The potential importance of the built-environment microbiome and its impact on human health.

There is increasing evidence that interactions between microbes and their hosts not only play a role in determining health and disease but also in emotions, thought, and behavior. Built environments greatly influence microbiome exposures because of their built-in highly specific microbiomes coproduced with myriad metaorganisms including humans, pets, plants, rodents, and insects. Seemingly static built structures host complex ecologies of microorganisms that are only starting to be mapped. These microbial ecologies of built environments are directly and interdependently affected by social, spatial, and technological norms. Advances in technology have made these organisms visible and forced the scientific community and architects to rethink gene-environment and microbe interactions respectively. Thus, built environment design must consider the microbiome, and research involving host-microbiome interaction must consider the built-environment. This paradigm shift becomes increasingly important as evidence grows that contemporary built environments are steadily reducing the microbial diversity essential for human health, well-being, and resilience while accelerating the symptoms of human chronic diseases including environmental allergies, and other more life-altering diseases. New models of design are required to balance maximizing exposure to microbial diversity while minimizing exposure to human-associated diseases. Sustained trans-disciplinary research across time (evolutionary, historical, and generational) and space (cultural and geographical) is needed to develop experimental design protocols that address multigenerational multispecies health and health equity in built environments.

The evosystem: A centerpiece for evolutionary studies.

In this paper, we redefine the target of evolutionary explanations by proposing the "evosystem" as an alternative to populations, lineages and species. Evosystems account for changes in the distribution of heritable variation within individual Darwinian populations (evolution by natural selection, drift, or constructive neutral evolution), but also for changes in the networks of interactions within or between Darwinian populations and changes in the abiotic environment (whether these changes are caused by the organic entities or not). The evosystem can thereby become a centerpiece for a redefined evolutionary science, that is, evolutionary studies, that apprehends through a single framework the variety of evolutionary processes that lie at various scales. To illustrate the importance of this broadened perspective on evolution, we use a case of antimicrobial resistance evolution: the spread of the blaNDM gene family and the related resistance to carbapenem antibiotics observed globally, and show how evolutionary studies can contribute to answering contemporary socially relevant challenges.

Molecular Characteristics of Colistin Resistance in Acinetobacter baumannii and the Activity of Antimicrobial Combination Therapy in a Tertiary Care Medical Center in Lebanon.

(1) Background: Infections with pan-drug-resistant (PDR) bacteria, such as A. baumannii, are becoming increasingly common, especially in healthcare facilities. In this study, we selected 15 colistin-resistant clinical A. baumannii isolates from a hospital in Beirut, Lebanon, to test combination therapies and determine their sequence types (STs) and the mechanism of colistin resistance using whole-genome sequencing (WGS). (2) Methods: Antimicrobial susceptibility testing via broth microdilution against 12 antimicrobials from different classes and growth rate assays were performed. A checkerboard assay was conducted on PDR isolates using six different antimicrobials, each in combination with colistin. Genomic DNA was extracted from all isolates and subjected to WGS. (3) Results: All isolates were resistant to all tested antimicrobials with the one exception that was susceptible to gentamicin. Combining colistin with either meropenem, ceftolozane-tazobactam, or teicoplanin showed synergistic activity. Sequencing data revealed that 67% of the isolates belonged to Pasteur ST2 and 33% to ST187. Furthermore, these isolates harbored a number of resistance genes, including blaOXA-23. Mutations in the pmrC gene were behind colistin resistance. (4) Conclusions: With the rise in antimicrobial resistance and the absence of novel antimicrobial production, alternative treatments must be found. The combination therapy results from this study suggest treatment options for PDR ST2 A. baumannii-infected patients.

Earliest observation of the tetracycline destructase tet(X3).

Tigecycline is an antibiotic of last resort for infections with carbapenem-resistant Acinetobacter baumannii. Plasmids harboring variants of the tetracycline destructase gene tetX promote rising tigecycline resistance rates. We report the earliest observation of tet(X3) in a clinical strain predating tigecycline's commercialization, suggesting selective pressures other than tigecycline contributed to its emergence. IMPORTANCE: We present the earliest observation of a tet(X3)-positive bacterial strain, predating by many years the earliest reports of this gene so far. This finding is significant as tigecycline is an antibiotic of last resort for carbapenem-resistant Acinetobacter baumannii (CRAB), which the World Health Organization ranks as one of its top three critical priority pathogens, and tet(X3) variants have become the most prevalent genes responsible for enabling CRAB to become tigecycline resistant. Moreover, the tet(X3)-positive strain we report is the first and only to be found that predates the commercialization of tigecycline, an antibiotic that was thought to have contributed to the emergence of this resistance gene. Understanding the factors contributing to the origin and spread of novel antibiotic resistance genes is crucial to addressing the major global public health issue, which is antimicrobial resistance.

The Microbiome and Infectious Diseases.

Our perception of microbes has considerably changed since the recognition of their pathogenic potential in the 19th century. The discovery of antibiotics and their subsequent widespread adoption have substantially altered the landscape of medicine, providing us with treatment options for many infectious diseases and enabling the deployment of previously risky interventions (eg, surgical procedures and chemotherapy), while also leading to the rise of AMR. The latter is commonly viewed as the predominant downside of antibiotic use. However, with the increasing recognition that all metazoan organisms rely on a community of microbes (the microbiota) for normal development and for most physiologic processes, the negative impacts of antibiotic use now extend well beyond AMR. Using the iceberg as a metaphor, we argue that the effects of antibiotics on AMR represent the tip of the iceberg, with much greater repercussions stemming from their role in the rise of so-called noncommunicable diseases (including obesity, diabetes, allergic and autoimmune diseases, neurodevelopmental disorders, and certain cancers). We highlight some of the emerging science around the intersection of the microbiome, antibiotic use, and health (including biological costs and future therapeutic avenues), and we advocate a more nuanced approach in evaluating the impacts of proposed antibiotic use, especially in the setting of preexposure and postexposure prophylaxis.

Antimicrobial-Resistant Infections after Turkey/Syria Earthquakes, 2023.

Increased rates of multidrug-resistant microbes have been reported after earthquakes. After the 2023 earthquakes in Turkey and Syria, the number of associated highly drug-resistant pathogens and nosocomial transmission will probably surge in hospitals treating injured patients. It is not too late to act to prevent antimicrobial-resistant infections from compounding these tragedies.

VANCOmycin dose adjustments comparing trough levels to the ratio of the area under de curve to the minimum inhibitory concentration method using a BAYESian approach: A feasibility study.

WHAT IS KNOWN AND OBJECTIVE?: The latest published guidelines advocate for the area under the concentration-time curve to minimal inhibitory concentration (AUC0-24h /MIC) estimated with bayesian calculations. This recommended pharmacokinetic monitoring transition is not based on randomized controlled prospective data. METHODS: In this open-label feasibility RCT, patients were assigned to have their vancomycin dosing adjusted based on bayesian-guided AUC0-24h /MIC or trough levels. Primary outcomes were consent rate, number of patients recruited per month, compliance with blood sampling schedule and compliance with bayesian software recommendations. Secondary outcomes focused on target attainment, safety and operational impacts. RESULTS AND DISCUSSION: Forty-five patients underwent randomization (23 bayesian, 22 trough). Consent rate was 37,5% for an average of 9.8 patients recruited per month meeting pre-specified objectives of 30% (p = 0.073) and 10 (p = 0.74) respectively. A 74.8% compliance with blood sampling schedule was below the pre-specified objective of 80% (p = 0.038). There was no statistically significant difference between the 83.7% compliance with bayesian software recommendations and the pre-specified objective of 90% (p = 0.21). Although exploratory, key clinical results were significant increases in the bayesian group for proportion of levels at target (RR 1.32; 95% CI 1.01-1.72; P = 0.038), number of blood samplings for patients (p = 0.036) and pharmacists' time spent on monitoring (p < 0.0001). A tendency towards a reduced incidence of nephrotoxicity in the Bayesian group was observed (RR 0.57; 95% CI 0.16-2.12; p = 0.46). WHAT IS NEW AND CONCLUSIONS?: This trial demonstrates that it would be feasible to conduct a properly sized RCT comparing vancomycin Bayesian-guided AUC0-24h /MIC to trough level monitoring. Although exploratory, this trial also showed a tendency towards reduced incidence of nephrotoxicity and an increased proportion of dosages at therapeutic targets with Bayesian monitoring.

