Novel β-lactam-β-lactamase inhibitors as monotherapy versus combination for the treatment of drug-resistant Pseudomonas aeruginosa infections: A multicenter cohort study

J Infect Chemother. 2024 Oct;30(10):1008-1014. doi: 10.1016/j.jiac.2024.03.015. Epub 2024 Mar 25.

Abstract

Background: Data comparing the clinical outcomes of novel β-lactam-β-lactamase inhibitors given in combination versus monotherapy for the treatment of multidrug-resistant (MDR) P. aeruginosa infections are lacking.

Method: This retrospective cohort study included patients who received novel β-lactam-β-lactamase inhibitors as monotherapy or in combination for the treatment of MDR P. aeruginosa infections. The study was conducted between 2017 and 2022 in 6 tertiary care hospitals in Saudi Arabia. Overall in-hospital mortality, 30-day mortality, clinical cure, and acute kidney injury (AKI) were compared between recipients of monotherapy versus combination using multivariate logistic regression analysis.

Result: 118 patients and 82 patients were included in monotherapy and combination therapy arms, respectively. The cohort represented an ill population with 56% in the intensive care unit and 37% in septic shock. A total of 19% of patients presented with bacteremia. Compared to monotherapy, combination therapy did not significantly differ in clinical cure (57% vs. 68%; P = 0.313; OR, 0.63; 95% CI, 0.36-1.14) in-hospital mortality (45% vs. 37%; P = 0.267; OR, 1.38; 95% CI, 0.78-2.45), or 30-day mortality (27% vs. 24%; P = 0.619; OR, 1.18; 95% CI, 0.62-1.25). However, AKI (32% vs. 12%; P = 0.0006; OR, 3.45; 95% CI, 1.67-7.13) was significantly more common in patients who received combination therapy.

Conclusion: Novel β-lactam-β-lactamase inhibitors when used in combination with other antibiotics did not add clinical benefit compared to their use as monotherapy in the treatment of MDR P. aeruginosa infections. A Combination regimen was associated with an increased risk of nephrotoxicity.

Keywords: Combination therapy; Monotherapy; Multidrug-resistant; Pseudomonas aeruginosa.

Publication types

  • Multicenter Study

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents* / therapeutic use
  • Bacteremia / drug therapy
  • Bacteremia / microbiology
  • Bacteremia / mortality
  • Drug Resistance, Multiple, Bacterial*
  • Drug Therapy, Combination
  • Female
  • Hospital Mortality
  • Humans
  • Male
  • Middle Aged
  • Pseudomonas Infections* / drug therapy
  • Pseudomonas Infections* / microbiology
  • Pseudomonas Infections* / mortality
  • Pseudomonas aeruginosa / drug effects
  • Retrospective Studies
  • Saudi Arabia / epidemiology
  • Tertiary Care Centers / statistics & numerical data
  • Treatment Outcome
  • beta-Lactamase Inhibitors* / therapeutic use
  • beta-Lactams / therapeutic use

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors
  • beta-Lactams
  • ceftolozane, tazobactam drug combination
  • avibactam, ceftazidime drug combination