کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5667082 | 1591747 | 2017 | 6 صفحه PDF | دانلود رایگان |
- Ceftolozane/tazobactam is highly active against certain Escherichia coli strains.
- Diminished activity was observed against a CTX-M-15-producing strain (MICTAZ4â=â8âmg/L).
- Rapid bactericidal activity against AmpC- and CMY-10-producing strains was detected.
The proliferation of multidrug-resistant Gram-negative pathogens has been exacerbated by a lack of novel agents in current development by pharmaceutical companies. Ceftolozane/tazobactam was recently approved by the FDA for the treatment of complicated intra-abdominal infections and complicated urinary tract infections. In the present study, the activity of ceftolozane/tazobactam against four isogenic Escherichia coli strains was investigated in a hollow-fibre infection model simulating various clinical dosing regimens. The four investigational E. coli strains included #2805 (no β-lactamase), #2890 (AmpC β-lactamase), #2842 (CMY-10 β-lactamase) and #2807 (CTX-M-15 β-lactamase). Each strain was exposed to regimens simulating 1âg ceftolozane, 2âg ceftolozane, 1âg ceftolozane/0.5âg tazobactam, and 2âg ceftolozane/1âg tazobactam utilising a starting inoculum of ca. 106 CFU/mL. Whereas 1âg of ceftolozane eradicated strains #2805 and #2842 without subsequent regrowth, 1âg ceftolozane/0.5âg tazobactam was required to eradicate strain #2890. For strain #2890, ceftolozane monotherapy led to bacterial growth on plates impregnated with 20âmg/L ceftolozane by 24âh, whilst combination treatment with tazobactam completely suppressed the development of ceftolozane resistance. In contrast, none of the regimens, including 2âg ceftolozane/1âg tazobactam, were able to entirely suppress bacterial growth in strain #2807, with bacterial counts exceeding 108âCFU/mL by 48âh and ceftolozane-resistant populations being amplified after 24âh. Thus, the combination of ceftolozane and tazobactam achieved bactericidal activity followed by sustained killing over 10 days for three of four isogenic E. coli strains. Ceftolozane/tazobactam is a promising new agent to counter multidrug-resistant Gram-negative bacteria.
Journal: International Journal of Antimicrobial Agents - Volume 49, Issue 1, January 2017, Pages 25-30