In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To describe the implementation and operationalization of a β-lactam (BL) therapeutic drug monitoring(TDM) program at a large academic center. BLs are the most used class of antibiotics. Suboptimal antibiotic exposure is a significant concern in hospitalized patients, particularly in those with altered pharmacokinetics. BL-TDM provides clinicians the opportunity to optimize drug concentrations to ensure maximal therapeutic efficacy while minimizing toxicity. However, BL-TDM has not been widely adopted due to the lack of access to assays. The University of Florida Shands Hospital developed a BL-TDM program in 2015. This is a consultative service primarily run by pharmacists and is conducted in all patient care areas. An analysis was performed on the first BL-TDM encounter for 1,438 patients. BL-TDM was most frequently performed for cefepime (61%, n = 882), piperacillin (15%, n = 218), and meropenem (11%, n = 151). BL-TDM was performed a median of 3 days (interquartile range, 1-5 days) from BL initiation. Among patients with available minimum inhibitory concentration (MIC) values and trough concentrations, the pharmacokinetic/pharmacodynamic (PK/PD) target of 100% fT>MIC was attained in 308 patients (88%). BL-TDM resulted in a dosage adjustment in 25% (n = 361) of patients. Implementation of a BL-TDM program requires the concerted efforts of physicians, pharmacists, nursing staff, phlebotomists, and personnel in the analytical laboratory. Standard antibiotic dosing failed to achieve optimal PK/PD targets in all patients; utilizing BL-TDM, dose adjustments were made in 1 of every 4 patients.

Objectives Skin and soft-tissue infections (SSTIs) encompass a diverse range of infections of varying severity. The Clinical Resource Efficiency Support Team (CREST) scoring system stratifies patients into four classes (I = least severe to IV = most severe) based on the Standardized Early Warning Score (SEWS). The objective of this study was to apply CREST to hospitalized patients with SSTIs in order to quantify disease severity and evaluate appropriateness of antibiotic management. Methods This was a retrospective, hypothesis-generating, single-centre evaluation of hospitalized patients with SSTIs admitted in 2011. Based on CREST classification, the empirical antimicrobial choices were categorized as appropriate, over-treatment or under-treatment. Results A total of 369 patients were screened and 200 met the inclusion criteria. The majority of patients were classified as either CREST class I (n = 68) or class II (n = 102). Over-treatment was more common in the less severe classes (88% and 32% in class I and class II, respectively; P < 0.05). Sixty-three percent of class I (n = 43) were over-treated due to both the use of intravenous antibiotics when oral therapy was sufficient and use of unnecessarily broad-spectrum antibiotics. In contrast, 25% (n = 26) of class II were over-treated due to use of unnecessarily broad-spectrum antibiotics. Overall clinical failure rates remained low with only 1%, 4% and 17% of patients unable to achieve initial response in class II, class III and class IV. Conclusions Retrospective application of CREST identified opportunities to improve the management of SSTIs. CREST can be of great value in discriminating less-severe SSTIs, which can be treated on an outpatient basis.

Objective: To re-examine the use of noncarbapenems (NCBPs), specifically piperacillin-tazobactam (PTZ) and cefepime (FEP), for extended-spectrum beta-lactamase–producing Enterobacterales bloodstream infections (ESBL-E BSIs). Design: Retrospective cohort study. Setting: Tertiary-care, academic medical center. Patients: The study included patients hospitalized between May 2016 and May 2019 with a positive blood culture for ESBL-E. Patients were excluded if they received treatment with antibiotics other than meropenem, ertapenem, PTZ, or FEP. Patients were also excluded if they were aged <18 years, received antibiotics for <24 hours, were treated for polymicrobial BSI, or received concomitant antibiotic therapy for a separate gram-negative infection. Methods: We compared CBPs with FEP or PTZ for the treatment of ESBL-E BSI. The primary outcome was in-hospital mortality. Secondary outcomes included clinical cure, microbiologic cure, infection recurrence, and resistance development. Results: Data from 114 patients were collected and analyzed; 74 (65%) patients received carbapenem (CBP) therapy and 40 (35%) patients received a NCBP (30 received FEP and 10 received PTZ). The overall in-hospital mortality was 6% (N = 7), with a higher death rate in the CBP arm than in the N-CBP arm, (8% vs 3%; P = .42). No difference in mortality was detected between subgroups with Pitt bacteremia score ≥4, those requiring ICU admission, those whose infections were cause by a nongenitourinary source or causative organism (ie, 76 had Escherichia coli and 38 had Klebsiella spp). We detected no differences in secondary outcomes between the groups. Conclusion: Compared to CBPs, FEP and PTZ did not result in greater mortality or decreased clinical efficacy for the treatment of ESBL-E BSI caused by susceptible organisms.