Evaluation of the performance of multiple immunoassay diagnostic platforms on the National Microbiology Laboratory SARS-CoV-2 National Serology Panel.

BACKGROUND: Serological assays designed to detect SARS-CoV-2 antibodies are being used in serological surveys and other specialized applications. As a result, and to ensure that the outcomes of serological testing meet high quality standards, evaluations are required to assess the performance of these assays and the proficiency of laboratories performing them. METHODS: A panel of 60 plasma/serum samples from blood donors who had reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections and 21 SARS-CoV-2 negative samples were secured and distributed to interested laboratories within Canada (n = 30) and the United States (n = 1). Participating laboratories were asked to provide details on the diagnostic assays used, the platforms the assays were performed on, and the results obtained for each panel sample. Laboratories were blinded with respect to the expected outcomes. RESULTS: The performance of the different assays evaluated was excellent, with the high-throughput platforms of Roche, Ortho, and Siemens demonstrating 100% sensitivity. Most other high-throughput platforms had sensitivities of >93%, with the exception of the IgG assay using the Abbott ARCHITECT which had an average sensitivity of only 87%. The majority of the high-throughput platforms also demonstrated very good specificities (>97%). CONCLUSION: This proficiency study demonstrates that most of the SARS-CoV-2 serological assays utilized by provincial public health or hospital laboratories in Canada have acceptable sensitivity and excellent specificity.

HISTORIQUE: Les dosages sérologiques conçus pour dépister les anticorps anti-SRAS-CoV-2 sont utilisés dans les études sérologiques et d'autres applications spécialisées. Par conséquent, et pour s'assurer que leurs résultats respectent des normes de qualité, il faut procéder à des évaluations de leur performance et de la compétence des laboratoires à les effectuer. MÉTHODOLOGIE: Les chercheurs ont obtenu une batterie de 60 prélèvements de plasma et de sérum chez des donneurs dont l'amplification en chaîne par polymérase après transcription inverse (RT-PCR) avait confirmé des infections par le SRAS-CoV-2 et de 21 prélèvements dont les résultats étaient négatifs au SRAS-CoV-2 et les ont distribués aux laboratoires intéressés du Canada (n = 30) et des États-Unis (n = 1). Ils ont invité les laboratoires participants à fournir de l'information détaillée sur les dosages diagnostiques utilisés, les plateformes sur lesquelles les dosages étaient exécutés et les résultats obtenus pour chaque échantillon. Les chercheurs ont demandé aux laboratoires participants de fournir de l'information détaillée sur les dosages diagnostiques utilisés, les plateformes sur lesquelles les dosages ont été effectués, et les résultats obtenus à l'égard de chaque échantillon. Les laboratoires ont mené les études à l'insu des résultats escomptés. RÉSULTATS: Les divers dosages avaient une excellente exécution, les plateformes à haut débit de Roche, d'Ortho et de Siemens démontrant une sensibilité de 100 %. La plupart des autres plateformes à haut débit avaient des sensibilités de plus de 93 %, à l'exception des dosages des IgG faisant appel à l'analyseur ARCHITECT d'Abbott, dont la sensibilité moyenne était de seulement 87 %. La majorité des plateformes à haut débit avaient également une très bonne spécificité (plus de 97 %). CONCLUSION: La présente étude de compétence démontre que la plupart des dosages sérologiques du SRAS-CoV-2 évalués dans des laboratoires sanitaires provinciaux ou les laboratoires hospitaliers du Canada possèdent une sensibilité acceptable et une excellente spécificité.

