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Data are limited on the attributable outcomes of Clostridium difficile-associated disease (CDAD), particularly in CDAD-endemic settings. We conducted a retrospective cohort study of nonsurgical inpatients admitted for >/=48 hours in 2003 (N = 18,050). The adjusted hazard ratios for readmission (hazard ratio 2.19, 95% confidence interval [CI] 1.87-2.55) and deaths within 180 days (hazard ratio 1.23, 95% CI 1.03-1.46) were significantly different among CDAD case-patients and noncase patients. In a propensity score matched-pairs analysis that used a nested subset of the cohort (N = 706), attributable length of stay attributable to CDAD was 2.8 days, attributable readmission at 180 days was 19.3%, and attributable death at 180 days was 5.7%. CDAD patients were significantly more likely than controls to be discharged to a long-term-care facility or outside hospital. Even in a nonoutbreak setting, CDAD had a statistically significant negative impact on patient illness and death, and the impact of CDAD persisted beyond hospital discharge. [ABSTRACT FROM AUTHOR]

BACKGROUND: Routine culturing of patients in intensive care units (ICUs) for methicillin-resistant Staphylococcus aureus (MRSA) identifies unrecognized carriers and facilitates timely isolation. However, the benefit of surveillance in detecting prevalent and incident carriers likely varies among ICUs. In addition, many assessments underestimate the incidence of acquisition by including prevalent carriers in the at-risk population. METHODS: We performed a retrospective cohort study using accurate at-risk populations to evaluate the range of benefit of admission and weekly surveillance cultures in detecting otherwise unrecognized MRSA in 12 ICUs in 5 states. RESULTS: We assessed 142 ICU-months. Among the 12 ICUs, the admission prevalence of imported MRSA was 5%-21%, with admission surveillance providing 30%-135% increases in rates of detection. The monthly hospital-associated incidence was 2%-6%, with weekly surveillance providing 7%-157% increases in detection. The common practice of reporting incidence using the total number of patients or total patient-days underestimated incidence by one-third. Surgical ICUs had lower MRSA importation but higher MRSA incidence. Overall, routine surveillance prevented the misclassification of 17% (unit range, 11%-29%) of 'incident' carriers, compared with clinical cultures, and increased precaution days by 18% (unit range, 11%-91%). CONCLUSIONS: Routine surveillance significantly increases the detection of MRSA, but this benefit is not uniform across ICUs, even with high compliance and the use of correct denominators. Copyright © 2007 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

BACKGROUND: Antimicrobial-resistant organisms are an emerging problem in the ICU. Therapy cycling empiric antibiotics between various classes may influence bacterial resistance patterns. Understanding the impact of cycling on the appropriate treatment of suspected Gram-negative infections is important. METHODS: Data were prospectively collected on patients who were admitted to a 19-bed medical ICU (MICU). A total of 1,172 patients were admitted to the MICU for > 48 h and were evaluated during a 28.5-month period. After 4.5 months of baseline data collection, an antibiotic-cycling protocol was implemented, using four different antibiotic classes with Gram-negative activity that were cycled every 3 to 4 months. Therapy was considered to be inappropriate if the subsequent bacterial isolate was resistant to the empiric drug used. RESULTS: There were 59 bloodstream infections (BSIs), 17 ventilator-associated pneumonias (VAPs), and 101 urinary tract infections (UTIs) involving Gram-negative bacteria among 139 patients. Fifty-five infections (31%) were due to Gram-negative bacteria resistant to one or more antibiotic agents (BSIs, 18 [30%]; VAPs, 4 [23%]; and UTIs, 33 [33%]). Fifteen patients received inappropriate empiral therapy for 18 resistant Gram-negative infections (BSIs, 7 [39%]; VAPs, 3 [75%]; UTIs, 8 [24%]). Patients receiving inappropriate therapy were more likely to die (10 patients [67%] vs 40 patients [32%], respectively; p < 0.01). There was no difference in the receipt of appropriate empirical antibiotic therapy during the baseline compared to cycling (infectious episodes, 15% vs 10%, respectively; p = 0.4). CONCLUSIONS: Antimicrobial resistance occurred in almost 30% of ICU infections involving Gram-negative bacteria. Antibiotic cycling was not associated with significant changes in the receipt of appropriate empirical antimicrobial therapy for the treatment of ICU infections. [ABSTRACT FROM AUTHOR]

A commercial rule base (Cerner Multum) was used to identify medication orders exceeding recommended dosage limits at five hospitals within BJC HealthCare, an integrated health care system. During initial testing, clinical pharmacists determined that there was an excessive number of nuisance and clinically insignificant alerts, with an overall alert rate of 9.2%. A method for customizing the commercial rule base was implemented to increase rule specificity for problematic rules. The system was subsequently deployed at two facilities and achieved alert rates of less than 1%. Pharmacists screened these alerts and contacted ordering physicians in 21% of cases. Physicians made therapeutic changes in response to 38% of alerts presented to them. By applying simple techniques to customize rules, commercial rule bases can be used to rapidly deploy a safety net to screen drug orders for excessive dosages, while preserving the rule architecture for later implementations of more finely tuned clinical decision support. [ABSTRACT FROM AUTHOR]

