Efficacy and safety of famciclovir for treating mucocutaneous herpes simplex infection in HIV-infected individuals. Collaborative Famciclovir HIV Study Group.

OBJECTIVE: To compare the efficacy and safety of 7 days' treatment with famciclovir 500 mg twice a day versus acyclovir 400 mg five times a day, for mucocutaneous herpes simplex virus (HSV) infection in HIV-infected individuals. DESIGN: Randomized, double-blind, parallel-group study to demonstrate equivalence for the primary efficacy parameter. SETTING: Forty-eight hospital-based or specialist public-health clinics in 12 countries. PATIENTS: Two-hundred and ninety-three HIV-positive patients with recurrent HSV infection (orolabial or genital) starting treatment within 48 h of first appearance of herpetic lesions. MAIN OUTCOME MEASURES: Proportion of patients developing new lesions during treatment (primary outcome measures); Time to complete healing of lesions, time to cessation of viral shedding, time to loss of lesion-associated symptoms, number of withdrawals due to treatment failure (secondary outcome measures). RESULTS: Equivalence was defined prospectively and famciclovir was equivalent to acyclovir in preventing new lesion formation: new lesions occurred in 16.7% and 13.3% of patients, respectively [difference, 3.4%; 95% confidence interval (CI), -4.8-11.5]. The groups were comparable in time to complete healing (median 7 days for both groups; hazard ratio, 1.01; 95% CI, 0.79-1.29; P = 0.95), cessation of viral shedding (median of 2 days [hazard ratio = 0.93; 95% C.I. 0.68, 1.27; p = 0.64]), and loss of lesion-associated symptoms (median 4 days; hazard ratio, 0.99; 95% CI, 0.75-1.30; P = 0.93). Similar numbers in each group withdrew because of treatment failure. There were no differences between groups in the incidence of adverse events. CONCLUSIONS: Famciclovir given twice a day is as effective and well tolerated as high-dose acyclovir for mucocutaneous HSV infections in HIV-infected individuals, and has the convenience of less frequent dosing.

Oral acyclovir in prevention of herpes labialis. A randomized, double-blind, multi-centered clinical trial.

OBJECTIVE: A three-center, randomized, double-blind, placebo-controlled acyclovir clinical trial was conducted among Canadian skiers over a 2-year period. STUDY DESIGN: All patients enrolled in the study reported a history of recurrent herpes labialis with a greater-than-50% chance of a sun-induced trigger. There were 239 patients enrolled, and 237 of these were included in the analysis. For a minimum of 3 days and a maximum of 7 days, each patient received 800 mg of oral acyclovir twice daily (1600 mg/day) 12 to 24 hours before exposure to the sun. A minimum of 3 hours of outdoor activity was required each day. RESULTS: No differences were detected in baseline and outcome measures among the centers, and results from all three centers were combined for further analysis. There was no difference in healing rate between the acyclovir and placebo groups for the first 4 days. Patients using acyclovir healed slightly faster on days 5 and 6, and nearly all patients in both the acyclovir and placebo groups were healed by day 7. Adverse events were evenly distributed; no withdrawals were required in either group. CONCLUSION: 800-mg oral acyclovir taken twice a day was not significantly better than a placebo either in effectiveness and prevention of recurrent herpes labialis or in adverse effects.

Herpes labialis in skiers: randomized clinical trial of acyclovir cream versus placebo.

OBJECTIVE: A randomized, double-blind trial at seven ski sites in Canada and the United States was conducted to compare the effectiveness and the patient tolerance of topically applied 5% acyclovir cream (MAC III formulation) with those of a placebo cream in the prevention of sun-induced herpes labialis lesions. STUDY DESIGN: All subjects had experienced more than three episodes of sun-induced herpes labialis during the previous year. There were 196 subjects enrolled; 5 did not receive medication, and 10 were excluded from the efficacy analysis for protocol violations. There were 191 subjects in the intent-to-treat analysis, and a separate efficacy analysis was done on 181 subjects. Log rank and Fisher exact tests were used in the analysis. RESULTS: There was no difference between the two groups at baseline with respect to any clinical or demographic factor. There was no substantial difference between the groups with respect to adverse experiences (15 for acyclovir; 13 for the placebo). The acyclovir group had significantly fewer lesions (p < 0.01) than the placebo group (21% vs. 40%) during the 4-day follow-up period. CONCLUSION: The acyclovir group was significantly better than the placebo group during the follow-up period. The safety record of the drug was satisfactory; there was no difference between acyclovir and the placebo in side effects or pain. Topically applied 5% acyclovir cream is an effective preventive step for those who are active and exposed to the sun.

Treatment of acute uncomplicated urinary tract infections with 3 days of lomefloxacin compared with treatment with 3 days of norfloxacin.