Management and clinical outcomes of Lyme disease in acute care facilities in 2 endemic regions of Quebec, Canada: a multicentre retrospective cohort study.

BACKGROUND: Despite increases in cases of Lyme disease, little is known about the management and clinical course of the disease in Canada. We aimed to describe the management and clinical course of Lyme disease in patients treated in acute care facilities in Quebec and to assess adherence to the 2006 Infectious Diseases Society of America (IDSA) guideline. METHODS: This retrospective multicentre cohort study included pediatric and adult patients with serologically confirmed Lyme disease treated in acute care facilities (12 community hospitals and 2 tertiary care centres) of 2 endemic regions of Quebec (Estrie and Montérégie), from 2004 to 2017. We considered drug choice, prescribed dose and treatment duration in assessing adherence of prescriptions to the 2006 IDSA guideline. The main outcome was complete resolution of symptoms at 3 months after the initiation of treatment. RESULTS: We included 272 patients from 14 institutions (age range 3-87 yr). Early disseminated Lyme disease (140 patients [51%]) was predominant. Adherence to the IDSA guideline was observed in 235 (90%) of the 261 cases with complete information, and adherence was stable over time (2004-2013: 57/64 [89%]; 2014-2015: 64/71 [90%]; 2016-2017: 114/126 [90%]; p = 0.8). Non-adherence to the guideline (n = 26) was predominantly due to longer-than-recommended treatment duration (16/26 [62%]). Resolution of objective signs at 3 months after treatment initiation occurred in 265 (99%) of 267 patients, whereas post-treatment Lyme disease syndrome was observed in 27 patients (10%) with increasing incidence over time (2004-2013: 3/65 [5%]; 2014-2015: 4/73 [5%]; 2016-2017: 20/129 [16%]; p = 0.02). INTERPRETATION: We observed clinical resolution of Lyme disease in 99% of the patients, and most treatments (90%) complied with the 2006 IDSA guideline. The incidence of post-treatment Lyme disease syndrome increased over the study period, warranting further prospective studies.

Oral Sex following Abortion: Case Report of a Sexually Transmitted Infection of Group A Streptococcus Causing Peritonitis.

Group A Streptococcus (GAS) is a rare cause of peritonitis with only a few reports of disease associated with surgical abortion, vaginal delivery, or intrauterine devices, most of which are speculated to be in association with the female genital tract. Only a single case of GAS infection transmission through contemporary oral sex has been previously reported. We report a strange case of GAS peritonitis occurring after abortion and oral sex.

Networked collective microbiomes and the rise of subcellular 'units of life'.

Microbiomes are generally conceived of as one element of a pair - their partner being the habitat they occupy. I call this common scientific practice 'pair-thinking'. Research into antimicrobial resistance and its underlying anthropogenic drivers highlights the growing footprint occupied by mobile genetic elements (MGEs). Furthermore, these MGEs are known to circulate widely between microbiomes. Using a pluralistic framework anchored within a processual microbial ontology, these observations point to a reframing of microbiomes as networked and collective, thus challenging pair-thinking. Such a shift has implications for the future of microbiome research, from conceptual and methodological perspectives, and exposes the impacts of anthropogenic forces on the evolution of microbiomes and the functions they carry out.

Teleclinical Microbiology: An Innovative Approach to Providing Web-Enabled Diagnostic Laboratory Services in Syria.