Study Objectives: To determine whether an educational initiative could decrease rates of ventilator-associated pneumonia in a regional health-care system.Setting: Two teaching hospitals (one adult, one pediatric) and two community hospitals in an integrated health system.Design: Preintervention and postintervention observational study.Patients: Patients admitted to the four participating hospitals between January 1, 1999, and June 30, 2002, who acquired ventilator-associated pneumonia.Intervention: An educational program for respiratory care practitioners and ICU nurses emphasizing correct practices for the prevention of ventilator-associated pneumonia. The program included a self-study module on risk factors for, and strategies to prevent, ventilator-associated pneumonia and education-based in-services. Fact sheets and posters reinforcing the information were posted throughout the ICU and respiratory care departments.Measurements and Results: Completion rates for the module were calculated by job title at each hospital. Rates of ventilator-associated pneumonia per 1,000 ventilator days were calculated for all hospitals combined and for each hospital separately. Overall 635 of 792 ICU nurses (80.1%) and 215 of 239 respiratory therapists (89.9%) completed the study module. There were 874 episodes of ventilator-associated pneumonia at the four hospitals during the 3.5-year study period out of 129,527 ventilator days. Ventilator-associated pneumonia rates for all four hospitals combined dropped by 46%, from 8.75/1,000 ventilator days in the year prior to the intervention to 4.74/1,000 ventilator days in the 18 months following the intervention (p < 0.001). Statistically significant decreased rates were observed at the pediatric hospital and at two of the three adult hospitals. No change in rates was seen at the community hospital with the lowest rate of study module completion among respiratory therapists (56%).Conclusions: Educational interventions can be associated with decreased rates of ventilator-associated pneumonia in the ICU setting. The involvement of respiratory therapy staff in addition to ICU nurses is important for the success of educational programs aimed at the prevention of ventilator-associated pneumonia. [ABSTRACT FROM AUTHOR]

Study Objective: To determine the sensitivity, specificity, and positive and negative predictive values of blood cultures obtained through a central vein catheter compared with peripheral venipuncture.Design: Prospective cohort study.Setting: A medical ICU (19 beds) from a university-affiliated urban teaching hospital.Patients: Between February 2001 and October 2001, 300 paired blood culture specimens were obtained from 119 patients (2.52 paired cultures per patient).Intervention: Prospective patient surveillance and data collection.Measurements and Main Results: Thirty-four paired culture results (11.3%; 95% confidence interval, 7.8 to 14.8%) were accepted as true-positives representing a true bacteremia. The sensitivity of catheter-drawn and peripheral venipuncture samples was 82.4% and 64.7%, respectively, and specificity was 92.5% and 95.9%. The positive predictive value was 58.3% for catheter-drawn samples and 66.7% for peripheral venipuncture samples, and the respective negative predictive values were 97.6% and 95.5%.Conclusions: In critically ill medical patients, the negative predictive value of blood samples obtained by catheter draw or peripheral venipuncture for suspected bloodstream infection is good. However, the sensitivity of blood samples obtained by either catheter draw or peripheral venipuncture alone is not adequate to recommend the elimination of blood samples obtained from the other site. Clinicians should also be aware that additional blood samples may be necessary when interpreting positive blood culture results for common skin or central vein catheter contaminants. [ABSTRACT FROM AUTHOR]

Study Objective: To assess factors associated with initiating therapy and compliance with treatment for latent tuberculosis infection among health-care workers with positive tuberculin skin test results.Design: Prospective cohort study.Setting: An urban midwestern teaching hospital in St. Louis, MO.Study Population: Health-care workers with positive tuberculin skin test results.Measurements: (1) Rates of initiating therapy for latent tuberculosis infection among all health-care workers with positive tuberculin skin test results, and (2) compliance rates with therapy for latent tuberculosis infection among health-care workers with recent tuberculin skin test conversion.Results: A total of 440 tuberculin skin test-positive health-care workers were evaluated from January 1, 1994, to May 1, 2000. Of those evaluated, 1 health-care worker had presumed active tuberculosis, 1 had no record of being evaluated, 1 had missing records, and 33 were not recommended isoniazid therapy, leaving 404 workers for analysis. Overall, 396 of 404 health-care workers (98%) with positive tuberculin skin test results initiated isoniazid therapy. In univariate analysis, bacille Calmette-Guérin (BCG) vaccination (p = 0.02) and foreign birth (p = 0.03) were significantly associated with not initiating isoniazid therapy. Compliance data were available for 388 of 404 health-care workers (96%). Of these, 318 of 388 health-care workers (82%) were compliant with 6 months of therapy. BCG vaccination (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8 to 7.1) and symptoms while receiving therapy (OR, 4.5; 95% CI, 2.0 to 10.1) were significantly associated with noncompliance in multivariate analysis. Among new converters, Asian race (p = 0.006), foreign birth (p = 0.01), BCG vaccination (p = 0.006), and symptoms while receiving therapy (p < 0.001) were significantly associated with noncompliance in univariate analysis.Conclusion: This hospital had a high rate of initiating isoniazid therapy for tuberculosis infection among their health-care workers, and a high rate of compliance with therapy. These rates of initiation and completion of isoniazid therapy were much higher than those previously reported in the literature. This may be largely due to a focused program, which includes active follow-up of health-care workers with positive tuberculin skin test results, consisting of physician counseling and monthly phone consultations by nurses, along with free services and medications provided on-site. [ABSTRACT FROM AUTHOR]

