Search

Summary Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries. Methods In this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability of outcome ranking at 30 days after the index culture, and, along with bacterial characteristics and 30-day all-cause mortality (a key secondary outcome), was compared between patients from China, South America, and the USA. The desirability of outcome ranking was adjusted for location before admission, Charlson comorbidity index, age at culture, Pitt bacteremia score, and anatomical culture source through inverse probability weighting; mortality was adjusted for the same confounders, plus region where relevant, through multivariable logistic regression. This study is registered at ClinicalTrials.gov , NCT03646227 , and is complete. Findings Between June 13, 2017, and Nov 30, 2018, 991 patients were enrolled, of whom 502 (51%) met the criteria for CRKP infection and 489 (49%) had positive cultures that were considered colonisation. We observed little intra-country genetic variation in CRKP. Infected patients from the USA were more acutely ill than were patients from China or South America (median Pitt bacteremia score 3 [IQR 2–6] vs 2 [0–4] vs 2 [0–4]) and had more comorbidities (median Charlson comorbidity index 3 [IQR 2–5] vs 1 [0–3] vs 1 [0–2]). Adjusted desirability of outcome ranking outcomes were similar in infected patients from China (n=246), South America (n=109), and the USA (n=130); the estimates were 53% (95% CI 42–65) for China versus South America, 50% (41–61) for the USA versus China, and 53% (41–66) for the USA versus South America. In patients with CRKP infections, unadjusted 30-day mortality was lower in China (12%, 95% CI 8–16; 29 of 246) than in the USA (23%, 16–30; 30 of 130) and South America (28%, 20–37; 31 of 109). Adjusted 30-day all-cause mortality was higher in South America than in China (adjusted odds ratio [aOR] 4·82, 95% CI 2·22–10·50) and the USA (aOR 3·34, 1·50–7·47), with the mortality difference between the USA and China no longer being significant (aOR 1·44, 0·70–2·96). Interpretation Global CRKP epidemics have important regional differences in patients’ baseline characteristics and clinical outcomes, and in bacterial characteristics. Research findings from one region might not be generalisable to other regions. Funding The National Institutes of Health.

In the United States, vanB-mediated resistance in enterococci is rare. We characterized three sequence type (ST) 6, vancomycin-resistant Enterococcus faecalis isolates causing bacteremia in unique patients in spatiotemporally distinct settings. Isolates were recovered between 2018 and 2020 in two cities in the United States (Houston, TX; Miami, FL). The isolates harbored the vanB operon on a chromosomally located Tn1549 transposon, and epidemiological data suggested multiple introductions of the vanB gene cluster into ST6 E. faecalis.

Background During the coronavirus disease 2019 (COVID-19) pandemic, healthcare facilities (HCFs) were overwhelmed with increasing patient volumes and limited resources. Reports of disruptions in routine practices at HCFs have emerged. We evaluated changes in policies, practices, and programs for antimicrobial stewardship (AMS), infection prevention and control (IPC), and clinical microbiology across six HCF in South America following the onset of the COVID-19 pandemic. Methods We conducted a survey in 6 HCFs in Argentina, Brazil, and Chile; 2 HCFs in each country. Data on 5 components (facility characteristics, antibiotic procurement and distribution, AMS activities, IPC activities, and clinical microbiology) were collected from designated specialists within each HCF from March 2018 – February 2021. We compared observations within these 5 components pre-pandemic (March 2018 – February 2020) to during pandemic (March 2020 – February 2021.) Results During the pandemic, the number of ICU beds increased across all the 6 HCFs by 57-633%, and the number of ventilators increased by 15-317% in 5 out of the 6 HCFs. Healthcare personnel shortages were observed in all 6 HCFs, notably common for nurses and laboratory personnel (Table 1). Extended use of N95 respirators was reported across all 6 HCFs with 2 doing extended use of gowns and medical masks. The only PPE reused was N95 respirators in 2 HCFs. Difficulties in cohorting patients with multi-drug resistance organism (MDRO) was reported by one of the HCFs. Three HCFs reported shortages in drugs with coverage for MRSA, gram-negative bacteria, and fungal pathogens despite no reports of interruption in AMS activities in these HCFs. Two hospitals reported delays on microbiology results. Facility characteristics and reported changes during COVID-19 pandemic (March 2020-February 2021) Conclusion The COVID-19 pandemic led to substantial increases in ICU beds, number of ventilators, and extended use of PPE suggesting increases in admission of severe patients and suboptimal IPC practices in HCFs in South America. It is unclear if shortages in agents commonly used to treat MDRO was related to overuse or access difficulties. Additional evaluation is needed to determine the impact of these findings on antimicrobial resistance and antimicrobial use. Disclosures Matias Salomao, MD, Cepheid: Lecture.

