Susceptibility of European respiratory tract isolates to trovafloxacin, ciprofloxacin, clarithromycin, azithromycin and ampicillin.

As part of the Artemis project, 11500 isolates (3000 from patients with respiratory tract infections) were collected throughout six European countries between 1994 and 1996. Twenty-seven hospitals or laboratories participated in this first phase of the study. The activities of three classes of antimicrobial agents (fluoroquinolones, beta-lactam agents, macrolides) are presented for the six most frequently isolated pathogens (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, Klebsiella pneumoniae). Overall, trovafloxacin and ciprofloxacin activities were similar for Haemophilus influenzae, Moraxella catarrhalis and Klebsiella pneumoniae isolates. Of the Streptococcus pneumoniae isolates, 6% were resistant to penicillin. Trovafloxacin had the highest activity against the Streptococcus pneumoniae isolates, with a minimum inhibitory concentration of 0.25 mg/l for 90% of isolates (MIC90); all strains tested were susceptible to trovafloxacin. The MIC90 of ciprofloxacin for Streptococcus pneumoniae was 3 mg/l, and overall 52% of the strains were susceptible; 9% were resistant. Azithromycin and clarithromycin exhibited similar activity against all collected pathogens, except Haemophilus influenzae. All strains of Haemophilus influenzae were susceptible to azithromycin compared with 79% for clarithromycin, with respective MIC90s of 2 and 16 mg/l. The data presented demonstrate differences in the susceptibility patterns of six major respiratory tract pathogens in Europe.

A comparison of oral azithromycin with topical oxytetracycline/polymyxin for the treatment of trachoma in children.

Trachoma, an infectious keratoconjunctivitis caused by Chlamydia trachomatis, is a leading cause of preventable blindness in developing countries. In this study we compared oral azithromycin with oxytetracycline/polymyxin eye ointment (once daily for 5 days every 4 weeks; total of six treatment cycles) for the treatment of active endemic trachoma in 168 rural Egyptian children. A suspension of azithromycin was administered to children as a dose of 20 mg/kg by one of three schedules: a single dose, one dose a week for 3 weeks, and one dose every 4 weeks for a total of six doses. The children's clinical status and chlamydial infection rates were evaluated for 1 year. The clinical cure rates were 35% 2 months after initial treatment, 16% at 8 months (during the annual autumn epidemic of purulent conjunctivitis), and 47% at 1 year. The pretreatment chlamydial infection rate of 33% (determined by direct immunofluorescence) decreased to 5% at 2 months and was 9% at 12 months. There were no significant clinical or laboratory differences among the four treatment groups. Thus, 1-6 doses of azithromycin were equivalent to 30 days of topical oxytetracycline/polymyxin ointment and may offer an effective alternative means of controlling endemic trachoma.

Prospective comparative trial of short course (four day) and continuous tobramycin in combination with cefoperazone or mezlocillin in febrile, granulocytopenic patients.

In a prospective, randomized trial of 195 febrile episodes in granulocytopenic patients short course aminoglycoside treatment (initial tobramycin and cefoperazone followed by tobramycin discontinuation at day four of therapy) was compared with two regimens (tobramycin plus cefoperazone and tobramycin plus mezlocillin) in which both drugs were continued for up to 26 days. All regimens were successful as empirical therapy with comparable response rates of just over seventy per cent. Fifty-three per cent of the initial episodes of fever were related to documented infections which responded less well (P = 0.007) than unexplained fever. Patients with bacteraemia, pneumonia or Gram-positive aerobic or Pseudomonas aeruginosa infections responded poorly to all regimens. The recovery from granulocytopenia was the most important determinant of successful response. Aminoglycoside discontinuation followed by cefoperazone monotherapy after day four was statistically as effective as the combination regimens. Short course tobramycin therapy eliminated the nephrotoxicity seen in the combination limbs. The use of cefoperazone was not associated with an increased incidence of hypoprothrombinemia; however, the only three bleeding episodes occurred in patients given cefoperazone but not vitamin K. Short course aminoglycoside therapy will reduce cost and nephrotoxicity when compared with prolonged combination therapy and should be further explored in this setting, with use of different agents and comparison with monotherapy.

Review of fluconazole: a new triazole antifungal agent.

Fluconazole is a new triazole antifungal agent with unique pharmacokinetic properties. It can be administered orally or parenterally and achieves rapid distribution by either route, and its absorption is not affected by the presence of food. It has a plasma half-life of approximately 25-30 hr and approximately 70% of dose is excreted in the urine unchanged. There is linearity of fluconazole plasma concentrations over the dose range and the elimination rate is independent of dose. No effect has been seen on basal or ACTH-stimulated cortisol or on testosterone, estrogen, progesterone, or other steroid hormones, and there is no interaction with an oral contraceptive. No interaction with concomitantly administered cyclosporine has been documented, and there are no clinically significant differences in absorption when fluconazole is given in the presence or absence of cimetidine or food. Patients who are concomitantly receiving coumarin anticoagulants should be monitored because there is an interaction between fluconazole and such anticoagulants. Patients taking oral hypoglycemics and fluconazole should be monitored, because fluconazole has been shown to inhibit the metabolism of tolbutamide. Fluconazole has been successfully used to treat a variety of fungal infections in a variety of contexts including vaginal candidiasis; oropharyngeal candidiasis in immunocompromised patients, those with malignancies, transplant recipients, and patients with systemic sclerosis; patients with cryptococcal meningitis; and patients with fungal infections who were also treated with chemotherapy or radiation therapy. In the treatment of all of these infections with doses ranging from 50 mg to 400 mg a day of fluconazole, there has been a very low incidence of side effects (9.3%) reported, and only 1.1% of all patients were withdrawn from therapy.

Multicenter clinical trial of cefoperazone sodium in the United States.

A total of 187 physician investigators throughout the United States participated in a multicenter trial to evaluate the safety and efficacy of a twice daily dosage of cefoperazone sodium; 91 percent of patients received a dosage of 4 g or less of cefoperazone per day. A total of 455 patients were included in the evaluation of efficacy: 100 patients with lower respiratory tract infection; 146 patients with skin and soft tissue infection; 14 patients with osteomyelitis; 18 patients with obstetric and gynecologic infections; 84 patients with urinary tract infection; and 44 patients with bacteremia. Overall, treatment achieved a satisfactory clinical outcome in 95.3 percent of these patients. Side effects of cefoperazone were evaluated in 659 patients. Prothrombin time increased during therapy in 4 percent of patients, all but one of whom was more than 65 years old. Prothrombin time became normal with the administration of vitamin K. Diarrhea (4 or more loose stools a day) was observed in 3 percent of patients. Other adverse reactions including leukopenia, elevation of serum liver enzyme levels, and eosinophilia were mild, reversible, and typical of beta-lactam antibiotics. These results suggest that (1) twice daily administration of cefoperazone sodium can be used to treat a variety of bacterial infections caused by susceptible pathogens; (2) the adverse reactions associated with this agent at the dosage schedule employed in this trial (2 g twice a day) are predictable and limited; (3) multicenter trials of this type allow for rapid collection of data regarding safety and efficacy of new antibiotics.

In vitro susceptibility of 30 strains of Chlamydia trachomatis to rosamicin.

A total of 13 of 30 clinical isolates of Chlamydia trachomatis were susceptible in vitro to 0.01 mug of rosamicin per ml. Only two of these strains were susceptible to tetracycline or erythromycin at this level. The results suggest that rosamicin may be useful for the treatment of chlamydial urethritis.