Antibiotic combinations for serious infections caused by carbapenem-resistant Acinetobacter baumannii in a mouse pneumonia model.
OBJECTIVE
Successful therapy of carbapenem-resistant Acinetobacter baumannii strains has been reported with colistin, but recently we argued against its use as monotherapy because of the poor results obtained in a mouse pneumonia model. Our aim was to identify antibiotic combinations that were valid therapeutic alternatives in the same model.


METHODS
We used two carbapenem-resistant A. baumannii strains (D and E; MICs of imipenem, 8 and 512 mg/L, respectively). MICs of tobramycin, rifampicin and colistin for both strains were 8, 8 and 0.5 mg/L, respectively.


RESULTS
In infections caused by strain D, lung bacterial counts (log(10) cfu/g, mean +/- s.d.) were: controls (10.86+/-0.25), imipenem (5.99+/-0.59, P < 0.05 versus controls), and colistin (10.43 +/- 1.09); imipenem + tobramycin was the most active combination (5.46+/-0.62, P < 0.05 versus controls). In infections caused by strain E, results were: controls (10.82+/-0.33), rifampicin (5.62+/-0.26, P < 0.05 versus controls), colistin (8.38+/-1.22, P < 0.05 versus controls), and imipenem (11.01+/-0.2); rifampicin + imipenem (3.79+/-0.99) and rifampicin + tobramycin (3.96+/-0.30) were the most active combinations (P < 0.05); results with rifampicin + colistin (5.59+/-1.17) were similar to those with rifampicin alone.


CONCLUSIONS
Our data indicate that imipenem can still be the best alternative for carbapenem-resistant A. baumannii infections with moderate levels of imipenem resistance, preferably combined with aminoglycosides. For strains highly resistant to imipenem, a combination of rifampicin with imipenem, tobramycin or colistin may be useful, if resistance to rifampicin is only moderate.
Montero
Abelardo
A
Laboratory of Experimental Infection, Infectious Disease Service, Hospital de Bellvitge, University of Barcelona, Spain. amontero@gencat.net
Ariza
Javier
J
Corbella
Xavier
X
Doménech
Alejandro
A
Cabellos
Carmen
C
Ayats
Josefina
J
Tubau
Fe
F
Borraz
Carmen
C
Gudiol
Francesc
F
D000151:Acinetobacter Infections / Q000188:drug therapy / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D015780:Carbapenems / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use; D014031:Tobramycin / Q000494:pharmacology / Q000627:therapeutic use; D047090:beta-Lactams / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D047090:beta-Lactams; D012293:Rifampin; D014031:Tobramycin; D003091:Colistin