OBJECTIVES: Telemedicine can compensate for the lack of health care specialists in response to protracted humanitarian crises. We sought to assess the usability of a teleclinical microbiology (TCM) program to provide diagnostic services in a hard-to-reach region of Syria. METHODS: A semimobile station was equipped with conventional micrograph and macrograph digital imaging systems. An electronic platform (Telemicrobiology in Humanitarian Crises, TmHC) was created to facilitate sharing, interpreting, and storing the results. A pilot study was conducted to identify the bacterial species and antimicrobial susceptibility pattern of 74 urinary clinical isolates. An experience survey was conducted to capture the feedback of 8 participants in the program. RESULTS: The TmHC platform (https://sdh.ngo/tmhc/) enabled systematic transmission of the laboratory records and co-interpretation of the results. The isolates were identified as Escherichia coli (n = 61), Klebsiella pneumoniae (n = 12), and Proteus mirabilis(n = 1). All the isolates were multidrug resistant. The performance of our TCM module was rated 4 (satisfying) and 5 (very satisfying) by 6 and 2 users, respectively. Data security of and cost-effectiveness were the main perceived concerns. CONCLUSIONS: Although we encountered several context-related obstacles, our TCM program managed to reach a highly vulnerable population of 4 million people confined in the northwest region of Syria.

Diversity of Sequence Types and Impact of Fitness Cost among Carbapenem-Resistant Acinetobacter baumannii Isolates from Tripoli, Libya.

We investigated the molecular epidemiology of 21 carbapenem-resistant Acinetobacter baumannii isolates from Libya and assessed their relative fitness. Core genome multilocus sequence typing (MLST) revealed five interhospital transmission clusters. Three clusters were associated with the international clones (IC) IC1, IC2, and IC7. Carbapenem-resistance was associated with blaOXA-23, blaGES-11, or blaNDM-1. Compared to that of A. baumannii DSM 30008, the doubling time was similar over 10 h, but after 16 h, half the isolates grew to higher densities, suggesting a fitness advantage.

An unequivocal superbug: PDR Klebsiella pneumoniae with an arsenal of resistance and virulence factor genes.

INTRODUCTION: Infections caused by extensively-drug resistant (XDR) and pan-drug resistant (PDR) Klebsiella pneumoniae represent an emerging threat due to the high associated mortality. This study aimed to characterize two carbapenem resistant K. pneumoniae strains from the same patient, the first being PDR (referred to as IMP 1078b) and the second being XDR (referred to IMP 1078s) isolated from the same patient. METHODOLOGY: Antimicrobial susceptibility testing was done for the 2 K. pneumoniae isolates, followed by carbapenem/ß-lactamase inhibitor combination assay, and fitness cost against cefepime and meropenem. Then, whole-genome sequence analysis was performed to decipher the molecular mechanisms behind the high level of resistance recorded in both isolates. Finally, qRT-PCR was done for ß-lactam resistant genes. RESULTS: This is the first report about a K. pneumoniae isolate harboring 47 antimicrobial resistance genes and having type IV pilli (Yersinia) and the fimbrial adherence determinant Stb (Salmonella) as virulence factors. Further analysis on both isolates are discussed within the article. CONCLUSION: The co-existence of a high number of antimicrobial resistant (AMR) genes and virulence factor genes may lead to a life threatening invasive and untreatable infection.

Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, bioRxiv, and medRxiv from 1 January to 30 April 2020, using subject headings or subheadings combined with text words for the concepts of covid-19 and serological tests for covid-19. ELIGIBILITY CRITERIA AND DATA ANALYSIS: Eligible studies measured sensitivity or specificity, or both of a covid-19 serological test compared with a reference standard of viral culture or reverse transcriptase polymerase chain reaction. Studies were excluded with fewer than five participants or samples. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using random effects bivariate meta-analyses. MAIN OUTCOME MEASURES: The primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset. RESULTS: 5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10 465/12 547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%). CONCLUSION: Higher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests. STUDY REGISTRATION: PROSPERO CRD42020179452.

Heavy Metal Toxicity in Armed Conflicts Potentiates AMR in A. baumannii by Selecting for Antibiotic and Heavy Metal Co-resistance Mechanisms.

