Vancomycin penetration into lung tissue was evaluated in thirty patients following the administration of 1 g of vancomycin as a 1 h i.v. infusion. Mean concentrations (range) of vancomycin in lung tissue were 9.6 (6.3-12.1) mg/kg at 1h, 5.7 (4.7-7.4) mg/kg at 2 h, 4.2 (0.8-6.5) mg/kg at 3-4 h, 2.4 (1.4-4.7) mg/kg at 6 h, and 2.8 (0.9-7.8) mg/kg at 12 h after the end of infusion. Ratios of lung tissue to serum concentration ranged 0.24 to 0.41 at 1 and 12 h, respectively. One of six patients observed at 6 h, and 3 of 7 patients at 12 h did not have detectable levels of vancomycin in lung tissue. A 1 h iv infusion of a 1 g dose of vancomycin does not achieve sustained lung concentrations above the MIC for susceptible staphylococci over a dosing interval of 12 h. Therefore, a more appropriate modality of administration, such as continuous infusion, should be considered.

This report, which has been updated to include data published or presented at conferences up to the end of August 2001, summarizes the data presented and issues discussed at the meeting. This article will guide the reader through the data and discussions that have allowed the panel to formulate a series of position statements regarding the current status and future applications of TDM in antiretroviral therapy. These statements have been formulated to provide suggestions for the design of future TDM clinical trials, as well as to provide useful points of reflection for centres in which TDM is already in use.

Patients with higher ritonavir concentrations are at a higher risk of experiencing neurological or gastrointestinal side-effects. Individualization of the dosage regimen, e.g. a downward titration of the ritonavir dose in patients with side-effects, guided by plasma level monitoring, may result in a substantial increase in the percentage of patients tolerating ritonavir without increasing the risk of treatment failure as a result of suboptimal systemic exposure.

The absolute oral bioavailability and pharmacokinetics of clindamycin administered to 16 healthy volunteers and 16 patients with AIDS were compared. Clindamycin was given intravenously (i.v.) (Cleocin phosphate) at a dose of 600 mg as a 25-min infusion and orally (Cleocin hydrochloride) by use of a crossover design in both study groups. Plasma samples were analyzed by gas-liquid chromatography. Plasma drug clearance and volume of distribution at the steady state following the i.v. dose differed between study groups. The clearances were 0.27 0.06 liter/h/kg in healthy volunteers and 0.21 0.06 liter/h/kg in AIDS patients (P = 0.014; Mann-Whitney U test); the volumes of distribution at the steady state were 0.79 + 0.13 and 0.66 0.12 liter/kg in healthy volunteers and AIDS patients, respectively (P = 0.005). The elimination half-life did not differ between the two groups. The bioavailability of clindamycin capsules in AIDS patients was approximately 1.5 times that in healthy volunteers (0.53 + 0.14 versus 0.75 + 0.20; P = 0.002). Peak concentrations following the oral dose were higher in AIDS patients as well (7.7 2.5 versus 5.3 1.0 mg/liter, P = 0.0008). Three AIDS patients experienced severe diarrhea following the oral dose; four patients had mild diarrhea following the i.v. dose. No adverse effects were reported by the healthy volunteers. The pharmacokinetic parameters observed in this study for AIDS patients may be useful for the consideration of clindamycin dosage regimens in patients treated for toxoplasmic encephalitis. These findings suggest that the effect of AIDS on drug disposition deserves further investigation, particulariy for orally administered drugs.Toxoplasmic encephalitis (TE) is considered the most common cause of intracerebral mass lesions in patients with AIDS, occurring in 3 to 40% of AIDS patients (16). Standard therapy for TE includes the synergistic combination of pyrimethamine and sulfadiazine, which provides a sequential blockade of folic acid metabolism. However, many patients with AIDS are unable to complete a course of therapy because of adverse reactions (18).Clindamycin has been used either alone or more frequently in combination with pyrimethamine to treat TE in patients with AIDS who develop untoward side effects to the sulfonamide component of the standard pyrimethaminesulfadiazine therapy (4,10,15,21,23,24). Recently, the results of an international prospective study comparing the combinations pyrimethamine-sulfadiazine and pyrimethamine-clindamycin suggest that the relative efficacies of the two combination treatments are approximately equal (3).The activity of clindamycin against Toxoplasma gondii is controversial: clindamycin was effective in a murine model of TE (11) but was ineffective in a model based on Taxoplasma-infected rat monocytes (9). Clindamycin does not penetrate adequately into cerebrospinal fluid, even in the presence of bacterial meningitis (7); however, it has been suggested that damage of the blood-brain barrier in AIDS patients, involving marked tissue de...

To assess if the relative infectiousness of patients with tuberculosis is enhanced by coinfection with human immunodeficiency virus type 1 (HIV-1), data from 6 studies of 1240 health care workers who had contact with tuberculosis patients were analyzed. Overall rates of tuberculin skin test conversion were similar regardless of HIV-1 positivity of tuberculosis patients (odds ratio [OR], 1.04; 95% confidence interval [CI], 0.23-1.84). However, when only 3 studies during nosocomial outbreaks of multidrug-resistant Mycobacterium tuberculosis were analyzed, rates of skin test conversion were higher among contacts of HIV-1-positive index cases (OR, 2.85; 95% CI, 1.85-3.85; P=.0002). A second meta-analysis included data from 11 studies of 10,714 household contacts of tuberculosis patients. Prevalence of both skin test positivity (OR, 0.45; 95% CI, 0.20-1.03) and active disease (OR, 1.17; 95% CI, 0.78-1.56) were similar regardless of HIV-1 positivity of index cases. These data suggest that tuberculosis patients with HIV-1 infection are not intrinsically more infectious to their contacts than are HIV-1-negative tuberculosis patients.