β-Lactamase Characterization of Gram-Negative Pathogens Recovered from Patients Enrolled in the Phase 2 Trials for Ceftazidime-Avibactam: Clinical Efficacies Analyzed against Subsets of Molecularly Characterized Isolates

March 5, 2016 at 11:21 am

Antimicrobial Agents and Chemotherapy March 2016 V.60 N.3 P.1328-1335

Rodrigo E. Mendes, Mariana Castanheira, Leanne Gasink, Gregory G. Stone, Wright W. Nichols, Robert K. Flamm, and Ronald N. Jones

aJMI Laboratories, North Liberty, Iowa, USA

bAstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA

The correlation of the clinical efficacies of ceftazidime-avibactam and comparators (carbapenems) was evaluated against baseline Gram-negative isolates having characterized β-lactam resistance mechanisms from complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) phase 2 trials. Enterobacteriaceae displaying ceftriaxone and/or ceftazidime MICs of ≥2 μg/ml (69 isolates) and nonfermentative Gram-negative bacilli (NF-GNB [three isolates]) with ceftazidime MICs of ≥16 μg/ml were characterized for their narrow- and extended-spectrum β-lactamase (ESBL) content. Enterobacteriaceae (one isolate) and NF-GNB (three isolates) with imipenem/meropenem MICs of ≥2 and ≥16 μg/ml, respectively, were tested for carbapenemases. All cUTI E. coli had the lineage background investigated (ST131-like versus non-ST131-like). The primary efficacy endpoint was microbiological response (eradication) at test of cure (TOC) for cUTI and clinical response (inferred microbiological eradication) at TOC for cIAI. A total of 34.1% of baseline cUTI (36.4%) and cIAI (33.1%) pathogens met the MIC-based screening criteria (screen positive). All screen-positive cUTI pathogens were CTX-M-producing E. coli, except for one E. cloacae isolate with AmpC overexpression. The majority (66.7%) of screen-positive cIAI isolates produced CTX-M-type coupled with a diverse array of other β-lactamases. Similar favorable responses were observed with ceftazidime-avibactam (93.3%) and carbapenems (90.9%), when a non-ESBL Enterobacteriaceae isolate was recovered at the baseline visit. When an ESBL Enterobacteriaceae isolate was present, the favorable responses were 85.7% and 80.0% with ceftazidime-avibactam and carbapenems, respectively. Higher favorable responses were observed with ceftazidime-avibactam (75.0%) than with carbapenems (66.7%) when an ST131-like E. coli isolate was recovered at baseline, as when a non-ST131-like isolate was present (93.8% versus 86.7%, respectively). The efficacy of ceftazidime-avibactam was similar to that of carbapenems for treatment of cUTI and cIAI caused by ESBL organisms.

PDF

http://aac.asm.org/content/60/3/1328.full.pdf

Entry filed under: Antimicrobianos, Bacterias, Bacteriemias, Biología Molecular, Infecciones intraabdominales, Infecciones urinarias, Metodos diagnosticos, Resistencia bacteriana, Sepsis, Update. Tags: .

Vital Signs: Preventing Antibiotic-Resistant Infections in Hospitals — United States, 2014 Comparison of Verona Integron-Borne Metallo-β-Lactamase (VIM) Variants Reveals Differences in Stability and Inhibition Profiles


Calendar

March 2016
M T W T F S S
« Feb   Apr »
 123456
78910111213
14151617181920
21222324252627
28293031  

Most Recent Posts


%d bloggers like this: