Distribution of β-Lactamase Genes in Clinical Isolates from California Central Valley Hospital Deviates from the United States Nationwide Trends.
ABSTRACT: The evolution and dissemination of antibiotic resistance genes throughout the world are clearly affected by the selection and migration of resistant bacteria. However, the relative contributions of selection and migration at a local scale have not been fully explored. We sought to identify which of these factors has the strongest effect through comparisons of antibiotic resistance gene abundance between a distinct location and its surroundings over an extended period of six years. In this work, we used two repositories of extended spectrum β-lactamase (ESBL)-producing isolates collected since 2013 from patients at Dignity Health Mercy Medical Center (DHMMC) in Merced, California, USA, and a nationwide database compiled from clinical isolate genomes reported by the National Center for Biotechnology Information (NCBI) since 2013. We analyzed the stability of average resistance gene frequencies over the years since collection of these clinical isolates began for each repository. We then compared the frequencies of resistance genes in the DHMMC collection with the averages of the nationwide frequencies. We found DHMMC gene frequencies are stable over time and differ significantly from nationwide frequencies throughout the period of time we examined. Our results suggest that local selective pressures are a more important influence on the population structure of resistance genes in bacterial populations than migration. This, in turn, indicates the potential for antibiotic resistance to be controlled at a regional level, making it easier to limit the spread through local stewardship.
Project description:NON-TECHNICAL SUMMARY:Antibiotic resistance is a global human health problem. We partnered with Dignity Health Mercy Medical Center to study antibiotic resistance in clinical isolates. We tested whether growth rates, a sensitive assay used to measure the fitness of bacterial samples, correlate with a clinical test to measure antibiotic resistance. We found a strong correlation between these two methods suggesting that growth rates could be reliably applied to evolutionary studies of clinically relevant problems. Moreover, the sensitivity of the growth rates assay enabled us to identify fitness effects of specific antibiotic resistance genes.
Project description:Acute rhinosinusitis (ARS) is a respiratory disease commonly caused by viral infections. Physicians regularly prescribe antibiotics despite bacterial etiologies being uncommon. This is of concern, as this use adds to the selection pressure for resistance. Here we present the descriptive epidemiology of acute rhinosinusitis and corresponding antibiotic prescribing practices by Canadian outpatient physicians from 2007-2013.Diagnosis and antibiotic prescription data for ARS were extracted from the Canadian Disease and Therapeutic Index for 2007 to 2013, and population data were acquired from Statistics Canada. ARS diagnosis and antibiotic prescription rates and frequencies of antibiotic classes were calculated.Eighty-eight percent of patients diagnosed with ARS in 2013 were adults, with a greater rate of antibiotic prescriptions observed among the adults relative to the pediatric patients (1632.9 and 468.6 antibiotic prescriptions per 10,000 inhabitants). Between 2007 and 2013, the ARS diagnosis rate decreased from 596 to 464 diagnoses per 10,000 inhabitants, while the percentage of diagnoses with antibiotic prescriptions at the national level remained stable (87% to 84%). From 2007 to 2013, prescription rates for macrolides decreased from 203.5 to 105.4 prescriptions per 10,000 inhabitants. In 2013, penicillins with extended spectrum were more commonly prescribed compared to macrolides among adult patients (153.5 and 105.4 prescriptions per 10,000 inhabitants, respectively).This study is the first to describe physician antibiotic prescribing practices for treatment of ARS in Canada. Results show that antibiotic treatment for ARS represents an area for implementing antimicrobial stewardship, and through it, managing antibiotic resistance. Further work is required to better understand diagnosing practices and treatment criteria for ARS, and use this information to further assist physicians to limit unnecessary antibiotic prescribing practices.
