Updates-By Carol A. Kemper, MD, FACP

Itraconazole in HIV

Source: Koks CH, et al. AIDS 2000;14: 89-90.

Ritonavir (rtv) is a potent inhibitor of the p450 hepatic enzyme system (CYP450), and is often used in combination with saquinavir (SQV) or other protease inhibitors to block the metabolism of these agents, thereby increasing their blood levels and allowing the use of lower dosages. However, RTV, even at the lower dosages used for these purposes (100-400 mg twice daily, depending on the agent used in combination) can be poorly tolerated. Why not a different and better tolerated blocking agent?

During routine drug monitoring of antiretroviral therapy in HIV-infected patients, Koks and colleagues noted that two patients had SQV levels 5-fold higher than expected in the absence of RTV. Both patients, it turned out, were receiving itraconazole, another inhibitor of CYP450. Serial blood samples to assess SQV levels were then obtained in three patients receiving long-term SQV 1200 mg t.i.d. (without RTV) before and after the administration of itraconazole for two weeks. Itraconazole was administered as a loading dosage of 200 mg twice daily for three days, and then 200 mg once daily.

Following the administration of itraconazole for two weeks, there was a median 5-fold increase (range, 2.5-6.9) in the area under the curve for SQV. Trough levels increased a median of 3.1-fold (range, 1.6-16.8). These SQV concentrations, in combination with itraconazole, were comparable to those observed when SQV is combined with RTV (using a dosage of 400 mg twice daily for both agents). Itraconazole may be a reasonable alternative in those patients receiving SQV therapy who are intolerant of RTV. Although it is not clear that the entire 1200 mg t.i.d. SQV dose is necessary when used in combination with itraconzole, Koks et al cautioned that because the pharmacokinetic interaction of itraconazole appears to be smaller and more varied than that of RTV, the dose of SQV should not be reduced to 400 mg twice daily as it is when combined with RTV.

Perinatal Hepatitis C Transmission

Source: Gibb DM, et al. Lancet 2000; 356:904-907.

Gibb and associates in the united Kingdom and Ireland assessed the risk of perinatal transmission of hepatitis C virus (HCV) in 441 mother-infant pairs. Twenty-two moms were co-infected with HIV (the HIV status was not known for 91 moms). Of 144 children who became HCV antibody-negative, 135 (93.8%) had negative confirmatory HCV RNA PCR test results. Of the remaining 297 children, 248 of whom were tested by PCR, HCV RNA PCR results were positive in 14 (5.6%), negative in 221 (89.1%), and discordant in 13 (5.2%). The overall risk of vertical transmission was estimated to be 6.7%. In children born to HIV-infected mothers, the risk of HCV transmission was significantly higher (odds ratio, 3.8).

Gibb et al acknowledged that the risk of transmission could only be based on estimates of the rate of loss of antibody to HCV and the known sensitivity/specificity of HCV RNA PCR. In apparently uninfected children, rates of detectable HCV antibody were ~50% at eight months and 5% at 13 months. Serological testing should, therefore, be delayed until at least 12-15 months of age. On the other hand, PCR testing was only 22% sensitive during the first month of life, but increased to 97% thereafter. While a negative PCR test after one month of life rules out infection, a positive PCR test after one month increases the risk of HCV infection to 73% and requires longer-term follow-up.

Urokinase of Benefit in Percutaneously Drained Abscesses

Source: Haaga JR, et al. AJR Am J Roentgenol 2000;174:1681-1685.

Forty-two patients with abscesses requiring percutaneous drainage were randomly assigned to receive intracavitary urokinase or sterile saline within 24 hours of placement of the drainage catheter. Urokinase or sterile saline was administered every eight hours for a total of four days; the dose was dependent on the size of the abscess cavity. Only those patients with abscess material that was culture positive or those who were receiving antibacterial therapy for treatment of an abscess were included. Patients with pancreatic abscess or pseudocyst were excluded from study.

Abscess location and size were similar between the two groups, as was the proportion of abscesses that were loculated. The proportion of patients with a partial or complete response to therapy was similar between the two groups (86% response rate). However, the length of hospital stay was significantly shorter for patients receiving urokinase compared with those receiving saline (29 vs 13 days; P = 0.0025), and the resulting treatment costs were significantly less. There was also a trend toward fewer days of fever, leukocytosis, and required catheter drainage in patients receiving urokinase. The number of days of catheter drainage for patients receiving urokinase was seven vs. 15 for those receiving saline (P = 0.14). No complications of urokinase therapy occurred.

Intracavitary administration of urokinase, whether for an empyema, intraabdominal abscess, or infected hematoma, may help to decrease the viscosity of the abscess material, resulting in more rapid and effective drainage.