Long-term suppression of recurrent genital herpes with acyclovir. A 5-year benchmark. Acyclovir Study Group.

BACKGROUND AND DESIGN: This multicenter trial (19 sites) was initiated in 1984 in more than 1100 immunocompetent individuals with a history of frequently recurring genital herpes (mean, > or = 12 episodes per year). The first year of this suppressive therapy trial was placebo controlled, with acyclovir being provided for episodic treatment in both groups. Thereafter, patients were treated with open-label acyclovir suppressive therapy on a long-term basis (400 mg twice daily) to continue to assess its long-term safety and efficacy. Complete data are available on 389 of the 430 patients who began the fifth year of the study. RESULTS: Patients were seen quarterly for review of diaries and clinical laboratory evaluations. The percentage of patients recurrence free for any 3-month quarter of the fifth year ranged from 86% to 90%. The mean annual number of recurrences per patient declined from 1.7 during the first year to 0.8 during the fifth year of suppressive therapy. The frequency of false prodromes has also decreased over time. More than 20% of the patients receiving suppressive therapy for 5 years have been recurrence free the entire time. The duration of herpetic outbreaks during suppressive therapy has not changed. CONCLUSION: This study extends the safety and efficacy profile of oral acyclovir in the suppression of genital herpes to 5 years. The majority of the patients were recurrence free on an annual basis during suppressive therapy. Therapy was well tolerated. Acyclovir usage was not associated with serious side effects or cumulative toxicity.

Continuous five-year treatment of patients with frequently recurring genital herpes simplex virus infection with acyclovir.

This study presents data relative to the efficacy and safety following the continuous use of oral acyclovir in the treatment of genital herpes over a 5-year period. In this study, 1,146 patients (53% males; 47% females) were originally enrolled. These included patients with a history of frequently recurring genital herpes (mean > 12 episodes per year). During the first year, patients were randomized between those receiving 400 mg of acyclovir twice daily and an equal number receiving placebo. Additionally, acyclovir was utilized for episodic treatment (ES) in both groups. Thereafter, patients received open-label acyclovir suppressive therapy for the remainder of the study period. Complete data are available on 389 patients who completed the fifth year of therapy. All the participants who completed the fifty year of the study had completed either 4 or 5 years of daily suppressive acyclovir therapy. During the first year, a significant decrease in the frequency of recurrences in patients receiving continuous acyclovir (SS) was noted as compared to the placebo group (1.7 vs. 12.5 recurrences; P < 0.0001). From year one to the end of year three, a progressive decrease in the frequency of recurrences was noted in both groups. Yet, those patients who had received SS for the full 3 years had significantly fewer recurrences than those who had received ES in the first year (P = 0.05). During years four and five, the decrease in frequency of recurrences between the ES and SS groups was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

A multicenter comparative trial of three-day norfloxacin vs ten-day sulfamethoxazole and trimethoprim for the treatment of uncomplicated urinary tract infections.

Two-hundred nine patients with symptoms of acute urinary tract infection and pyuria were randomized to 400 mg of administered norfloxacin twice daily for three days, or 800 mg of sulfamethoxazole and 160 mg of trimethoprim administered twice daily for ten days. Therapeutic outcome was assessed five to nine days and four to six weeks after treatment. The cure rates were 71/74 (96%) with norfloxacin and 81/81 (100%) with sulfamethoxazole and trimethoprim five to nine days after treatment. Only seven patients had a recurrence at the second follow-up visit; four in the norfloxacin group and three in the sulfamethoxazole and trimethoprim group. No isolates were resistant to norfloxacin, but three Escherichia coli were resistant to sulfamethoxazole and trimethoprim. Fifteen patients in each group reported a side effect during treatment. Two patients in the norfloxacin group and four patients in the sulfamethoxazole and trimethoprim group discontinued therapy due to an adverse effect. In this multicenter study, a three-day course of norfloxacin was as effective and safe as a ten-day regimen of sulfamethoxazole and trimethoprim in the treatment of acute uncomplicated urinary tract infections.

Successful treatment of spinal arachnoiditis due to coccidioidomycosis. Case report.

An unusual case is reported of a patient with spastic paraparesis who was found to have severe spinal arachnoiditis due to Coccidioides immitis. Despite an obstructive hydrocephalus and a spinal subarachnoid block, the patient was treated effectively with surgery (shunting) and antifungal therapy (amphotericin and ketoconazole). He remains asymptomatic 3 years after diagnosis. Aggressive surgical and medical treatment of coccidioidal infection of the central nervous system can be beneficial, even in patients with the worst prognosis.

