Erratum: Implementation of an asymptomatic bacteriuria assessment protocol for patients discharged from the emergency department - CORRIGENDUM.

[This corrects the article DOI: 10.1017/ash.2023.117.].

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2022.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.

Impact of restrictive urinalysis reflex to culture criteria at a large community hospital.

Treatment of asymptomatic bacteriuria (ASB) is a common, but often unnecessary, practice. Our objective was to determine the impact of restrictive urinalysis reflex to culture (UARC) criteria on rate of urine cultures (UC) ordered and ASB treatment. Criteria were modified from positive leukocyte esterase, positive nitrites, or white blood cells (WBC) >10 cells to only WBC >10 cells. This pre-post study evaluated UARCs ordered in the emergency department or inpatient units. The primary outcome was the proportion of reflex UCs prevented. Secondary outcomes included the frequency of repeat UARCs and stand-alone UCs, gram-negative rod (GNR) bacteremia, and ASB treatment. In the pre-intervention, there were 4761 UARCs compared to 5420 in the post-intervention; 37.9 % and 21.4 % reflexed to UCs, a 43.5 % reduction in UCs. The rate of repeat UARCs, stand-alone UCs, and GNR bacteremia in the pre- and post-interventions were similar. ASB treatment rate was numerically lower in the post-intervention.

Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.

IMPORTANCE: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.

Impact of Gram-Negative Rod Bacteremia Rapid Diagnostic Testing and Real-Time Clinical Pharmacist Intervention.

Background: The optimal method for implementing rapid diagnostic testing (RDT) into clinical practice has not been determined for gram-negative rod (GNR) bacteremia. At our institution, RDT was implemented in conjunction with real-time notification of results to decentralized clinical pharmacists. Objective: To determine the impact of RDT result notification plus real-time clinical pharmacist review on the management of GNR bacteremia. Methods: This retrospective, matched cohort study included patients with a positive blood culture for a GNR on the BIOFIRE® Blood Culture Identification 2 panel from September 2020 to August 2021 (historical) and October 2021 to September 2022 (interventional). Exclusion criteria were polymicrobial bacteremia, discrepant RDT results from traditional culture, 24-hour mortality, and comfort care or not admitted at the time of RDT result. Patients were matched based on age, pathogen, and resistance. The primary endpoint was time from Gram stain to appropriate antibiotic therapy. Results: This study consisted of 240 patients (n = 120 historical, n = 120 interventional). Escherichia coli was isolated in 71% of patients with extended-spectrum beta-lactamase-producing organisms isolated in 8%. There was no difference in median time to appropriate therapy (0 vs 0 hours, P = 0.28). There was a statistically significant decrease in time to first organism-directed change in therapy (40 vs 11 hours; P < 0.01). Length of stay, days of anti-pseudomonal therapy, and inpatient mortality did not differ between groups. Conclusion: Implementation of RDT plus real-time clinical pharmacist review did not significantly decrease time to appropriate therapy in patients with GNR bacteremia but significantly reduced time to organism-directed antibiotic changes.

Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49-67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4 - 14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).

Implementation of an asymptomatic bacteriuria assessment protocol for patients discharged from the emergency department.

Objective: We evaluated the impact of an asymptomatic bacteriuria (ASB) assessment protocol on the number of antibiotics prescribed for ASB after discharge from the emergency department (ED). Design: Single-center, before-and-after, retrospective cohort study. Setting: The study was conducted at a large community health system in North Carolina. Patients: Eligible patients were discharged from an ED without an antibiotic prescription and had a positive urine culture result after discharge from May through July 2021 (preimplementation group) and October through December 2021 (postimplementation group). Methods: Patient records were reviewed to determine the number of antibiotic prescriptions for ASB on follow-up call before and after implementation of an ASB assessment protocol. Secondary outcomes included 30-day admissions, 30-day ED visits, 30-day UTI-related encounters, and projected antibiotic days of therapy. Results: The study included 263 patients: 147 in the preimplementation group and 116 in the postimplementation group). There were significantly fewer antibiotic prescriptions for ASB in the postimplementation group (50% vs 87%; P < .0001). There were no differences in the incidence of 30-day admissions (7% vs 8%; P = .9761), 30-day ED visits (14% vs 16%; P = .7805), or 30-day UTI-related encounters (0% vs 0%, NA). Conclusions: Implementation of an ASB assessment protocol for patients discharged from the ED significantly reduced the number of antibiotic prescriptions for ASB on follow-up call without an increase in 30-day admissions, ED visits, or UTI-related encounters.

