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| Content Provider | PubMed Central |
|---|---|
| Author | Guillard, T. Cambau, E. Chau, F. Massias, L. Champs, C. De Fantin, B. |
| Copyright Year | 2013 |
| Abstract | AAC(6′)-Ib-cr is a plasmid-mediated quinolone resistance mechanism described worldwide for Escherichia coli. Since it confers in vitro only a low level of resistance to ciprofloxacin, we evaluated its impact on the in vivo activity of ciprofloxacin. Isogenic strains were obtained by transferring plasmid p449, harboring aac(6′)-Ib-cr, into the quinolone-susceptible strain E. coli CFT073-RR and its D87G gyrA mutant. MICs were 0.015, 0.06, 0.25, and 0.5 μg/ml against E. coli strains CFT073-RR, CFT073-RR/p449, CFT073-RR GyrAr, and CFT073-RR GyrAr/p449, respectively. Bactericidal activity was reduced at 1× the MIC for the three resistant derivatives, while at a fixed concentration of 0.5 μg/ml, 99.9% killing was observed for all strains except E. coli CFT073-RR GyrAr/p449. In the murine model of pyelonephritis, an optimal regimen of ciprofloxacin (10 mg/kg of body weight twice a day [b.i.d.]) significantly decreased the bacterial count in the kidneys of mice infected with E. coli CFT073 (1.6 versus 4.3 log10 CFU/g of kidney compared to untreated controls; P = 0.0001), while no significant decrease was observed for E. coli CFT073-RR/p449 (2.7 versus 3.1 log10 CFU/g; P = 0.84), E. coli CFT073-RR GyrAr (4.2 versus 4.1 log10 CFU/g; P = 0.35), or E. coli CFT073-RR GyrAr/p449 (2.9 versus 3.6 log10 CFU/g; P = 0.47). While pharmacokinetic and pharmacodynamic (PK/PD) parameters accounted for ciprofloxacin failure against gyrA-containing mutants, this was not the case for the aac(6′)-Ib-cr-containing strains, suggesting an in situ hydrolysis of ciprofloxacin in the latter case. |
| Related Links | http://dx.doi.org/10.1128/AAC.01489-13 |
| Ending Page | 5835 |
| Page Count | 6 |
| Starting Page | 5830 |
| File Format | |
| ISSN | 10986596 |
| e-ISSN | 10986596 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Issue Number | 12 |
| Volume Number | 57 |
| Language | English |
| Publisher | American Society for Microbiology |
| Publisher Date | 2013-12-01 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Pharmacology Pharmacology (medical) |
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