Prevalence and Predictors of Pseudomonas aeruginosa Among Hospitalized Patients With Diabetic Foot Infections.

Background: Diabetic foot infections (DFIs) are commonly associated with antibiotic overuse. Empiric DFI treatment often includes coverage for Pseudomonas aeruginosa (PsA), but the frequency of PsA DFIs is poorly understood. The study objectives were to quantify the prevalence of and determine predictors for PsA DFIs. Methods: This multicenter, retrospective cohort included hospitalized patients with DFI from 2013 through 2020 who were age ≥18 years; diabetes mellitus diagnosis; and DFI based on International Classification of Diseases, Tenth Revision coding, antibiotic treatment, and DFI culture with organism growth. Osteomyelitis was excluded. Patient characteristics were described and compared; the primary outcome was presence of PsA on DFI culture. Predictors of PsA DFI were identified using multivariable logistic regression. Results: Two hundred ninety-two patients were included. The median age was 61 (interquartile range [IQR], 53-69) years; the majority were men (201 [69%]) and White (163 [56%]). The most commonly isolated organisms were methicillin-susceptible Staphylococcus aureus (35%) and streptococci (32%); 147 (54%) cultures were polymicrobial. Two hundred fifty-seven (88%) patients received empiric antibiotics active against PsA, but only 27 (9%) patients had PsA DFI. Immunocompromised status (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 1.3-16.7]) and previous outpatient DFI antibiotic treatment failure (aOR, 4.8 [95% CI, 1.9-11.9]) were associated with PsA DFI. Conclusions: PsA DFI is uncommon, but most patients receive empiric antipseudomonal antibiotics. Empiric broad-spectrum antibiotics are warranted given the frequency of mixed infections, but patient-specific risk factors should be considered before adding antipseudomonal coverage.

Pharmacist-Driven Transitions of Care Practice Model for Prescribing Oral Antimicrobials at Hospital Discharge.

Importance: Although prescribers face numerous patient-centered challenges during transitions of care (TOC) at hospital discharge, prolonged duration of antimicrobial therapy for common infections remains problematic, and resources are needed for antimicrobial stewardship throughout this period. Objective: To evaluate a pharmacist-driven intervention designed to improve selection and duration of oral antimicrobial therapy prescribed at hospital discharge for common infections. Design, Setting, and Participants: This quality improvement study used a nonrandomized stepped-wedge design with 3 study phases from September 1, 2018, to August 31, 2019. Seventeen distinct medicine, surgery, and specialty units from a health system in Southeast Michigan participated, including 1 academic tertiary hospital and 4 community hospitals. Hospitalized adults who had urinary, respiratory, skin and/or soft tissue, and intra-abdominal infections and were prescribed antimicrobials at discharge were included in the analysis. Data were analyzed from February 18, 2020, to February 28, 2022. Interventions: Clinical pharmacists engaged in a new standard of care for antimicrobial stewardship practices during TOC by identifying patients to be discharged with a prescription for oral antimicrobials and collaborating with primary teams to prescribe optimal therapy. Academic and community hospitals used both antimicrobial stewardship and clinical pharmacists in a multidisciplinary rounding model to discuss, document, and facilitate order entry of the antimicrobial prescription at discharge. Main Outcomes and Measures: The primary end point was frequency of optimized antimicrobial prescription at discharge. Health system guidelines developed from national guidelines and best practices for short-course therapies were used to evaluate optimal therapy. Results: A total of 800 patients prescribed oral antimicrobials at hospital discharge were included in the analysis (441 women [55.1%]; mean [SD] age, 66.8 [17.3] years): 400 in the preintervention period and 400 in the postintervention period. The most common diagnoses were pneumonia (264 [33.0%]), upper respiratory tract infection and/or acute exacerbation of chronic obstructive pulmonary disease (214 [26.8%]), and urinary tract infection (203 [25.4%]). Patients in the postintervention group were more likely to have an optimal antimicrobial prescription (time-adjusted generalized estimating equation odds ratio, 5.63 [95% CI, 3.69-8.60]). The absolute increase in optimal prescribing in the postintervention group was consistent in both academic (37.4% [95% CI, 27.5%-46.7%]) and community (43.2% [95% CI, 32.4%-52.8%]) TOC models. There were no differences in clinical resolution or mortality. Fewer severe antimicrobial-related adverse effects (time-adjusted generalized estimating equation odds ratio, 0.40 [95% CI, 0.18-0.88]) were identified in the postintervention (13 [3.2%]) compared with the preintervention (36 [9.0%]) groups. Conclusions and Relevance: The findings of this quality improvement study suggest that targeted antimicrobial stewardship interventions during TOC were associated with increased optimal, guideline-concordant antimicrobial prescriptions at discharge.

