Pneumonia and Renal Replacement Therapy Are Risk Factors for Ceftazidime-Avibactam Treatment Failures and Resistance among Patients with Carbapenem-Resistant Enterobacteriaceae Infections
- 1 May 2018
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 62 (5)
- https://doi.org/10.1128/aac.02497-17
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.Keywords
Funding Information
- HHS | NIH | NIH Clinical Center (K08AI114883)
- HHS | NIH | NIH Clinical Center (R21AI117338)
- HHS | NIH | NIH Clinical Center (R01AI090155)
- HHS | NIH | NIH Clinical Center (R21AI111037)
- HHS | NIH | NIH Clinical Center (R21AI128338)
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