in the final analysis. An evidenced-based committee's expert panel reviewed all the references as mentioned in Data Collection and determined if the articles met the inclusion criteria. Data from extractions were captured within an extraction template in the US Agency for Healthcare Research and Quality's Systematic Review Data Repository (https://srdr.ahrq.gov/). BCC rates were captured as the number of events (contaminated samples) per arm (standard practice versus improvement practice). Modified versions of the National Heart, Lung, and Blood Institute Study Quality Assessment Tools were used for risk of bias assessment (https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools). We used Grading of Recommendations, Assessment, Development and Evaluations to assess strength of evidence. There are several interventions that resulted in significant reduction in BCC rates: chlorhexidine as a disinfectant for skin preparation, using a diversion device prior to drawing BCs, using sterile technique practices, using a phlebotomy team to obtain BCs, and education/training programs. While there were no substantial differences between methods of decreasing BCC, our results indicate that the method of implementation can determine the success or failure of the intervention. Our evidence-based systematic review and meta-analysis support several interventions to effectively reduce BCC by approximately 40%-60%. However, devices alone without an education/training component and buy-in from key stakeholders to implement various interventions would not be as effective in reducing BCC rates.
Lyme borreliosis in Brazil: a critical review on the Baggio-Yoshinari syndrome (Brazilian Lyme-like disease).
Labruna MB, Faccini-Martínez ÁA, Muñoz-Leal S … +2 more , Szabó MPJ, Angerami RN
Clin Microbiol Rev · 2024 Dec · PMID 39494872 · Full text
SUMMARYLyme borreliosis or Lyme disease is the most frequently reported tick-borne disease in the Northern Hemisphere. In countries of the Southern Hemisphere, such as Brazil, since the early 1990s, some researchers have...
SUMMARYLyme borreliosis or Lyme disease is the most frequently reported tick-borne disease in the Northern Hemisphere. In countries of the Southern Hemisphere, such as Brazil, since the early 1990s, some researchers have argued for the existence of an autochthonous Lyme-like borreliosis, known locally as the Baggio-Yoshinari syndrome (BYS), an alleged "Brazilian borreliosis" supposedly caused by a different strain of and transmitted by hard ticks. Currently, the existence of BYS in Brazil is still accepted by a large part of the human health care workers, scientists, medical societies, and patients. In fact, this alleged "Brazilian borreliosis" has been the tick-borne zoonotic disease with the greatest number of reported cases and published studies in Brazil during this century, second only to Brazilian spotted fever. In this manuscript, we reviewed all manuscripts directly related to BYS that have been published in Brazil during the last 35 years. This analysis included 199 individual human cases that have been reported in Brazil since 1989, plus multiple studies on ticks, domestic, and wild animals. Our revision aimed to provide a critical opinion on whether the current published works allow healthcare workers, public health agencies, and patients to accept the existence of Lyme disease, BYS, or other Lyme borreliosis-related disease in Brazil. For this purpose, we evaluated the strengths and weaknesses of each published study, considering the diagnostic methods used, such as serological, microbiological, and molecular analyses. Based on these evaluations, we conclude that there is not enough evidence to support the occurrence of Lyme borreliosis in Brazil or that BYS (Brazilian Lyme-like disease) is caused by a bacterium of the genus . This assumption is based on the inaccuracy, unreliability, and misinterpretation of the different diagnostic methods that have been used in Brazil. Recognizing the lack of technical evidence for the occurrence of Lyme borreliosis in Brazil has highly relevant implications. For example, it becomes imperative to raise awareness among the country's medical profession, as they have adopted unnecessary and extreme therapies recommended for patients with a supposed borrelial infection, including BYS, in Brazil. Finally, the technical analyses carried out in this study could be applied to other countries in the Southern Hemisphere (, Argentina, South Africa, Australia), where cases classified and alleged as Lyme disease have been reported.
Comprehensive analysis of the global impact and distribution of tick paralysis, a deadly neurological yet fully reversible condition.