Treatment of persistent methicillin-susceptible Staphylococcus aureus bacteremia and presumed osteomyelitis with oxacillin and ertapenem in a premature neonate.

Neonatal sepsis remains a high cause of morbidity and mortality in preterm neonates. Methicillin-susceptible Staphylococcus aureus (MSSA) can cause persistent bloodstream infections and invasive disease in neonates. We report the first published case of persistent MSSA bacteremia in a preterm neonate successfully treated with oxacillin and ertapenem combination therapy.

Clinical Outcomes of Eravacycline in Patients Treated Predominately for Carbapenem-Resistant Acinetobacter baumannii.

Forty-six patients were treated with eravacycline (ERV) for Acinetobacter baumannii infections, where 69.5% of isolates were carbapenem resistant (CRAB). Infections were primarily pulmonary (58.3%), and most patients received combination therapy (84.4%). The median (IQR) ERV duration was 6.9 days (5.1 to 11.1). Thirty-day mortality was 23.9% in the cohort and 21.9% in CRAB patients. One patient experienced an ERV-possible adverse event. IMPORTANCE Acinetobacter baumannii, particularly when carbapenem resistant (CRAB), is one of the most challenging pathogens in the health care setting. This is complicated by the fact that there is no consensus guideline regarding management of A. baumannii infections. However, the recent Infectious Diseases Society of America guidelines for treatment of resistant Gram-negative infections provided expert recommendations for CRAB management. The panel suggest using minocycline among tetracycline derivatives rather than eravacycline (ERV) until sufficient clinical data are available. Therefore, we present the largest multicenter real-world cohort in patients treated with ERV for A. baumannii, where the majority of isolates were CRAB (69.5%). Our analysis demonstrate that patients treated with ERV-based regimens achieved a 30-day mortality of 23.9% and had a low incidence of ERV-possible adverse events (2.1%). This study is important as it fills the gap in the literature regarding the use of a novel tetracycline (i.e., ERV) in the treatment of this challenging health care infection.

Real-World, Multicenter Case Series of Patients Treated with Oral Omadacycline for Resistant Gram-Negative Pathogens.

INTRODUCTION: Antibiotic-resistant Gram-negative bacteria have been associated with substantial morbidity and mortality and have limited treatment options available. Omadacycline (OMC) is an aminomethylcycline antibiotic that has been shown to exhibit broad in vitro activity against antibiotic-resistant Gram-negative bacteria. Given the lack of real-world data, the primary objective of our report was to describe early experience with OMC for the treatment of resistant Gram-negative infections. METHODS: This was a real-world, multicenter, observational cases series/pilot study conducted in the USA. Inclusion criteria included any adult patient aged ≥ 18 years who received OMC for ≥ 72 h either in the inpatient and/or outpatient setting. Clinical success was defined as a composite of 90-day survival from initiation of OMC, lack of alteration in treatment/addition of other antibiotic due to concerns of OMC failure, and lack of microbiologic recurrence within 30 days from the end of therapy. RESULTS: Oral OMC was used in nine cases primarily for multidrug-resistant (MDR)/extensively drug-resistant (XDR) Gram-negative bacterial infections (55.6% XDR and/or carbapenem-resistant Acinetobacter baumannii [CRAB]). The majority of infections were of bone/joint (55.6%) origin, followed by intra-abdominal (33.3%) origin. Clinical success occurred in 66.7% of cases, with 80.0% success each in infections of bone/joint origin or those caused by CRAB. One patient experienced an adverse effect that was not treatment limiting while on therapy (gastrointestinal). CONCLUSION: The use of oral OMC in MDR/XDR Gram-negative infections exhibited a relatively high success rate with minimal adverse effects. Real-world studies with larger case numbers are needed to confirm our initial findings.

Crushing and Splitting Direct-Acting Antivirals for Hepatitis C Virus Treatment: A Case Series and Literature Review.