Background Reports showing high rates of antibiotic use (AU) in patients with coronavirus disease 2019 (COVID-19) despite low rates of secondary bacterial infection have emerged from various countries across the globe. We evaluated the impact of the COVID-19 pandemic on AU in healthcare facilities (HCFs) in Argentina, Brazil, and Chile. Methods We conducted an ecologic evaluation of AU in inpatient adult acute care wards (excluding maternity wards) in 6 HCFs in Argentina, Brazil, and Chile; 2 HCFs per country. AU data for intravenously administered antibiotics commonly used to treat respiratory infections were collected from pharmacy dispensing records and aggregated to monthly defined daily dose (DDD)/1000 patient days. Graphs were created to depict AU and COVID-19 discharges over time throughout the 36-month study period (03/2018–02/2021). Relative changes in AU for all antibiotics combined and specific classes were calculated by comparing median AU for the 24-month pre-pandemic period (3/2018–2/2020) with the 12-month pandemic period (3/2020–2/2021). Only statistically significant differences (P< 0.05) determined by the Wilcoxon signed-rank test are reported. Results Compared to the pre-pandemic period, the use of all included antibiotics combined increased in 4/6 HCFs (6.7–35.1%). In the 4 HCFs that experienced increases in AU, Figure 1 shows that use was high during months when COVID-19 patient surges occurred. In 3/4 of these HCFs, AU remained high despite significant decreases in COVID-19 discharges. Ceftriaxone use increased in 2/6 HCFs (27.1–51.6%). Use of β-lactam antibiotics with activity against Pseudomonas aeruginosa increased in 3/6 HCFs (31.3–82.5%) and decreased in 1/6 HCFs (-18.9%). Vancomycin and linezolid use increased in 3/6 HCFs (36.9–77.1%). Conclusion Increases in AU among hospitalized adults were observed in 4 of 6 South American HCFs included in this study. The high rates of broad-spectrum antibiotic use in the HCFs may impact further emergence of antibiotic resistance. Understanding how this increase in antibiotic use compares to rates of bacterial infections during this time period is critical. Disclosures Jose M. Munita, MD, BioMerieux: Grant/Research Support|MSD: Grant/Research Support|Pfizer: Grant/Research Support Matias Salomao, MD, Cepheid: Lecture.

Background Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA. Methods We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS. Results A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16–0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST. Conclusions Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa.

The long-acting lipoglycopeptides (LGPs) dalbavancin and oritavancin are semisynthetic antimicrobials with broad and potent activity against Gram-positive bacterial pathogens. While they are approved by the Food and Drug Administration for acute bacterial skin and soft tissue infections, their pharmacological properties suggest a potential role of these agents for the treatment of deep-seated and severe infections, such as bloodstream and bone and joint infections. The use of these antimicrobials is particularly appealing when prolonged therapy, early discharge, and avoidance of long-term intravascular catheter access are desirable or when multidrug-resistant bacteria are suspected. This review describes the current evidence for the use of oritavancin and dalbavancin in the treatment of invasive infections, as well as the hurdles that are preventing their optimal use. Moreover, this review discusses the current knowledge gaps that need to be filled to understand the potential role of LGPs in highly needed clinical scenarios and the ongoing clinical studies that aim to address these voids in the upcoming years.

Background Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) compromise the clinical efficacy of vancomycin. The hVISA isolates spontaneously produce vancomycin-intermediate Staphylococcus aureus (VISA) cells generated by diverse and intriguing mechanisms. Objective To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches. Methods 39 hVISA and 305 VSSA and their genomes were included. Core genome-based Bayesian phylogenetic reconstructions were built and alterations in predicted proteins in VISA/hVISA were interrogated. Linear discriminant analysis and a Genome-Wide Association Study were performed. Differentially expressed genes were identified in hVISA-VSSA by RNA-sequencing. The undirected profiles of metabolites were determined by liquid chromatography and hydrophilic interaction in six CC5-MRSA. Results Genomic relatedness of MRSA associated to hVISA phenotype was not detected. The change Try38 → His in Atl (autolysin) was identified in 92% of the hVISA. We identified SNPs and k-mers associated to hVISA in 11 coding regions with predicted functions in virulence, transport systems, carbohydrate metabolism and tRNA synthesis. Further, capABCDE, sdrD, esaA, esaD, essA and ssaA genes were overexpressed in hVISA, while lacABCDEFG genes were downregulated. Additionally, valine, threonine, leucine tyrosine, FAD and NADH were more abundant in VSSA, while arginine, glycine and betaine were more abundant in hVISA. Finally, we observed altered metabolic pathways in hVISA, including purine and pyrimidine pathway, CoA biosynthesis, amino acid metabolism and aminoacyl tRNA biosynthesis. Conclusions Our results show that the mechanism of hVISA involves major changes in regulatory systems, expression of virulence factors and reduction in glycolysis via TCA cycle. This work contributes to the understanding of the development of this complex resistance mechanism in regional strains.

Highlights • Due to the rapidly emerging SARS-CoV-2 pandemic and its tremendous public health challenges worldwide, there is a critical demand for rapid and easy to perform diagnostic assays. • The evaluated rapid antigen detection test had a high diagnostic sensitivity and specificity in respiratory samples obtained from patients who mainly presented during the first week of Covid-19. • Rapid antigen detection has the potential to become an important tool for the early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods., Objectives In the context of the Covid-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. We evaluated a novel rapid antigen detection test (RDT) for SARS-CoV-2 in respiratory samples. Methods The fluorescence immunochromatographic SARS-CoV-2 antigen test (Bioeasy Biotechnology Co., Shenzhen, China) was evaluated using universal transport medium with nasopharyngeal (NP) and oropharyngeal (OP) swabs from suspected Covid-19 cases. Diagnostic accuracy was determined in comparison to SARS-CoV-2 real time (RT)-PCR. Results A total of 127 samples were included; 82 were RT-PCR positive. Median patients’ age was 38 years, 53.5% were male, and 93.7% were from the first week after symptom onset. Overall sensitivity and specificity were 93.9% (CI95% 86.5–97.4) and 100% (CI95% 92.1–100), respectively, with a diagnostic accuracy of 96.1% and Kappa coefficient of 0.9. Sensitivity was significantly higher in samples with high viral loads. Conclusions The evaluated RDT showed a high sensitivity and specificity in samples mainly obtained during the first week of symptoms and with high viral loads, despite the use of a non-validated sample material. The assay has the potential to become an important tool for early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods.

