Nacim Ammenouche

Avibactam activity against extended-spectrum AmpC β-lactamases

Area de Bioquimica y Biologia Molecular, Universidad de La Rioja, Logrono, Spain; Area de Microbiologia Molecular, Centro de Investigacion Biomedica de La Rioja (CIBIR), Logrono, Spain; Service de Reanimation polyvalente, Centre HospitaloUniversitaire d’Amiens, Hopital Nord, France; INSERM U1088, Universite de Picardie Jules Verne, Amiens, France; Service de Bacteriologie-Virologie-Hygiene hospitaliere, Centre HospitaloUniversitaire de Reims, Hopital Robert Debre, Faculte de Medecine de Reims, Universite Reims-Champagne-Ardennes, Reims, France; Equipe d’accueil 4687 ERA—Resistance aux antibiotiques chez les enterobacteries, Universite Reims-Champagne-Ardennes, Reims, France; Service de Bacteriologie, Centre Hospitalo-Universitaire d’Amiens, Hopital sud, Faculte de Medecine d’Amiens, Universite de Picardie Jules Verne, Amiens, France

Characterization of a Novel AmpC β-Lactamase Produced by a Carbapenem-Resistant Cedecea davisae Clinical Isolate

ABSTRACT A Cedecea davisae isolate, which was intermediate or resistant to third-generation cephalosporins and carbapenems, was recovered from a urine sample. Susceptibility testing, isoelectric focusing, and analysis of outer membrane proteins showed that AmpC β-lactamase expression combined with porin deficiency accounted for the carbapenem resistance. A cloning experiment followed by phenotypic and enzymatic characterization identified a novel class C enzyme that was phylogenetically and biochemically close to the chromosome-borne β-lactamases of the genera Enterobacter and Citrobacter.

Use of aztreonam in association with cefepime for the treatment of nosocomial infections due to multidrug-resistant strains of Pseudomonas aeruginosa to β-lactams in ICU patients: A pilot study

OBJECTIVES Resistance to all β-lactams is emerging among Pseudomonas aeruginosa (PA) clinical isolates. Aztreonam and cefepime act synergistically in vitro against AmpC overproducing PA isolates. The objective of this study was to evaluate the clinical efficacy of this treatment in ICU patients infected with multidrug-resistant PA. MATERIAL AND METHODS Retrospective study (2 years, 2 ICUs) in a tertiary university hospital. Inclusion criteria were proven infection with evidence of a bacterial strain of PA resistant to all β-lactams and treated with the association of at least aztreonam plus cefepime. Treatment was considered effective for pneumonia using CPIS scores at the end of treatment and for other infections, using the SOFA score and signs of infection improvement at the end of treatment. Infectious episodes were classified as cure or failure. RESULTS Thirteen patients were included (10 nosocomial pneumonia, 3 nosocomial intra-abdominal infections). The median [25th-75th percentiles] admission SAPS2 score was 54 [51-69] and the median SOFA score at the beginning of infection was 7 [4-8]. The median CPIS scores for pneumonia at the beginning and end of treatment were 9 [7-10.5] and 2 [0.75-5.5]. The duration of treatment with the combination of aztreonam plus cefepime was 14 days [9.5-16]. Nine episodes were classified as cures and 4 as failures, indicating a clinical efficacy of 69.2%. Overall mortality was 38.5%. DISCUSSION These data suggest that the association of cefepime plus aztreonam could be an attractive alternative in the treatment of infections with multidrug-resistant PA to all β-lactams with a clinical efficacy rate of 69%.

Determinants of amikacin first peak concentration in critically ill patients

Amikacin antimicrobial effect has been correlated with the ratio of the peak concentration (Cmax) to the minimum inhibitory concentration. A target Cmax ≥ 60–80 mg/L has been suggested. It has been shown that such target is not achieved in a large proportion of critically ill patients in intensive care units. A retrospective analysis was performed to examine the determinants of Cmax ≥ 80 mg/L on the first peak in 339 critically ill patients treated by amikacin. The influence of available variables on Cmax target attainment was analyzed using a classification and regression tree (CART) and logistic regression. Mean Cmax in the 339 patients was 73.0 ± 23.9 mg/L, with a target attainment rate (TAR, Cmax ≥ 80 mg/L) of 37.5%. In CART analysis, the strongest predictor of amikacin target peak attainment was dose per kilogram of lean body weight (dose/LBW). TAR was 60.1% in patients with dose/LBW ≥ 37.8 vs. 19.9% in patients with lower dose/LBW (OR = 6.0 (95% CI: 3.6–10.2)). Renal function was a secondary predictor of Cmax. Logistic regression analysis identified dose per kilogram of ideal body weight (OR = 1.13 (95% CI: 1.09–1.17)) and creatinine clearance (OR = 0.993 (95% CI: 0.988–0.998)) as predictors of target peak achievement. Based on our results, an amikacin dose ≥ 37.8 mg/kg of LBW should be used to optimize the attainment of Cmax ≥ 80 mg/L after the first dose in critically ill patients. An even higher dose may be necessary in patients with normal renal function.