Limited data exist regarding the use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) in patients who are unable to swallow tablets. This case series describes HCV treatment in patients requiring tablet manipulation, providing evidence for safety and effectiveness of HCV DAA tablet manipulation.

Early clinical trial data and real-world assessment of COVID-19 vaccines: Insights from the Society of Infectious Diseases Pharmacists.

As of August 2021, there were three COVID-19 vaccines available in the United States for the prevention of coronavirus 2019 (COVID-19). The purpose of this narrative review is to examine the early experience from the Emergency Use Authorization (EUA) of BNT162b2 (Pfizer, Inc./BioNTech), mRNA-1273 (Moderna, Inc.), and Ad26.COV2.S (Johnson and Johnson/Janssen Global Services, LLC) through July 2021. The EUA data from the clinical trials have largely been corroborated by real-world effectiveness investigations post-authorization. These studies indicate that immunity is obtained within 2 weeks post-vaccination and may endure for 6 months. The immunity conferred by the vaccines may also be effective against SARS-CoV-2 variants of concern. Additionally, populations not included in the emergency use authorization studies may also benefit from vaccination. This look back at the initial clinical experience can be used by the global community to inform and develop COVID-19 vaccine programs.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2020.

The number of articles related to antimicrobial stewardship published each year has increased significantly over the last decade. Keeping up with the literature, particularly the most innovative, well-designed, or applicable to one's own practice area, can be challenging. The Southeastern Research Group Endeavor (SERGE-45) network reviewed antimicrobial stewardship-related, peer-reviewed literature from 2020 that detailed actionable interventions. The top 13 publications were summarized following identification using a modified Delphi technique. This article highlights the selected interventions and may serve as a key resource for teaching and training, and to identify novel or optimized stewardship opportunities within one's institution.

Preliminary, Real-world, Multicenter Experience With Omadacycline for Mycobacterium abscessus Infections.

Twelve patients were treated with omadacycline (OMC) as part of a multidrug regimen for Mycobacterium abscessus. The majority of infections were of pulmonary origin (7/12; 58.3%). The median (interquartile range) duration of OMC was 6.2 (4.2-11.0) months. Clinical success occurred in 9/12 (75.0%) patients. Three patients experienced a possible adverse effect while on therapy.

Use of continuous-infusion ceftolozane/tazobactam for resistant Gram-negative bacterial infections: a retrospective analysis and brief review of the literature.

Ceftolozane/tazobactam (C/T), a novel antipseudomonal cephalosporin plus ß-lactamase inhibitor, is used in multidrug-resistant Gram-negative infections. Continuous infusion (CI) of C/T is an attractive concept for aiding in transitions of care and maximising the pharmacodynamics of cephalosporins (T>MIC). This was a single-centre retrospective analysis of CI C/T use in adults from December 2016 to June 2019 in the inpatient or outpatient setting. Safety and effectiveness were assessed. When therapeutic drug monitoring (TDM) was performed, area under the concentration-time curve (AUC) and target attainment were calculated. Summary statistics were used to describe the data. CI C/T was used in seven unique regimens over the 31-month evaluation period. Patient age ranged from 23-70 years and the indication was primarily for treatment of deep-seated infections caused by multidrug-resistant Pseudomonas aeruginosa. Four regimens (57%) were used for outpatient transitions of care. The typical dose was 6 g every 24 h, although a renally adjusted dose was used in two instances (29%). TDM was performed in four uses (57%) and target attainment was confirmed in each. Ceftolozane AUC ranged from 365.7-818.2 µg•(h/mL). All patients had positive outcomes with no significant adverse events. One patient developed acute gout flares. One patient had recurrent infection with C/T-resistant P. aeruginosa after ~3 months of reduced dose for suppression. CI C/T was successfully utilised for deep-seated infections in inpatient and outpatient settings. TDM confirmed that CI C/T achieved pharmacodynamic targets for the entire dosing interval, suggesting an effective alternative dosing regimen applicable across the continuum of care.

The Mbeya Antimicrobial Stewardship Team: Implementing Antimicrobial Stewardship at a Zonal-Level Hospital in Southern Tanzania.