Objective. To identify socioeconomic factors associated with antimicrobial resistance of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli in Chilean hospitals (2008–2017). Methods. We reviewed the scientific literature on socioeconomic factors associated with the emergence and dissemination of antimicrobial resistance. Using multivariate regression, we tested findings from the literature drawing from a longitudinal dataset on antimicrobial resistance from 41 major private and public hospitals and a nationally representative household survey in Chile (2008–2017). We estimated resistance rates for three priority antibiotic–bacterium pairs, as defined by the Organisation for Economic Co-operation and Development; i.e., imipenem and meropenem resistant P. aeruginosa, cloxacillin resistant S. aureus, and cefotaxime and ciprofloxacin resistant E. coli. Results. Evidence from the literature review suggests poverty and material deprivation are important risk factors for the emergence and transmission of antimicrobial resistance. Most studies found that worse socioeconomic indicators were associated with higher rates of antimicrobial resistance. Our analysis showed an overall antimicrobial resistance rate of 32.5%, with the highest rates for S. aureus (40.6%) and the lowest for E. coli (25.7%). We found a small but consistent negative association between socioeconomic factors (income, education, and occupation) and overall antimicrobial resistance in univariate (p < 0.01) and multivariate analyses (p < 0.01), driven by resistant P. aeruginosa and S. aureus. Conclusion. Socioeconomic factors beyond health care and hospital settings may affect the emergence and dissemination of antimicrobial resistance. Preventing and controlling antimicrobial resistance requires efforts above and beyond reducing antibiotic consumption.

BackgroundVancomycin is a common first-line option for MRSA infections. The heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) phenotype is associated with therapeutic failure. However, hVISA isolates are usually reported as vancomycin susceptible by routine susceptibility testing procedures.ObjectivesTo detect and characterize the hVISA phenotype in MRSA isolates causing infections in nine Latin American countries.MethodsWe evaluated a total of 1189 vancomycin-susceptible MRSA isolates recovered during 2006–08 and 2011–14. After an initial screening of hVISA using glycopeptide-supplemented agar strategies, the detection of hVISA was performed by Etest (GRD) and Macro-method (MET). Isolates deemed to be hVISA were subjected to population analysis profile/AUC (PAP/AUC) and WGS for further characterization. Finally, we interrogated alterations in predicted proteins associated with the development of the VISA phenotype in both hVISA and vancomycin-susceptible S. aureus (VSSA) genomes.ResultsA total of 39 MRSA isolates (3.3%) were classified as hVISA (1.4% and 5.6% in MRSA recovered from 2006–08 and 2011–14, respectively). Most of the hVISA strains (95%) belonged to clonal complex (CC) 5. Only 6/39 hVISA isolates were categorized as hVISA by PAP/AUC, with 6 other isolates close (0.87–0.89) to the cut-off (0.9). The majority of the 39 hVISA isolates exhibited the Leu-14→Ile (90%) and VraT Glu-156→Gly (90%) amino acid substitutions in WalK. Additionally, we identified 10 substitutions present only in hVISA isolates, involving WalK, VraS, RpoB and RpoC proteins.ConclusionsThe hVISA phenotype exhibits low frequency in Latin America. Amino acid substitutions in proteins involved in cell envelope homeostasis and RNA synthesis were commonly identified. Our results suggest that Etest-based methods are an important alternative for the detection of hVISA clinical isolates.

Background Vancomycin-resistant enterococci (VRE) are major therapeutic challenges. Prospective contemporary data characterizing the clinical and molecular epidemiology of VRE bloodstream infections (BSIs) are lacking. Methods The Vancomycin-Resistant Enterococcal BSI Outcomes Study (VENOUS I) is a prospective observational cohort of adult patients with enterococcal BSI in 11 US hospitals. We included patients with Enterococcus faecalis or Enterococcus faecium BSI with ≥1 follow-up blood culture(s) within 7 days and availability of isolate(s) for further characterization. The primary study outcome was in-hospital mortality. Secondary outcomes were mortality at days 4, 7, 10, 12, and 15 after index blood culture. A desirability of outcome ranking was constructed to assess the association of vancomycin resistance with outcomes. All index isolates were subjected to whole genome sequencing. Results Forty-two of 232 (18%) patients died in hospital and 39 (17%) exhibited microbiological failure (lack of clearance in the first 4 days). Neutropenia (hazard ratio [HR], 3.13), microbiological failure (HR, 2.4), VRE BSI (HR, 2.13), use of urinary catheter (HR, 1.85), and Pitt BSI score ≥2 (HR, 1.83) were significant predictors of in-hospital mortality. Microbiological failure was the strongest predictor of in-hospital mortality in patients with E faecium bacteremia (HR, 5.03). The impact of vancomycin resistance on mortality in our cohort changed throughout the course of hospitalization. Enterococcus faecalis sequence type 6 was a predominant multidrug-resistant lineage, whereas a heterogeneous genomic population of E faecium was identified. Conclusions Failure of early eradication of VRE from the bloodstream is a major factor associated with poor outcomes.

Injured and orphaned wildlife are often brought to Wildlife Rehabilitation Centers (WRC) to be cared for by professionals to ultimately be released back to their natural habitats. In these centers, animals may spend months and frequently receive prolonged antibiotic therapy. Therefore, WRC may play a role in the emergence and dissemination of antimicrobial resistance (AMR). The goal of this study was to investigate the presence and antibiotic resistance profiles of Gram-negative bacteria with reduced susceptibility to cephalosporins in both the wildlife admitted to a WRC and in the WRC built environment in Chile. A cross-sectional study was conducted sampling animals undergoing rehabilitation (n = 64) and the WRC environment (n = 160). Isolated bacterial species were identified with MALDI-TOF, and antimicrobial susceptibility determined using the disk diffusion method. Enterobacteriaceae and Pseudomonadaceae were the dominant bacterial families among the environmental (n = 78) and animal (n = 31) isolates. For Enterobacteriaceae, isolates of the most abundant species (E. coli) were classified into 20 antibiotic resistance profiles, with eight of those isolates being resistant to more than nine antibiotics, including imipenem. Isolates of the Pseudomonadaceae family identified 11 isolates with resistance to antibiotics such as carbapenems and quinolones. Even though a cluster analysis based on antibiotic resistance patterns did not show a clear overlap between environmental and animal isolates, it is important to highlight the identification of isolates resistant to carbapenems, which is very relevant from a public health perspective. Further, numerous antibiotic resistance profiles were observed in different bacterial species, indicating not only environmental contamination with a wide diversity of bacteria, but also a wide diversity of resistant bacteria in animals at the WRC. The approach taken by sampling animals and their hospital environment can be useful in understanding AMR dynamics in wildlife rehabilitation settings, as well as the potential dissemination of AMR into the natural environment., Highlights • The wildlife center was contaminated with wide diversity of resistant bacteria. • There was wide diversity of resistant bacteria in wildlife at the center. • Resistant isolates to carbapenems were present, which has public health relevance. • No clear overlap between wildlife and the center antibiotic resistance patterns. • Wildlife rehabilitation should be considered in antimicrobial resistance dynamics.