Study Objectives: To prospectively identify the occurrence of ventilator-associated pneumonia (VAP) in a community hospital, and to determine the risk factors for VAP and the influence of VAP on patient outcomes in a nonteaching institution.Design: Prospective cohort study.Setting: A medical ICU and a surgical ICU in a 500-bed private community nonteaching hospital: Missouri Baptist Hospital.Patients: Between March 1998 and December 1999, all patients receiving mechanical ventilation who were admitted to the ICU setting were prospectively evaluated.Intervention: Prospective patient surveillance and data collection.Results: During a 22-month period, 3,171 patients were admitted to the medical and surgical ICUs. Eight hundred eighty patients (27.8%) received mechanical ventilation. VAP developed in 132 patients (15.0%) receiving mechanical ventilation. Three hundred one patients (34.2%) who received mechanical ventilation died during hospitalization. Logistic regression analysis demonstrated that tracheostomy (adjusted odds ratio [AOR], 6.71; 95% confidence interval [CI], 3.91 to 11.50; p < 0.001), multiple central venous line insertions (AOR, 4.20; 95% CI, 2.72 to 6.48; p < 0.001), reintubation (AOR, 2.88; 95% CI, 1.78 to 4.66; p < 0.001), and the use of antacids (AOR, 2.81; 95% CI, 1.19 to 6.64; p = 0.019) were independently associated with the development of VAP. The hospital mortality of patients with VAP was significantly greater than the mortality of patients without VAP (45.5% vs 32.2%, respectively; p = 0.004). The occurrence of bacteremia, compromised immune system, higher APACHE (acute physiology and chronic health evaluation) II scores, and older age were identified as independent predictors of hospital mortality.Conclusions: These data suggest that VAP is a common nosocomial infection in the community hospital setting. The risk factors for the development of VAP and risk factors for hospital mortality in a community hospital are similar to those identified from university-affiliated hospitals. These risk factors can potentially be employed to develop local strategies for the prevention of VAP.Clinical Implications: ICU clinicians should be aware of the risk factors associated with the development of VAP and the impact of VAP on clinical outcomes. More importantly, they should cooperate in the development of local multidisciplinary strategies aimed at the prevention of VAP and other nosocomial infections. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence and incidence of and the relative risks for positive tuberculin skin tests among employees of a large, urban teaching hospital.Design: Retrospective cohort study.Setting: Barnes Hospital, St. Louis, Missouri.Participants: Hospital personnel employed at any time between January 1989 and July 1991.Results: 684 of 6070 employees screened (11.3% [95% CI, 10.4% to 12.1%]) had positive tuberculin skin tests. Factors associated with a positive result were age (odds ratio, 2.02 per decade [CI, 1.87 to 2.18]; P < 0.0001); black race (odds ratio, 1.58 [Cl, 1.26 to 2.00]; P < 0.0001); Asian race (odds ratio, 16.7 [CI, 9.33 to 29.9]; P < 0.0001); Hispanic ethnicity (odds ratio, 9.45 [CI, 3.58 to 25.0]; P < 0.0001); and percentage of low-income persons within the employee's residential postal zone (odds ratio, 1.14 per 10% [CI, 1.05 to 1.23]; P = 0.001). Twenty-nine of 3106 employees who had at least two tests had skin-test conversions (0.93% [CI, 0.60% to 1.3%]); 15 of these conversions (52%) occurred among employees who had no direct contact with patients. Only the percentage of low-income persons within the employee's residential postal zone (odds ratio 1.39 [CI, 1.09 to 1.78]; P = 0.0075) was independently associated with conversion.Conclusions: The most important associations with a positive tuberculin skin test were older age, minority group status, and the proportion of low-income persons within the employee's residential postal zone. Skin-test conversion was independently associated only with the percentage of low-income persons in the employee's postal zone. Stratifying employees according to degree of contact with patients or according to departmental group was not useful in determining risk for a positive tuberculin skin test or for skin-test conversion. For certain groups of employees, an exposure to tuberculosis in the community probably poses a greater risk than exposure in the hospital setting. [ABSTRACT FROM AUTHOR]

Chronic fatigue syndrome is a poorly understood disease characterized by debilitating fatigue and neuromuscular and neuropsychological symptoms. Despite numerous studies on the subject, the epidemiology of the syndrome in the community remains largely unexplored. An estimate of the prevalence in the population is presented, approximating the Centers for Disease Control criteria as well as the prevalence estimates of the fatigue symptom complex that include fatigue, disability, and neuromuscular and neuropsychological symptoms. The study population consisted of a very large, multicenter, stratified, and random sample of a general population health survey known as the Epidemiologic Catchment Area Program. Data used for this study were gathered between 1981 and 1984. The Diagnostic Interview Schedule, a highly structured mental health interview, was used to assess the lifetime prevalence of medical and psychological symptoms. Chronic fatigue was common. A total of 23 percent of the subjects reported having experienced the symptom of persistent fatigue sometime during their lives. Chronic fatigue syndrome, however, as defined by the Centers for Disease Control, appeared to be quite rare in the general population. Only 1 of 13,538 people examined was found to meet a diagnosis of the syndrome with an approximation of the CDC criteria. Fatigue symptom complex was frequently related to medical or psychiatric illness or substance abuse; thus, persons meeting partial criteria of chronic fatigue syndrome were also found to be rare when psychiatric or medical exclusions were applied. [ABSTRACT FROM AUTHOR]

