Ceftazidime-avibactam as salvage therapy for infections caused by carbapenem-resistant organisms: a case series from the compassionate-use program (original) (raw)
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Antimicrobial Agents and Chemotherapy, 2017
Ceftazidime-avibactam is a novel cephalosporin–beta-lactamase inhibitor combination that is active against many carbapenem-resistant Enterobacteriaceae (CRE). We describe a retrospective chart review for 60 patients who received ceftazidime-avibactam for a CRE infection. In-hospital mortality was 32%, 53% of patients had microbiological cure, and 65% had clinical success. In this severely ill population with CRE infections, ceftazidime-avibactam was an appropriate option.
BMC Infectious Diseases, 2019
Background: Carbapenem-resistant Enterobacteriaceae (CRE) represent an important global threat. The aim of this study is to describe the clinical course and outcomes of patients with CRE infections treated with ceftazidimeavibactam (CAZ-AVI) compared to patients treated with other agents. Methods: A retrospective cohort study of patients with established CRE infections from January 2017 until August 2018 was conducted. All patients who received CAZ-AVI and all cultures with carbapenem-resistant isolates were screened. We compared patients who received CAZ-AVI for CRE infections with patients who received other agents. Results: A total of 38 consecutive patients with CRE infections were identified. Age and baseline comorbidities were similar between the two groups. The median time from admission to isolation of CRE culture was 22.5 days in the CAZ-AVI group and 17 days in the comparative group (P = 0.7). The incidence of CRE bacteremia was similar between the two groups: 7 patients (70%) in the CAZ-AVI group and 15 patients (53.6%) in the comparative group (P = 0.47). The most common type of CRE infections in both groups was hospital acquired pneumonia (HAP). Klebsiella pneumoniae was the predominant pathogen in both groups. A carbapenemase gene was detected in 35 (92%) patients; the OXA-48 gene was the predominant gene identified in 28 (74%) isolates. Eight out of ten patients in the CAZ-AVI group and fifteen out of twenty-eight in the comparative group achieved clinical remission (P = 0.14). After thirty days, all-cause mortality was observed in five patients in the CAZ-AVI group and 16 patients in the comparative group, accounting for 50 and 57% respectively. Conclusions: In patients with established OXA-48-type CRE infection, CAZ-AVI is a reasonable alternative to standard therapy. These findings need to be confirmed in prospective studies.
Cureus, 2021
Introduction Among the several newer beta lactam+beta lactase inhibitors (BL/BLI), ceftazidime-avibactam is the only drug showing activity against OXA-48-like producers. Hence, it is being increasingly used in India to treat infections caused by carbapenem-resistant Enterobacteriaceae (CRE), especially as a colistin-sparing agent. We have used ceftazidime-avibactam in patients suspected and confirmed to have CRE infections in our center, and present a retrospective analysis of our experience. Methods We conducted a single-center, retrospective study involving all patients who were treated with ceftazidimeavibactam for suspected and proven CRE infections during a one-year period at our 500-bedded hospital. Our primary objective for this study was taken as all-cause mortality. The secondary objectives were to determine the clinical cure, defined as the end of the treatment regimen with a resolution of primary infection and resistance to ceftazidime-avibactam in patients who underwent the Epsilometer test (E-test). Results A total of 103 patients who received ceftazidime-avibactam were identified. The all-cause mortality was 27% while a clinical cure was achieved in 73%. Fifty-two patients received empirical therapy and 51 patients received ceftazidime-avibactam for confirmed CRE infection. Forty-eight patients had an E-test done, out of which 79% of patients had CREs sensitive to ceftazidime-avibactam, and 21% of patients had ceftazidimeavibactam resistant CREs. A higher Sequential Organ Failure Assessment (SOFA) score, Charlson comorbidity index (CCI) score, intensive care unit (ICU) admission, inotrope requirement, and lower days of therapy (DOT) with ceftazidime-avibactam were found to be associated with increased mortality. Conclusion Colistin has been considered to be the last-line agent in CRE infections, but there are concerns about its adverse effects and the emergence of resistance. Given our relatively low mortality of 27% in CRE infections treated with ceftazidime-avibactam, coupled with the high susceptibility of the tested isolates, there may be a role for the empirical use of this drug in infections caused by CRE, especially in a setting where colistin may not be ideal.
