Association of anti-anaerobic antibiotics with mortality and the gut microbiome: a sub-study of the BALANCE randomized clinical trial

Patients with suspected bloodstream infection often receive broad-spectrum antibiotics with anaerobic activity in the absence of clinical indication for anaerobic coverage. Anti-anaerobic antibiotics have been linked to adverse clinical outcomes in other populations, potentially by depleting intestinal anaerobes.MethodsWe conducted a planned sub-study of the multisite BALANCE randomized controlled trial of antibiotic duration for bloodstream infection to assess the impact of anti-anaerobic antibiotics (receipt from three days pre-index culture to seven days post-index) on mortality and gut microbiome composition with metagenomic sequencing in patients without clinical indication for anaerobic coverage who survived to seven days post-index culture. The primary exposure was receipt of anti-anaerobic antibiotics from three days prior to the index culture to seven days post-index culture.ResultsAmong the 2851 eligible patients included in our primary analysis, 2106 (74%) received anti-anaerobic antibiotics and 745 (26%) did not. After balancing measured potential confounders through inverse probability of treatment weighting, anti-anaerobic antibiotics were associated with higher 90-day mortality (OR = 1.41, 95% CI 1.03 to 1.92, p = 0.03) and depletion of gut anaerobe relative abundance (fixed effect estimate = -16.59, 95% CI -30.67 to -2.52, p = 0.02). Increased duration of anti-anaerobic antibiotics was associated with greater mortality risk and additional gut anaerobe depletion.ConclusionsAnti-anaerobic antibiotics are associated with increased mortality and gut microbiome disruption in patients with bloodstream infection. Minimizing exposure to anti-anaerobic antibiotics for bloodstream infection should be further explored in clinical trials as a potential treatment strategy to improve patient outcomes.

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Molecular Epidemiology and Drug Resistance of Extraintestinal Pathogenic Escherichia coli Bloodstream Isolates From Adults Worldwide (2011–2023)

AbstractBackground. Extraintestinal pathogenic Escherichia coli (ExPEC) can colonize and infect body sites outside the intestines, which can lead to invasi

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Systematic review of implementing stewardship activities to promote appropriate antimicrobial use

View abstract Objective:This systematic review aims to describe the impact of specific antimicrobial stewardship program (ASP) strategies on implementation and stewardship-related outcomes.Design:Systematic literature review.Methods:We systematically searched multiple databases using search terms that focused on stewardship and implementation. An original search was completed on October 29, 2021, and then updated on February 26, 2025. Studies were eligible for inclusion if they were in English, reported an antimicrobial resource outcome, and using either a comparison group or a pre/post design as a minimum level of rigor. Data from articles were extracted to understand the context and design of the evaluation, the types of approaches used, and outcomes assessed.Results:Out of 2035 studies that were identified, we included 250 full-text peer-reviewed manuscripts. Of the 250 studies included, 52% were conducted in the USA. The majority (80%) of studies were conducted in inpatient settings, particularly in adult academic hospitals (29%). Programs were often implemented hospital-wide or across multiple specialties, with a focus on emergency medicine and intensive care units. Education or learning (64% of studies) and handshake stewardship (56% of studies) were by far the most common ASP strategies used. Mortality (36% of studies) and drug choice (57% of studies) were the most tracked patient and resource outcomes, respectively.Conclusions:Our review highlights the variability in approaches as part of ASPs, indicating a need for a more systematic understanding of how different approaches are implemented and their subsequent impact on antimicrobial use.

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The Clean Margin in Diabetic Foot Osteomyelitis: Conceptual Appeal, Practical Uncertainty

AbstractUpdated guidelines endorse tailoring antimicrobial treatment for diabetic foot osteomyelitis (DFO) based on resection margins, representing a shift toward more individualized therapy. While conceptually appealing, this approach relies on a construct that remains ill-defined and inconsistently measured. Historically, infectious diseases management has emphasized source control without formal operationalization of resection margins. In DFO, the concept has evolved from descriptive assessments of residual infected bone to categorical designations of “positive” or “negative” margins, largely without prospective validation. Current recommendations are informed in part by limited trial data with uncertain ascertainment of residual infection. At the bedside, resection margin assessment varies across surgical, histopathological, and microbiological domains that are not interchangeable and often discordant, limiting reliability and complicating treatment decisions. Standardized definitions and prospective validation are needed before routine implementation.

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Antimicrobial Use in U.S. Hospitals: Comparison of 2015 and 2023 Prevalence Surveys

Prevalence surveys in U.S. hospitals in 2011 and 2015 showed that half of inpatients received antimicrobials on the survey day or day before. We repeated the survey in 2023 to assess changes in antimicrobial use (AU).MethodsTen Emerging Infections Program (EIP) sites recruited up to 25 hospitals each, prioritizing prior participants. EIP staff reviewed medical records of randomly selected inpatients from the survey day morning census and documented AU on the survey day or day before. We compared AU and stewardship characteristics between 2023 and 2015 and used multivariable log-binomial regression to identify factors associated with AU in 2023.ResultsAntimicrobial stewardship programs were present in 215/218 hospitals in 2023 (98.6%) compared with 158/199 (79.4%) in 2015. Of 13,653 patients in 2023, 6,785 (49.7%) received ≥1 antimicrobial on the survey day or day before. Among 151 hospitals participating in both surveys, overall AU prevalence was similar in 2015 and 2023 (49.2% vs 49.1%), with decreases in neonatal critical care (23.4% to 17.1%) and increases in mother–baby units (24.4% to 32.8%). Fluoroquinolone use declined (9.2% to 2.8%), while third- or fourth-generation cephalosporin use increased (12.3% to 18.6%). In 2023, higher AU was associated with patient factors (medical devices, inpatient location, obesity, 4–17 day hospital stays, suburban residence) and hospital factors (Northeast and South regions, AU audits).ConclusionOne in two inpatients received an antimicrobial in 2023, similar to 2015. However, changes in AU by inpatient location and antimicrobial class suggest evolving prescribing practices and may inform targeted surveillance and stewardship efforts.

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PCR-based syndromic tests for antibiotic stewardship in non-ventilated patients with hospital-acquired pneumonia: a multicentre randomized controlled trial

AbstractObjectivesTo evaluate whether syndromic multiplex PCR (mPCR) with expert guidance improves antibiotic stewardship in patients with hospital-acquired pneumonia (HAP).MethodsWe conducted a multicentre, open-label randomized controlled trial across seven French tertiary hospitals. Adults with non-ventilator-associated HAP in intensive care unit (ICU) or non-ICU wards were randomized (1:1) to conventional microbiology or mPCR testing. Empirical therapy was clinician-guided. In the intervention group, treatment was subsequently adapted according to mPCR results with expert advice. The primary endpoint was duration of broad-spectrum antibiotics (days of therapy/100 patient-days) in patients alive at end of follow-up. Secondary outcomes included appropriateness of antibiotic therapy, adverse outcomes, length of stay and costs.ResultsFrom February 2020 to August 2023, 116 patients were randomized and 109 included in follow-up (mPCR n = 55; control n = 54). Recruitment was disrupted by the COVID-19 pandemic, leading to early trial termination at half of the planned sample size. Median age was 66 years (IQR: 55–76), 66% patients were in ICU. Mean duration of broad-spectrum antibiotics was 37.6 days of therapy/100 patient-days (standard deviation, SD 44.1) in the mPCR group versus 48.7 (SD 54.5) in controls (P = 0.41). mPCR significantly increased appropriate antibiotic therapy at day 0 (47% versus 24%, P = 0.01). No differences were evidenced in adverse outcomes, length of stay or costs.ConclusionsIn this prematurely discontinued trial, mPCR with expert guidance did not reduce broad-spectrum antibiotic exposure, but improved early appropriateness of antibiotic therapy in HAP. These findings highlight the potential role of rapid diagnostics in optimizing initial antibiotic decisions, while underscoring challenges of demonstrating reductions in antibiotic consumption.

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Notes from the Field: Misidentification of a Specimen as ...

This report describes a suspected exposure to ...

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Speed Is Necessary but Not Sufficient: Aligning Direct-From-Blood Diagnostics with Stewardship to Reduce Empiric Broad-Spectrum Antibiotic Use

To the  Editor—Gaston et al [1] report a pragmatic randomized trial evaluating direct-from-blood bacterial testing in addition to conventional blood cultures versus blood cultures alone among 500 emergency department (ED) adults receiving empiric intravenous vancomycin. The intervention markedly accelerated microbiologic diagnosis, reducing the median time to a definitive result from 5.5 days to 0.4 days [1]. Despite this substantial diagnostic gain, no corresponding reduction in empiric antibiotic exposure was observed: the time to the last vancomycin dose (median, 12.5 vs 19.0 hours; hazard ratio [HR], 1.08) and to the last antipseudomonal β-lactam dose (median, 1.6 vs 1.7 days; HR, 1.04) did not differ significantly between groups [1]. Collectively, these findings highlight a persistent challenge in sepsis diagnostics—accelerated pathogen identification alone does not necessarily translate into earlier antimicrobial de-escalation [2].

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Long-Term Serologic Outcomes Following Treatment of Syphilis in People With HIV: A Prospective Cohort Study

This study aimed to evaluate the factors associated with rate and time to serological response, serofast status, and seroreversion in people with HIV (PWH) with a first diagnosis of syphilis.MethodsThe primary endpoint was serological response as determined by a 4-fold decline in rapid plasma regain (RPR) titer or seroreversion at 12 months. A secondary endpoint was cumulative serological response by 24 months of follow-up. Survival and multivariate analysis were used to compare different associated factors.ResultsA total of 184 PWH had a first syphilis episode in 642 person-years of follow-up. After treatment, the median time to serological response was 6.53 months (95% CI 6.055–7.012). In the Cox model, only secondary syphilis (HR 3.091, 95% CI 1.330–11.440; P = .013) and higher nadir CD4+ count (HR 1.002; 95% CI 1.001–1.004; P = .043) were associated with a faster response. At 12 months, 155 PWH (84%, 95% CI 78%–89%) achieved response and a lower baseline RPR (RR 0.972; 95% CI .947–.997; P = .028) was associated with failure. After response, 79 (51%) with higher CD4+ count remained as serofast status, and 33 of them (46%) seroreverted during follow-up. Of the 29 PWH without response, 11 (38%) reached serological response in a longer follow-up (29.3 months, 95% CI 23.03–35.7), and 2 out of 4 (14%) had confirmed neurosyphilis, whereas 14 (48%) had reinfections. Thus, 89% of PWH had serological response by 24 months.ConclusionsThe time to serological response, the rate of serofast, and the outcome are the result of the interaction of nontreponemal test titers, syphilis stage, and the patient's immune status.

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State-of-the-Art Review: Infections in Patients With Cerebrospinal Fluid Shunts

AbstractCerebrospinal fluid shunt infections pose major diagnostic and therapeutic challenges that necessitate multidisciplinary management and shared decision-making. However, published evidence to guide practice remains limited. This state-of-the-art review synthesizes current knowledge of the epidemiology, pathogenesis, and clinical presentation of these infections. Approaches to intravenous and intraventricular antimicrobial therapy are discussed, with particular attention to areas of persistent uncertainty. The role of neurosurgical interventions in the management of these infections is also reviewed. Emerging challenges, such as fungal and multidrug-resistant gram-negative shunt infections, are examined and key priorities for future research are outlined.