Background Antimicrobial resistance is a global health emergency. Persons colonized with multidrug-resistant organisms (MDROs) are at risk for developing subsequent multidrug-resistant infections, as colonization represents an important precursor to invasive infection. Despite reports documenting the worldwide dissemination of MDROs, fundamental questions remain regarding the burden of resistance, metrics to measure prevalence, and determinants of spread. We describe a multi-site colonization survey protocol that aims to quantify the population-based prevalence and associated risk factors for colonization with high-threat MDROs among community dwelling participants and patients admitted to hospitals within a defined population-catchment area. Methods Researchers in five countries (Bangladesh, Chile, Guatemala, Kenya, and India) will conduct a cross-sectional, population-based prevalence survey consisting of a risk factor questionnaire and collection of specimens to evaluate colonization with three high-threat MDROs: extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Healthy adults residing in a household within the sampling area will be enrolled in addition to eligible hospitalized adults. Colonizing isolates of these MDROs will be compared by multilocus sequence typing (MLST) to routinely collected invasive clinical isolates, where available, to determine potential pathogenicity. A colonizing MDRO isolate will be categorized as potentially pathogenic if the MLST pattern of the colonizing isolate matches the MLST pattern of an invasive clinical isolate. The outcomes of this study will be estimates of the population-based prevalence of colonization with ESCrE, CRE, and MRSA; determination of the proportion of colonizing ESCrE, CRE, and MRSA with pathogenic characteristics based on MLST; identification of factors independently associated with ESCrE, CRE, and MRSA colonization; and creation an archive of ESCrE, CRE, and MRSA isolates for future study. Discussion This is the first study to use a common protocol to evaluate population-based prevalence and risk factors associated with MDRO colonization among community-dwelling and hospitalized adults in multiple countries with diverse epidemiological conditions, including low- and middle-income settings. The results will be used to better describe the global epidemiology of MDROs and guide the development of mitigation strategies in both community and healthcare settings. These standardized baseline surveys can also inform future studies seeking to further characterize MDRO epidemiology globally.

Background Carbapenem-resistant Klebsiella pneumoniae (CRKp) have become an increasing public health problem worldwide. While most CRKp around the world harbour a carbapenemase enzyme, the clinical relevance of non-carbapenemase-producing CRKp (non-CP-CRKp) is increasingly recognized. Selective digestive decontamination (SDD) has been proven successful as a decolonization strategy for patients colonized with Gram-negatives in the ICU. However, it is not regularly used to treat invasive infections. Objectives To report the use of SDD as a useful strategy for managing recalcitrant CRKp bloodstream infections. Patients and methods We present a neutropenic patient with a recalcitrant bloodstream infection with non-CP-CRKp treated with SDD. Besides, genomic analyses of five isolates of non-CP-CRKp was performed. Results After 11 days of SDD treatment with oral colistin and gentamicin, bacteraemia was successfully eradicated. Genomic analysis indicates a fully carbapenem-resistant phenotype evolved in vivo and suggests that the mechanism of carbapenem resistance in our strains relates to gene amplification of narrow-spectrum β-lactamases. Conclusions Our report highlights that SDD might be a useful strategy to manage CRKp bloodstream infections, when intestinal translocation is the likely source of the bacteraemia. In addition, the development of a resistant phenotype during therapy is worrisome as therapies directed against these organisms are likely to favour the amplification process.

Coccidioides is a primary pathogenic fungus, which infects humans through highly infectious arthroconidia, causing substantial morbidity including life-threatening disseminated infections. Due to the low infectious dose, laboratory personnel might become infected during diagnostic procedures. Accordingly, coccidioidomycosis is reported as the most frequent laboratory-acquired systemic mycosis worldwide. This risk is aggravated in non-endemic countries, where the diagnosis may not be suspected. We report on an inadvertent exposure of 44 persons to Coccidioides posadasii in a clinical microbiology laboratory in Chile, the measures of containment after rapid diagnosis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the lessons learnt in a non-endemic setting.

Background Healthcare workers (HCWs) are at high risk of exposure to SARS-CoV-2. Cross-sectional studies have provided variable rates of seroprevalence in HCWs. Longitudinal assessments of the serological response to Covid-19 among HCWs are crucial to understanding the risk of infection and changes in antibody titers over time. We aimed to investigate seroprevalence and risk factors associated with seroconversion in a prospective cohort of HCWs during the peak of the first wave of the Covid-19 pandemic. Methods We conducted a longitudinal study among 446 front-line HCWsin a tertiary-care hospital in Chile from April to July 2020. IgG was determined monthly using two different ELISAs in serum samples of HCWs, during the three-month period. In each visit, demographic data, symptoms, risk factors, and exposure risks were also assessed. Results The overall seroprevalence at the end of the study period was 24% (95% CI20.2–28.3), with 43% of seropositive HCWs reporting no prior symptoms. Seroconversion rates significantly differed over the study period, from 2.1% to as high as 8.8% at the peak of the epidemic. There were no statistically significant differences observed between HCWs in direct clinical care of patients with Covid-19 and those working in low risk areas. Antibody titers appeared to wane over time. Conclusions HCWs were severely affected with a high rate of seroconversion that appeared to mirror the local epidemiological situation. A significant amount of participants underwent an asymptomatic infection, highlighting the need for improved surveillance policies. Antibody titers appear to wane over time; further studies to understand this finding’s impact on the risk of reinfection are warranted.

