Effect of dexamethasone and pentoxifylline in combination with amoxicillin in the treatment of penicillin-insensitive pneumococcal pneumonia in guinea pigs.
A fatal guinea pig model of pneumococcal pneumonia was developed in order to evaluate the efficacy of amoxicillin combined with either pentoxifylline or dexamethasone. Parameters assessed were survival time and lung changes (alterations, bacterial colony counts, inducible nitric oxide synthase [iNOS] and cyclooxygenase-2 [COX-2] protein expression). Animals receiving pentoxifylline (50 mg/kg) showed higher survival rates than controls (p < 0.05). Animals which received amoxicillin (50 mg/kg), alone or combined, showed significantly higher survival rates than controls (p < 0.05). Animals dying in spite of receiving amoxicillin alone or combined had lung colony counts significantly lower than those that did not receive the antibiotic (p < 0.001), but their lungs showed identical changes. The correlation between COX-2 protein expression and mortality was rather high (r = 0.75). The addition of either dexamethasone or pentoxifylline to amoxicillin improved neither survival rates nor lung pathology when compared with the antibiotic alone.
Dept. of Medical Microbiology, Fundación Jiménez Díaz, Madrid, Spain
A
A
Parra
M
M
García-Olmos
E
E
Nieto
G
G
García-Calvo
C
C
Ponte
F
F
Soriano
D000658:Amoxicillin / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D003907:Dexamethasone / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006168:Guinea Pigs; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D010431:Pentoxifylline / Q000009:adverse effects / Q000494:pharmacology*; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000401:mortality; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome
D003907:Dexamethasone; D000658:Amoxicillin; D010431:Pentoxifylline