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 multi-drug 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 st, 2012 through September 2 nd, 2020 for publications detailing use of C/T, C/A, and M/V. Meta-analysis determined the pooled effectiveness of C/T, C/A, and M/V. The literature search returned 1,950 publications, 29 publications representing 1,620 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 infections and limited treatment options. Larger studies comparing C/T, C/A, and M/V against other antibiotic regimens are needed.
Background: Ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (C/A) are new β-lactam/β-lactamase combination antibiotics that were approved by the FDA in 2014 and 2015, respectively, to treat complicated intra-abdominal and urinary tract infections. They are commonly used to treat multidrug-resistant Pseudomonas aeruginosa (MDRPA) and carbapenem-resistant Enterobacteriaceae (CRE) infections at any site. Both medications are also often used as salvage therapy when empiric therapy has failed or when the infectious organism tests resistant to all other available antibiotics. The purpose of this review is to present the clinical experience and reported clinical success rates of C/T and C/A. Methods: PubMed, EMBASE, and Google Scholar were searched from January 1, 2013, through October 1, 2019, for publications detailing clinical experience with C/T and C/A in patients with CRE and MDRPA infections. Included study designs were extended cases series and clinical observational studies. Information on infection type, bacterial agent, salvage therapy uses, clinical success, and resistance development during treatment were abstracted. Meta-regression analysis was used to determine the pooled effectiveness of C/T and C/A among included studies. Results: The literature search returned 1,645 publications. After exclusion criteria were applied, 16 publications representing 769 patients were retained. The study population was mostly male (pooled average, 62%). The major comorbidities represented in the pooled population were solid organ transplantation (20.0%), kidney disease (19.5%), cardiovascular disease (15.3%), and diabetes (15.3%). Pneumonia was the predominant infection type (41.4%) and MDRPA was the pathogen most frequently evaluated (57.7%). The pooled clinical success rate was 70.2% (95% CI, 64.5%–75.3%). Also, 10 studies explicitly evaluated C/A or C/T as salvage therapy. The pooled clinical success rate for salvage therapy studies was 75.2% (95% CI, 69.7%–80.0%). Development of resistance to C/T or C/A during or after treatment was reported for 2.0% of the population. Conclusion: Overall, these medications have a high clinical success rate in patients with severe and complicated infections and limited treatment options. Pooled clinical success rates were high (70.2%) and the medications were particularly effective as salvage therapy. Resistance rates were low, although this could have been biased by the small percentage of studies that reported on this outcome. More longitudinal studies comparing the effectiveness of C/T and C/A against other antibiotic regimens are needed.Funding: NoneDisclosures: None
Background: Ceftazidime/avibactam (C/A), ceftolozane/tazobactam (C/T), imipenem/relebactam (I/R), and meropenem/vaborbactam (M/V) combine either a cephalosporin (C/T and C/A) or a carbapenem antibiotic (M/V and I/R) with a β-lactamase inhibitor. They are used to treat carbapenem-resistant Enterobacterales (CRE) and/or multidrug-resistant Pseudomonas aeruginosa (MDRPA). Objective: We compared the pooled clinical success of these medications to older therapies. Methods: PubMed and EMBASE were searched from January 1, 2012, through September 2, 2020, for C/A, C/T, I/R, and M/V studies. The main outcome was clinical success, which was assessed using random-effects models. Stratified analyses were conducted for study drug, sample size, quality, infection source, study design, and multidrug-resistant gram-negative organism (MDRGNO) population. Microbiological success and 28- and 30-day mortality were assessed as secondary outcomes. Heterogeneity was determined using I2 values. Results: Overall, 25 articles met the inclusion criteria; 8 observational studies and 17 randomized control trials. We detected no difference in clinical success comparing new combination antibiotics with standard therapies for all included organisms (pooled OR, 1.21; 95% CI, 0.96–1.51). We detected a moderate level of heterogeneity among the included studies I2 = 56%. Studies that focused on patients with CRE or MDRPA infections demonstrated a strong association between treatment with new combination antibiotics and clinical success (pooled OR, 2.20; 95% CI, 1.60–3.57). Conclusions: C/T, C/A, I/R, and M/V are not inferior to standard therapies for treating various complicated infections, but they may have greater clinical success for treating MDRPA and CRE infections. More studies that evaluate the use of these antibiotics for drug-resistant infections are needed to determine their effectiveness.
Background Ceftolozane/ Tazobactam (C/T), Ceftazidime/ Avibactam (C/A), Meropenem/ Vaborbactam (M/V) and Imipenem/ Relebactam (I/R) are new combination beta-lactam/ beta-lactamase inhibitor antibiotics primarily used to treat multidrug-resistant (MDR) Gram-negative infections. This study synthesized outcomes of comparative observational studies and randomized control trials (RCTs) that evaluated clinical success of these antibiotics compared to other therapies. Methods PubMed, EMBASE, and Google Scholar were searched from January 1st, 2013 through October 1st, 2019 for comparative observational studies and RCTs of C/T, C/A, M/V and I/R in patients with pneumonia, complicated intra-abdominal and urinary tract infections. Study and patient demographics were collected along with clinical and microbiological success rates. Meta-regression analysis was used to determine the pooled effectiveness of C/T, C/A, M/V, and I/R. Heterogeneity and publication bias were assessed via I2 values and funnel plots, respectively. Results Literature search returned 1,645 results. After exclusion criteria, 21 publications representing 6,246 patients were retained: 16 RCTs (8 C/A, 3 C/T, 3 I/R, 2 M/V) and 5 comparative observational studies (3 C/A, 2 C/T). Pooled risk ratios for clinical success showed that all four antibiotics were non-inferior to comparator antibiotics (0.99 (95% CI (0.97-1.01)). Eleven of the sixteen RCTs evaluated microbiological success; pooled risk ratio was 1.08 (95% CI 1.04-1.13), indicating that older therapies were more successful at microbiological eradication than newer antibiotics. Only 6 of the included studies (3 RCTs and 2 observational studies) focused on patients with MDR infections. Limiting the analysis to MDR RCTs did not change the overall conclusions. Conclusion Although older therapies had slightly higher microbiologic clearance, pooled clinical success rates for C/A, C/T, M/V, and I/R were non-inferior to older therapies, including in studies focused on patients with MDR infections. Additional studies are needed to further evaluate these drugs’ effectiveness for treatment of MDR infections. Disclosures All Authors: No reported disclosures
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