Volume 57, issue 9, e00798-19, 2019, . The following funding information and acknowledgments should have appeared in the article. Jose M. Munita was supported by Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) (grant number FONDECYT

Antibiotic-resistant bacteria of critical importance for global health such as extended-spectrum beta-lactamases-producing (ESBL)-Escherichia coli have been detected in livestock, dogs, and wildlife worldwide. However, the dynamics of ESBL-E. coli between these animals remains poorly understood, particularly in small-scale farms of low and middle-income countries where contact between species can be frequent. We compared the prevalence of fecal carriage of ESBL-E. coli among 332 livestock (207 cows, 15 pigs, 60 horses, 40 sheep, 6 goats, 4 chickens), 82 dogs, and wildlife including 131 European rabbits, 30 rodents, and 12 Andean foxes sharing territory in peri-urban localities of central Chile. The prevalence was lower in livestock (3.0%) and wildlife (0.5%) compared to dogs (24%). Among 47 ESBL-E. coli isolates recovered, CTX-M-group 1 was the main ESBL genotype identified, followed by CTX-M-groups 2, 9, 8, and 25. ERIC-PCR showed no cluster of E. coli clones by either host species nor locality. To our knowledge, this is the first report of ESBL-E. coli among sheep, cattle, dogs, and rodents of Chile, confirming their fecal carriage among domestic and wild animals in small-scale farms. The high prevalence of ESBL-E. coli in dogs encourages further investigation on their role as potential reservoirs of this bacteria in agricultural settings.

Objective:To assess the impact of antimicrobial stewardship programs (ASPs) in adult medical–surgical intensive care units (MS-ICUs) in Latin America.Design:Quasi-experimental prospective with continuous time series.Setting:The study included 77 MS-ICUs in 9 Latin American countries.Patients:Adult patients admitted to an MS-ICU for at least 24 hours were included in the study.Methods:This multicenter study was conducted over 12 months. To evaluate the ASPs, representatives from all MS-ICUs performed a self-assessment survey (0–100 scale) at the beginning and end of the study. The impact of each ASP was evaluated monthly using the following measures: antimicrobial consumption, appropriateness of antimicrobial treatments, crude mortality, and multidrug-resistant microorganisms in healthcare-associated infections (MDRO-HAIs). Using final stewardship program quality self-assessment scores, MS-ICUs were stratified and compared among 3 groups: ≤25th percentile, >25th to Results:In total, 77 MS-ICU from 9 Latin American countries completed the study. Twenty MS-ICUs reached at least the 75th percentile at the end of the study in comparison with the same number who remain within the 25th percentile (score, 76.1 ± 7.5 vs 28.0 ± 7.3; P < .0001). Several indicators performed better in the MS-ICUs in the 75th versus 25th percentiles: antimicrobial consumption (143.4 vs 159.4 DDD per 100 patient days; P < .0001), adherence to clinical guidelines (92.5% vs 59.3%; P < .0001), validation of prescription by pharmacist (72.0% vs 58.0%; P < .0001), crude mortality (15.9% vs 17.7%; P < .0001), and MDRO-HAIs (9.45 vs 10.96 cases per 1,000 patient days; P = .004).Conclusion:MS-ICUs with more comprehensive ASPs showed significant improvement in antimicrobial utilization.

Background Klebsiella pneumoniae is the most frequent KPC-producing bacteria. The blaKPC gene is frequently embedded in Tn4401 transposon, and less frequently in non-Tn4401 elements (NTEKPC) variants I-III. The first case of KPC in the UC-CHRISTUS Clinical Hospital was detected in Pseudomonas aeruginosa. Soon after this event, KPC was detected in 2 additional Pseudomonas aeruginosa, 3 Escherichia coli, 3 Enterobacter cloacae, 3 Klebsiella pneumoniae, and 1 Citrobacter freundii, isolated from 6 different patients. We aimed to elucidate the possible mechanisms of genetic transfer and dissemination of the blaKPC gene among isolates of this multispecies outbreak. A molecular epidemiology analysis of the above mentioned clinical isolates (n = 13) through Multi-Locus Sequence Typing, plasmid analysis, Pulsed-Field Gel-Electrophoresis, and Whole-genome sequencing (WGS) was performed. Results High-risk sequence types were found: K. pneumoniae ST11, P. aeruginosa ST654, and E. cloacae ST114. All enterobacterial isolates were not clonal except for 3 E. coli isolated from the same patient. WGS analysis in 6 enterobacterial isolates showed that 4 of them had blaKPC embedded in a novel variant of NTEKPC designated NTEKPC-IIe. Upstream of blaKPC gene there was a 570 pb truncated blaTEM-1 gene followed by an insertion sequence that was 84% similar to ISEc63, a 4473 bp element of the Tn3 family. Downstream the blaKPC gene there was a truncated ISKpn6 gene, and the inverted repeat right sequence of Tn4401. The ISec63-like element together with the blaKPC gene plus Tn4401 remnants were inserted in the Tra operon involved in conjugative transfer of the plasmid. This NTE was carried in a broad host-range IncN plasmid. P. aeruginosa isolates carried blaKPC gene embedded in a typical Tn4401b transposon in a different plasmid, suggesting that there was no plasmid transfer between Enterobacteriaceae and P. aeruginosa as initially hypothesized. Conclusions Most enterobacterial isolates had blaKPC embedded in the same NTEKPC-IIe element, suggesting that this multispecies KPC outbreak was due to horizontal gene transfer rather than clonal spread. This poses a greater challenge to infection control measures often directed against containment of clonal spread.