Project description:OBJECTIVES:This study aimed to explore how adult patients who received free mission-based elective surgery experienced surgery and its outcomes, in order to provide recommendations for improved service delivery, measurement of impact and future quality initiatives for the humanitarian organisation Mercy Ships and other mission-based surgical platforms. SETTING:Data were collected in June 2017 in Cotonou, Benin, where the participants had previously received free mission-based elective surgery aboard the Africa Mercy, a non-governmental hospital ship. PARTICIPANTS:Sixteen patients (seven male, nine female, age range 22-71, mean age 43.25) who had previously received surgical care aboard the Africa Mercy hospital ship between September 2016 and May 2017 participated in the study. METHODS:Using a qualitative design, 16 individual semistructured interviews were conducted with the assistance of two interpreters. Participants were recruited using purposive sampling from the Mercy Ships patient database. Interview data were coded and organised into themes and subthemes using thematic content analysis in an interpretivist approach. FINDINGS:Analysis of interview data revealed three main themes: barriers to surgery, experiences with Mercy Ships and changes in perspectives of surgery after their experiences. Key findings included barriers to local surgical provision such as cost, a noteworthy amount of fear and distrust of local surgical teams, exceptional positive experiences with the care at Mercy Ships, and impactful surgery, resulting in high levels of trust in foreign surgical teams. CONCLUSIONS:While foreign surgical teams are meeting an immediate need for surgical care, the potential enduring legacy is one of trusting only foreigners for surgery. Patients are a critical component to a well-functioning surgical system, and mission-based surgical providers must formulate strategies to mitigate this legacy while strengthening the local surgical system.
Project description:BACKGROUND:Ineffective antibiotic therapy increases mortality of acute cholangitis. The choice of antibiotics should reflect local resistance patterns and avoid the overuse of broad-spectrum agents. In this study, we analysed how results of bile and blood cultures and patient data can be used for selection of empirical antibiotic therapy in acute cholangits. METHODS:Pathogen frequencies and susceptibility rates were determined in 423 positive bile duct cultures and 197 corresponding blood cultures obtained from 348 consecutive patients with acute cholangitis. Patient data were retrieved from the medical records. Associations of patient and microbiological data were assessed using the Chi-2 test and multivariate binary logistic regression. RESULTS:In bile cultures, enterobacterales and enterococci were isolated with equal frequencies of approximately 30% whereas in blood cultures, enterobacterales predominated (56% compared to 21% enterococci). Antibiotic resistance rates of enterobacterales were?>?20% for fluorochinolones, cephalosporines and acylureidopenicillins but not for carbapenems (<?2%). The efficacy of empirical therapy was poor with a coverage of bacterial bile and blood culture isolates in 51 and 69%, respectively. By multivariate analysis, predictors for pathogen species, antibiotic susceptibility and expected antibiotic coverage were identified. CONCLUSIONS:In unselected patients treated for acute cholangitis in a large tertiary refferential center, use of carbapenems seems necessary to achieve a high antibiotic coverage. However, by analysis of patient and microbiological data, subgroups for highly effective carbapenem-sparing therapy can be defined. For patients with community-acquired cholangitis without biliary prosthesis who do not need intensive care, piperacillin/tazobactam represents a regimen with an expected excellent antibiotic coverage.
Project description:Background:There is a lack of official national antimicrobial resistance (AMR) data in Lebanon. Individual hospitals generate their own antibiotic susceptibility data in the form of yearly pamphlets. Methods:In this study, antibiotic susceptibility data from 13 hospitals distributed across different governorates of Lebanon were collected to conduct a compilation-based surveillance of AMR in Lebanon for the years 2015-2016. The findings were compared with those of a previous nationwide study in this country conducted between 2011 and 2013 as well as with similar data obtained from the 2015 and 2016 European surveillance reports of AMR. To provide a clear presentation of the AMR situation, mean percent susceptibility of different antibiotic-microbe combinations was calculated. Results:During 2015-2016, the percent susceptibility of Enterobacteriaceae to third-generation cephalosporins and to carbapenems was 59 and 97%, respectively. Among Pseudomonas aeruginosa and Acinetobacter spp., carbapenem susceptibility reached 70 and 12%, respectively. Among Gram positive organisms, the percent susceptibility to methicillin in Staphylococcus aureus was 72%, that to vancomycin in Enterococcus spp. was 98% and that to penicillin in Streptococcus pneumoniae was 75%. Compared with results of 2011-2013, there was an overall trend of decreased susceptibility of bacteria to the tested antibiotics, with a variation of 5 to 10%. The antibiotic susceptibility data from Lebanon were found to be comparable with those from Eastern and South-eastern European countries. Conclusion:This study highlights the need to establish a robust national AMR surveillance system that enables data from Lebanon to be included in global AMR maps.
