Extended-Infusion ß-Lactam Therapy, Mortality, and Subsequent Antibiotic Resistance Among Hospitalized Adults With Gram-Negative Bloodstream Infections.

Importance: Current evidence is conflicting for associations of extended-infusion ß-lactam (EI-BL) therapy with clinical outcomes. Objective: To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI). Design, Setting, and Participants: This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion ß-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023. Exposures: EI-BL (ie, ≥3-hour infusion). Main Outcomes and Measures: EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the ß-lactam used to treat the index GN-BSI). Results: Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35). Conclusions and Relevance: In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.

Transition to Oral Antibiotic Therapy for Hospitalized Adults With Gram-Negative Bloodstream Infections.

Importance: Management of gram-negative bloodstream infections (GN-BSIs) with oral antibiotics is highly variable. Objective: To examine the transition from intravenous (IV) to oral antibiotics, including selection, timing, and associated clinical and microbial characteristics, among hospitalized patients with GN-BSIs. Design, Setting, and Participants: A retrospective cohort study was conducted of 4581 hospitalized adults with GN-BSIs at 24 US hospitals between January 1 and December 31, 2019. Patients were excluded if they died within 72 hours. Patients were excluded from the oral therapy group if transition occurred after day 7. Statistical analysis was conducted from July 2022 to October 2023. Exposures: Administration of antibiotics for GN-BSIs. Main Outcomes and Measures: Baseline characteristics and clinical parameters reflecting severity of illness were evaluated in groups receiving oral and IV therapy. The prevalence of transition from IV to oral antibiotics by day 7, median day of transition, sources of infection, and oral antibiotic selection were assessed. Results: Of a total of 4581 episodes with GN-BSIs (median age, 67 years [IQR, 55-77 years]; 2389 men [52.2%]), 1969 patients (43.0%) receiving IV antibiotics were transitioned to oral antibiotics by day 7. Patients maintained on IV therapy were more likely than those transitioned to oral therapy to be immunosuppressed (833 of 2612 [31.9%] vs 485 of 1969 [24.6%]; P < .001), require intensive care unit admission (1033 of 2612 [39.5%] vs 334 of 1969 [17.0%]; P < .001), have fever or hypotension as of day 5 (423 of 2612 [16.2%] vs 49 of 1969 [2.5%]; P < .001), require kidney replacement therapy (280 of 2612 [10.7%] vs 63 of 1969 [3.2%]; P < .001), and less likely to have source control within 7 days (1852 of 2612 [70.9%] vs 1577 of 1969 [80.1%]; P < .001). Transitioning patients from IV to oral therapy by day 7 was highly variable across hospitals, ranging from 25.8% (66 of 256) to 65.9% (27 of 41). A total of 4109 patients (89.7%) achieved clinical stability within 5 days. For the 3429 episodes (74.9%) with successful source control by day 7, the median day of source control was day 2 (IQR, 1-3 days) for the oral group and day 2 (IQR, 1-4 days) for the IV group (P < .001). Common infection sources among patients administered oral therapy were the urinary tract (1277 of 1969 [64.9%]), hepatobiliary (239 of 1969 [12.1%]), and intra-abdominal (194 of 1969 [9.9%]). The median day of oral transition was 5 (IQR, 4-6 days). Total duration of antibiotic treatment was significantly shorter among the oral group than the IV group (median, 11 days [IQR, 9-14 days] vs median, 13 days [IQR, 8-16 days]; P < .001]. Fluoroquinolones (62.2% [1224 of 1969]), followed by ß-lactams (28.3% [558 of 1969]) and trimethoprim-sulfamethoxazole (11.5% [227 of 1969]), were the most commonly prescribed oral antibiotics. Conclusions and Relevance: In this cohort study of 4581 episodes of GN-BSIs, transition to oral antibiotic therapy by day 7 occurred in fewer than half of episodes, principally with fluoroquinolones, although this practice varied significantly between hospitals. There may have been additional opportunities for earlier and more frequent oral antibiotic transitions because most patients demonstrated clinical stability by day 5.

Multiple-Dose Dalbavancin Regimens as the Predominant Treatment of Deep-Seated or Endovascular Infections: A Scoping Review.

Off-label use of dalbavancin for deep-seated and endovascular infections has been increasing. We performed a scoping review to evaluate the evidence for use of multiple-dose dalbavancin regimens as the predominant therapy for these indications. Predominant therapy was defined as use of dalbavancin without other concurrent antibiotics for more than half of the total treatment duration. Fifteen publications were identified; 2 were small, open-label randomized controlled trials and the remainder were retrospective observational studies or case reports. A total of 144 cases from these publications met eligibility criteria for inclusion in this review. Types of infections included osteoarticular infections, catheter-related or complicated bloodstream infections, and infective endocarditis. Overall, the evidence for use of multiple-dose regimens of dalbavancin for deep-seated and endovascular infections is limited by a paucity of data from controlled trials, heterogeneity of dosing regimens, and a lack of standardized clinical outcomes.

Factors Associated With Longer Than Recommended Durations of Antibiotic Therapy for Uncomplicated Ambulatory Infections in an Integrated Healthcare System.

Across the ambulatory care network of an integrated health care system, durations of antibiotic therapy prescribed for uncomplicated infections were longer than recommended in 39% of cases. By logistic regression, site of care, prescriber characteristics, and type of infection were independently associated with longer than recommended durations of therapy.

Use of a Standardized Dalbavancin Approach to Facilitate Earlier Hospital Discharge for Vulnerable Patients Receiving Prolonged Inpatient Antibiotic Therapy.

Twenty-seven patients receiving prolonged inpatient antibiotic therapy for a serious bacterial infection received a single dose of dalbavancin 7-10 days before the planned end date to facilitate earlier hospital discharge. Eighty-one percent met criteria for clinical success, 7% experienced a potential adverse event, and 182 hospital days were averted.

Antibiotic Prescribing Patterns for Acute Otitis Media for Children 2 Years and Older.

OBJECTIVE: To determine the frequency that non-first-line antibiotics, safety-net antibiotic prescriptions (SNAPS), and longer than recommended durations of antibiotics were prescribed for children ≥2 years of age with acute otitis media and examine patient and system level factors that contributed to these outcomes. STUDY DESIGN: Children age ≥2 years with acute otitis media seen at Denver Health Medical Center outpatient locations from January to December 2018 were included. The percentages of patients who received first-line antibiotics, SNAPs, and recommended durations of antibiotics were determined. Factors associated with non-first-line and longer than recommended antibiotic durations were evaluated using multivariate logistic regression modeling. RESULTS: Of the 1025 visits evaluated, 98.0% were prescribed an antibiotic; only 4.5% of antibiotics were SNAPs. Non-first-line antibiotics were prescribed to 18.8% of patients. Most antibiotic durations (94.1%) were longer than the institution recommended 5 days and 54.3% were ≥10 days. Private insurance was associated with non-first-line antibiotics (aOR, 1.89; 95% CI, 1; 14-3.14, P = .01). Patients who were younger (2-5 years; aOR 2.01; 95% CI, 1.32-3.05; P < .001) or seen in emergency/urgent care sites (aOR, 1.73; 95% CI, 1.26-2.38; P < .001) were more likely to receive ≥10 days of antibiotic compared with those in pediatric clinics. CONCLUSIONS: Antibiotic stewardship interventions that emphasize the duration of antibiotic therapy as well as the use of SNAPs or observation may be higher yield than those focusing on first-line therapy alone. Numerous system and patient level factors are associated with off-guideline prescribing.

A Novel Approach to Evaluate Antibiotic Utilization Across the Spectrum of Inpatient and Ambulatory Care and Implications for Prioritization of Antibiotic Stewardship Efforts.

BACKGROUND: Antibiotic overuse remains a significant problem. The objective of this study was to develop a methodology to evaluate antibiotic use across inpatient and ambulatory care sites in an integrated healthcare system to prioritize antibiotic stewardship efforts. METHODS: We conducted an epidemiologic study of antibiotic use across an integrated healthcare system on 12 randomly selected days from 2017 to 2018. For inpatients and perioperative patients, administrations of antibiotics were recorded, whereas prescriptions were recorded for outpatients. RESULTS: On the study days, 10.9% (95% confidence interval [CI], 10.6%-11.3%) of patients received antibiotics. Of all antibiotics, 54.1% were from ambulatory care (95% CI, 52.6%-55.7%), 38.0% were from the hospital (95% CI, 36.6%-39.5%), and 7.8% (95% CI, 7.1%-8.7%) were perioperative. The emergency department/urgent care centers, adult outpatient clinics, and adult non-critical care inpatient wards accounted for 26.4% (95% CI, 25.0%-27.7%), 23.8% (95% CI, 22.6%-25.2%), and 23.9% (95% CI, 22.7%-25.3%) of antibiotic use, respectively. Only 9.2% (95% CI, 8.3%-10.1%) of all antibiotics were administered in critical care units. Antibiotics with a broad spectrum of gram-negative activity accounted for 30.4% (95% CI, 29.0%-31.9%) of antibiotics. Infections of the respiratory tract were the leading indication for antibiotics. CONCLUSIONS: In an integrated healthcare system, more than half of antibiotic use occurred in the emergency department/urgent care centers and outpatient clinics. Antibiotics with a broad spectrum of gram-negative activity accounted for a large portion of antibiotic use. Analysis of antibiotic utilization across the spectrum of inpatient and ambulatory care is useful to prioritize antibiotic stewardship efforts.

