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The prevalence and effects of inappropriate empirical antibiotic therapy for bloodstream infections are unclear. We aimed to establish the population-level burden, predictors, and mortality risk of in-vitro susceptibility-discordant empirical antibiotic therapy among patients with bloodstream infections. Our retrospective cohort analysis of electronic health record data from 131 hospitals in the USA included patients with suspected—and subsequently confirmed—bloodstream infections who were treated empirically with systemic antibiotics between Jan 1, 2005, and Dec 31, 2014. We included all patients with monomicrobial bacteraemia caused by common bloodstream pathogens who received at least one systemic antibiotic either on the day blood cultures were drawn or the day after, and for whom susceptibility data were available. We calculated the prevalence of discordant empirical antibiotic therapy—which was defined as receiving antibiotics on the day blood culture samples were drawn to which the cultured isolate was not susceptible in vitro—overall and by hospital type by using regression tree analysis. We used generalised estimating equations to identify predictors of receiving discordant empirical antibiotic therapy, and used logistic regression to calculate adjusted odds ratios for the relationship between in-hospital mortality and discordant empirical antibiotic therapy. 21 608 patients with bloodstream infections received empirical antibiotic therapy on the day of first blood culture collection. Of these patients, 4165 (19%) received discordant empirical antibiotic therapy. Discordant empirical antibiotic therapy was independently associated with increased risk of mortality (adjusted odds ratio 1·46 [95% CI, 1·28–1·66]; p<0·0001), a relationship that was unaffected by the presence or absence of resistance or sepsis or septic shock. Infection with antibiotic-resistant species strongly predicted receiving discordant empirical therapy (adjusted odds ratio 9·09 [95% CI 7·68–10·76]; p<0·0001). Most incidences of discordant empirical antibiotic therapy and associated deaths occurred among patients with bloodstream infections caused by Staphylococcus aureus or Enterobacterales. Approximately one in five patients with bloodstream infections in US hospitals received discordant empirical antibiotic therapy, receipt of which was closely associated with infection with antibiotic-resistant pathogens. Receiving discordant empirical antibiotic therapy was associated with increased odds of mortality overall, even in patients without sepsis. Early identification of bloodstream pathogens and resistance will probably improve population-level outcomes. US National Institutes of Health, US Centers for Disease Control and Prevention, and US Agency for Healthcare Research and Quality.

Testing of asymptomatic patients for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) (ie, “asymptomatic screening) to attempt to reduce the risk of nosocomial transmission has been extensive and resource intensive, and such testing is of unclear benefit when added to other layers of infection prevention mitigation controls. In addition, the logistic challenges and costs related to screening program implementation, data noting the lack of substantial aerosol generation with elective controlled intubation, extubation, and other procedures, and the adverse patient and facility consequences of asymptomatic screening call into question the utility of this infection prevention intervention. Consequently, the Society for Healthcare Epidemiology of America (SHEA) recommends against routine universal use of asymptomatic screening for SARS-CoV-2 in healthcare facilities. Specifically, preprocedure asymptomatic screening is unlikely to provide incremental benefit in preventing SARS-CoV-2 transmission in the procedural and perioperative environment when other infection prevention strategies are in place, and it should not be considered a requirement for all patients. Admission screening may be beneficial during times of increased virus transmission in some settings where other layers of controls are limited (eg, behavioral health, congregate care, or shared patient rooms), but widespread routine use of admission asymptomatic screening is not recommended over strengthening other infection prevention controls. In this commentary, we outline the challenges surrounding the use of asymptomatic screening, including logistics and costs of implementing a screening program, and adverse patient and facility consequences. We review data pertaining to the lack of substantial aerosol generation during elective controlled intubation, extubation, and other procedures, and we provide guidance for when asymptomatic screening for SARS-CoV-2 may be considered in a limited scope.