Project description:Antibiotic resistance is a global health challenge that threatens human and animal lives, especially among low-income and vulnerable populations in less-developed countries. Its multi-factorial nature requires integrated studies on antibiotics and resistant bacteria in humans, animals, and the environment. To achieve a comprehensive understanding of the situation and management of antibiotic use and environmental transmission, this paper describes a study protocol to document human exposure to antibiotics from major direct and indirect sources, and its potential health outcomes. Our mixed-methods approach addresses both microbiological and pathogen genomics, and epidemiological, geospatial, anthropological, and sociological aspects. Implemented in two rural residential areas in two provinces in Eastern China, linked sub-studies assess antibiotic exposure in population cohorts through household surveys, medicine diaries, and biological sampling; identify the types and frequencies of antibiotic resistance genes in humans and food-stock animals; quantify the presence of antibiotic residues and antibiotic resistance genes in the aquatic environment, including wastewater; investigate the drivers and behaviours associated with human and livestock antibiotic use; and analyse the national and local policy context, to propose strategies and systematic measurements for optimising and monitoring antibiotic use. As a multidisciplinary collaboration between institutions in the UK and China, this study will provide an in-depth understanding of the influencing factors and allow comprehensive awareness of the complexity of AMR and antibiotic use in rural Eastern China.
Project description:Sporadic literature reports describe isolates of pathogenic bacteria that harbor an antibiotic resistance determinant but remain susceptible to the corresponding antibiotic as a consequence of a genetic defect. Such strains represent a source from which antibiotic resistance may reemerge to cause treatment failure in patients. Here, we report a systematic investigation into the prevalence and nature of this phenomenon, which we term silencing of antibiotic resistance by mutation (SARM). Instances of SARM were detected among 1,470 Staphylococcus aureus isolates through side-by-side comparison of antibiotic resistance genotype (as determined by whole-genome sequencing) versus phenotype (as assessed through susceptibility testing). Of the isolates analyzed, 152 (10.3%) harbored a silenced resistance gene, including 46 (3.1%) that exhibited SARM to currently deployed antistaphylococcal drugs. SARM resulted from diverse mutational events but most commonly through frameshift mutation of resistance determinants as a result of point deletion in poly(A) tracts. The majority (?90%) of SARM strains reverted to antibiotic resistance at frequencies of ?10-9; thus, while appearing antibiotic sensitive in the clinical microbiology laboratory, most S. aureus isolates exhibiting SARM will revert to antibiotic resistance at frequencies achievable in patients. In view of its prevalence in a major pathogen, SARM represents a significant potential threat to the therapeutic efficacy of antibiotics.IMPORTANCE Antibiotic resistance hinders the treatment of bacterial infection. To guide effective therapy, clinical microbiology laboratories routinely perform susceptibility testing to determine the antibiotic sensitivity of an infecting pathogen. This approach relies on the assumption that it can reliably distinguish bacteria capable of expressing antibiotic resistance in patients, an idea challenged by the present study. We report that the important human pathogen Staphylococcus aureus frequently carries antibiotic resistance genes that have become inactivated ("silenced") by mutation, leading strains to appear antibiotic sensitive. However, resistance can rapidly reemerge in most such cases, at frequencies readily achievable in infected patients. Silent antibiotic resistance is therefore prevalent, transient, and evades routine detection, rendering it a significant potential threat to antibacterial chemotherapy.