Effectiveness of Shorter Versus Longer Durations of Therapy for Common Inpatient Infections Associated With Bacteremia: A Multicenter, Propensity-Weighted Cohort Study.

BACKGROUND: National guidelines for pneumonia (PNA), urinary tract infection (UTI), and acute bacterial skin and skin structure infection (ABSSSI) do not address treatment duration for infections associated with bacteremia. We evaluated clinical outcomes of patients receiving shorter (5-9 days) versus longer (10-15 days) duration of antibiotics. METHODS: This was a multicenter retrospective cohort study of inpatients with uncomplicated PNA, UTI, or ABSSSI and associated bacteremia. The primary outcome was clinical failure, a composite of rehospitalization, reinitiation of antibiotics, or all-cause mortality within 30 days of antibiotic completion. Secondary outcomes included individual components of the primary outcome, Clostridioides difficile infection, and antibiotic-related adverse effects necessitating change in therapy. A propensity score-weighted logistic regression model was used to mitigate potential bias associated with nonrandom assignment of treatment duration. RESULTS: Of 408 patients included, 123 received a shorter treatment duration (median 8 days) and 285 received a longer duration (median 13 days). In the propensity-weighted analysis, the probability of the primary outcome was 13.5% in the shorter group and 11.1% in the longer group (average treatment effect, 2.4%; odds ratio [OR], 1.25; 95% confidence interval [CI], .65-2.40; P = .505). However, shorter courses were associated with higher probability of restarting antibiotics (OR, 1.62; 95% CI, 1.01-2.61; P = .046) and C. difficile infection (OR, 4.01; 95% CI, 2.21-7.59; P < .0001). CONCLUSIONS: Shorter courses of antibiotic treatment for PNA, UTI, and ABSSSI with bacteremia were not associated with increased overall risk of clinical failure; however, prospective studies are needed to further evaluate the effectiveness of shorter treatment durations.

Patterns of use and perceptions of an institution-specific antibiotic stewardship application among emergency department and urgent care clinicians.

We surveyed emergency department and urgent care clinicians to assess patterns of use and perceived usefulness of a local antibiotic stewardship application to deliver institution-specific prescribing guidance. Among 114 eligible respondents, the application was widely utilized, and it was perceived to be a useful clinical resource that improved prescribing.

Corticosteroids for Posttransplant Immune Reconstitution Syndrome in Cryptococcus gattii Meningoencephalitis: Case Report and Literature Review.

Cryptococcus gattii represents an emerging fungal pathogen of immunocompromised and immunocompetent hosts in the United States. To our knowledge, this is the first case of posttransplant immune reconstitution syndrome due to C. gattii meningoencephalitis successfully treated with corticosteroids. We also report successful maintenance phase treatment with isavuconazole, a novel triazole, following fluconazole-induced prolonged QT syndrome.

Omadacycline: A New Tetracycline Antibiotic.

OBJECTIVE: To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, dosage, and administration of omadacycline, a new tetracycline antibiotic. DATA SOURCES: A literature search through PubMed, Google Scholar, and clinicaltrials.gov was conducted (2008 to October 2018) using the search terms omadacycline and PTK-0796. Abstracts presented at recent conferences, prescribing information and information from the FDA and the manufacturer's website were reviewed. STUDY SELECTION AND DATA EXTRACTION: Preclinical data and published phase 1, 2, and 3 studies were evaluated. DATA SYNTHESIS: Omadacycline displays in vitro activity against a wide range of bacteria. Clinical trials have shown that omadacycline is noninferior to linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia (CABP). A loading dose of 200 mg intravenously (IV) once or 100 mg IV twice or 450 mg orally once is recommended followed by a maintenance dose of 100 mg IV or 300 mg orally once daily. No dosage adjustment is needed in patients with renal or hepatic impairment. Omadacycline is well tolerated, with nausea being a common adverse effect, but is associated with food and drug interactions. Relevance to Patient Care and Clinical Practice: Omadacycline is active against staphylococci, including methicillin-resistant strains, and streptococci, including tetracycline-resistant strains, as well as atypical bacteria. Omadacycline provides clinicians with an additional parenteral and oral option for the treatment of adults with ABSSSI and CABP. CONCLUSION: Omadacycline is an alternative treatment option for ABSSSI and CABP.

