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Pneumonia and Renal Replacement Therapy Are Risk Factors for Ceftazidime-Avibactam Treatment Failures and Resistance among Patients with Carbapenem-Resistant Enterobacteriaceae Infections.

ABSTRACT: Ceftazidime-avibactam was used to treat 77 patients with carbapenem-resistant Enterobacteriaceae (CRE) infections at our center. Thirty- and 90-day survival rates were 81% and 69%, respectively; these rates were higher than those predicted by SAPS II and SOFA scores at the onset of infection. Clinical success was achieved for 55% of patients but differed by the site of infection. Success rates were lowest for pneumonia (36%) and higher for bacteremia (75%) and urinary tract infections (88%). By multivariate analysis, pneumonia (P = 0.045) and receipt of renal replacement therapy (RRT) (P = 0.046) were associated with clinical failure. Microbiologic failures occurred in 32% of patients and occurred more commonly among patients infected with KPC-3-producing CRE than among those infected with KPC-2-producing CRE (P = 0.002). Pneumonia was an independent predictor of microbiologic failure (P = 0.007). Ceftazidime-avibactam resistance emerged in 10% of patients, including 14% of those infected with Klebsiella pneumoniae and 32% of those with microbiologic failure. RRT was an independent predictor of the development of resistance (P = 0.009). Resistance was identified exclusively among K. pneumoniae bacteria harboring variant KPC-3 enzymes. Upon phylogenetic analysis of whole-genome sequences, resistant isolates from 87.5% (7/8) of patients clustered within a previously defined sequence type 258 (ST258) clade II sublineage; resistant isolates from one patient clustered independently from other ST258 clade II isolates. In conclusion, our report offers new insights into the utility and limitations of ceftazidime-avibactam across CRE infection types. Immediate priorities are to identify ceftazidime-avibactam dosing and therapeutic regimens that improve on the poor outcomes among patients with pneumonia and those receiving RRT.

SUBMITTER: Shields RK

PROVIDER: S-EPMC5923134 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Pneumonia and Renal Replacement Therapy Are Risk Factors for Ceftazidime-Avibactam Treatment Failures and Resistance among Patients with Carbapenem-Resistant Enterobacteriaceae Infections.

Shields Ryan K RK Nguyen M Hong MH Chen Liang L Press Ellen G EG Kreiswirth Barry N BN Clancy Cornelius J CJ

Antimicrobial agents and chemotherapy 20180426 5

Ceftazidime-avibactam was used to treat 77 patients with carbapenem-resistant <i>Enterobacteriaceae</i> (CRE) infections at our center. Thirty- and 90-day survival rates were 81% and 69%, respectively; these rates were higher than those predicted by SAPS II and SOFA scores at the onset of infection. Clinical success was achieved for 55% of patients but differed by the site of infection. Success rates were lowest for pneumonia (36%) and higher for bacteremia (75%) and urinary tract infections (88 ...[more]

PMID: 29507064

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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.

Dataset Information

Pneumonia and Renal Replacement Therapy Are Risk Factors for Ceftazidime-Avibactam Treatment Failures and Resistance among Patients with Carbapenem-Resistant Enterobacteriaceae Infections.

Publications

Pneumonia and Renal Replacement Therapy Are Risk Factors for Ceftazidime-Avibactam Treatment Failures and Resistance among Patients with Carbapenem-Resistant Enterobacteriaceae Infections.

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