Incidence of neutropenia during treatment of bone-related infections with piperacillin-tazobactam.

Of 41 patients with bone-related infections who were treated for > or =10 days with piperacillin-tazobactam, 14 (34%) developed neutropenia. Cumulative doses of piperacillin administered to neutropenic patients were higher than those administered to nonneutropenic ones (330 vs. 237 g; P=.008), and an inverse correlation was detected between the absolute neutrophil count at the end of treatment and the cumulative dose of piperacillin (r=-0.47, P=.002). Moreover, the incidence of piperacillin-tazobactam-induced neutropenia increased with an increase in the cumulative dose of piperacillin: 0% of patients in the first quartile of cumulative piperacillin doses, 33.3% in the second quartile, 40% in the third quartile, and 66.7% in the fourth quartile.

Miconazole oral gel enhances acenocoumarol anticoagulant activity: a report of three cases.

OBJECTIVE: To describe three cases of interaction between miconazole oral gel and acenocoumarol, manifested as an increase in the international normalized ratio (INR). CASE SUMMARIES: Three patients (62-year-old woman, 89-year-old woman, 43-year-old man) following oral antithrombotic treatment with acenocoumarol for different pathologies were diagnosed with oral candidiasis and started miconazole oral gel. In all cases, the previous INR values were repeatedly within the therapeutic range. The following routine monitoring of the antithrombotic therapy showed a marked increase in anticoagulant activity in all cases, which returned to the therapeutic range after miconazole was withdrawn. None of the patients needed substantial changes in their habitual dosages of acenocoumarol in subsequent measurements of the INR to stay within the therapeutic range. DISCUSSION: We report three cases in which a possible interaction between miconazole oral gel and acenocoumarol is suggested by the chronological relationship between the introduction of miconazole and an increase in the INR. Miconazole exerts its fungistatic action by inhibiting some isoenzymes of the fungal cytochrome P450 system. Oral mucosa inflammation (as in oral candidiasis) may enhance its transmucosal absorption. In this setting, cytochrome P450 isoenzymes belonging to the host may be inhibited too. This mechanism provides an explanation for different interactions observed with miconazole oral gel. CONCLUSIONS: Miconazole oral gel enhances acenocoumarol anticoagulant activity. Although we did not observe major bleeding complications, we suggest the use of other families of antifungal drugs, such as nystatin, to treat oral candidiasis in patients taking acenocoumarol.