The growth of human immunodeficiency virus type-1 (HIV) infection among women in the USA has been coincident with an international momentum to better address the specific health care needs of women. This paper provides an overview of a demonstration model for comprehensive HIV care of adolescent and adult women in an academic setting. The paper contains a descriptive summary of a university-based demonstration model of comprehensive care for women with HIV infection. During 1997-1998, there were 279 urban and rural Midwest adolescent and adult women with HIV infection in care at this model programme. Medical care encompassed subspecialty HIV care, obstetrical and gynaecological care, primary care of non-HIV comorbidities, mental health assessments and family planning in a safe, university-based environment. For 279 women during the two-year period, health services included the detection and treatment of sexually transmitted diseases (56%) and cervical dysplasia (35%), perinatal care (12%) and screening and referral for substance abuse treatment (30%). There was no mother-to-child HIV transmission among 33 pregnant women enrolled in the Center prior to delivery, and transmission by three of nine women enrolled after delivery. Only 167 (60%) women were compliant with biannual medical visits during 1997-1998. Integral to the health services delivery was the provision of ancillary support services intended to enhance optimal medical care for this cohort of women. This university-based model of care also incorporated HIV provider training and formative HIV research. Structured medical and public health experiential learning opportunities occurred for medical and social work students, medicine residents, infectious diseases fellows, nurses and other professional health care workers. Clinical investigations of adolescent and adult women have complemented care and training, with funded research in HIV medication adherence and health services research. In follow-up, 71% of these women remained active in care in 1999. Retention of vulnerable populations in care may be a big challenge over the next decade, despite the availability of potent antiretroviral therapies. [ABSTRACT FROM AUTHOR]

Background: Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults., Methods: We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18-64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2-90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes., Results: Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% β-lactam, 3% β-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., β-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10-0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25-0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09-0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding., Conclusions: Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To measure SARS-CoV-2 anti-nucleocapsid (anti-N) antibody seropositivity among healthcare personnel (HCP) without a history of COVID-19 and to identify HCP characteristics associated with seropositivity., Design: Prospective cohort study from September 22, 2020, to March 3, 2022., Setting: A tertiary care academic medical center., Participants: 727 HCP without prior positive SARS-CoV-2 PCR testing were enrolled; 559 HCP successfully completed follow-up., Methods: At enrollment and follow-up 1-6 months later, HCP underwent SARS-CoV-2 anti-N testing and were surveyed on demographics, employment information, vaccination status, and COVID-19 symptoms and exposures., Results: Of 727 HCP enrolled, 27 (3.7%) had a positive SARS-CoV-2 anti-N test at enrollment. Seropositive HCPs were more likely to have a household exposure to COVID-19 in the past 30 days (OR 7.92, 95% CI 2.44-25.73), to have had an illness thought to be COVID-19 (4.31, 1.94-9.57), or to work with COVID-19 patients more than half the time (2.09, 0.94-4.77). Among 559 HCP who followed-up, 52 (9.3%) had a positive SARS-CoV-2 anti-N antibody test result. Seropositivity at follow-up was associated with community/household exposures to COVID-19 within the past 30 days (9.50, 5.02-17.96; 2.90, 1.31-6.44), having an illness thought to be COVID-19 (8.24, 4.44-15.29), and working with COVID-19 patients more than half the time (1.50, 0.80-2.78)., Conclusions: Among HCP without prior positive SARS-CoV-2 testing, SARS-CoV-2 anti-N seropositivity was comparable to that of the general population and was associated with COVID-19 symptomatology and both occupational and non-occupational exposures to COVID-19., Competing Interests: C.W.F. has received grants or contracts from Abbott Laboratories, Roche Diagnostics, Beckman Coulter, Qiagen, Cepheid, Sebia, The Binding Site, and Siemens; consulting fees from Roche, Abbott Laboratories, Biorad, Cytovale, and Siemens; honoraria and meeting support from AACC; and has a leadership role on the Clinical Chemistry Editorial Board. V.J.F. has received grants or contracts from the Foundation for Barnes-Jewish Hospital, the Doris Duke Charitable Foundation, and the National Center for Advancing Translational Science (NIH); royalties or licenses from Elsevier; has had a leadership role in the Infectious Diseases Society of America; and reports other financial or non-financial interests in Cigna/Express-Scripts. C.D.B. has received grants or contracts from Cepheid, bioMerieux, and Biofire; consulting fees from Pattern Bioscience, Roche, Cepheid, and Beckman Coulter; honoraria from Roche and bioMerieux; meeting support from the American Society for Microbiology and AACC; and has stock or stock options in Pattern Bioscience. J.H.K. has received additional support for this work from the National Institute of Allergy and Infectious Diseases (NIH). All other authors report no potential conflict of interests., (© The Author(s) 2024.)

