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Ceftazidime-Avibactam Therapy Versus Ceftazidime-Avibactam-Based Combination Therapy in Patients With Carbapenem-Resistant Gram-Negative Pathogens: A Meta-Analysis.

ABSTRACT: Objective: To systematically review and compare the efficacy and posttreatment resistance of ceftazidime-avibactam therapy and ceftazidime-avibactam-based combination therapy in patients with Gram-negative pathogens. Methods: PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases were searched from their inception up to March 31, 2021, to obtain studies on ceftazidime-avibactam therapy versus ceftazidime-avibactam-based combination therapy in patients with carbapenem-resistant Gram-negative pathogens. The primary outcome was mortality rate, and the second outcomes were microbiologically negative, clinical success, and the development of resistance after ceftazidime-avibactam treatment. Results: Seventeen studies representing 1,435 patients (837 received ceftazidime-avibactam-based combination therapy and 598 received ceftazidime-avibactam therapy) were included in the meta-analysis. The results of the meta-analysis showed that no statistically significant difference was found on mortality rate (Petos odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.79-1.34), microbiologically negative (OR = 0.99, 95% CI 0.54-1.81), and clinical success (OR =0.95, 95% CI 0.64-1.39) between ceftazidime-avibactam-based combination therapy and ceftazidime-avibactam therapy. Although there was no difference in posttreatment resistance of ceftazidime-avibactam (OR = 0.65, 95% CI 0.34-1.26) in all included studies, a trend favoring the combination therapy was found (according to the pooled three studies, OR = 0.18, 95% CI 0.04-0.78). Conclusions: The current evidence suggests that ceftazidime-avibactam-based combination therapy may not have beneficial effects on mortality, microbiologically negative, and clinical success to patients with carbapenem-resistant Gram-negative pathogens. A trend of posttreatment resistance occurred more likely in ceftazidime-avibactam therapy than the combination therapy. Due to the limited number of studies that can be included, additional high-quality studies are needed to verify the above conclusions.

SUBMITTER: Li D

PROVIDER: S-EPMC8476997 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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 (n = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment (n = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population. CONCLUSIONS:Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE.

Project description:Background:The efficacy of ceftazidime-avibactam-a cephalosporin-?-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE)-compared with colistin remains unknown. Methods:Patients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study. Efficacy, safety, and benefit-risk analyses were performed using intent-to-treat analyses with partial credit and the desirability of outcome ranking approaches. The ordinal efficacy outcome was based on disposition at day 30 after starting treatment (home vs not home but not observed to die in the hospital vs hospital death). All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). Results:Thirty-eight patients were treated first with ceftazidime-avibactam and 99 with colistin. Most patients received additional anti-CRE agents as part of their treatment. Bloodstream (n = 63; 46%) and respiratory (n = 30; 22%) infections were most common. In patients treated with ceftazidime-avibactam versus colistin, IPTW-adjusted all-cause hospital mortality 30 days after starting treatment was 9% versus 32%, respectively (difference, 23%; 95% bootstrap confidence interval, 9%-35%; P = .001). In an analysis of disposition at 30 days, patients treated with ceftazidime-avibactam, compared with those treated within colistin, had an IPTW-adjusted probability of a better outcome of 64% (95% confidence interval, 57%-71%). Partial credit analyses indicated uniform superiority of ceftazidime-avibactam to colistin. Conclusions:Ceftazidime-avibactam may be a reasonable alternative to colistin in the treatment of K. pneumoniae carbapenemase-producing CRE infections. These findings require confirmation in a randomized controlled trial.

Project description:Data on the effectiveness of ceftazidime-avibactam (CAZ-AVI) in critically ill, mechanically ventilated patients are limited. The present retrospective observational cohort study, which was conducted in two general intensive care units (ICUs) in central Greece, compared critically ill, mechanically ventilated patients suffering from carbapenem-resistant Enterobacteriaceae (CRE) infections receiving CAZ-AVI to patients who received appropriate available antibiotic therapy. Clinical and microbiological outcomes and safety issues were evaluated. A secondary analysis in patients with bloodstream infections (BSIs) was conducted. Forty-one patients that received CAZ-AVI (the CAZ-AVI group) were compared to 36 patients that received antibiotics other than CAZ-AVI (the control group). There was a significant improvement in the Sequential Organ Failure Assessment (SOFA) score on days 4 and 10 in the CAZ-AVI group compared to that in the control group (P?=?0.006, and P?=?0.003, respectively). Microbiological eradication was accomplished in 33/35 (94.3%) patients in the CAZ-AVI group and 21/31 (67.7%) patients in the control group (P?=?0.021), and clinical cure was observed in 33/41 (80.5%) versus 19/36 (52.8%) patients (P?=?0.010), respectively. The results were similar in the BSI subgroups for both outcomes (P?=?0.038 and P?=?0.014, respectively). The 28-day survival was 85.4% in the CAZ-AVI group and 61.1% in the control group (log-rank test?=?0.035), while there were 2 and 12 relapses in the CAZ-AVI and control groups, respectively (P?=?0.042). A CAZ-AVI-containing regime was an independent predictor of survival and clinical cure (odds ratio [OR] = 5.575 and P?=?0.012 and OR?=?5.125 and P?=?0.004, respectively), as was illness severity. No significant side effects were recorded. In conclusion, a CAZ-AVI-containing regime was more effective than other available antibiotic agents for the treatment of CRE infections in the high-risk, mechanically ventilated ICU population evaluated.

Project description:BACKGROUND:Rates of colonization and infection with carbapenem-resistant Gram-negative pathogens are on the rise, particularly in southeastern European countries, and this is increasingly true in Germany as well. The organisms in question include enterobacteriaceae such as Klebsiella pneumoniae and Escherichia coli and non-fermenting bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. As the carbapenems have been the gold standard to date for the systemic treatment of serious infections with Gram-negative bacteria, carbapenem resistance presents new and difficult challenges in therapeutic decision-making, particularly because of the high frequency of coresistance. METHODS:This review is based on pertinent publications retrieved by a selective search in PubMed and on other applicable literature. RESULTS:Multiresistant Gram-negative (MRGN) pathogens are classified in Germany according to their resistance to four different classes of antibiotics; fluoroquinolones, piperacillin, third-generation cephalosporins, and carbapenems. Quadruple MRGN pathogens are resistant to all four groups, triple MRGN pathogens to three of them. There are a number of therapeutic alternatives to carbapenems that can be applied with the aid of sensitive microbiological and/or molecular genetic testing. The following antibiotics are often the only ones that can be used to treat quadruple MRGN pathogens: colistin, aminoglycosides, tigecycline, fosfomycin, ceftazidime/avibactam, and ceftolozan/tazobactam. Carbapenems, too, may still be an option in certain situations. There is also evidence that combinations of antibiotics against which the pathogen is resistant individually can some- times be a valid treatment option; these include combinations of colistin with one or two carbapenems. CONCLUSION:The treatment of severe infection with carbapenem-resistant pathogens should be individualized and carried out in an interdisciplinary framework, in consideration of antibiotic pharmacokinetics and pharmacodynamics in each case. The treat- ment options are based on evidence from in vitro studies, retrospective studies, and case series, which must be interpreted with caution. Randomized clinical trials are needed to test each of the various combined approaches.

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Ceftazidime-Avibactam Therapy Versus Ceftazidime-Avibactam-Based Combination Therapy in Patients With Carbapenem-Resistant Gram-Negative Pathogens: A Meta-Analysis.

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