The hospital environment is a potential reservoir of bacteria with plasmids conferring carbapenem resistance. Our Hospital Epidemiology Service routinely performs extensive sampling of high-touch surfaces, sinks, and other locations in the hospital. Over a 2-year period, additional sampling was conducted at a broader range of locations, including housekeeping closets, wastewater from hospital internal pipes, and external manholes. We compared these data with previously collected information from 5 years of patient clinical and surveillance isolates. Whole-genome sequencing and analysis of 108 isolates provided comprehensive characterization of bla KPC / bla NDM -positive isolates, enabling an in-depth genetic comparison. Strikingly, despite a very low prevalence of patient infections with bla KPC -positive organisms, all samples from the intensive care unit pipe wastewater and external manholes contained carbapenemase-producing organisms (CPOs), suggesting a vast, resilient reservoir. We observed a diverse set of species and plasmids, and we noted species and susceptibility profile differences between environmental and patient populations of CPOs. However, there were plasmid backbones common to both populations, highlighting a potential environmental reservoir of mobile elements that may contribute to the spread of resistance genes. Clear associations between patient and environmental isolates were uncommon based on sequence analysis and epidemiology, suggesting reasonable infection control compliance at our institution. Nonetheless, a probable nosocomial transmission of Leclercia sp. from the housekeeping environment to a patient was detected by this extensive surveillance. These data and analyses further our understanding of CPOs in the hospital environment and are broadly relevant to the design of infection control strategies in many infrastructure settings. IMPORTANCE Carbapenemase-producing organisms (CPOs) are a global concern because of the morbidity and mortality associated with these resistant Gram-negative bacteria. Horizontal plasmid transfer spreads the resistance mechanism to new bacteria, and understanding the plasmid ecology of the hospital environment can assist in the design of control strategies to prevent nosocomial infections. A 5-year genomic and epidemiological survey was undertaken to study the CPOs in the patient-accessible environment, as well as in the plumbing system removed from the patient. This comprehensive survey revealed a vast, unappreciated reservoir of CPOs in wastewater, which was in contrast to the low positivity rate in both the patient population and the patient-accessible environment. While there were few patient-environmental isolate associations, there were plasmid backbones common to both populations. These results are relevant to all hospitals for which CPO colonization may not yet be defined through extensive surveillance. Carbapenemase-producing organisms (CPOs) are a global concern because of the morbidity and mortality associated with these resistant Gram-negative bacteria. Horizontal plasmid transfer spreads the resistance mechanism to new bacteria, and understanding the plasmid ecology of the hospital environment can assist in the design of control strategies to prevent nosocomial infections. A 5-year genomic and epidemiological survey was undertaken to study the CPOs in the patient-accessible environment, as well as in the plumbing system removed from the patient. This comprehensive survey revealed a vast, unappreciated reservoir of CPOs in wastewater, which was in contrast to the low positivity rate in both the patient population and the patient-accessible environment. While there were few patient-environmental isolate associations, there were plasmid backbones common to both populations. These results are relevant to all hospitals for which CPO colonization may not yet be defined through extensive surveillance.

Our case highlights the need to monitor for visual symptoms in patients with Zika virus and to refer symptomatic patients urgently for ophthalmic assessment. Visual symptoms and ocular findings might be the only manifestation of Zika virus infection in some patients. The right diagnosis of posterior uveitis is important because lesions involving the macula threaten vision, and long-term follow-up of patients with Zika virus-associated posterior uveitis is essential to monitor the sequelae of inflammatory chorioretinal lesions.

Brucellosis is the most common bacterial zoonosis, and causes a considerable burden of disease in endemic countries. Cardiovascular involvement is the main cause of mortality due to infection with Brucella spp, and most commonly manifests as endocarditis, peripheral and cerebrovascular aneurysms, or arterial and venous thromboses. We report a case of brucellosis presenting as bacteraemia and aortic endarteritis 18 years after the last known exposure to risk factors for brucella infection. The patient was treated with doxycycline, rifampicin, and gentamicin, and underwent surgical repair of a penetrating aortic ulcer, with a good clinical recovery. We review the signs and symptoms, diagnostic approach, prognosis, and treatment of brucella arteritis. We draw attention to the absence of consensus about the optimum therapy for vascular brucellosis, and the urgent need for additional studies and renewed scientific interest in this major pathogen.

Carbapenem-resistant Klebsiella pneumoniae strains are formidable hospital pathogens that pose a serious threat to patients around the globe due to a rising incidence in health care facilities, high mortality rates associated with infection, and potential to spread antibiotic resistance to other bacterial species, such as Escherichia coli . Over 6 months in 2011, 17 patients at the National Institutes of Health (NIH) Clinical Center became colonized with a highly virulent, transmissible carbapenem-resistant strain of K. pneumoniae . Our real-time genomic sequencing tracked patient-to-patient routes of transmission and informed epidemiologists’ actions to monitor and control this outbreak. Two of these patients remained colonized with carbapenemase-producing organisms for at least 2 to 4 years, providing the opportunity to undertake a focused genomic study of long-term colonization with antibiotic-resistant bacteria. Whole-genome sequencing studies shed light on the underlying complex microbial colonization, including mixed or evolving bacterial populations and gain or loss of plasmids. Isolates from NIH patient 15 showed complex plasmid rearrangements, leaving the chromosome and the bla KPC -carrying plasmid intact but rearranging the two other plasmids of this outbreak strain. NIH patient 16 has shown continuous colonization with bla KPC -positive organisms across multiple time points spanning 2011 to 2015. Genomic studies defined a complex pattern of succession and plasmid transmission across two different K. pneumoniae sequence types and an E. coli isolate. These findings demonstrate the utility of genomic methods for understanding strain succession, genome plasticity, and long-term carriage of antibiotic-resistant organisms. IMPORTANCE In 2011, the NIH Clinical Center had a nosocomial outbreak involving 19 patients who became colonized or infected with bla KPC -positive Klebsiella pneumoniae . Patients who have intestinal colonization with bla KPC -positive K. pneumoniae are at risk for developing infections that are difficult or nearly impossible to treat with existing antibiotic options. Two of those patients remained colonized with bla KPC -positive Klebsiella pneumoniae for over a year, leading to the initiation of a detailed genomic analysis exploring mixed colonization, plasmid recombination, and plasmid diversification. Whole-genome sequence analysis identified a variety of changes, both subtle and large, in the bla KPC -positive organisms. Long-term colonization of patients with bla KPC -positive Klebsiella pneumoniae creates new opportunities for horizontal gene transfer of plasmids encoding antibiotic resistance genes and poses complications for the delivery of health care. In 2011, the NIH Clinical Center had a nosocomial outbreak involving 19 patients who became colonized or infected with bla KPC -positive Klebsiella pneumoniae . Patients who have intestinal colonization with bla KPC -positive K. pneumoniae are at risk for developing infections that are difficult or nearly impossible to treat with existing antibiotic options. Two of those patients remained colonized with bla KPC -positive Klebsiella pneumoniae for over a year, leading to the initiation of a detailed genomic analysis exploring mixed colonization, plasmid recombination, and plasmid diversification. Whole-genome sequence analysis identified a variety of changes, both subtle and large, in the bla KPC -positive organisms. Long-term colonization of patients with bla KPC -positive Klebsiella pneumoniae creates new opportunities for horizontal gene transfer of plasmids encoding antibiotic resistance genes and poses complications for the delivery of health care.