Deng Y-P, Fu Y-T, Elsheikha HM … +7 more , Cao M-L, Zhu X-Q, Wang J-L, Zhang X, Xie S-C, Yao C, Liu G-H
Clin Microbiol Rev · 2024 Dec · PMID 39440956 · Full text
SUMMARYTick paralysis is a potentially fatal condition caused by neurotoxins secreted by the salivary glands of certain ticks. Documented cases have been reported worldwide, predominantly in the United States, Canada, an...
SUMMARYTick paralysis is a potentially fatal condition caused by neurotoxins secreted by the salivary glands of certain ticks. Documented cases have been reported worldwide, predominantly in the United States, Canada, and Australia, with additional reports from Europe and Africa. This condition also affects animals, leading to significant economic losses and adverse impacts on animal health and welfare. To date, 75 tick species, mostly hard ticks, have been identified as capable of causing this life-threatening condition. Due to symptom overlap with other conditions, accurate diagnosis of tick paralysis is crucial to avoid misdiagnosis, which could result in adverse patient outcomes. This review provides a comprehensive analysis of the current literature on tick paralysis, including the implicated tick species, global distribution, tick toxins, molecular pathogenesis, clinical manifestations, diagnosis, treatment, control, and prevention. Enhancing awareness among medical and veterinary professionals is critical for improving the management of tick paralysis and its health impacts on both humans and animals.
Artemisinin-resistant malaria.
White NJ, Chotivanich K
Clin Microbiol Rev · 2024 Dec · PMID 39404268 · Full text
SUMMARYThe artemisinin antimalarials are the cornerstone of current malaria treatment. The development of artemisinin resistance in poses a major threat to malaria control and elimination. Recognized first in the Greate...
SUMMARYThe artemisinin antimalarials are the cornerstone of current malaria treatment. The development of artemisinin resistance in poses a major threat to malaria control and elimination. Recognized first in the Greater Mekong subregion of Southeast Asia nearly 20 years ago, artemisinin resistance has now been documented in Guyana, South America, in Papua New Guinea, and most recently, it has emerged in East Africa (Rwanda, Uganda, South Sudan, Tanzania, Ethiopia, Eritrea, and eastern DRC) where it has now become firmly established. Artemisinin resistance is associated with mutations in the propeller region of the Kelch gene, which play a causal role, although the parasites' genetic background also makes an important contribution to the phenotype. Clinically, artemisinin resistance manifests as reduced parasiticidal activity and slower parasite clearance and thus an increased risk of treatment failure following artemisinin-based combination therapy (ACT). This results from the loss of artemisinin activity against the younger circulating ring stage parasites. This loss of activity is likely to diminish the life-saving advantage of artesunate in the treatment of severe falciparum malaria. Gametocytocidal and thus transmission blocking activities are also reduced. At current levels of resistance, artemisinin-resistant parasites still remain susceptible at the trophozoite stage of asexual development, and so, artemisinin still contributes to the therapeutic response. As ACTs are the most widely used antimalarial drugs in the world, it is essential from a malaria control perspective that ACT cure rates remain high. Better methods of identifying uncomplicated hyperparasitemia, the main cause of ACT treatment failure, are required so that longer courses of treatment can be given to these high-risk patients. Reducing the use of artemisinin monotherapies will reduce the continued selection pressure which could lead potentially to higher levels of artemisinin resistance. Triple artemisinin combination therapies should be deployed as soon as possible to protect the ACT partner drugs and thereby delay the emergence of higher levels of resistance. As new affordable antimalarial drugs are still several years away, the control of artemisinin resistance must depend on the better use of available tools.
Molecular diagnostics in cerebrospinal fluid for the diagnosis of central nervous system infections.
Olie SE, Andersen CØ, van de Beek D … +1 more , Brouwer MC
Clin Microbiol Rev · 2024 Dec · PMID 39404267 · Full text
SUMMARYCentral nervous system (CNS) infections can be caused by various pathogens, including bacteria, viruses, fungi, and parasites. Molecular diagnostic methods are pivotal for identifying the different causative patho...