Between May and June 2021, healthcare personnel at two long-term care facilities underwent SARS-CoV-2 anti-nucleocapsid immunoglobulin G testing and completed a survey on COVID-19 exposures and symptoms. Antibody positivity rate was 8.9%. Similar rates of COVID-19 exposure occurred in non-occupational and occupational settings, with high self-reported adherence to workplace infection prevention practices., Competing Interests: All authors report no conflicts of interest relevant to this manuscript., (© The Author(s) 2024.)

Background: Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI (rUTI) that is thought to be facilitated by a gut reservoir of uropathogenic Escherichia coli (UPEC)., Methods: 125 patients with UTI caused by an antibiotic-resistant organism (ARO) were enrolled from July 2016 to May 2019 in a longitudinal, multi-center cohort study. Multivariate statistical models were used to assess the relationship between uropathogen colonization and recurrent UTI (rUTI), controlling for clinical characteristics. 644 stool samples and 895 UPEC isolates were interrogated for taxonomic composition, antimicrobial resistance genes, and phenotypic resistance. Cohort UTI gut microbiome profiles were compared against published healthy and UTI reference microbiomes, as well as assessed within-cohort for timepoint- and recurrence-specific differences., Findings: Risk of rUTI was not independently associated with clinical characteristics. The UTI gut microbiome was distinct from healthy reference microbiomes in both taxonomic composition and antimicrobial resistance gene (ARG) burden, with 11 differentially abundant taxa at the genus level. rUTI and non-rUTI gut microbiomes in the cohort did not generally differ, but gut microbiomes from urinary tract colonized patients were elevated in E. coli abundance 7-14 days post-antimicrobial treatment. Corresponding UPEC gut isolates from urinary tract colonizing lineages showed elevated phenotypic resistance against 11 of 23 tested drugs compared to non-colonizing lineages., Interpretation: The gut microbiome is implicated in UPEC urinary tract colonization during rUTI, serving as an ARG-enriched reservoir for UPEC. UPEC can asymptomatically colonize the gut and urinary tract, and post-antimicrobial blooms of gut E. coli among urinary tract colonized patients suggest that cross-habitat migration of UPEC is an important mechanism of rUTI. Thus, treatment duration and UPEC populations in both the urinary and gastrointestinal tract should be considered in treating rUTI and developing novel therapeutics., Funding: This work was supported in part by awards from the U.S. Centers for Disease Control and Prevention Epicenter Prevention Program (grant U54CK000482; principal investigator, V.J.F.); to J.H.K. from the Longer Life Foundation (an RGA/Washington University partnership), the National Center for Advancing Translational Sciences (grants KL2TR002346 and UL1TR002345), and the National Institute of Allergy and Infectious Diseases (NIAID) (grant K23A1137321) of the National Institutes of Health (NIH); and to G.D. from NIAID (grant R01AI123394) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD092414) of NIH. R.T.'s research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; grant 402733540). REDCap is Supported by Clinical and Translational Science Award (CTSA) Grant UL1 TR002345 and Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant P30 CA091842. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies., Competing Interests: E.R.D. reports grants from Theriva Biologics, trial enrollment support and consulting fees from Ferring, and consulting fees from Seres. V.F. reports grants from The Foundation for Barnes-Jewish Hospital, grants from Doris Duke Charitable Foundation, grants from NIH/NCATS (project numbers KL2TR002346, UL1TR002345), and royalties/licenses from Elsevier (Goldman-Cecil Medicine, 2-Volume Set, 27e). She has served various roles at the Infectious Diseases Society of America (Board of Directors 2017–2020, IDSA Leadership Institute 2018–2022, Editor-in-Chief Search Committee Chair of the Open Forum Infectious Disease Journal 2022). Her spouse is a consultant and former Senior Vice President/Chief Medical Officer at Cigna/Express-Scripts. M.A.O. reports consulting fees from Pfizer. C.A.B. reports paid roles as editor at the Journal of Clinical Microbiology, and unpaid roles with the Clinical and Laboratory Standards Institute. She has served as Chief Clinical Officer at Pattern Bioscience since 2022 and holds shares. All other authors declare no conflict of interests., (© 2024 The Authors.)