Pharmacokinetics of Cefazolin in Patients With Obesity Undergoing Surgery Requiring Cardiopulmonary Bypass.

OBJECTIVE: The authors' objective was to determine the adequacy of an institutional standard dosing practice for infection prophylaxis in open cardiac surgery in patients heavier than 120 kg undergoing cardiopulmonary bypass. DESIGN: A prospective, single-center, open-label study was used to determine if cefazolin serum concentrations were maintained above the minimum inhibitory concentration (MIC) throughout surgery. A pharmacokinetic model describing cefazolin disposition was developed for perioperative patients with morbid obesity, based on these values. Probability of target attainment was evaluated across the clinically relevant MIC spectrum. SETTING: Maine Medical Center is an academic hospital in Portland, Maine, affiliated with Tufts University School of Medicine. PARTICIPANTS: Twenty patients scheduled for cardiac surgery requiring cardiopulmonary bypass who weighed at least 120 kg. INTERVENTIONS: All patients received 2 g of cefazolin intravenously (IV) within 1 hour before incision, an additional 1 g injected into the cardiopulmonary bypass circuit at the initiation of bypass, and 2 g administered IV every 3 hours after the initial IV dose. MEASUREMENTS AND MAIN RESULTS: Cefazolin serum concentrations were collected after incision, after initiation of bypass, each hour of bypass, at the end of bypass, and at sternal closure. For patients weighing >120 kg undergoing cardiac surgery, the studied dosing regimen met or exceeded targeted cefazolin concentrations for all study patients. The authors conducted probability of target attainment analyses using both 65% and 100% of time with unbound drug concentrations across clinically relevant MICs. CONCLUSION: The authors found that their current dosing strategy achieved a probability of target attainment >90% throughout surgery for both total and unbound cefazolin concentrations, independent of cardiopulmonary bypass times.

Antimicrobial never events: Objective application of a framework to assess vancomycin appropriateness.

To address appropriateness of antibiotic use, we implemented an electronic framework to evaluate antibiotic "never events" (NEs) at 2 medical centers. Patient-level vancomycin administration records were classified as NEs or non-NEs. The objective framework allowed capture of true-positive vancomycin NEs in one-third of patients identified by the electronic strategy.

It is time to define antimicrobial never events.

Inappropriate antibiotic use is associated with increased antimicrobial resistance and adverse events that can lead to further downstream patient harm. Preventative strategies must be employed to improve antibiotic use while reducing avoidable harm. We use the term "antibiotic never events" to globally recognize and define the most inappropriate antibiotic use.

Combatting resistant enterococcal infections: a pharmacotherapy review.

INTRODUCTION: The role of enterococci in infectious diseases has evolved from a gut and urinary commensal to a major pathogen of concern. Few options exist for resistant enterococci, and appropriate use of the available agents is crucial. AREAS COVERED: Herein, the authors discuss antibiotics with clinically useful activity against Enterococcus faecalis and E. faecium. The article specifically discusses: antibiotics active against enterococci and their mechanism of resistance, pharmacokinetic and pharmacodynamic principles, in vitro combinations, and clinical studies which focus on urinary tract, intra-abdominal, central nervous system, and bloodstream infections due to enterococci. EXPERT OPINION: Aminopenicillins are preferred over all other agents when enterococci are susceptible and patients can tolerate them. Daptomycin and linezolid have demonstrated clinical efficacy against vancomycin-resistant enterococci (VRE). Synergistic combinations are often warranted in complex infections of high inoculum and biofilms while monotherapies are generally appropriate for uncomplicated infections. Although active against resistant enterococci, the pharmacokinetics, efficacy and safety of tigecycline and quinupristin/dalfopristin can problematical for severe infections. For cystitis, amoxicillin, nitrofurantoin, or fosfomycin are ideal. Recently, approved agents such as tedizolid and oritavancin have good in vitro activity against VRE but clinical studies against other resistant enterococci are lacking.