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3.
J Antimicrob Chemother ; 56(4): 783-6, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16144869

ABSTRACT

OBJECTIVE: To evaluate the effect of delayed administration of erythromycin in the course of acute otitis media caused by an erythromycin-susceptible Streptococcus pneumoniae strain in the gerbil model. METHODS: The bacterium was inoculated by transbullar challenge in the middle ear (ME) and antibiotic treatment at different doses was administered at various times thereafter. RESULTS: When 2.5 mg/kg of erythromycin was administered as a single dose 2, 5, 18 or 21 h post-inoculation (pi) the bacterial eradication rate was 55, 40, 0 and 0%, respectively. A higher dose (5 mg/kg) administered also as a single dose 2, 5, 18 and 21 h pi achieved bacterial eradication rates of 62.5, 43.8, 0 and 0%, respectively. Using a very high dose (50 mg/kg) repeated three times at 3 h intervals (total dose 150 mg/kg) and starting the treatment 21 h pi only achieved bacterial eradication in 25% of cases. The concentration of erythromycin achieved in the ME 90 min after administration of 5 mg/kg 5 or 21 h pi was very similar (0.74 and 0.79 mg/L) but the ME half-life was longer (98.2 min) with the early administration as compared with the delayed form (47.5 min), which could partially explain the different results. Further experiments showed that the failures observed with the delayed administration were not related to the time elapsed from antibiotic administration to ME sampling or selection of antibiotic-resistant mutants. CONCLUSION: Bacteriological and clinical efficacies were significantly diminished if antibiotic administration was delayed.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Erythromycin/administration & dosage , Erythromycin/therapeutic use , Otitis Media/drug therapy , Pneumococcal Infections/drug therapy , Animals , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/pharmacokinetics , Disease Models, Animal , Dose-Response Relationship, Drug , Erythromycin/blood , Erythromycin/pharmacokinetics , Gerbillinae , Microbial Sensitivity Tests , Time Factors , Treatment Outcome
4.
J Clin Microbiol ; 42(4): 1832-6, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15071063

ABSTRACT

Seven cases of disseminated infection due to Dipodascus capitatus are reported. Infections occurred in a hematological unit of a tertiary hospital during a period of 5 years. Five cases were refractory to antifungal therapy. Antifungal susceptibility testing of seven isolates was performed, and strains were typed by PCR fingerprinting with the core sequence of phage M13 and by random amplification of polymorphic DNA with two primers, Ap12h and W-80A. A very short range of MICs of each antifungal agent was observed. The MICs of amphotericin B ranged between 0.50 and 2 microg/ml. Strains were susceptible in vitro to flucytosine and susceptible (dose-dependent) to fluconazole and itraconazole. Voriconazole exhibited an activity in vitro comparable to that of itraconazole. Typing techniques allowed seven additional isolates of D. capitatus neither geographically nor temporally related to be classified into two different genomic patterns. The genomic type of the seven strains from the hematological unit was identical regardless of typing technique utilized. It would indicate that the seven cases of disseminated infection could be related epidemiologically.


Subject(s)
Fungemia/microbiology , Leukemia/complications , Mycoses/microbiology , Saccharomycetales/classification , Saccharomycetales/drug effects , Adult , Aged , Antifungal Agents/pharmacology , Cerebrospinal Fluid/microbiology , DNA Fingerprinting/methods , Female , Genotype , Hospitals , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Mycological Typing Techniques , Polymerase Chain Reaction , Random Amplified Polymorphic DNA Technique , Saccharomycetales/genetics , Saccharomycetales/isolation & purification
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