Project description:Wastewater treatment plants (WWTPs) receive a confluence of sewage containing antimicrobials, antibiotic resistant bacteria, antibiotic resistance genes (ARGs), and pathogens and thus are a key point of interest for antibiotic resistance surveillance. WWTP monitoring has the potential to inform with respect to the antibiotic resistance status of the community served as well as the potential for ARGs to escape treatment. However, there is lack of agreement regarding suitable sampling frequencies and monitoring targets to facilitate comparison within and among individual WWTPs. The objective of this study was to comprehensively evaluate patterns in metagenomic-derived indicators of antibiotic resistance through various stages of treatment at a conventional WWTP for the purpose of informing local monitoring approaches that are also informative for global comparison. Relative abundance of total ARGs decreased by ∼50% from the influent to the effluent, with each sampling location defined by a unique resistome (i.e., total ARG) composition. However, 90% of the ARGs found in the effluent were also detected in the influent, while the effluent ARG-pathogen taxonomic linkage patterns identified in assembled metagenomes were more similar to patterns in regional clinical surveillance data than the patterns identified in the influent. Analysis of core and discriminatory resistomes and general ARG trends across the eight sampling events (i.e., tendency to be removed, increase, decrease, or be found in the effluent only), along with quantification of ARGs of clinical concern, aided in identifying candidate ARGs for surveillance. Relative resistome risk characterization further provided a comprehensive metric for predicting the relative mobility of ARGs and likelihood of being carried in pathogens and can help to prioritize where to focus future monitoring and mitigation. Most antibiotics that were subject to regional resistance testing were also found in the WWTP, with the total antibiotic load decreasing by ∼40-50%, but no strong correlations were found between antibiotics and corresponding ARGs. Overall, this study provides insight into how metagenomic data can be collected and analyzed for surveillance of antibiotic resistance at WWTPs, suggesting that effluent is a beneficial monitoring point with relevance both to the local clinical condition and for assessing efficacy of wastewater treatment in reducing risk of disseminating antibiotic resistance.
Project description:Surveillance of antimicrobial resistance (AMR) is essential for clinical decision-making and for public health authorities to monitor patterns in resistance and evaluate the effectiveness of interventions and control measures. Existing AMR surveillance is typically based on reports from hospital laboratories and public health laboratories, comprising reports of pathogen frequencies and resistance frequencies among each species detected. Here we propose an improved framework for AMR surveillance, in which the unit of surveillance is patients with specific conditions, rather than biological samples of a particular type. In this 'case-based' surveillance, denominators as well as numerators will be clearly defined with clinical relevance and more comparable at the local, national and international level. In locations with sufficient resources, individual-based data on patient characteristics and full antibiotic susceptibility profiles would provide high-quality evidence for monitoring resistant pathogens of clinical importance, clinical treatment of infections and public health responses to outbreaks of infections with resistant bacteria.
Project description:<h4>Background</h4>Antimicrobial overuse and misuse of broad-spectrum antibiotics increases the risk for antimicrobial resistance. Investigating unwarranted variation in antibiotic prescription has therefore gained global priority.<h4>Methods</h4>We examined recent time trends in the utilization of narrow- and broad-spectrum antibiotics as well as the variation in antibiotic use by sex, age, and municipality of residence. Complete individual-level data on all redeemed out-of hospital prescriptions for antibiotics in the entire adult population of Central Denmark (1.3 million inhabitants) was obtained for the period 2006-2015.<h4>Results</h4>Following an initial increase of 2% between 2006 and 2011, the overall rate of redeemed prescriptions for antibiotics per 1000 person years declined by 17% between 2011 and 2015. Among persons aged over 65?years, the decline in use began later (from 2013) and was less pronounced. Antibiotic use in 2015 remained substantially higher among females (289/1000 person-years) vs. males (182/1000 person-years) and among the very old (520/1000 person-years in >85y old) vs. middle-aged (204/1000 person-years in 45-65y old). A decreasing trend in antibiotic use over time was observed in all municipalities, mainly due to a decrease in narrow-spectrum antibiotics. However, a striking and unexplained 1.6-fold geographical variation in antibiotic use, including tetracyclines, macrolides and fluoroquinolones remained in 2015. Of concern, among females aged ?65?years and males aged ?85?years, a continuous increasing trend in broad-spectrum antibiotic use was observed.<h4>Conclusions</h4>Antibiotic use has decreased almost 20% in Central Denmark after 2011, possibly related to a nationwide antibiotic stewardship program in Denmark. However, substantial geographical variation in antibiotic prescription remains and the use of broad-spectrum antibiotics has increased in adults of older age. Continuous focus on avoiding unnecessary use of broad-spectrum antibiotics is requested.