ABSTRACT
We describe the epidemiology of New Delhi Metallo-Beta-Lactamase-Producing Carbapenem-Resistant Enterobacterales (NDM-CRE) colonization/infection in a cohort of COVID-19 patients in an Italian teaching hospital. These patients had an increased risk of NDM-CRE acquisition versus the usual patients (75.9 vs. 25.3 cases/10,000 patient days). The co-infection significantly increased the duration of hospital stay (32.9 vs. 15.8 days).
ABSTRACT
Introduction: Novel last resort beta-lactam antibiotics are now available for management of infections due to New-Delhi Metallo-Beta-Lactamase (NDM) producing Enterobacterales and non-fermenters with Difficult-to-Treat Resistance. However, data regarding the use of imipenem-cilastatin-relebactam (IMI-REL), cefiderocol (CFD) and ceftazidime-avibactam plus aztreonam (CAZ-AVI-ATM) are scarce in real-life settings. This study aimed to describe the use of last resort beta-lactam antibiotics, the microbiology and the outcome, in patients hospitalized in a tertiary hospital. Methods: We conducted a monocentric observational cohort study from 2020/01/01, to 2022/08/31. We screened all patients admitted to Nimes University Hospital who have received ≥ 1 dose of last resort beta-lactam antibiotics during the study period, using the Pharmacy database. We included patients treated with IMI-REL, CFD and CAZ-AVI-ATM. The primary endpoint was the infection-free survival rate. We also calculated rates of microbiological and clinical cure, recurrent infection, death and adverse events. Results: Twenty-seven patients were included in the study and 30 treatment courses were analyzed: CFD (N=24; 80%), CAZ-AVI-ATM (N=3; 10%) and IMI-REL (N=3; 10%). Antibiotics were used in 21 males (70%) and 9 females (30%) with a median age at 65-year-old [50-73.5] and a median Charlson index at 1 [0-2]. Almost all the patients had ≥ 1 risk factor for carbapenem resistant bacteria, a half of them was hospitalized for severe COVID-19, and most of antibiotic courses (N=26; 87%) were associated with ICU admission. In the study population, the probability of infection-free survival at day-90 after last resort beta-lactam therapy initiation was 48.4% CI95% [33.2-70.5]. Clinical failure rate was at 30%, microbiological failure rate at 33% and mortality rate at 23%. Adverse events were documented in 5 antibiotic courses (17%). In details, P. aeruginosa were mainly treated with CFD and IMI-REL, S. maltophilia with CFD and CAZ-AVI-ATM, A. baumannii with CFD, and NDM producing-K. pneumoniae with CAZ-AVI-ATM and CFD. After a treatment course with CFD, CAZ-AVI-ATM and IMI-REL, the probability of infection-free survival was 48% CI95% [10.4-73.5], 33.3% CI95% [6.7-100], 66.7% CI95% [30-100], respectively. Discussion/conclusion: Use of last resort beta-lactam antimicrobials in real-life settings was a safe and efficient therapeutic option for severe infections related to Gram-negative bacteria with Difficult-to-Treat Resistance.
Subject(s)
COVID-19 , Male , Female , Humans , Aged , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , beta-Lactamases , Gram-Negative Bacteria , Drug Combinations , Klebsiella pneumoniae , Microbial Sensitivity TestsABSTRACT
SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 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;51:102599. 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