When More Is Still Not Enough: A Case of Ceftazidime-Avibactam Resistance in a Burn Patient

• Published in: Journal of burn care & research 2022-03, Vol.43 (2), p.474-478
• Main Authors: Herbin, Shelbye R, Barber, Katie E, Isaacson, Andrew R, Dolman, Heather S, McGee, Jessica D, Baylor, Alfred E, Tyburski, James G, White, Michael T, Faris, Janie
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamases - genetics; Burns - drug therapy; Cefepime; Ceftazidime - pharmacokinetics; Ceftazidime - therapeutic use; Drug Combinations; Drug Resistance, Multiple, Bacterial; Genetic Markers; Humans; Meropenem - pharmacology; Microbial Sensitivity Tests; Middle Aged
• ISSN: 1559-047X; 1559-0488
• DOI: 10.1093/jbcr/irab160

Abstract Burn patients have numerous risk factors for multidrug-resistant organisms (MDROs) and altered pharmacokinetics, which both independently increase the risk of treatment failure. Data on appropriate antimicrobial dosing are limited in this population and therapeutic drug monitoring (TDM) for beta-lactams is impractical at most facilities. Technology is available that can detect genetic markers of resistance, but they are not all encompassing, and often require specialized facilities that can detect less common genetic markers. Newer antimicrobials can help combat MDROs, but additional resistance patterns may evolve during treatment. Considering drug shortages and antimicrobial formularies, clinicians must remain vigilant when treating infections. This case report describes the development of resistance to ceftazidime-avibactam in a burn patient. The patient was a 54-year-old burn victim with a 58% total body surface area (TBSA) thermal burn who underwent multiple courses of antibiotics for various Pseudomonal infections. The initial Pseudomonal wound infection was sensitive to cefepime, aminoglycosides, and meropenem. A subsequent resistant pseudomonal pneumonia was treated with ceftazidime-avibactam 2.5 g every 6 hours due to the elevated MIC to cefepime (16 mcg/mL) and meropenem (>8 mcg/mL). Although the patient improved over 7 days, the patient again spiked fevers and had increased white blood counts (WBC). Repeat blood cultures demonstrated a multidrug-resistant (MDR) Pseudomonas with a minimum inhibitory concentration (MIC) to ceftazidime-avibactam of 16 mcg/mL, which is above the Clinical and Laboratory Standards Institute (CLSI) breakpoint of 8 mcg/mL. At first, resistance was thought to have occurred due to inadequate dosing, but genetic work demonstrated multiple genes encoding beta-lactamases.