Antibiotics, 2020
Background: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram−negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. Methods: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≥72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events. Results: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P. aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia (n = 20; 48.8%), primary bacteremia (n = 7; 17.1%), intra-abdominal infection (n = 4; 9.8%), and bone infection
Infectious Diseases and Therapy, 2021
Introduction: A systematic literature review was undertaken to evaluate real-world use of ceftazidime-avibactam for infections due to aerobic Gram-negative organisms in adults with limited treatment options. Methods: Literature searches retrieved peer-reviewed publications and abstracts from major international infectious disease congresses from January 2015 to February 2021. Results were meningitis, febrile neutropenia, osteomyelitis, and cystic fibrosis were also included. Carbapenem-resistant or carbapenemase-producing Enterobacterales (CRE; n = 1718) and carbapenem-resistant, multidrug-resistant (MDR), and extensively drug-resistant Pseudomonas aeruginosa (n = 150) were the most common pathogens. Most publications reported positive outcomes for ceftazidime-avibactam treatment (clinical success rates ranged from 45 to 100% and reported 30-day mortality from 0 to 63%), which were statistically superior versus comparators in some studies. ceftazidime-avibactam resistance emergence occurred infrequently and mostly in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains. Conclusion: This review provides qualitative evidence of successful use of ceftazidime-avibactam for the treatment of hospitalised patients with CRE and MDR P. aeruginosa infections with limited treatment options.
Antibiotics
Ceftazidime-avibactam (CZA) is a novel beta-lactam beta-lactamase inhibitor combination approved for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and for hospital-acquired/ventilator-associated pneumonia. The aim of this systematic review (PROSPERO registration number: CRD42019128927) was to evaluate the effectiveness of CZA combination therapy versus CZA monotherapy in the treatment of severe infections. The databases included in the search, until 12 February 2020, were MEDLINE by PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials. We included both randomized controlled trials (RCTs) and non-randomized studies published in peer-reviewed journals and in the English language. The primary outcome was all-cause mortality (longest follow-up) evaluated in patients with the diagnosis of infection with at least one pathogen; secondary outcomes were clinical and microbiological improvement/cure. Thirteen studies were incl...
Indian Journal of Critical Care Medicine
Introduction: Gram-negative sepsis remains one of the most difficult to treat infections in intensive care units (ICUs). Carbapenems are often considered to be robust and reliable options for treating infections due to Gram-negative bacteria. The dominance of carbapenem-resistant enterobacteriaceae (CRE) has emerged as one of the greatest challenges faced by the medical community today. Carbapenem-resistant enterobacteriaceae may be resistant to all beta lactam antimicrobials including carbapenems and often, are even resistant to other classes of drugs. There are limited studies comparing polymyxin-based therapies with ceftazidime-avibactam (CAZ-AVI)-based therapies for treating infections caused by CRE. Methods: A retrospective study comparing outcomes between patients with bacteremia caused by CRE treated with polymyxin-based combination therapy and CAZ-AVI-based therapy (with or without aztreonam). Results: Of total 104 patients, 78 (75%) were in the CAZ-AVI group. There was no significant difference in the underlying comorbidities between the two groups. The incidence of nephrotoxicity was significantly higher in the polymyxin group (p = 0.017). Ceftazidime-avibactam-based therapy was 66% less likely to be associated with day 14 mortality (p = 0.048) and 67% less likely to be associated with day 28 mortality (p = 0.039) as compared with polymyxin-based therapy. Conclusion: Ceftazidime-avibactam-based therapy may be a superior option to polymyxin-based therapy for infections caused by CRE. This can have significant practical applications, in terms of optimizing therapy for the individual patient as well as sparing polymyxins and reducing the use of polymyxins in our hospitals.
Open Forum Infectious Diseases, 2021
Ceftolozane-tazobactam (C/T), ceftazidime-avibactam (C/A), and meropenem/vaborbactam (M/V) are new beta-lactam/beta-lactamase combination antibiotics commonly used to treat multidrug-resistant Pseudomonas aeruginosa (MDRPA) and carbapenem-resistant Enterobacteriaceae (CRE) infections. This review reports the clinical success rates for C/T, C/A, and M/V. PubMed and EMBASE were searched from January 1, 2012, through September 2, 2020, for publications detailing the use of C/T, C/A, and M/V. A meta-analysis determined the pooled effectiveness of C/T, C/A, and M/V. The literature search returned 1950 publications; 29 publications representing 1620 patients were retained. Pneumonia was the predominant infection type (49.8%). MDRPA was the major pathogen treated (65.3%). The pooled clinical success rate was 73.3% (95% CI, 68.9%–77.5%). C/T, C/A, or M/V resistance was reported in 8.9% of the population. These antibiotics had a high clinical success rate in patients with complicated infecti...
Antimicrobial Agents and Chemotherapy, 2016
The activity of ceftazidime-avibactam was assessed against 961 isolates of meropenem-nonsusceptibleEnterobacteriaceae. Most meropenem-nonsusceptible metallo-β-lactamase (MBL)-negative isolates (97.7%) were susceptible to ceftazidime-avibactam. Isolates that carried KPC or OXA-48-like β-lactamases, both alone and in combination with extended-spectrum β-lactamases (ESBLs) and/or AmpC β-lactamases, were 98.7% and 98.5% susceptible to ceftazidime-avibactam, respectively. Meropenem-nonsusceptible, carbapenemase-negative isolates demonstrated 94.7% susceptibility to ceftazidime-avibactam. Ceftazidime-avibactam activity was compromised only in isolates for which carbapenem resistance was mediated through metallo-β-lactamases.