| Autor: |
Pires João, Taracila Magdalena, Bethel Christopher R., Doi Yohei, Kasraian Sara, Tinguely Regula, Sendi Parham, Bonomo Robert A., Endimiani Andrea |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
Antimicrobial Agents and Chemotherapy |
| Popis: |
Cefepime is frequently prescribed to treat infections caused by AmpC producing Gram negative bacteria. CMY 2 is the most common plasmid mediated AmpC (pAmpC) ? lactamase. Unfortunately CMY variants conferring enhanced cefepime resistance are reported. Here we describe the evolution of CMY 2 to an extended spectrum AmpC (ESAC) in clonally identical E. coli isolates obtained from a patient. The CMY 2 producing E. coli (CMY 2 Ec) was isolated from a wound. Thirty days later one CMY 33 producing E. coli (CMY 33 Ec) was detected in bronchoalveolar lavage. Two weeks before the isolation of CMY 33 Ec the patient received cefepime. CMY 33 Ec and CMY 2 Ec were identical by rep PCR being of hyperepidemic ST131 but showed different ß lactam MICs (e.g. cefepime 16 vs. =0.5 µg/ml). Identical CMY 2 Ec isolates were also found in a rectal swab. CMY 33 differs from CMY 2 by a Leu293 Ala294 deletion. Expressed in E. coli DH10B both CMYs conferred resistance to ceftazidime (=256 µg/ml) but cefepime MICs were higher for CMY 33 than CMY 2 (8 vs. 0.25 µg/ml). The kcat/Km or kinact/KI (µM 1 s 1) indicated that CMY 33 possesses an ESBL like spectrum compared to CMY 2 (cefoxitin: 0.2 vs. 0.4; ceftazidime: 0.2 vs. not measurable; cefepime: 0.2 vs. not measurable; tazobactam 0.0018 vs. 0.0009). Using molecular modeling we show that a widened active site (4 Å shift) may play a significant role in enhancing cefepime hydrolysis. This is the first in vivo demonstration of a pAmpC that under cephalosporin treatment expands its substrate spectrum resembling an ESBL. The prevalence of CMY 2 Ec isolates is rapidly increasing worldwide therefore awareness that cefepime treatment may select for resistant isolates is critical. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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