SUMMARYCentral nervous system (CNS) infections can be caused by various pathogens, including bacteria, viruses, fungi, and parasites. Molecular diagnostic methods are pivotal for identifying the different causative pathogens of these infections in clinical settings. The efficacy and specificity of these methods can vary per pathogen involved, and in a substantial part of patients, no pathogen is identified in the cerebrospinal fluid (CSF). Over recent decades, various molecular methodologies have been developed and applied to patients with CNS infections. This review provides an overview of the accuracy of nucleic acid amplification methods in CSF for a diverse range of pathogens, examines the potential value of multiplex PCR panels, and explores the broad-range bacterial and fungal PCR/sequencing panels. In addition, it evaluates innovative molecular approaches to enhance the diagnosis of CNS infections.
Harnessing the host response for precision infectious disease diagnosis.
Woodhouse EW, McClain MT, Woods CW
Clin Microbiol Rev · 2024 Dec · PMID 39404266 · Full text
SUMMARYDetection of the presence of infection and its etiology must be accurate and timely to facilitate appropriate antimicrobial use. Diagnostic strategies that rely solely on pathogen detection often are insufficient...
SUMMARYDetection of the presence of infection and its etiology must be accurate and timely to facilitate appropriate antimicrobial use. Diagnostic strategies that rely solely on pathogen detection often are insufficient due to poor test characteristics, inability to differentiate colonization from infection, or protracted delay to result. Understanding the human response across different pathogens on a clinical and molecular level can provide more accurate, timely, and useful answers, especially in critical illness and diagnostic uncertainty. Improvements in understanding the human immune response including genomics, protein analysis, gene expression, and cellular morphology have led to rapid innovation of new host response-based diagnostic tests. This review describes the limitations of pathogen-focused technology and the benefits of examining the breadth of immune response to diagnose infection. It then explores biomarkers that have been studied for this purpose and scrutinizes the performance of host-based multianalyte testing. Currently cleared diagnostics and those in late-stage development are described in depth, with a focus on the purpose of testing and its utility for clinicians. Finally, it concludes by examining opportunities for further host response-derived diagnostic innovation.
How long do bacteria, fungi, protozoa, and viruses retain their replication capacity on inanimate surfaces? A systematic review examining environmental resilience versus healthcare-associated infection risk by "fomite-borne risk assessment".
Kramer A, Lexow F, Bludau A … +7 more , Köster AM, Misailovski M, Seifert U, Eggers M, Rutala W, Dancer SJ, Scheithauer S
Clin Microbiol Rev · 2024 Dec · PMID 39388143 · Full text
SUMMARYIn healthcare settings, contaminated surfaces play an important role in the transmission of nosocomial pathogens potentially resulting in healthcare-associated infections (HAI). Pathogens can be transmitted direct...
SUMMARYIn healthcare settings, contaminated surfaces play an important role in the transmission of nosocomial pathogens potentially resulting in healthcare-associated infections (HAI). Pathogens can be transmitted directly from frequent hand-touch surfaces close to patients or indirectly by staff and visitors. HAI risk depends on exposure, extent of contamination, infectious dose (ID), virulence, hygiene practices, and patient vulnerability. This review attempts to close a gap in previous reviews on persistence/tenacity by only including articles ( = 171) providing quantitative data on re-cultivable pathogens from fomites for a better translation into clinical settings. We have therefore introduced the new term "replication capacity" (RC). The RC is affected by the degree of contamination, surface material, temperature, relative humidity, protein load, organic soil, UV-light (sunlight) exposure, and pH value. In general, investigations into surface RC are mainly performed using reference strains with high inocula. data from studies on 14 Gram-positive, 26 Gram-negative bacteria, 18 fungi, 4 protozoa, and 37 viruses. It should be regarded as a worst-case scenario indicating the upper bounds of risks when using such data for clinical decision-making. Information on RC after surface contamination could be seen as an opportunity to choose the most appropriate infection prevention and control (IPC) strategies. To help with decision-making, pathogens characterized by an increased nosocomial risk for transmission from inanimate surfaces ("fomite-borne") are presented and discussed in this systematic review. Thus, the review offers a theoretical basis to support local risk assessments and IPC recommendations.