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Retrospective multicenter evaluation of oral step-down versus intravenous carbapenem treatment of extended-spectrum beta-lactamase-producing Escherichia coli urinary tract infections

View abstract Objectives:This study evaluated whether treatment with oral step-down therapy compared with intravenous carbapenems alone for extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli urinary tract infections (UTIs) impacted patient venous catheter days and clinical outcomes.Methods:This multicenter retrospective study at six different hospitals in a large health system included adults (≥ 18 years) admitted for ≥ 24 hours with ≥ 1 documented UTI symptom, a ceftriaxone-resistant Escherichia coli urine culture, and receipt of ≥ 1 dose of meropenem or ertapenem between August 2022 and July 2025. The primary outcome was median venous catheter line days directly associated with antibiotic use inpatient and outpatient. Secondary outcomes included pharmacist antibiotic intervention, incidence of antibiotic-related adverse events, hospital length of stay, duration of therapy, inpatient catheter line days, projected outpatient catheter line days, presence of peripherally inserted central catheter or midline, central line-associated bloodstream infection, and treatment failure (defined as escalation of antibiotics, in-hospital mortality, urgent care/emergency department visit or readmission, or recurrence of symptomatic UTI with ESBL Escherichia coli within 30 days).Results:120 patients were included, with 60 in the oral step-down and carbapenem groups, respectively. Primary outcome of median venous catheter days in the oral step-down group was 0 (IQR 0–0) vs 5 (IQR 0–7) in the carbapenem group, p < .001. Secondary outcome of treatment failure in the oral step-down group was 2 (3%) vs 8 (13%) in the carbapenem group, p < .09.Conclusions:Oral step-down therapy for ESBL Escherichia coli UTIs was associated with a significant reduction in venous catheter line use.

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Can Chlorhexidine Bathing Reduce Candidozyma auris Shedding?

AbstractThis settle plate study demonstrated rapid Candidozyma auris shedding during nursing home caregiving activities, with an 80% reduction when residual chlorhexidine gluconate concentrations ≥156 µg/mL. Findings highlight high-contact care as key transmission points and provide novel evidence that chlorhexidine-based decolonization can effectively mitigate C. auris transmission risk in long-term care.

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The intersection of sexually transmitted infections and antimicrobial stewardship: opportunities for synergy | Antimicrobial Stewardship & Healthcare Epidemiology | Cambridge Core

The intersection of sexually transmitted infections and antimicrobial stewardship: opportunities for synergy - Volume 6 Issue 1

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Does the Evidence Support High-Dose Liposomal Amphotericin B in the Treatment of Mucormycosis?

AbstractGuidelines recommend liposomal amphotericin B (L-AMB) at 5–10 mg/kg/day as first-line therapy for invasive mucormycosis, but whether doses exceeding 5–6 mg/kg/day improve outcomes enough to justify added nephrotoxicity and cost remains unclear. We critically appraised pharmacokinetic, preclinical, and clinical evidence from 58 publications, defining standard-dose L-AMB as 5–6 mg/kg/day and high-dose (HD) L-AMB as >6 mg/kg/day. Animal models show dose-dependent efficacy, but the only prospective trial (Ambizygo) examining HD-L-AMB was a single-arm pilot trial whose response rates were similar to historical 5 mg/kg/day cohorts. Retrospective studies have not found survival benefit favoring HD L-AMB, with consistently higher rates of nephrotoxicity. Saturable pharmacokinetics and altered liposome distribution at doses >10 mg/kg/day may explain this lack of benefit. Routine dose escalation beyond 5–6 mg/kg/day is not supported by current evidence; early diagnosis, surgical debridement, and reversal of immunosuppression appear more critical. However, selected cases may still warrant higher L-AMB doses based on individualized risk–benefit assessment.

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Validate User

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Health Care–Associated Infections in U.S. Hospitals, 2023 versus 2015 | NEJM

Prevalence surveys in U.S. hospitals showed that on any given day, 1 of 25 patients had a health care–associated infection in 2011, as compared with 1 of 31 patients in 2015. We repeated the survey...

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The intersection of sexually transmitted infections and antimicrobial stewardship: opportunities for synergy | Antimicrobial Stewardship &amp; Healthcare Epidemiology | Cambridge Core

The intersection of sexually transmitted infections and antimicrobial stewardship: opportunities for synergy - Volume 6 Issue 1

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