Fluconazole-resistant candidosis in an HIV cohort.

OBJECTIVES: To report the occurrence of HIV-related mucosal candidosis that fails to respond to fluconazole, to establish the correlation between in vitro susceptibility testing and clinical failure, and to assess the efficacy of alternative treatments. DESIGN: Chart review of all patients with fluconazole failure and all patients with CD4 counts < 50 x 10(6)/l continuing to respond to fluconazole, and prospective in vitro susceptibility testing of Candida. SETTING: A regional treatment centre for HIV-infected individuals in north-west England. PATIENTS: A cohort of 155 HIV-positive individuals with CD4 counts < 300 x 10(6)/l cells. MAIN OUTCOME MEASURES: Clinical fluconazole failure was defined as symptomatic oropharyngeal or oesophageal candidosis despite fluconazole > or = 100 mg per day for 10 days. In vitro susceptibility to fluconazole was determined for Candida isolates. Cumulative 12-month fluconazole dose and time from first fluconazole therapy and prophylaxis were recorded. RESULTS: Nine (5.8%) patients meeting the definition of fluconazole failure were identified. In vitro susceptibility to fluconazole of temporally related oropharyngeal isolates was reduced in all cases. Intravenous amphotericin B was the only effective treatment for these patients when symptoms were severe suggesting azole cross-resistance. One patient, who had received alternative treatments for 9 months, reverted from in vitro and clinical fluconazole sensitivity but relapsed within 6 weeks of resuming fluconazole. The median fluconazole dose over the preceding 12 months for the eight adult cases was 386 mg weekly. The median dose for the same period was 79 mg weekly in 28 patients with CD4 counts < 50 x 10(6)/l but without fluconazole failure (difference, 307; 95% confidence interval, 199-514; P < 0.0001). CONCLUSION: A substantial problem of clinical fluconazole failure has developed among HIV-positive patients who have recurrent problematic mucosal candidosis.

Open study of ciprofloxacin in enteric fever.

Thirty adult patients with typhoid or paratyphoid fever were treated with ciprofloxacin. All patients were cured with eradication of the causative organism. No major adverse reactions were seen. Ciprofloxacin is an effective agent for the treatment of enteric fever.

Hyperbaric oxygen treatment: 10 years' experience of a Regional Infectious Diseases Unit.

Ten years' experience of a Regional Centre for Infectious Diseases in the use of hyperbaric oxygen in 87 patients have been reviewed. Its efficacy in the treatment of non-infectious cases has been confirmed. Fifty-eight (67 per cent) patients had anaerobic infections associated with peripheral vascular disease, limb trauma, abdominal surgery or occurred spontaneously. All patients had failed to respond to surgery and antimicrobial agents, and were transferred for hyperbaric treatment as the infection was progressive. Marked improvement in general condition, wound infection and limitation of extension of the anaerobic infection occurred following hyperbaric treatment. These improvements had benefits in terms of surgical risk, demarcation and mortality. Symptoms suggestive of oxygen toxicity occurred in up to 24 per cent of all patients, but in many this took the form of anxiety and anxiety-related symptoms. Despite the beneficial effects of hyperbaric oxygen, many surgeons appear to be unaware or sceptical of the facility. A prospective controlled trial is advocated.

Mecillinam in enteric fever.

Twelve consecutive patients with enteric fever entered a trial of 14 days' treatment with mecillinam. Only three patients became afebrile within three days; four continued unimproved with fever and toxaemia for seven to nine days, when treatment was changed to chloramphenicol with good results. In one case the fever did not settle until the 13th day, and five days later the patient had a clinical relapse. Although all organisms recovered were fully sensitive to mecillinam, this drug is not an effective or consistent treatment for enteric fever.