Clostridioides difficile infection (CDI) threatens vulnerable populations in health care. Two-step testing improves specificity, avoiding over-treatment. This study analyzed inpatient records to estimate diagnostic outcomes and identify characteristics associated with treatment after discordant testing. Among discordant patients, those aged 65+ years were significantly more likely to be prescribed antibiotics (67% vs 39%).

Abstract Background Resistance to all first-line antibiotics necessitates the use of less effective or more toxic \"reserve\" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic. Methods The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories. Results Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0. Conclusion Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance. Resistance to all first-line agents or difficult-to-treat resistance (DTR) was observed in 1% of gram-negative bacteremias. DTR was identified at half the hospitals; nearly 80% of patients with DTR received \"reserve\" agents. Mortality risk increased with decreasing active first-line categories.

In the National Institutes of Health (NIH) Clinical Center, patients colonized or infected with vancomycin-resistant Enterococcus (VRE) are placed in contact isolation until they are deemed \"decolonized,\" defined as having 3 consecutive perirectal swabs negative for VRE. Some decolonized patients later develop recurrent growth of VRE from surveillance or clinical cultures (ie, \"recolonized\"), although that finding may represent recrudescence or new acquisition of VRE. We describe the dynamics of VRE colonization and infection and their relationship to receipt of antibiotics. In this retrospective cohort study of patients at the National Institutes of Health Clinical Center, baseline characteristics were collected via chart review. Antibiotic exposure and hospital days were calculated as proportions of VRE decolonized days. Using survival analysis, we assessed the relationship between antibiotic exposure and time to VRE recolonization in a subcohort analysis of 72 decolonized patients. In total, 350 patients were either colonized or infected with VRE. Among polymerase chain reaction (PCR)-positive, culture (Cx)-negative (PCR+/Cx-) patients, PCR had a 39% positive predictive value for colonization. Colonization with VRE was significantly associated with VRE infection. Among 72 patients who met decolonization criteria, 21 (29%) subsequently became recolonized. VRE recolonization was 4.3 (P = .001) and 2.0 (P = .22) times higher in patients with proportions of antibiotic days and antianaerobic antibiotic days above the median, respectively. Colonization is associated with clinical VRE infection and increased mortality. Despite negative perirectal cultures, re-exposure to antibiotics increases the risk of VRE recolonization.

Antibiotic-resistant bacteria are a serious threat to medically fragile patient populations. The spread of antibiotic resistance through plasmid-mediated mechanisms is of grave concern as it can lead to the conversion of endogenous patient-associated strains to difficult-to-treat pathogens. Antibiotics, which are used both to prevent and to treat infections, are a mainstay therapy for lifesaving procedures such as transplantation. For this reason, and many others, increased antibiotic resistance among human-associated pathogens, such as the carbapenem-resistant Enterobacteriaceae species, is of grave concern. In this study, we report on a hematopoietic stem cell transplant recipient in whom cultures detected the emergence of carbapenem resistance and spread across five strains of bacteria that persisted for over a year. Carbapenem resistance in Citrobacter freundii , Enterobacter cloacae , Klebsiella aerogenes , and Klebsiella pneumoniae was linked to a pair of plasmids, each carrying the Klebsiella pneumoniae carbapenemase gene ( bla KPC ). Surveillance cultures identified a carbapenem-susceptible strain of Citrobacter freundii that may have become resistant through horizontal gene transfer of these plasmids. Selection of a multidrug-resistant Klebsiella pneumoniae strain was also detected following combination antibiotic therapy. Here we report a plasmid carrying the bla KPC gene with broad host range that poses the additional threat of spreading to endogenous members of the human gut microbiome. IMPORTANCE Antibiotic-resistant bacteria are a serious threat to medically fragile patient populations. The spread of antibiotic resistance through plasmid-mediated mechanisms is of grave concern as it can lead to the conversion of endogenous patient-associated strains to difficult-to-treat pathogens.