[Comparative study of treatment with quinupristin-dalfopristin alone or in combination with gentamicin, teicoplanin, imipenem or levofloxacin in experimental endocarditis due to a multidrug-resistant Enterococcus faecium].
The incidence of multidrug-resistant Enterococcus faecium is increasing despite advances in antibacterial therapy. Thus, new antibiotics are required to treat hospital- or community-acquired infections caused by these multidrug-resistant organisms. The aim of this study was to compare the therapeutic efficacy of quinupristin-dalfopristin (QD) alone, or in combination with gentamicin (G), teicoplanin (T), imipenem (I) or levofloxacin (L) against a strain of multidrug-resistant E. faecium in an experimental model of aortic valve endocarditis in rabbits. The study group consisted of 28 control animals. Eighty-two animals were treated with one of the following antibiotic regimens: G1: 18 animals QD (30 mg/kg/8 h); G2: 18 animals QD+G (6 mg/kg/12 h); G3: 16 animals QD+T (20 mg/kg/12 h); G4: 14 animals QD+I (60 mg/kg/8 h); and G5: 16 animals QD+L (20 mg/kg/12 h). The response to therapy was determined by the comparison of the number of CFU/g of E. faecium in each vegetation. In vitro, time-kill studies looking for synergy for the combinations that showed better efficacy in vivo were done. The sensitivity of the strain was intermediate to QD, resistant to T and I, and sensitive to L. There was no high-level resistance to G. QD alone revealed a significant decrease (p <0.001) in the CFU/g in the control group (9.49 vs. 7.31). There were no differences in the average of CFU/g between the QD alone (G1), QD+G (G2) and QD+T (G3) groups. These three groups revealed a significant difference in decrease of CFU/g respect of the group control (p <0.001). There were no differences in the average of CFU/g between QD+I (G4) and QD+T (G5). These two groups revealed the greatest decrease in average CFU/g (G4: 4.38 and G5: 4.04) with differences respect of the group control (p <0.0001) and respect of the groups G1, G2 and G3 (p <0.001). We did not detect any alteration of MIC from QD in the course of the treatment for either of the final isolations. Only the time kill corresponding to concentrations of I 32 mg/l (0.25 x MIC) and QD 1 mg/l (0.25 x MIC presents a descending slope in the curve at 4 and 8 h, suggesting an early synergy phenomenon, which was lost after 8 h. In light of these results, the combination QD with I and L may be considered suitable alternatives for the treatment of multiresistant E. faecium.
Pérez Salmerón
J
J
Servicios de Cardiologia y Microbiologia, Hospital Universitario Virgen de la Arrixaca, 30005 Murcia, Spain.
Martínez García
F
F
Roldán Conesa
D
D
Lorente Salinas
I
I
López Fornás
F
F
Ruiz Gómez
J
J
Gómez Gómez
J
J
Segovia Hernández
M
M
Valdés Chávarri
M
M
D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D016984:Enterococcus faecium / Q000187:drug effects* / Q000302:isolation & purification; D005260:Female; D005839:Gentamicins / Q000627:therapeutic use; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000627:therapeutic use; D011817:Rabbits; D017334:Teicoplanin / Q000627:therapeutic use; D014769:Virginiamycin / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D014769:Virginiamycin; C062940:quinupristin-dalfopristin; D017334:Teicoplanin; D064704:Levofloxacin; D015378:Imipenem; D015242:Ofloxacin