The bacteriologic and clinical efficacies of 3 days of lomefloxacin therapy were compared with those of 3 days of norfloxacin therapy for the treatment of acute uncomplicated urinary tract infections in a prospective, randomized, double-blind study. One hundred sixty-four subjects were enrolled at five Canadian centers; 84 received lomefloxacin, and 80 received norfloxacin. Escherichia coli (84%) and Staphylococcus saprophyticus (11%) were the most common organisms isolated. Forty subjects (24%) had low quantitative counts in their pretherapy urine specimens. In the intent-to-treat analysis, 76 lomefloxacin subjects (91%) and 76 norfloxacin subjects (95%) were cured or improved at follow-up 5 to 9 days posttreatment and 73 (87%) and 71 (89%) subjects from the lomefloxacin and norfloxacin groups, respectively, were cured or improved at 4 to 6 weeks posttreatment. Bacteriologic eradication occurred in 61 of 63 lomefloxacin subjects (97%) with > or = 10(8) CFU/liter in their pretherapy specimens and 56 of 59 norfloxacin subjects (95%) at 5 to 9 days and 55 (87%) and 53 (90%) subjects from the lomefloxacin and norfloxacin groups, respectively, at 4 to 6 weeks. There were no statistically significant differences in outcome. Adverse effects which were potentially related to the study medications were reported by 26% of the subjects who received lomefloxacin and 25% of the subjects who received norfloxacin. There were no severe adverse events, and only one subject discontinued therapy. These data suggest that 3 days of therapy with either lomefloxacin or norfloxacin is effective in the treatment of acute uncomplicated urinary tract infections.

Randomized, double-blind, placebo-controlled, clinic-initiated, Canadian multicenter trial of topical edoxudine 3.0% cream in the treatment of recurrent genital herpes. Canadian Cooperative Study Group.

Treatment for recurrent genital herpes using edoxudine 3% cream for 5 days was evaluated in 200 patients in a randomized, multicenter, double-blind, placebo-controlled, clinic-initiated trial. Lesion tenderness was predictive of and more sensitive and longer-lasting than the symptom of pain. Among patients receiving placebo, times to crusting (P = .043), cessation of investigator-observed signs (P = .005), lesion-associated signs (P = .02), and groin signs (P = .05) were longer in women. Edoxudine reduced viral shedding in men (mean 2.7 vs. 3.4 days, P = .009) and women (2.0 days vs. 3.5 days, P = .0001). Loss of investigator-observed signs (4.4 vs. 6.2 days, P = .002), investigator-observed lesion tenderness (P = .01), lesion signs (P = .02), groin adenopathy (P = .01), and tenderness (P = .01) occurred earlier in women taking edoxudine. Edoxudine was well-tolerated and reduced several signs of herpes in women. Its clinical role in recurrent genital herpes remains to be fully determined.

Isolation and biochemical characterization of Haemophilus species isolated simultaneously from the oropharyngeal and anogenital areas.

Several reports have described the high frequency of pharyngeal isolation of Haemophilus species. Few studies have compared the simultaneous isolation rate of this species in the oropharyngeal and anogenital areas. Using two selective media, heart infusion agar (HIA) supplemented with 5% defibrinated rabbit blood, 1% IsoVitaleX, and either bacitracin alone (100 micrograms/ml) or bacitracin (5 micrograms/ml), vancomycin (3 micrograms/ml), and polymyxin B (1 microgram/ml), we isolated Haemophilus species in both areas in 89 of 399 (22.2%) patients consulting a sexually transmitted disease clinic. Of those, 56 were males and 33 were females. We recovered Haemophilus species in the oropharyngeal area in 384 patients (96%), while rectal and genital areas were colonized in 48 (12.0%) and 55 (13.8%) patients, respectively (both areas were colonized in 14 patients). Haemophilus parainfluenzae was isolated almost twice as often in the anogenital area as was H. influenzae. H. influenzae biotypes II and III and H. haemolyticus were the more prevalent XV-requiring haemophili isolated from the oropharynx, while H. influenzae biotype IV was more prevalent in the anogenital area. H. parainfluenzae biotypes I, II, and III were more prevalent in the oropharynx, while biotypes I and II were more prevalent in the anogenital area.

Isolation and molecular characterization of beta-lactamase-producing Haemophilus parainfluenzae from the genital tract.

Three Haemophilus parainfluenzae strains isolated from the urogenital tract harbored a beta-lactamase-coding 3.2-megadalton plasmid identical, by restriction endonuclease digestion and hybridization with radioactive and biotin-labeled probes specific for the TEM-1 beta-lactamase and TnA sequences, to the 3.2-megadalton "African-type" plasmid found in Neisseria gonorrhoeae.

Susceptibility of Haemophilus aegyptius to trooleandomycin: lack of taxonomic value.

Two hundred and nine strains of Haemophilus influenzae and Haemophilus aegyptius were screened for trooleandomycin susceptibility. Four strains were shown to be sensitive to the drug. Of these four, two were Haemophilus aegyptius (ATCC 11116, NCTC 8134), and the other two were Haemophilus influenzae biotype I (1-605) and IV (80-212. One strain of Haemophilus aegyptius (NCTC 8135) was resistant to trooleandomycin. Restriction enzyme assays and DNA homology were carried out to establish relationships between the strains. It is concluded that trooleandomycin susceptibility has no taxonomic value to differentiate between Haemophilus aegyptius and biotype III Haemophilus influenzae.