Made available in DSpace on 2021-06-25T12:38:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-02-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) FONDECYT National Agency for Research and Development (ANID) FONDECYT Iniciacion ANID Millennium Science Initiative/Millennium Initiative for Collaborative Research on Bacterial Resistance, MICROB-R The extensive use of antibiotics is a leading cause for the emergence and spread of antimicrobial resistance (AMR) among dogs. However, the impact of using antibiotics to treat viral infections on AMR remains unknown. In this study, we compared the prevalence of extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E) between dogs with a suspected infection of canine parvovirus (CPV) and canine distemper (CDV) before and after treatment with third-generation cephalosporins. We found a higher prevalence of ESCR-E faecal carriage in dogs suspected of CPV (37%) and CDV (15%) compared to dogs with noninfectious pathologies (9%) even prior to the start of their treatment. A 7-day course of ceftriaxone or ceftiofur administrated to CPV and CDV-suspected dogs substantially increased their ESCR-E faecal carriage during treatment (85% for CPV and 57% for CDV), and 4 weeks after the treatment ended (89% for CPV and 60% for CDV) when dogs were back in their households. Most of the observed resistance was carried by ESCR-E. coli carrying bla(CTX-M) genes. Our results suggest the need to optimize prophylactic antibiotic therapy in dogs treated for a suspected viral infection to prevent ESCR-E emergence and spread in the community. Sao Paulo State Univ, Sch Vet Med & Anim Sci, Dept Anim Prod & Prevent Vet Med, BR-18618000 Botucatu, SP, Brazil Millennium Initiat Collaborat Res Bacterial Resis, Santiago 7550000, Chile Pontificia Univ Catolica Chile, Escuela Med Vet, Santiago 8940000, Chile Univ Cayetano Heredia Peru, Fac Vet Med & Zootech, Lima 15102, Peru Univ Desarrollo, Fac Med Clin Alemana, Genom & Resistant Microbes Grp, Santiago 7550000, Chile Univ Andres Bello, Fac Ciencias Vida, Dept Ecol & Biodiversidad, Santiago 8320000, Chile Univ Andres Bello, Fac Ciencias Vida, Ctr Invest Sustentabilidad, Santiago 8320000, Chile Sao Paulo State Univ, Sch Vet Med & Anim Sci, Dept Anim Prod & Prevent Vet Med, BR-18618000 Botucatu, SP, Brazil CAPES: 001 FONDECYT: 1181167 National Agency for Research and Development (ANID) FONDECYT Iniciacion: 11181017 ANID Millennium Science Initiative/Millennium Initiative for Collaborative Research on Bacterial Resistance, MICROB-R: NCN17_081

Gut microbiota is known to be transferred from the mother to their offspring. This study determines whether the innate microbiota of rats selectively bred for generations as high alcohol drinkers play a role in their alcohol intake. Wistar-derived high-drinker UChB rats (intake 10-g ethanol/kg/day) administered nonabsorbable oral antibiotics before allowing access to alcohol, reducing their voluntary ethanol intake by 70%, an inhibition that remained after the antibiotic administration was discontinued. Oral administration of Lactobacillus rhamnosus Gorbach-Goldin (GG) induced the synthesis of FGF21, a vagal β-Klotho receptor agonist, and partially re-invoked a mechanism that reduces alcohol intake. The vagus nerve constitutes the main axis transferring gut microbiota information to the brain ("microbiota-gut-brain" axis). Bilateral vagotomy inhibited rat alcohol intake by 75%. Neither antibiotic treatment nor vagotomy affected total fluid intake. A microbiota-mediated marked inflammatory environment was observed in the gut of ethanol-naive high-drinker rats, as gene expression of proinflammatory cytokines (TNF-α; IL-6; IL-1β) was significantly reduced by nonabsorbable antibiotic administration. Gut cytokines are known to activate the vagus nerve, while vagal activation induces pro-rewarding effects in nucleus accumbens. Both alcoholics and alcohol-preferring rats share a marked preference for sweet tastes-likely an evolutionary trait to seek sweet fermented fruits. Saccharin intake by UChB rats was inhibited by 75%-85% by vagotomy or oral antibiotic administration, despite saccharin-induced polydipsia. Overall, data indicate that the mechanisms that normally curtail heavy drinking are inhibited in alcohol-preferring animals and inform a gut microbiota origin. Whether it applies to other mammals and humans merits further investigation.

Background Understanding the characteristics of the Covid-19 pandemic in different geographical regions, ethnic and socioeconomic settings are of emerging importance. This study presents the demographic and clinical features of SARS-CoV-2 infected patients in a large private healthcare center in Santiago, Chile, during the first month of the pandemic. Methods We analyzed the demographics, laboratory and clinical characteristics including severity and outcome of all patients diagnosed with Covid-19 during the first month of the pandemic. SARS-2-CoV infection was confirmed by RT-PCR in nosopharyngeal samples. The primary outcome was a composite of ICU admission or all-cause, in-hospital mortality. Clinical and laboratory parameters of hospitalized patients were analyzed regarding their association with the primary outcome. Results From March 3 to April 4, 2020, 3679 individuals were tested for SARS-CoV-2 in our hospital. Of those, 381 had Covid-19 and were included into this analysis. Most patients (99.2%) were Chileans, 12% returning from recent travel. The median age was 39 years (IQR 31–49) and 52% were female. A total of 88 patients (23.1%) were hospitalized; 18 (3.7%) required ICU and/or died. The overall mortality was 0.7%. Increased body mass index (BMI) and elevated C-reactive protein (CRP) were independently associated with ICU care or death. Conclusion During the first weeks of the pandemic in Chile, most Covid-19 patients were young, with low rates of hospitalization, ICU requirement, and fatality. BMI and CRP on admission were predictors for severity. Our data provide important information on the clinical course and outcome of Covid-19 in a Latin American setting.