Background: Sepsis is a major cause of morbidity and mortality worldwide. When selecting empiric antibiotics for sepsis, clinicians are encouraged to use local resistance rates, but their impact on individual outcomes is unknown. Improved methods to predict outcomes are needed to optimize treatment selection and improve antibiotic stewardship., Methods: We expanded on a previously developed theoretical model to estimate the excess risk of death in gram-negative bacilli (GNB) sepsis due to discordant antibiotics using 3 factors: the prevalence of GNB in sepsis, the rate of antibiotic resistance in GNB, and the mortality difference between discordant and concordant antibiotic treatments. We focused on ceftriaxone, cefepime, and meropenem as the anti-GNB treatment backbone in sepsis, pneumonia, and urinary tract infections. We analyzed both publicly available data and data from a large urban hospital., Results: Publicly available data were weighted toward culture-positive cases. Excess risk of death with discordant antibiotics was highest in septic shock and pneumonia. In septic shock, excess risk of death was 4.53% (95% confidence interval [CI], 4.04%-5.01%), 0.6% (95% CI, .55%-.66%), and 0.19% (95% CI, .16%-.21%) when considering resistance to ceftriaxone, cefepime, and meropenem, respectively. Results were similar in pneumonia. Local data, which included culture-negative cases, showed an excess risk of death in septic shock of 0.75% (95% CI, .57%-.93%) for treatment with discordant antibiotics in ceftriaxone-resistant infections and 0.18% (95% CI, .16%-.21%) for cefepime-resistant infections., Conclusions: Estimating the excess risk of death for specific sepsis phenotypes in the context of local resistance rates, rather than relying on population resistance data, may be more informative in deciding empiric antibiotics in GNB infections., Competing Interests: Potential conflicts of interest. All authors report no potential conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: Aminoglycosides and β-lactams have been recommended for treatment of sepsis/septic shock despite a lack of mortality benefit. Previous studies have examined resistance emergence for the same bacterial isolate using old dosing regimens and during a narrow follow-up window. We hypothesised that combination regimens employing aminoglycosides will decrease the cumulative incidence of infections due to multidrug-resistant (MDR) Gram-negative bacilli (GNB) compared with β-lactams alone., Methods: All adult patients admitted to Barnes Jewish Hospital between 2010 and 2017 with a diagnosis of sepsis/septic shock were included in this retrospective cohort study. Patients were divided into two treatment groups, with and without aminoglycosides. Patient demographics, severity of presentation, administered antibiotics, follow-up cultures with susceptibility results for a period of 4-60 days, and mortality were extracted. After propensity score matching, a Fine-Gray subdistribution proportional hazards model summarised the estimated incidence of subsequent infections with MDR-GNB in the presence of all-cause death as a competing risk., Results: A total of 10 212 septic patients were included, with 1996 (19.5%) treated with at least two antimicrobials including one aminoglycoside. After propensity score matching, the cumulative incidence of MDR-GNB infections between 4-60 days was lower in the combination group (incidence at 60 days 0.073, 95% CI 0.062-0.085) versus patients not receiving aminoglycosides (0.116, 95% CI 0.102-0.130). Patients aged ≤65 years and with haematological malignancies had a larger treatment effect in subgroup analyses., Conclusion: Addition of aminoglycosides to β-lactams may protect against subsequent infections due to MDR-GNB in patients with sepsis/septic shock., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To characterize experiences, beliefs, and perceptions of risk related to coronavirus disease 2019 (COVID-19), infection prevention practices, and COVID-19 vaccination among healthcare personnel (HCP) at nonacute care facilities., Design: Anonymous survey., Setting: Three non-acute-care facilities in St. Louis, Missouri., Participants: In total, 156 HCP responded to the survey, for a 25.6% participation rate). Among them, 32% had direct patient-care roles., Methods: Anonymous surveys were distributed between April-May 2021. Data were collected on demographics, work experience, COVID-19 exposure, knowledge, and beliefs about infection prevention, personal protective equipment (PPE) use, COVID-19 vaccination, and the impact of COVID-19., Results: Nearly all respondents reported adequate knowledge of how to protect oneself from COVID-19 at work (97%) and had access to adequate PPE supplies (95%). Many HCP reported that wearing a mask or face shield made communication difficult (59%), that they had taken on additional responsibilities due to staff shortages (56%), and that their job became more stressful because of COVID-19 (53%). Moreover, 28% had considered quitting their job. Most respondents (78%) had received at least 1 dose of COVID-19 vaccine. Common reasons for vaccination were a desire to protect family and friends (84%) and a desire to stop the spread of COVID-19 (82%). Potential side effects and/or inadequate vaccine testing were cited as the most common concerns by unvaccinated HCP., Conclusions: A significant proportion of HCP reported increased stress and responsibilities at work due to COVID-19. The majority were vaccinated. Improving workplace policies related to mental health resources and sick leave, maintaining access to PPE, and ensuring clear communication of PPE requirements may improve workplace stress and burnout.