Background: Multidrug-resistant (MDR) gram-negative infections are a substantial threat to patients and public health. Imipenem-cilastatin-relebactam (IMI/REL) is a β-lactam/β-lactamase inhibitor with expanded activity against MDR Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales. This study aims to describe the patient characteristics, prescribing patterns, and clinical outcomes associated with IMI/REL. Methods: This was a retrospective, multicenter, observational study of patients ≥18 years old who received IMI/REL for ≥48 hours for a suspected or confirmed gram-negative infection. The primary outcome was clinical success, defined as improvement or resolution of infection-related signs or symptoms while receiving IMI/REL and the absence of 30-day microbiologic failure. Multivariable logistic regression analysis was performed to identify independent predictors of clinical success. Results: The study included 151 patients from 24 US medical centers. IMI/REL was predominantly prescribed for lower respiratory tract infections, accounting for 52.3% of cases. Most patients were infected with a carbapenem-nonsusceptible pathogen (85.4%); P aeruginosa was frequently targeted (72.2%). Clinical success was achieved in 70.2% of patients. Heart failure, receipt of antibiotics within the past 90 days, intensive care unit admission at time of index culture collection, and isolation of difficult-to-treat resistant P aeruginosa were independently associated with a reduced odds of clinical success. Adverse events were reported in 6.0% of patients, leading to discontinuation of IMI/REL in 3 instances. Conclusions: This study provides a comprehensive analysis of the real-world effectiveness and safety of IMI/REL. Comparative studies and investigations of specific subgroups will further enhance our understanding of IMI/REL in treating MDR infections.

Background: The antibiotic armamentarium used to combat multi-drug resistant organisms (MDROs) include carbapenems. Continuous infusion (CI) dosing is frequently employed to maximize beta-lactam efficacy; however, use of meropenem CI has been limited due to concerns with product instability. Objective: The primary objective of this study was to quantify meropenem serum concentrations to reflect drug stability when administered as CI over 8- or 12-h exchanges. In addition, a stability experiment was performed to further establish meropenem integrity over 12 h. The secondary objectives were to assess the ability of meropenem to achieve target pharmacokinetic/pharmacodynamic (PK/PD) exposures relative to the minimum inhibitory concentration (MIC) of the pathogen, and to determine clinical cure. Methods: This was a retrospective, observational study on use of CI meropenem (infused either over 8- or 12- h) at a 1% concentration. The stability experiment was conducted on 1% meropenem at room temperature. Results: In 22 patients, a median meropenem daily dose of 6 g/day (range 2-6 g/day) resulted in a median serum concentration of 17.8 mg/L (interquartile range, 9.3-27.8 mg/L). In 95% of cases, meropenem delivered as CI resulted in free drug concentrations at or above the MIC of the pathogen for the entire dosing interval. Clinical cure was achieved in 80% of patients included in this review. The stability experiment revealed negligible drug degradation at the end of the 12-h dosing interval. Conclusions: The data from this study provides compelling evidence for the use of meropenem as CI utilizing either a 12- or 8-h exchange process.