title: Effect of dexamethasone or HWA-138 in combination with antibiotics in experimental Haemophilus influenzae type b infection.
abstract: Modulation of the host's inflammatory response in bacterial meningitis may be beneficial. In this study, the effects of dexamethasone and HWA-138, an analog of pentoxifylline, on CSF cultures and cochlear inflammation in an infant rat model of Haemophilus influenzae type b were studied. Five-day-old infant rats were inoculated once intraperitoneally with 1 x 10(4) to 10 x 10(4) CFU of H. influenzae type b (strain 1406). Twenty-four hours later, infant rats were treated intraperitoneally with one dose of ampicillin (0.1 mg/g of body weight), cefotaxime (0.05 mg/g), or cefuroxime (0.05 mg/g) alone or in combination with one dose of dexamethasone (0.00015 mg/g) or HWA-138 (0.005 mg/g). Twenty-four hours after treatment with cefuroxime plus dexamethasone, animals had a significantly (P less than or equal to 0.04) greater incidence of bacteremia and meningitis (eight of nine animals) than that in animals of the other treatment groups. Overall, dexamethasone was associated with less inflammation (P less than 0.04) of the cochlear nerve compared with that from antibiotic treatment alone. In this model, when suboptimal antimicrobial therapy is administered, anti-inflammatory agents may be beneficial with respect to reducing cochlear inflammation. However, dexamethasone and cefuroxime lead to a higher rate of positive blood and cerebral spinal fluid cultures than cefuroxime alone.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: A F
authors.initials: AF
authors.lastname: Rodriguez
authors.forename: S L
authors.initials: SL
authors.lastname: Kaplan
authors.forename: E P
authors.initials: EP
authors.lastname: Hawkins
authors.forename: E O
authors.initials: EO
authors.lastname: Mason
mesh_terms: D000667:Ampicillin / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002439:Cefotaxime / Q000627:therapeutic use; D002444:Cefuroxime / Q000627:therapeutic use; D002648:Child; D003907:Dexamethasone / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D007758:Ear, Inner / Q000382:microbiology; D006192:Haemophilus Infections / Q000188:drug therapy* / Q000382:microbiology; D006193:Haemophilus influenzae; D006801:Humans; D010431:Pentoxifylline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000900:Anti-Bacterial Agents; D001993:Bronchodilator Agents; C062028:1-(5-hydroxy-5-methylhexyl)-3-methylxanthine; D000667:Ampicillin; D003907:Dexamethasone; D002439:Cefotaxime; D002444:Cefuroxime; D010431:Pentoxifylline