Acinetobacter baumannii has become increasingly resistant to leading antimicrobial agents since the 1970s. Increased resistance appears linked to armed conflicts, notably since widespread media stories amplified clinical reports in the wake of the American invasion of Iraq in 2003. Antimicrobial resistance is usually assumed to arise through selection pressure exerted by antimicrobial treatment, particularly where treatment is inadequate, as in the case of low dosing, substandard antimicrobial agents, or shortened treatment course. Recently attention has focused on an emerging pathogen, multi-drug resistant A. baumannii (MDRAb). MDRAb gained media attention after being identified in American soldiers returning from Iraq and treated in US military facilities, where it was termed "Iraqibacter." However, MDRAb is strongly associated in the literature with war injuries that are heavily contaminated by both environmental debris and shrapnel from weapons. Both may harbor substantial amounts of toxic heavy metals. Interestingly, heavy metals are known to also select for antimicrobial resistance. In this review we highlight the potential causes of antimicrobial resistance by heavy metals, with a focus on its emergence in A. baumanni in war zones.

Vitamin E is an effective treatment for nonalcoholic steatohepatitis in HIV mono-infected patients.

OBJECTIVE: HIV-infected patients are at increased risk of nonalcoholic steatohepatitis (NASH). Vitamin E is recommended for treatment of NASH in the general population. However, its safety and efficacy among HIV-infected patients remain unknown. DESIGN: Single-centre, phase IV, open-label, single arm clinical trial. METHODS: HIV mono-infected patients without significant alcohol intake or viral hepatitis coinfection were included. The diagnosis of NASH was based on the co-existence of fatty liver, diagnosed by controlled attenuation parameter (CAP) at least 248 dB/m and significant hepatocyte apoptosis, defined by the serum biomarker cytokeratin 18 (CK-18) greater than 130.5 U/L. Participants were treated with 800 IU daily of oral vitamin E (alpha-tocopherol) for 24 weeks, and followed for an additional 24 weeks postdiscontinuation. Generalized linear mixed effects models were used to evaluate changes in alanine aminotransferase (ALT), CAP and CK-18 at the completion of treatment and end of follow-up, controlling for pretreatment trends. RESULTS: A total of 27 patients were included. Four (15%) had a pretreatment liver biopsy, which confirmed the diagnosis of NASH in all cases. Compared with baseline, 24 weeks of vitamin E treatment improved ALT [-27 units/l; 95% confidence interval (CI) -37 to -17], CAP scores (-22 dB/m; 95% CI -42 to -1) and CK-18 (-123 units/l; 95% CI -201 to -46). Conversely, there was no change in BMI. No serious adverse event was reported and no patient was lost to follow-up. CONCLUSION: In this first clinical trial, we showed that vitamin E is an effective and well tolerated treatment for NASH in HIV-infected patients.

Antimicrobial Resistance in the Tropics.

Antimicrobial resistance (AMR) is on the rise and spreading rapidly worldwide. Low- and middle-income countries, because of weak health systems, are particularly vulnerable to this increase. Population mobility further fuels the globalization of AMR, with travelers and migrants at significant risk of harboring drug-resistant organisms. This article provides an overview of the factors that contribute to the emergence, spread, and persistence of AMR, particularly antibiotic-resistance, in the tropics. Also addressed are clinical implications of this emergent global crisis for migrants and travelers, using specific scenarios commonly encountered in those populations.

Polyclonal outbreak of KPC-3-producing Enterobacter cloacae at a single hospital in Montreal, Quebec, Canada.

From September 2010 to December 2011, 26 KPC-3-producing Enterobacter cloacae isolates were identified from 16 patients at a single hospital. Analyses revealed the blaKPC gene to be localized on multiple plasmids in a diverse nonclonal E. cloacae genetic background. These findings highlight the potential complexity of a KPC outbreak at a single hospital.