(1) Background: Dalbavancin is a long-acting lipoglycopeptide antibiotic approved for skin and soft-tissue infections. Post-marketing experience suggests dalbavancin is being used for off-label indications that normally require long-term intravenous (IV) antibiotics; however, data assessing this off-label usage are limited. The purpose of this study was to evaluate the real-world efficacy, safety, and financial impact of off-label dalbavancin use. (2) Methods: This is a retrospective, observational study conducted within a 4-hospital health system. Adult patients who received dalbavancin from January 2018 to January 2021 for an off-label indication were included. The primary outcome was clinical success at 90 days. Secondary outcomes included safety (nephrotoxicity and hepatotoxicity). A pharmacoeconomic analysis was performed by comparing the cost of dalbavancin to the anticipated cost of patient stay if standard IV therapy was given. (3) Results: Forty-eight patients met study criteria. Indications included osteomyelitis (54%), endocarditis (23%), bacteremia (15%), and prosthetic joint infection (8%). The predominant organism was S. aureus (60%), with 42% caused by methicillin-resistant S. aureus. Overall, 41 (85%) patients achieved clinical success at 90 days, including 85% with osteomyelitis, 82% with endocarditis, and 86% with bacteremia. There were no instances of nephrotoxicity or hepatotoxicity. Estimated cost avoidance per patient was USD 5313 and USD 1683 if traditional IV therapy would have been completed in the hospital and skilled nursing facility, respectively. (4) Conclusion: Dalbavancin was associated with a relatively high success rate for the treatment of off-label indications and may be a cost-effective alternative to traditional IV antibiotic therapy.

Background: Nocardia-related endocarditis is rare. Intravenous drug use with nonsterile injection practices is a potential risk factor for nocardia infection. Disseminated nocardiosis with endovascular involvement is rarely reported in immunocompetent individuals. Case presentation: A 54-year-old male was diagnosed with infective endocarditis due to Nocardia asteroides with septic emboli in the brain and spleen. The use of a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) rapid diagnostic system was beneficial in identifying the causative organism. He was empirically treated with combination therapy consisting of three antibiotics. Antimicrobial susceptibility testing indicated that all three antibiotics had favorable minimum inhibitory concentrations (MICs). Due to his clinical status, he was not a surgical candidate. Patient passed away after discharge to hospice. Conclusions: This case demonstrates unique challenges in the identification, diagnosis, and management of Nocardia-related infective endocarditis. A detailed history of injection practices should guide clinicians in assessing the risk for environmental pathogens. Valvular surgery and combination antibiotic therapy should be recommended for all eligible patients to improve the chances of survival.

Background: Antimicrobial stewardship programs (ASPs) aim to optimize antimicrobial use through coordinated interventions that improve patient outcomes and reduce adverse events. While guidance exists from organizations including the Centers for Disease Control and Prevention and the Infectious Diseases Society of America, recommendations on effort allocation, working hours, and initiatives remain unclear. Methods: This cross-sectional survey assessed the institutional structure, effort allocation, initiatives, and on-call participation of adult ASPs in the United States from September to October 2024. The survey was distributed via email to several ASP-related listservs. Respondents indicating on-call participation were also inquired about working hours, initiatives performed, participants, and compensation. Results: Of 69 responses, most were from academic medical centers (59%) or community hospitals (35%), with 65% covering >500 beds. ASPs were often system-wide (78%) and primarily funded by their respective departments of pharmacy (87%). Common initiatives performed by all ASPs include answering ASP/infectious diseases questions, therapy de-escalation, and prospective audit and feedback. Twenty-four (69%) respondents indicated having an on-call model, with said programs reporting higher median inpatient full-time equivalents (FTEs) for physicians (0.5 vs 0.25) and pharmacists (2.9 vs 1.45) than those without. Commonly performed after-hours initiatives include preauthorization and answering microbiology inquiries. On-call coverage was generally performed during weekend daytimes and holidays, most often by pharmacists. Conclusions: This survey highlights differences in structure, effort allocation, and initiatives of ASPs based on on-call participation. Institutions participating in on-call reported higher FTE assignments for physicians and pharmacists and were more likely to perform time-sensitive initiatives.

Background: Enterobacterales considered at risk of inducible AmpC production are denoted by mnemonics including SPACE and HECK-Yes! However, these mnemonics may fail to account for the variability in AmpC induction potential, which lends to variation in antibiotics chosen for management of associated infections and susceptibility reporting. This study aimed to evaluate clinical and microbiologic practice patterns for the management of infections caused by Enterobacterales at risk of inducible AmpC production. Methods: This cross-sectional survey was developed by a multidisciplinary infectious diseases (ID) team and distributed via ID-related listservs (November-December 2024). The survey assessed institutional demographics, β-lactam of choice, and microbiologic reporting for Enterobacterales with a moderate risk (Enterobacter cloacae complex, Klebsiella aerogenes, Citrobacter freundii) and low risk (Serratia marcescens, Morganella morganii, Providencia spp.) of inducible AmpC production. Results: Of 94 complete responses, most were from pharmacists (58.5%) and physicians (38.3%) working in adult academic medical centres (39.4%) or community hospitals (37.2%). Cefepime was the preferred β-lactam for invasive (87.2%) and non-invasive (68.1%) infections caused by moderate-risk inducible AmpC producers, while ceftriaxone was preferred for invasive (57.4%) and non-invasive (60.7%) infections caused by low-risk inducible AmpC Inducers. Cefepime (98.8% versus 98.8%), meropenem (85.5% versus 83.1%), piperacillin/tazobactam (72.3% versus 83.1%), and ceftriaxone (67.5% versus 94.0%) were commonly reported antibiotics on non-urinary antibiograms for moderate risk and low risk Enterobacterales, respectively. The beta-lactams reported in institutional antibiograms and microbiology susceptibility reporting were generally similar. Conclusions: This survey highlights differences in practice patterns for management of infections caused by inducible AmpC-producing Enterobacterales. These results emphasize the importance of standardized, evidence-based antimicrobial stewardship approaches and continued clinical investigation to better optimize therapy for infections caused by Enterobacterales capable of inducible AmpC production.

Objective: Many studies have evaluated the safety and efficacy of oral stepdown therapy for treatment of gram-negative bacteremia (GNB). There are currently no studies comparing the safety and effectiveness of various dosing strategies of sulfamethoxazole-trimethoprim (SMX-TMP) in these patients. Methods: This retrospective cohort study included adult patients at 6 hospitals within a health system with GNB, excluding Stenotrophomonas spp. that received at least 72 hours of oral SMX-TMP. Patients were grouped based on high- (≥8 mg/kg) or low-dose (<8 mg/kg) SMX-TMP. The primary outcome was a composite of all-cause mortality and recurrence at 30 days. Secondary outcomes included readmission, hyperkalemia requiring intervention, acute kidney injury, and intolerance leading to SMX-TMP discontinuation. Results: There were 176 patients included (25.6% high-dose, 74.4% low-dose) in this study. Baseline characteristics were similar except for age, sex, and dosing body weight. Median total duration of therapy for both groups was approximately 14 days; time to initiation of antibiotics was similar between groups. Six patients met the composite outcome (high-dose: 4.4% vs. low-dose: 3.1%; P = .646). Secondary outcomes did not differ significantly between groups. Conclusions: SMX-TMP is commonly used as oral stepdown therapy in GNB. Results of this study indicate that low-dose (<8 mg/kg) SMX-TMP may be sufficient, as outcomes were similar between the groups. To date, this is the first study evaluating different dosing strategies of SMX-TMP for this indication.