Background: In 2017, Mbeya Zonal Referral Hospital (MZRH) and the University of South Carolina (UofSC) agreed to collaboratively strengthen antimicrobial prescribing in the southern highlands of Tanzania and train a new generation of clinicians in responsible antimicrobial use. Methods: Key stakeholders and participants were identified and the Mbeya Antimicrobial Stewardship Team (MAST) was created. The team identified assets brought by the collaborators, and four investigations of baseline needs were developed. These investigations included (a) a baseline clinician survey regarding antimicrobial resistance and stewardship, (b) a serial chart review of inpatient antimicrobial prescribing practices, (c) an investigation of antimicrobial resistance rates using existing isolates at the MZRH laboratory, and (d) a survey of antimicrobial availability at community pharmacies in the city. Results: 91% of physicians believe antimicrobial resistance is problem in Tanzania, although only 29% of physicians were familiar with the term "antimicrobial stewardship". Escherichia coli isolates had resistance rates of over 60% to the commonly used agents ciprofloxacin, trimethoprim-sulfamethoxazole, and ceftriaxone. Thirteen out of 14 community pharmacies offered over-the-counter antibiotics for upper respiratory symptoms. Conclusions: International antimicrobial stewardship collaborations can successfully identify opportunities and needs. Evaluating the team's efforts to improve patient outcomes will be essential.

Inpatient Antibiotic Stewardship Interventions in the Adult Oncology and Hematopoietic Stem Cell Transplant Population: A Review of the Literature.

Objective: To review the use of antibiotic stewardship interventions in the adult oncology and hematopoietic cell transplantation (HCT) populations. Data Sources: A literature search of PubMed was performed from inception to October 31, 2019. The general search terms used were oncology, cancer, hematologic malignancy, antimicrobial stewardship, antibiotic stewardship, febrile neutropenia, neutropenic fever, de-escalation, discontinuation, prophylaxis, practice guidelines, clinical pathway, rapid diagnostics, Filmarray, Verigene, MALDI-TOF, antibiotic allergy, and antimicrobial resistance. Study Selection and Data Extraction: Relevant English-language studies describing interventions supported by the Infectious Diseases Society of America guidelines on "Implementing an Antibiotic Stewardship Program" were included. Data Synthesis: Antibiotic stewardship publications in the oncology population have increased in recent years. Studies have described the impact of stewardship interventions, including preauthorization, prospective audit and feedback, implementation of clinical pathways, de-escalation of empirical antibiotics for febrile neutropenia (FN) prior to neutrophil recovery, allergy assessments, and use of rapid diagnostic testing. Many of these interventions have been shown to decrease antibiotic use without increased negative consequences, such as affecting length of stay or mortality. Relevance to Patient Care and Clinical Practice: This review synthesizes available evidence for implementing antibiotic stewardship interventions, particularly de-escalation of antibiotics for FN and implementation of clinical pathways for FN and sepsis, in oncology patients and HCT recipients. Summary tables highlight studies and specific research needs for clinicians. Conclusions: Immunocompromised populations, including oncology patients, have often been excluded from stewardship studies. Antibiotic stewardship is effective in reducing antibiotic consumption and improving outcomes in this patient population, although more quality data are needed.

Levofloxacin-induced rhabdomyolysis in a patient on concurrent atorvastatin: Case report and literature review.

WHAT IS KNOWN AND OBJECTIVE: The combination of HMG-CoA reductase inhibitors (statins) and fluoroquinolones generally is not considered a significant risk factor for rhabdomyolysis. Rhabdomyolysis is a known risk associated with statin therapy but has seldom been described with fluoroquinolone use. We describe a case of acute rhabdomyolysis involving the co-administration of atorvastatin and levofloxacin. CASE DESCRIPTION: A 65-year-old white male presented with clinical and laboratory evidence of rhabdomyolysis after approximately 19 days of levofloxacin therapy for treatment of a prosthetic joint infection. His symptoms resolved after discontinuation of levofloxacin and atorvastatin therapy and did not recur following reintroduction of atorvastatin therapy. WHAT IS NEW AND CONCLUSION: Delayed-onset rhabdomyolysis may occur in patients receiving levofloxacin. Weekly complete metabolic panels along with patient education about symptoms of rhabdomyolysis should be considered, particularly in patients on concurrent medications known to cause rhabdomyolysis.