Background: SARS-CoV-2 vaccines are effective at reducing symptomatic and asymptomatic COVID-19. Limited studies have compared symptoms, threshold cycle (Ct) values from reverse transcription (RT)-PCR testing, and serological testing results between previously vaccinated vs unvaccinated populations with SARS-CoV-2 infection., Methods: Healthcare personnel (HCP) with a positive SARS-CoV-2 RT-PCR test within the previous 14 to 28 days completed surveys including questions about demographics, medical conditions, social factors, and symptoms of COVID-19. Ct values were observed, and serological testing was performed for anti-nucleocapsid (anti-N) and anti-Spike (anti-S) antibodies at enrollment and 40 to 90 days later. Serological results were compared to HCP with no known SARS-CoV-2 infection and negative anti-N testing., Results: There were 104 unvaccinated/not fully vaccinated and 77 vaccinated HCP with 2 doses of an mRNA vaccine at time of infection. No differences in type or duration of symptoms were reported (P = 0.45). The median (interquartile range [IQR]) Ct was 21.4 (17.6-24.6) and 21.5 (18.1-24.6) for the unvaccinated and vaccinated HCP, respectively. Higher anti-N IgG was observed in unvaccinated HCP (5.08 S/CO, 3.08-6.92) than vaccinated (3.61 signal to cutoff ratio [S/CO], 2.16-5.05). Anti-S IgG was highest among vaccinated HCP with infection (34 285 aribitrary units [AU]/mL, 17 672-61 775), followed by vaccinated HCP with no prior infection (1452 AU/mL, 791-2943), then unvaccinated HCP with infection (829 AU/mL, 290-1555). Anti-S IgG decreased 1.56% (0.9%-1.79%) per day in unvaccinated and 0.38% (0.03%-0.94%) in vaccinated HCP., Conclusions: Vaccinated HCP infected with SARS-CoV-2 reported comparable symptoms and had similar Ct values relative to unvaccinated. However, vaccinated HCP had increased and prolonged anti-S and decreased anti-N response relative to unvaccinated., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To determine the prevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) IgG nucleocapsid (N) antibodies among healthcare personnel (HCP) with no prior history of COVID-19 and to identify factors associated with seropositivity., Design: Prospective cohort study., Setting: An academic, tertiary-care hospital in St. Louis, Missouri., Participants: The study included 400 HCP aged ≥18 years who potentially worked with coronavirus disease 2019 (COVID-19) patients and had no known history of COVID-19; 309 of these HCP also completed a follow-up visit 70-160 days after enrollment. Enrollment visits took place between September and December 2020. Follow-up visits took place between December 2020 and April 2021., Methods: At each study visit, participants underwent SARS-CoV-2 IgG N-antibody testing using the Abbott SARS-CoV-2 IgG assay and completed a survey providing information about demographics, job characteristics, comorbidities, symptoms, and potential SARS-CoV-2 exposures., Results: Participants were predominately women (64%) and white (79%), with median age of 34.5 years (interquartile range [IQR], 30-45). Among the 400 HCP, 18 (4.5%) were seropositive for IgG N-antibodies at enrollment. Also, 34 (11.0%) of 309 were seropositive at follow-up. HCP who reported having a household contact with COVID-19 had greater likelihood of seropositivity at both enrollment and at follow-up., Conclusions: In this cohort of HCP during the first wave of the COVID-19 pandemic, ∼1 in 20 had serological evidence of prior, undocumented SARS-CoV-2 infection at enrollment. Having a household contact with COVID-19 was associated with seropositivity., Competing Interests: C.W.F. reports research support from Abbott Laboratories and consulting fees and honoraria from Roche Diagnostics. M.A.O. reports consulting work and grants for an unrelated project from Pfizer. C.A.B. reports receipt of grants from BioFire, bioMerieux, Luminex, and Cepheid and consulting for Pattern, Cepheid, Roche, Beckman Coulter, Accelerate, Thermo Fisher, and Bio-Rad Laboratories. C.A.B. has leadership roles with the Journal of Clinical Microbiology, ASM Press, Clinical Chemistry, and Clinical Microbiology Newsletter. C.A.B. has received speaker fees from bioMerieux, Roche, and AACC. All other authors report no conflicts of interest related to this study., (© The Author(s) 2023.)

Background: A greater proportion of patients with surgical risk factors are undergoing immediate breast reconstruction after mastectomy, resulting in the need for better risk prediction to inform decisions about the procedure. The objective of this study was to leverage clinical data to restructure a previously developed risk model to predict serious infectious and noninfectious wound complications after mastectomy alone and mastectomy plus immediate reconstruction for use during a surgical consultation., Methods: The study established a cohort of women age 21 years or older treated with mastectomy from 1 July 2010 to 31 December 2015 using electronic health records from two hospitals. Serious infectious and non-infectious wound complications, defined as surgical-site infection, dehiscence, tissue necrosis, fat necrosis requiring hospitalization, or surgical treatment, were identified within 180 days after surgery. Risk factors for serious wound complications were determined using modified Poisson regression, with discrimination and calibration measures. Bootstrap validation was performed to correct for overfitting., Results: Among 2159 mastectomy procedures, 1410 (65.3%) included immediate implant or flap reconstruction. Serious wound complications were identified after 237 (16.8%) mastectomy-plus-reconstruction and 30 (4.0%) mastectomy-only procedures. Independent risk factors for serious wound complications included immediate reconstruction, bilateral mastectomy, higher body mass index, depression, and smoking. The optimism-corrected C statistic of the risk prediction model was 0.735., Conclusions: Immediate reconstruction, bilateral mastectomy, obesity, depression, and smoking were significant risk factors for serious wound complications in this population of women undergoing mastectomy. Our risk prediction model can be used to counsel women before surgery concerning their individual risk of serious wound complications after mastectomy., (© 2022. Society of Surgical Oncology.)

Coronavirus disease 2019 (COVID-19) vaccine effectiveness in the early months of vaccine availability was high among healthcare personnel (HCP) at 88.3% for 2-doses. Among those testing positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2), those with breakthrough infection after vaccination were more likely to have had a non-work-related SARS-CoV-2 exposure compared to unvaccinated HCP., (© The Author(s) 2022.)

