Real-world Multicenter Analysis of Clinical Outcomes and Safety of Meropenem-Vaborbactam in Patients Treated for Serious Gram-Negative Bacterial Infections

Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV

Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas Aeruginosa

Background: We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE). Methods: This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR). Results: Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081-0.941). Conclusions: Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs

Trowels and Tribulations: Review of Antimicrobial-Impregnated Bone Cements in Prosthetic Joint Surgery

Antimicrobial-impregnated bone cement (AIBC) is a staple of contemporary orthopedic surgery and has been used to either treat or prevent prosthetic joint infection. Applied intraoperatively during primary arthroplasty or prosthetic joint exchange, this drug-delivery vehicle has become a popular means of maximizing drug concentrations within a joint space while minimizing systemic exposure. Antimicrobial characteristics conducive to cement loading include availability of a crystalline powder formulation, molecular characteristics, minimal impact on cement integrity, and other variables promoting drug elution. Antimicrobials most commonly incorporated into cements are vancomycin and aminoglycosides, usually in combination due to synergistic antibacterial activity and enhanced cement elution. Other classes include the β-lactams, lipopeptides, oxazolidinones, and antifungals. With the exception of several commercially available AIBCs, most products are compounded extemporaneously without a formal safety or efficacy assessment. Few randomized controlled trials have been conducted to assess the benefit or optimal use of these cement preparations, and variable methodology renders cross-study comparison challenging. Given the lack of standardization and multidisciplinary oversight often seen with practical AIBC use, additional data are needed. This review presents information intended to guide AIBC preparation, selection, dosing, and safe use. In addition, opportunities for best practice development, antimicrobial stewardship, and future research are discussed

Outpatient use of ceftaroline fosamil versus vancomycin for osteoarticular infection: a matched cohort study

OBJECTIVES: There are few convenient intravenous options for long-term outpatient treatment of osteoarticular infection (OAI) and limited effectiveness and safety data exist for this off-label use of ceftaroline. The objective of this study was to describe the long-term effectiveness and safety of ceftaroline for the treatment of OAI. METHODS: This was a matched retrospective cohort study of patients receiving ceftaroline- or vancomycin-based therapy for OAI in the outpatient setting. Patients were matched according to infection subtype, anatomical site and microbiology. The primary endpoint was 180 day infection-related readmission (IRR). Secondary endpoints included all-cause readmission, time-to-IRR and adverse event incidence. RESULTS: The final matched cohort consisted of 50 ceftaroline-treated patients and 50 vancomycin-treated patients. The IRR incidence was 22% for ceftaroline patients and 30% for vancomycin patients; OR = 0.66 (95% CI = 0.27-1.62; P = 0.362). There was no significant difference between groups in all-cause readmission or time-to-IRR. Attributable adverse event incidences were 24% and 18% for ceftaroline and vancomycin, respectively. Rash (10%) and nausea (6%) were the most common ceftaroline adverse events, while acute kidney injury (6%) and rash (4%) were the most common vancomycin adverse events. CONCLUSIONS: Attributable readmission and adverse events were common among patients treated with outpatient intravenous antimicrobials for OAI. This study found no appreciable difference in effectiveness or tolerability between ceftaroline- or vancomycin-treated patients. Although further research will be important to delineate the role of ceftaroline in the management of OAI, data derived from this study may aid clinicians in determining therapy when limited options exist

1575. Predictors of Negative Clinical Outcomes among Patients treated with Meropenem-Vaborbactam for Serious Gram-Negative Bacterial Infections: Impact of Delayed Appropriate Antibiotic Selection

Abstract Background Numerous number of studies have found a positive correlation between delayed appropriate antibiotic therapy and negative clinical outcomes (NCO) in Gram-negative bacterial infections (GNBI). The combination of meropenem with vaborbactam (MVB) received Food and Drug Administration approval for the treatment of complicated urinary tract infections and acute pyelonephritis caused by susceptible organisms in August 2017. We sought to determine the impact of delayed appropriate therapy with MVB on NCO among patients with GNBI. Methods Multi-center, retrospective cohort study from October 2017 to March 2020. We included adult patients treated with MVB for >72 hours. We excluded patients who received alternative appropriate antibiotics for GNB prior to MVB and patients with unknown dates for index culture. NCO were defined as 30-day mortality and/or microbiological recurrence. All outcomes were measured from MVB start date. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineates the risk of NCO. Multivariable logistic regression analysis (MLR) was used to examine the independent association between the CART-derived-BP and NCO. Variables were retained in the model if P< 0.2 and removed in a backward stepwise approach. Results A total of 86 patients were included from 13 institutions in the United States: median(IQR) age 55 (37-67) years, 67% male, and 48% Caucasian. Median(IQR) APACHE II and Charlson Comorbidity index scores were 18(11-26) and 4(2-6), respectively. Common sources of infection were respiratory (37%) and intra-abdominal (21%). The most common pathogens were carbapenem-resistant Enterobacterales (83%). CART-derived BP between early and delayed treatment was 48 hours, where NCO was increased (36% vs.7%; P=0.04). Delayed MVB initiation was independently associated with NCO in the MLR (aOR=7.4, P=0.02). Results of Regression Analysis of Variables Associated With Negative Clinical Outcomes and Delayed Appropriate Therapy with Meropenem-vaborbactam Conclusion Our results suggest that delaying appropriate antibiotic therapy with MVB for >48 hours significantly increases the risk of NCO in patients with GNBI. Clinicians must ensure timely administration of MVB to assure best outcomes in patients with GNBI. Disclosures Kevin W. Garey, PharMD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator) Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support