Moxalactam for treatment of nosocomial infections.

Sixty-five episodes of nosocomial infections of the blood, lungs, urinary tract, soft tissues, bones, or central nervous system were treated with intravenous moxalactam (3-12 g per day). Bacteremia was documented in 21 patients. Despite the severely compromised condition of many patients, 80% of the infections responded satisfactorily, as defined by clinical and microbiologic cure or improvement. Of the 21 cases of nosocomial bacteremia, 14 (67%) responded satisfactorily. Of the six cases of bacteremia caused by gram-negative bacilli resistant to aminoglycosides, three responded satisfactorily. Moxalactam therapy also resulted in cure or improvement in nine (69%) of 13 pulmonary infections, and it was used alone to cure one case of meningitis-ventriculitis due to Klebsiella pneumoniae. Seven of 13 therapeutic failures involved Pseudomonas aeruginosa, and moxalactam-resistant P. aeruginosa emerged during therapy for 12 patients. Adverse effects, usually mild diarrhea, occurred in 9.2% of the patients. Except for some severe infections due to P. aeruginosa, moxalactam is effective and safe therapy for nosocomial infections caused by susceptible organisms.

Moxalactam therapy for bacterial infections.

Moxalactam, a novel beta-lactam antimicrobial agent in which oxygen has replaced sulfur in the six-membered ring of the conventional cephem nucleus, has in vitro activity against almost all commonly isolated bacterial pathogens including Staphylococcus aureus, the Enterobacteriaceae, Pseudomonas aeruginosa, Bacteroides fragilis, and Haemophilus influenzae. The clinical efficacy an toxicity of moxalactam alone was evaluated in the treatment of 100 infections, including 22 septicemias. Thirty-two infections involved P aeruginosa, while organisms resistant to one or more of the currently available cephalosporins or cefoxitin were isolated from cultures in 63 of the cases. The overall clinical response was favorable (infection cured or improved) in 86% of the infections. A child with Klebsiella pneumoniae ventriculitis and meningitis was cured with intravenous moxalactam alone. Six of 14 treatment failures involved P. aeruginosa, and P aeruginosa isolates resistant to moxalactam emerged during therapy of 12 infections. Side effects, usually mild diarrhea, occurred in only 8.8% of the patients. Except for some severe P aeruginosa infections outside the urinary tract, moxalactam is effective and safe single-agent therapy for infections caused by susceptible organisms and represents a major advancement in beta-lactam antimicrobial therapy.

Comparative in vitro synergistic activity of new beta-lactam antimicrobial agents and amikacin against Pseudomonas aeruginosa and Serratia marcescens.

The in vitro synergistic activities of moxalactam, cefoperazone, or cefotaxime in combination with amikacin or piperacillin were compared against aminoglycoside-susceptible and aminoglycoside-resistant isolates of Pseudomonas aeruginosa and Serratia marcescens by the checkerboard agar dilution method. All antimicrobial combinations demonstrated some synergy, and no antagonism was observed. Moxalactam plus amikacin and piperacillin plus amikacin were most frequently synergistic (two-thirds of the isolates inhibited synergistically by each combination), whereas combinations of moxalactam, cefotaxime, or cefoperazone with piperacillin were synergistic against only 18 to 25% of the isolates. Moxalactam plus amikacin was the combination most often synergistic for amikacin-susceptible P. aeruginosa, and piperacillin plus amikacin was the combination most frequently synergistic for amikacin-resistant P. aeruginosa and amikacin-susceptible S. marcescens. These results demonstrate frequent in vitro synergistic activity between the new beta-lactam agents and amikacin (especially moxalactam or piperacillin with amikacin), but comparative clinical trials are needed to establish the relative efficacy and toxicity of these combinations.

Comparative in vitro activity of moxalactam, cefotaxime, cefoperazone, piperacillin, and aminoglycosides against gram-negative bacilli.

The in vitro activities of four new beta-lactam antimicrobial agents (moxalactam, cefotaxime, cefoperazone, and piperacillin) and the aminoglycosides against 744 recent clinical isolates of facultative gram-negative bacilli were compared simultaneously by the agar dilution method. The major in vitro difference of these newer beta-lactam compounds appeared to be their antipseudomonal activity; cefoperazone was the most active, whereas cefotaxime had the least potency. The aminoglycosides, however, had the most effective in vitro activity on a weight basis against Pseudomonas aeruginosa.