Meropenem-Vaborbactam as Salvage Therapy for Ceftazidime-Avibactam-Resistant Klebsiella pneumoniae Bacteremia and Abscess in a Liver Transplant Recipient

Abstract

We report a case of a 24-year-old liver transplant recipient who developed hepatic artery thrombosis and graft failure, which was complicated by subphrenic abscess and persistent Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bacteremia. Ceftazidime-avibactam treatment led to emergence of resistance, and alternative combination therapy failed due to persistent infection and toxicity. The infection resolved after initiation of meropenem-vaborbactam, which created a bridge to retransplantation. Treatment-emergent ceftazidime-avibactam resistance is increasingly recognized, suggesting a role for meropenem-vaborbactam.

Difficult-to-Treat Antibiotic-Resistant Gram-Negative Pathogens in the Intensive Care Unit: Epidemiology, Outcomes, and Treatment

“…Notably, real-world experience is lacking with meropenem-vaborbactam as compared with ceftazidime-avibactam although a recent case report was published which showed efficacy of meropenem-vaborbactam as salvage therapy in a patient with bacteremia with a ceftazidime-avibactam-resistant K. pneumoniae. 101 One advantage of meropenem-vaborbactam over ceftazidime-avibactam is that it may have a higher barrier to resistance. 102 Adding to the antibiotic armamentarium against CRE is plazomicin, a novel aminoglycoside that was FDA approved in 2018 for complicated urinary tract infections, that is, able to evade most of the aminoglycoside-modifying enzymes and is not affected by the presence of carbapenemase (►Table 1).…”

“…As a result, many patients are treated for longer courses when they have a highly resistant infection primarily out of an inherent concern for relapse, recrudescence, or treatment failure. 101,137 Adjunctive Therapy…”

Resistance to Ceftazidime/Avibactam Plus Meropenem/Vaborbactam When Both are Used Together Achieved in Four Steps From Metallo-β-Lactamase Negative Klebsiella pneumoniae

“…Finally, we wanted to test whether the two β-lactam/inhibitor pairs would work synergistically, to give hope of clinical efficacy for the double combination therapy that has been discussed as a possibility for clinical use in the literature (20,21). Checkerboard assays ( Figure ) confirmed that KP21 M[ ompK36 ](pOXA-232) and KP21 ompK36 (pOXA-232) carrying pCTX-M14-P170S, pKPC-3 or pKPC-3-V239G are all susceptible to meropenem (MIC ≤ 8 μg.mL −1 ) in the presence of vaborbactam plus ceftazidime/avibactam suggesting that combined therapy would still work.…”

“…Given the appearance of K. pneumoniae clinical isolates and laboratory selected mutants that are resistant to meropenem/vaborbactam or ceftazidime/avibactam, there has been some discussion in the literature about whether a combination of both β-lactam/β-lactamase inhibitor pairs given together would overcome isolates resistant to either, and to both when used separately (20,21). In the work reported here we identified the steps required to generate resistance to each β-lactam/β-lactamase inhibitor pair, both pairs when used separately, and both pairs when used together.…”

Meropenem Combined with Ertapenem Rescues a Patient with Multi-Drug Resistant Klebsiella pneumoniae V113 Isolate Infection and Acute-on-Chronic Liver Failure: A Case Report

“…The proportion of KPC-producing K. pneumoniae strains has remarkably increased year-by-year, associating with high mortality (3,4). Recently, Athans et al (5) reported that persistent KPC-producing K. pneumoniae infection could be resolved after initiating meropenemvaborbactam. Colistin, which has a narrow therapeutic window, has been previously recommended, however, it has still remained controversial in patients with renal dysfunction (5).…”