The evaluated SARS-CoV-2 antigen rapid fluorescence immunoassays reliably identified patients within the first 5 days of symptom onset, when respiratory secretions carried high viral loads. This high performance suggests that these tests might play an important role for future PCR-independent strategies to detect early or infective cases.

IntroductionUnderstanding the clinical course and outcomes of patients with Covid-19 in underrepresented populations like Latin America is paramount. In this study, we report the clinical characteristics of Covid-19 in Chile, with a focus on subjects requiring hospitalization during the initial phases of the SARS-CoV-2 pandemic.MethodsThis is a single center study including all consecutive patients diagnosed with Covid-19 during the first month of the pandemic. Demographics, clinical characteristics and laboratory data were collected within 24 hours of admission. The primary outcome was a composite of ICU admission or all-cause, in-hospital mortality.ResultsDuring the first month of the pandemic, 381 patients were confirmed as positive for SARS-CoV-2 by molecular testing; 88 (23.1%) of them eventually required hospitalization. Median age of the cohort was 39 years (IQR 31-49). Overall mortality was 0.7% and 18 (3.7%) out of the 88 subjects who required hospitalization either died and/or required ICU. Increased body mass index (BMI), C-reactive protein levels (CRP) and the SaTO2/FiO2 index on admission were independently associated with a higher risk of ICU care or death.DiscussionThe lower mortality observed in our prospective cohort during the first month of SARS-Cov-2 pandemic was lower than previously reported. This finding could be due to a lower threshold for admission, a healthcare system not yet overburdened and a younger population, among other factors. BMI, CRP on admission were strong predictors for ICU care or all-cause, in-hospital mortality. Our data provide important information regarding the clinical course of Covid-19 in Latin America.

A multicenter, retrospective study of patients infected with carbapenem-resistant Pseudomonas aeruginosa who were treated with ceftolozane/tazobactam was performed. Among 35 patients, pneumonia was the most common indication and treatment was successful in 26 (74%). Treatment failure was observed in all cases where isolates demonstrated ceftolozane-tazobactam minimum inhibitory concentrations ≥8 μg/mL.

Made available in DSpace on 2021-06-25T10:55:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 Faecal carriage of extended-spectrum cephalosporin-resistant Escherichia coli (ESC-R E. coli) in dogs has been reported worldwide and can reduce the effectiveness of treatments against bacterial infections. However, the drivers that influence faecal carriage of ESC-R E. coli in dogs are poorly understood. The aims of this study were to estimate the prevalence of ESC-R E. coli among dogs prior to their admission to a veterinary teaching hospital and to identify risk factors associated with the faecal carriage of ESC-R E. coli. Rectal swabs (n = 130) were collected from dogs and screened for ESC-R E. coli using MacConkey agar supplemented with cefotaxime (2 μg/mL). E. coli species was confirmed by MALDI-TOF and screening of extended-spectrum beta-lactamase (ESBL) genes was conducted by multiplex PCR. Questionnaires were completed by each dog's owner to test several human and dog characteristics associated with ESC-R E. coli. The prevalence of faecal carriage of ESC-R E. coli was 9.2 % and 67 % of ESC-R E. coli isolates harboured ESBL genes including CTX-M alone or in combination with TEM. All ESC-R E. coli isolates were resistant to ceftriaxone, cefpodoxime, and cefotaxime and were susceptible to cefoxitin and carbapenems. The likelihood of carrying ESC-R E. coli was 15 times higher (OR = 14.41 [95 % CI: 1.80−38.02], p < 0.01) if the dog was treated with antibiotics 3–12 months prior to sampling and 8 times higher (OR = 7.96 [95 % CI: 2.96−92.07], p < 0.01) if the dog had direct contact with livestock, but 15 times lower (OR = 0.07 [95 % CI: 0.01−0.32], p < 0.01) if the dog was dewormed during the previous year. Our findings confirm the faecal carriage of ESC-R E. coli in subclinical dogs and call for further investigation regarding the impact of deworming on antibiotic-resistant bacteria in companion animals. Department of Animal Production and Preventive Veterinary Medicine School of Veterinary Medicine and Animal Science Sao Paulo State University (UNESP) Millennium Initiative for Collaborative Research On Bacterial Resistance (MICROB-R) Departamento de Ecología y Biodiversidad Facultad de Ciencias de la Vida Universidad Andres Bello Centro de Investigación para la Sustentabilidad Universidad Andres Bello, Facultad de Ciencias de la Vida Genomics and Resistant Microbes Group Facultad de Medicina Clínica Alemana Universidad del Desarrollo Escuela de Medicina Facultad de Medicina Pontificia Universidad Católica de Chile Escuela de Medicina Veterinaria Pontificia Universidad Católica de Chile Department of Animal Production and Preventive Veterinary Medicine School of Veterinary Medicine and Animal Science Sao Paulo State University (UNESP)

Introduction: Antimicrobial drug resistance (AMR) is considered a serious threat to public health worldwide. The relation between AMR and human mobility, particularly international migration, has drawn attention from the scientific community in recent years. However, several aspects about this relation remain unclear. Therefore, we aimed at expanding and updating previous systematic review studies, with a novel focus on the AMR prevalence in migrants compared to the local population of the host country, to examine external validity of previous findings.Methods: We searched in Ovid MEDLINE all types of observational studies, without language or year of publication restrictions. We aimed at exploring differences in countries´ bacterial drug resistance rates based on immigration rates. All types of AMR were included, except for those related to HIV/AIDS and Tuberculosis. The comparator group of interest was the local population of the host country. The study protocol is registered with PROSPERO, number CRD42018114436. Results: After screening of 322 articles, 15 papers were selected for data extraction, including 1930 migrants. Compared to the local population, higher rates of methicillin-resistant Staphylococcus aureus, Panton-Valentine leucocidin positive strains, multidrug-resistant Gram-negative bacteria, vancomycin-resistant Enterococcus, and having at least one multidrug-resistant organism were found in migrants in 12 of the 15 papers. Rates of AMR did not differ significantly in two studies and only one of them reported a lower burden of AMR in migrants.Conclusions: Higher prevalence of AMR in migrants were presented in the majority of the included articles, addressing the emerge of the circulation of resistant strains within this group. More detailed descriptions, including time span and route taken by migrants to arrive to country of destination and length of stay by the time of inclusion are essential to gain a deeper understanding of the relation in between AMR and migration. Countries with high migration rates outside Europe should be encouraged to implement strategies for screening of both local population and migrants in countries.

