Background. Reverse-transcriptase inhibitors have only moderate clinical efficacy against the human immunodeficiency virus type 1 (HIV-1). Ritonavir is an inhibitor of HIV-1 protease with potent in vitro anti-HIV properties and good oral bioavailability.Methods. We evaluated the antiviral activity and safety of ritonavir in a double-blind, randomized, placebocontrolled phase 1 and 2 study of 84 HIV-positive patients with 50 or more CD4 ϩ lymphocytes per cubic millimeter. The patients were randomly assigned to one of four regimens of ritonavir therapy, or to placebo for four weeks and then (by random assignment) to one of the ritonavir regimens.Results. During the first 4 weeks, increases in CD4 ϩ lymphocyte counts and reductions in the log number of copies of HIV-1 RNA per milliliter of plasma were similar among the four dosage groups, but in the three lowerdosage groups there was a return to base-line levels by 16 weeks. After 32 weeks, in the seven patients in the highest-dosage group (600 mg of ritonavir every 12 hours), the median increase from base line in the CD4 ϩ lymphocyte count was 230 cells per cubic millimeter, and the mean decrease in the plasma concentration of HIV-1 RNA (as measured by a branched-chain DNA assay) was 0.81 log (95 percent confidence interval, 0.40 to 1.22). In a subgroup of 17 patients in the two higher-dosage groups, RNA was also measured with an assay based on the polymerase chain reaction, and after eight weeks of treatment there was a mean maximal decrease in viral RNA of 1.94 log (95 percent confidence interval, 1.37 to 2.51). Adverse events included nausea, circumoral paresthesia, elevated hepatic aminotransferase levels, and elevated triglyceride levels. Ten withdrawals from the study were judged to be related to ritonavir treatment.Conclusions. In this short-term study, ritonavir was well tolerated and had potent activity against HIV-1, but its clinical benefits remain to be established. (N Engl J Med 1995;333:1528-33.)

A nationwide susceptibility surveillance of 1,113Streptococcus pneumoniae isolates was carried out and found the following percentages of resistance: cefuroxime, 46%; penicillin, 37%; macrolides, 33%; aminopenicillins, 24%; cefotaxime, 13%; and ceftriaxone, 8%. A significant (P < 0.05) seasonality pattern for β-lactam antibiotics was observed. Resistance to macrolides was higher (P < 0.05) in middle-ear samples. Higher percentages of resistance to cefuroxime and macrolides were observed among penicillin-intermediate and -resistant strains, whereas high frequencies of resistance to aminopenicillins and expanded-spectrum cephalosporins were observed only among penicillin-resistant strains.

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SummaryBackground and objectives Data are needed to assess safety and efficacy of the 2009 pandemic influenza A H1N1 vaccine in renal patients.Design, setting, participants, & measurements We prospectively evaluated seroconversion, predictors of response, and vaccine safety in renal patients. Hemagglutination inhibition tests to detect serum antibodies against a new influenza A-H1N1 virus were performed in 79 transplant patients, 48 hemodialysis patients, and 15 healthy workers before and 1 month after vaccination. Healthy controls and 88 of 127 renal patients were vaccinated. Seroconversion was defined as at least 2 dilutions increase in titer.Results We excluded 19 individuals seroprotected (Ն1/40) against the novel H1N1 in the initial sample. Efficacy rate in the 96 vaccinated individuals was 43.7% (42 of 96 seroconverted versus four of 27 nonvaccinated patients, P ϭ 0.007). For vaccinated subgroups, efficacy was 41.8% in transplant patients (P ϭ 0.039 versus nonvaccinated), 33.3% in hemodialysis patients (P ϭ 0.450), and 81.8% in controls. Healthy controls showed better response to vaccine than transplant (P ϭ 0.021) and dialysis (P ϭ 0.012) patients. For the transplant subgroup, longer time after transplantation (P ϭ 0.028) was associated with seroconversion, but no influence was found for age, gender, renal function, or immunosuppression. In the hemodialysis subgroup, younger age was associated with response (55.7 Ϯ 20.8 versus 71.6 Ϯ 10.1 years, P ϭ 0.042), but other specific variables, including Kt/V or time on dialysis, were not. No serious adverse events were reported, and kidney function was stable. ConclusionThe novel influenza A 2009 H1N1 vaccine was safe in renal patients, although administration of a single dose of adjuvanted vaccine induced a poor response in these patients.

A nationwide susceptibility surveillance study of beta-hemolytic streptococcal isolates from pharyngeal swabs obtained in 11 Spanish hospitals between May 1996 and April 1997 against 12 antibiotics was carried out. Of the isolates 86% (786 of 914 isolates) were group A and 8.4% (77 of 914 isolates) were group C. No resistance was found to β-lactam antibiotics, but significant differences (P< 0.001) with respect to lack of susceptibility to macrolides were found between groups (27% for group A and 12% for group C) and between seasons (13.2% in summer and 31.7% in winter). Most of these isolates displayed the M phenotype (low-level resistance to erythromycin and susceptibility to clindamycin).