Abstract
Abstract Background Treatment of infections due to multidrug resistant (MDR) Pseudomonas aeruginosa is complicated by co-resistance amongst traditional anti-pseudomonal β-lactams, as 50% of MDR isolates exhibit extensive β-lactam resistance (EBR, non-susceptible to cefepime, ceftazidime, piperacillin/tazobactam, and meropenem). Ceftolozane/tazobactam (C/T) was developed to combat MDR and EBR P. aeruginosa. Unfortunately, C/T resistance has proliferated. We designed this retrospective case-control study to identify risk factors for C/T non-susceptibility (NS) amongst EBR P. aeruginosa. Methods Between 2015 to 2020, hospitalized adult patients infected or colonized with EBR P. aeruginosa were identified. C/T susceptibility was defined per the 2023 Clinical and Laboratory Standards Institute (CLSI) guidelines (susceptible (S) if minimum inhibitory concentration (MIC) ≤ 4 mg/L, NS if MIC ≥ 8 mg/L). Patients with an EBR P. aeruginosa NS to C/T were classified as cases, whereas those with S isolates were controls. Patients with multiple EBR P. aeruginosa isolates over the study period were only included once. If a patient had a C/T NS isolate, they were classified as cases and the first C/T NS isolate was included as the index culture. If the patient did not have a C/T NS isolate over the study period, they were considered a control and the first C/T S isolate was the index culture. Bivariate and multivariate modeling was performed to identify independent predictors for C/T NS. Results 188 unique patients with C/T susceptibility performed were included in the study; 96 (51%) were C/T NS and 92 (49%) were C/T S. Table 1 shows the bivariate comparisons of key baseline characteristics between groups. Independent predictors of C/T NS are displayed in table 2. Conclusion Independent predictors for C/T NS amongst EBR P. aeruginosa isolates were a history of cancer, cystic fibrosis, and isolation of EBR P. aeruginosa in the past 90 days. While receipt of cefepime or ceftazidime in the past 90 days was associated with C/T NS in bivariate comparisons, the association did not remain in multivariate modeling. C/T exposure was not a statistically significant risk factor, but it was numerically associated with NS and the lack of significance was likely due to the small number of patients (n = 15) who received it. Disclosures Virginia M. Pierce, MD, FIDSA, UpToDate, Inc.: Authorship royalties jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant
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