Background: Prophylactic antibiotics are commonly prescribed at discharge for mastectomy, despite guidelines recommending against this practice. We investigated factors associated with postdischarge prophylactic antibiotic use after mastectomy with and without immediate reconstruction and the impact on surgical-site infection (SSI)., Study Design: We studied a cohort of women aged 18-64 years undergoing mastectomy between January 1, 2010, and June 30, 2015, using the MarketScan commercial database. Patients with nonsurgical perioperative infections were excluded. Postdischarge oral antibiotics were identified from outpatient drug claims. SSI was defined using International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnosis codes. Generalized linear models were used to determine factors associated with postdischarge prophylactic antibiotic use and SSI., Results: The cohort included 38,793 procedures; 24,818 (64%) with immediate reconstruction. Prophylactic antibiotics were prescribed after discharge after 2,688 mastectomy-only procedures (19.2%) and 17,807 mastectomies with immediate reconstruction (71.8%). The 90-day incidence of SSI was 3.5% after mastectomy only and 8.8% after mastectomy with immediate reconstruction. Antibiotics with anti-methicillin-sensitive Staphylococcus aureus (MSSA) activity were associated with decreased SSI risk after mastectomy only (adjusted relative risk [aRR], 0.74; 95% confidence interval [CI], 0.55-0.99) and mastectomy with immediate reconstruction (aRR, 0.80; 95% CI, 0.73-0.88), respectively. The numbers needed to treat to prevent 1 additional SSI were 107 and 48, respectively., Conclusions: Postdischarge prophylactic antibiotics were common after mastectomy. Anti-MSSA antibiotics were associated with decreased risk of SSI for patients who had mastectomy only and those who had mastectomy with immediate reconstruction. The high numbers needed to treat suggest that potential benefits of postdischarge antibiotics should be weighed against potential harms associated with antibiotic overuse.

In this prospective, longitudinal study, we examined the risk factors for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among a cohort of chronic hemodialysis (HD) patients and healthcare personnel (HCPs) over a 6-month period. The risk of SARS-CoV-2 infection among HD patients and HCPs was consistently associated with a household member having SARS-CoV-2 infection., (© The Author(s) 2022.)

Objective: To identify characteristics associated with positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) tests in healthcare personnel., Design: Retrospective cohort study., Setting: A multihospital healthcare system., Participants: Employees who reported SARS-CoV-2 exposures and/or symptoms of coronavirus disease 2019 (COVID-19) between March 30, 2020, and September 20, 2020, and were subsequently referred for SARS-CoV-2 PCR testing., Methods: Data from exposure and/or symptom reports were linked to the corresponding SARS-CoV-2 PCR test result. Employee demographic characteristics, occupational characteristics, SARS-CoV-2 exposure history, and symptoms were evaluated as potential risk factors for having a positive SARS-CoV-2 PCR test., Results: Among 6,289 employees who received SARS-CoV-2 PCR testing, 873 (14%) had a positive test. Independent risk factors for a positive PCR included: working in a patient care area (relative risk [RR], 1.82; 95% confidence interval [CI], 1.37-2.40), having a known SARS-CoV-2 exposure (RR, 1.20; 95% CI, 1.04-1.37), reporting a community versus an occupational exposure (RR, 1.87; 95% CI, 1.49-2.34), and having an infected household contact (RR, 2.47; 95% CI, 2.11-2.89). Nearly all HCP (99%) reported symptoms. Symptoms associated with a positive PCR in a multivariable analysis included loss of sense of smell (RR, 2.60; 95% CI, 2.09-3.24) or taste (RR, 1.75; 95% CI, 1.40-2.20), cough (RR, 1.95; 95% CI, 1.40-2.20), fever, and muscle aches., Conclusions: In this cohort of >6,000 healthcare system and academic medical center employees early in the pandemic, community exposures, and particularly household exposures, were associated with greater risk of SARS-CoV-2 infection than occupational exposures. This work highlights the importance of COVID-19 prevention in the community and in healthcare settings to prevent COVID-19., (© The Author(s) 2022.)

Large-scale genomic studies have identified within-host adaptation as a hallmark of bacterial infections. However, the impact of physiological, metabolic, and immunological differences between distinct niches on the pathoadaptation of opportunistic pathogens remains elusive. Here, we profile the within-host adaptation and evolutionary trajectories of 976 isolates representing 119 lineages of uropathogenic Escherichia coli (UPEC) sampled longitudinally from both the gastrointestinal and urinary tracts of 123 patients with urinary tract infections. We show that lineages persisting in both niches within a patient exhibit increased allelic diversity. Habitat-specific selection results in niche-specific adaptive mutations and genes, putatively mediating fitness in either environment. Within-lineage inter-habitat genomic plasticity mediated by mobile genetic elements (MGEs) provides the opportunistic pathogen with a mechanism to adapt to the physiological conditions of either habitat, and reduced MGE richness is associated with recurrence in gut-adapted UPEC lineages. Collectively, our results establish niche-specific adaptation as a driver of UPEC within-host evolution., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In a prospective cohort of healthcare personnel (HCP), we measured severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) nucleocapsid IgG antibodies after SARS-CoV-2 infection. Among 79 HCP, 68 (86%) were seropositive 14-28 days after their positive PCR test, and 54 (77%) of 70 were seropositive at the 70-180-day follow-up. Many seropositive HCP (95%) experienced an antibody decline by the second visit., (© The Author(s) 2022.)