Antibiotic tolerance among clinical isolates: mechanisms, detection, prevalence, and significance.
Deventer AT, Stevens CE, Stewart A … +1 more , Hobbs JK
Clin Microbiol Rev · 2024 Dec · PMID 39364999 · Full text
SUMMARYAntibiotic treatment failures in the absence of resistance are not uncommon. Recently, attention has grown around the phenomenon of antibiotic tolerance, an underappreciated contributor to recalcitrant infections...
SUMMARYAntibiotic treatment failures in the absence of resistance are not uncommon. Recently, attention has grown around the phenomenon of antibiotic tolerance, an underappreciated contributor to recalcitrant infections first detected in the 1970s. Tolerance describes the ability of a bacterial population to survive transient exposure to an otherwise lethal concentration of antibiotic without exhibiting resistance. With advances in genomics, we are gaining a better understanding of the molecular mechanisms behind tolerance, and several studies have sought to examine the clinical prevalence of tolerance. Attempts have also been made to assess the clinical significance of tolerance through infection models and prospective/retrospective clinical studies. Here, we review the data available on the molecular mechanisms, detection, prevalence, and clinical significance of genotypic tolerance that span ~50 years. We discuss the need for standardized methodology and interpretation criteria for tolerance detection and the impact that methodological inconsistencies have on our ability to accurately assess the scale of the problem. In terms of the clinical significance of tolerance, studies suggest that tolerance contributes to worse outcomes for patients (e.g., higher mortality, prolonged hospitalization), but historical data from animal models are varied. Furthermore, we lack the necessary information to effectively treat tolerant infections. Overall, while the tolerance field is gaining much-needed traction, the underlying clinical significance of tolerance that underpins all tolerance research is still far from clear and requires attention.
Toward better cures for lung disease.
Dartois V, Dick T
Clin Microbiol Rev · 2024 Dec · PMID 39360834 · Full text
SUMMARYThe opportunistic pathogen (Mab) causes fatal lung infections that bear similarities-and notable differences-with tuberculosis (TB) pulmonary disease. In contrast to TB, no antibiotic is formally approved to trea...
SUMMARYThe opportunistic pathogen (Mab) causes fatal lung infections that bear similarities-and notable differences-with tuberculosis (TB) pulmonary disease. In contrast to TB, no antibiotic is formally approved to treat Mab disease, there is no reliable cure, and the discovery and development pipeline is incredibly thin. Here, we discuss the factors behind the unsatisfactory cure rates of Mab disease, namely intrinsic resistance and persistence of the pathogen, and the use of underperforming, often parenteral and toxic, repurposed drugs. We propose preclinical strategies to build injectable-free sterilizing and safe regimens: (i) prioritize oral bactericidal antibiotic classes, with an initial focus on approved agents or advanced clinical candidates to provide immediate options for desperate patients, (ii) test drug combinations early, (iii) optimize novel leads specifically for , and (iv) consider pharmacokinetic-pharmacodynamic targets at the site of disease, the lung lesions in which drug tolerant bacterial populations reside. Knowledge and tool gaps in the preclinical drug discovery process are identified, including validated mouse models and computational platforms to enable mouse-human translation. We briefly discuss recent advances in clinical development, the need for readouts and biomarkers that correlate with cure, and clinical trial concepts adapted to the uniqueness of Mab patient populations for new regimen development. In an era when most pharmaceutical firms have withdrawn from antimicrobial drug discovery, the breakthroughs needed to fill the regimen development pipeline will likely come from partnerships between academia, biotech, pharma, non-profit organizations, and governments, with incentives that reward cooperation.
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