In the context of the Covid-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. We compared the performance of four rapid antigen detection tests for SARS-CoV-2 in respiratory samples. Immunochromatographic SARS-CoV-2 assays from RapiGEN, Liming bio, Savant, and Bioeasy were evaluated using universal transport medium containing naso-oropharyngeal swabs from suspected Covid-19 cases. The diagnostic accuracy was determined in comparison to SARS-CoV-2 RT-PCR. A total of 111 samples were included; 80 were RT-PCR positive. Median patients’ age was 40 years, 55% were female, and 88% presented within the first week after symptom onset. The evaluation of the Liming bio assay was discontinued due to insufficient performance. The overall sensitivity values of RapiGEN, Liming bio, and Bioeasy tests were 62.0% (CI95% 51.0–71.9), 16.7% (CI95% 10.0–26.5), and 85.0% (CI95% 75.6–91.2), respectively, with specificities of 100%. Sensitivity was significantly higher in samples with high viral loads (RapiGEN, 84.9%; Bioeasy, 100%). The study highlighted the significant heterogeneity of test performance among evaluated assays, which might have been influenced by the use of a non-validated sample material. The high sensitivity of some tests demonstrated that rapid antigen detection has the potential to serve as an alternative diagnostic method, especially in patients presenting with high viral loads in early phases of infection. This is particularly important in situations with limited access to RT-PCR or prolonged turnaround time. Further comparative evaluations are necessary to select products with high performance among the growing market of diagnostic tests for SARS-CoV-2.

Background: High rates of resistance to third-generation cephalosporins and carbapenems in Enterobacterales have been reported in Latin America. Ceftazidime/avibactam (CZA) is the combination of a third-generation cephalosporin and a non-β-lactam β-lactamase inhibitor, which hasshown activity against isolates producing class A, C and D β-lactamases. Herein, we evaluated the activity of CZA and comparators against clinical isolates of Enterobacterales in Latin America. Methods: The activity of CZA and comparators was evaluated against clinical isolates of Enterobacterales from Argentina, Brazil, Chile, Colombia and Mexico that were collected between January 2016 andOctober 2017. One specific phenotypic subset was evaluated. A carbapenem non-susceptible (CNS) phenotype was defined as any isolate displaying a minimum inhibitory concentration (MIC) ≥1 mg/L for ertapenem. Results: CZA was active against 95.8% of all isolates and 77.5% of CNS isolates. Fosfomycin (FOS) and tigecycline (TGC) were the second most active antibiotics with 93.4% ofEnterobacterales being susceptible. Conclusions: The results of this study underline the potential therapeutic role of CZA in Latin America Fil: Appel, Tobias Manuel. Universidad El Bosque; Colombia Fil: Mojica, Maria Fernanda. Universidad El Bosque; Colombia Fil: De La Cadena, Elsa. Universidad El Bosque; Colombia Fil: Pallares, Cristian. Universidad El Bosque; Colombia Fil: Radice, Marcela Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Castañeda Méndez, Paulo. Hospital Médica Sur; México Fil: Jaime-Villalón, Diego. Hospital San Angel; México Fil: Gales, Ana. Universidade de Sao Paulo; Brasil Fil: Munita, Jose. No especifíca; Fil: Villegas, Maria. Universidad El Bosque; Colombia

Background: In the context of the COVID-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority to enable the required testing scale up in most countries. We evaluated a novel rapid antigen detection test (RDT) for SARS-CoV-2 in respiratory samples. Method: sA new fluorescence immunochromatographic SARS-CoV-2 antigen detection test (Bioeasy Biotechnology Co., Shenzhen, China) was evaluated in nasophayngeal (NP) and oropharyngeal (OP) swabs from patients with suspected COVID-19 in Santiago, Chile. Diagnostic accuracy was determined in comparison to SARS-CoV-2 real time (RT)-PCR, using the same material (universal transport medium with NP and OP swab). Findings: A total of 127 samples were included. The median patients’ age was 38 years (IQR 29·5–44), 53·5% were male, and 93·7% were in the first week after symptom onset. Among 82 RT-PCR positive specimens, 77 were correctly detected by RDT. All 45 RT-PCR negative samples were correctly identified. The overall sensitivity and specificity of the RDT were 93·9% (CI95% 86·5–97·4) and 100% (CI95% 92·1–100), respectively, with a diagnostic accuracy of 96·1% and Kappa coefficient of 0·9. Sensitivity was significantly higher in samples with increased viral loads. Interpretation: The antigen-based immunofluorescence RDT showed a high sensitivity and specificity in respiratory samples obtained from patients who mainly presented during the first week of COVID-19, despite the use of a non-validated sample. The assay was easy to use and provided results in a timely manner. It has the potential to become an important tool for early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods. Funding Statement: This work did not receive funding. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The study was approved by the local Institutional Review Board (Comite Etico Cientifico, Facultad de Medicina Clinica Alemana, Universidad del Desarrollo, Santiago, Chile) and need for informed consent was waived.