IN VITRO TO IN VIVO: COMBATING MULTIDRUG-RESISTANT ENTEROBACTERIACAE IN THE AGE OF COVID-19

ABSTRACT

SESSION TITLE COVID-19 Co-Infections SESSION TYPE Rapid Fire Case Reports PRESENTED ON 10/19/2022 1245 pm - 145 pm INTRODUCTION: The COVID-19 pandemic has highlighted the emergence of multidrug-resistant bacterial pathogens. Here we present a case of the successful treatment of a COVID-19 superinfection with Citrobacter freundii, which produced both a Klebsiella pneumoniae carbapenemase (KPC) as well as a New Delhi Metallo-Beta-Lactamase (NDM-1). CASE PRESENTATION A 53-year-old male without significant past medical history was admitted to the intensive care unit for acute hypoxemic respiratory failure due to COVID-19 pneumonia. His hospital course was complicated by progressive hypoxia requiring intubation and mechanical ventilation. Due to persistent fevers and increased respiratory secretions, he was placed on empiric antibiotic therapy including vancomycin, cefepime, and briefly meropenem. Blood cultures were periodically drawn and ultimately demonstrated no growth. However, a respiratory culture via bronchoalveolar lavage was positive for multidrug-resistant Citrobacter freundii. Susceptibilities showed high level of resistance to meropenem, Imipenem, Ceftazidime-Avibactam as well as Aztreonam. Molecular testing confirmed the presence of both KPC and NDM-1 β-lactamases. The patient was treated with a combination of Aztreonam 2g plus Ceftazidime-Avibactam 2.5g IV every eight hours via simultaneous infusion for fourteen days, resulting in clinical improvement and discharge to a rehabilitation facility. DISCUSSION: The emergence of carbapenem-resistant enterobacteria has been identified as a major clinical problem. The high rates and high mortality of carbapenem-resistant enterobacteria complicating the course of COVID patients during the pandemic highlighted the importance of this issue. Among the Enterobacteriaceae, β-lactam resistance is primarily caused by enzymatic degradation by β-lactamases. Two carbapenemase subclasses are especially problematic KPC and NDM-1. Horizontal gene transfer and clonal expansion have enabled KPC and NDM-1 to spread worldwide. However, coexistence of these two resistant mechanisms within the same pathogen has rarely been reported. Recently, high stability, non-inferior fitness, and transferability among patients of KPC-2-NDM-1-CRKPs have been documented, raising further concerns about the risk for further spread and increasing rates [1]. Therapeutic options are limited. We used a combination of Ceftazidime/Avibactam plus Aztreonam for treatment, based on limited in vitro studies demonstrating a synergistic effect and superior clearance rather than either antibiotic alone or administered in sequence [2,3]. CONCLUSIONS: Superinfections with carbapenem-resistant enterobacteria have increased in the context of the COVID-19 pandemic and are likely to become more prevalent in our hospitals. Prompt recognition and appropriate therapeutic selection are paramount for treating these highly resistant organisms. Reference #1 Gao H, Liu Y, Wang R, Wang Q, Jin L, Wang H. The transferability and evolution of NDM-1 and KPC-2 co-producing Klebsiella pneumoniae from clinical settings. EBioMedicine. 2020 Jan;51102599. doi 10.1016/j.ebiom.2019.102599. Epub 2020 Jan 3. PMID 31911273;PMCID PMC6948161. Reference #2 Marshall S, Hujer AM, Rojas LJ, Papp-Wallace KM, Humphries RM, Spellberg B, Hujer KM, Marshall EK, Rudin SD, Perez F, Wilson BM, Wasserman RB, Chikowski L, Paterson DL, Vila AJ, van Duin D, Kreiswirth BN, Chambers HF, Fowler VG Jr, Jacobs MR, Pulse ME, Weiss WJ, Bonomo RA. Can Ceftazidime-Avibactam and Aztreonam Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae? Antimicrob Agents Chemother. 2017 Mar 24;61(4)e02243-16. doi 10.1128/AAC.02243-16. PMID 28167541;PMCID PMC5365724. Reference #3 Lodise TP, Smith NM, O'Donnell N, et al. Determining the optimal dosing of a novel combination regimen of ceftazidime/avibactam with aztreonam against NDM-1-producing Enterobacteriaceae using a hollow-fibre infection model. J Antimicrob Chemother 202 ;75(9) 2622-32 DISCLOSURES No relevant relationships by wisam daoud No relevant relationships by Christopher Walker No relevant relationships by Amanda Westbrook No relevant relationships by Nicola Zetola