Implementation of an institution-specific antimicrobial stewardship smartphone application.

Smartphones are increasingly used to access clinical decision support, and many medical applications provide antimicrobial prescribing guidance. However, these applications do not account for local antibiotic resistance patterns and formularies. We implemented an institution-specific antimicrobial stewardship smartphone application and studied patterns of use over a 1-year period.

Appropriateness of antibiotic prescriptions for acute sinusitis and pharyngitis in an integrated healthcare system.

We evaluated the appropriateness of antibiotic prescriptions for acute sinusitis and pharyngitis. Overall, 81% of antibiotic prescriptions for acute sinusitis were inappropriate and 48% of antibiotic prescriptions for pharyngitis were inappropriate. Types of prescribing errors differed between the 2 infections, including lack of an indication for antibiotics and excessive duration in ~50% of sinusitis cases and incorrect antibiotic dose in ~33% of pharyngitis cases.Infect Control Hosp Epidemiol 2018; 0, 1-3.

A Statewide Antibiotic Stewardship Collaborative to Improve the Diagnosis and Treatment of Urinary Tract and Skin and Soft Tissue Infections.

Background: Colorado hospitals participated in a statewide collaborative to improve the management of inpatient urinary tract infections (UTIs) and skin and soft tissue infections (SSTIs). We evaluated the effects of the intervention on diagnostic accuracy and antibiotic use. Methods: The main collaborative outcomes were proportion of UTI diagnoses that met criteria for symptomatic UTI; exposure to fluoroquinolones (UTI only); duration of therapy (UTIs and SSTIs); and exposure to antibiotics with broad gram-negative activity (SSTIs only). Outcomes were compared between pre-intervention and intervention periods overall and by hospital. Secondary analyses were changes in outcome trends by time series analysis. Results: Twenty-six hospitals, including 9 critical access hospitals, participated in the collaborative. Data were reported for 4060 UTIs and 1759 SSTIs. Between the pre-intervention and intervention periods, the proportion of diagnosed UTIs that met criteria for symptomatic UTI was similar (51% vs 54%, respectively; P = .10), exposure to fluoroquinolones declined (49% vs 41%; P < .001), and the median duration of therapy was unchanged (7 vs 7 days; P = .99). Among SSTIs, exposure to antibiotics with broad gram-negative activity declined (61% vs 53%; P = .001) and the median duration of therapy declined (11 vs 10 days; P = .03). There was substantial variation in performance among hospitals. By time series analysis, only the declining trend of fluoroquinolone use was significant (P = .03). Conclusions: The collaborative model is a feasible approach to engage hospitals in a common antibiotic stewardship intervention. Performance improvement was observed for several outcomes but varied substantially by hospital.

Preferential Use of Nitrofurantoin Over Fluoroquinolones for Acute Uncomplicated Cystitis and Outpatient Escherichia coli Resistance in an Integrated Healthcare System.

OBJECTIVES To evaluate changes in outpatient fluoroquinolone (FQ) and nitrofurantoin (NFT) use and resistance among E. coli isolates after a change in institutional guidance to use NFT over FQs for acute uncomplicated cystitis. DESIGN Retrospective preintervention-postintervention study. SETTING Urban, integrated healthcare system. PATIENTS Adult outpatients treated for acute cystitis. METHODS We compared 2 time periods: January 2003-June 2007 when FQs were recommended as first-line therapy, and July 2007-December 2012, when NFT was recommended. The main outcomes were changes in FQ and NFT use and FQ- and NFT-resistant E. coli by time-series analysis. RESULTS Overall, 5,714 adults treated for acute cystitis and 11,367 outpatient E. coli isolates were included in the analysis. After the change in prescribing guidance, there was an immediate 26% (95% CI, 20%-32%) decrease in FQ use (P<.001), and a nonsignificant 6% (95% CI, -2% to 15%) increase in NFT use (P=.12); these changes were sustained over the postintervention period. Oral cephalosporin use also increased during the postintervention period. There was a significant decrease in FQ-resistant E. coli of -0.4% per quarter (95% CI, -0.6% to -0.1%; P=.004) between the pre- and postintervention periods; however, a change in the trend of NFT-resistant E. coli was not observed. CONCLUSIONS In an integrated healthcare system, a change in institutional guidance for acute uncomplicated cystitis was associated with a reduction in FQ use, which may have contributed to a stabilization in FQ-resistant E. coli. Increased nitrofurantoin use was not associated with a change in NFT resistance. Infect Control Hosp Epidemiol 2017;38:461-468.