A randomized trial of ciprofloxacin versus cefixime for treatment of gonorrhea after rapid emergence of gonococcal ciprofloxacin resistance in The Philippines.

From 1994 through 1996-1997, high-level ciprofloxacin resistance (minimum inhibitory concentration [MIC], > or = 4.0 microg/mL) increased from 9% to 49% of gonococcal isolates recovered from consecutive female sex workers in Cebu and Manila, The Philippines (P < .01). During 1996-1997, 105 female sex workers with gonorrhea were prospectively randomized to receive treatment with oral ciprofloxacin, 500 mg, or cefixime, 400 mg, and followed for test of cure. Neisseria gonorrhoeae was reisolated within 28 days after treatment from 1 (3.8%) of 26 women given cefixime versus 24 (32.3%) of 72 women given ciprofloxacin (P < .01). Treatment failure (reisolation of pretreatment auxotype/serovar) occurred in 14 (46.7%) of 30 women infected with strains with MICs of ciprofloxacin > or = 4.0 microg/mL versus 1 (3.6%) of 28 infected by strains with MICs < 4.0 microg/mL (P < .01). High-level, clinically significant gonococcal resistance to ciprofloxacin has rapidly emerged in The Philippines, and spread of fluoroquinolone resistance through commercial sex poses a threat to control of gonorrhea and prevention of human immunodeficiency virus infection and the acquired immunodeficiency syndrome.

A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis is a hypersensitivity disorder that can progress from an acute phase to chronic disease. The main treatment is systemic corticosteroids, but data from uncontrolled studies suggest that itraconazole, an orally administered antifungal agent, may be an effective adjunctive therapy. METHODS: We conducted a randomized, double-blind trial of treatment with either 200 mg of itraconazole twice daily or placebo for 16 weeks in patients who met immunologic and pulmonary-function criteria for corticosteroid-dependent allergic bronchopulmonary aspergillosis. A response was defined as a reduction of at least 50 percent in the corticosteroid dose, a decrease of at least 25 percent in the serum IgE concentration, and one of the following: an improvement of at least 25 percent in exercise tolerance or pulmonary-function tests or resolution or absence of pulmonary infiltrates. In a second, open-label part of the trial, all the patients received 200 mg of itraconazole per day for 16 weeks. RESULTS: There were responses in 13 of 28 patients in the itraconazole group (46 percent), as compared with 5 of 27 patients in the placebo group (19 percent, P=0.04). The rate of adverse events was similar in the two groups. In the subsequent open-label phase, 12 of the 33 patients who had not had a response during the double-blind phase (36 percent) had responses, and none of the patients who had a response in the double-blind phase of the trial had a relapse. CONCLUSIONS: For patients with corticosteroid-dependent allergic bronchopulmonary aspergillosis, the addition of itraconazole can lead to improvement in the condition without added toxicity.

A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. National Institute of Allergy and Infectious Diseases Mycoses Study Group.

This study was designed to compare the effectiveness of fluconazole vs. itraconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. HIV-infected patients who had been successfully treated (achieved negative culture of CSF) for a first episode of cryptococcal meningitis were randomized to receive fluconazole or itraconazole, both at 200 mg/d, for 12 months. The study was stopped prematurely on the recommendation of an independent Data Safety and Monitoring Board. At the time, 13 (23%) of 57 itraconazole recipients had experienced culture-positive relapse, compared with 2 relapses (4%) noted among 51 fluconazole recipients (P = .006). The factor best associated with relapse was the patient having not received flucytosine during the initial 2 weeks of primary treatment for cryptococcal disease (relative risk = 5.88; 95% confidence interval, 1.27-27.14; P = .04). Fluconazole remains the treatment of choice for maintenance therapy for AIDS-associated cryptococcal disease. Flucytosine may contribute to the prevention of relapse if used during the first 2 weeks of primary therapy.

Randomized trial of itraconazole oral solution for oropharyngeal candidiasis in HIV/AIDS patients.

PURPOSE: Oropharyngeal candidasis (thrush) is the most common opportunistic infection in individuals who are positive for the human immunodeficiency virus (HIV) and those who have progressed to AIDS. Itraconazole has a broad in vitro spectrum of activity, including a wide variety of Candida species. Our study determined the relative efficacy of a new oral solution formulation of itraconazole and fluconazole tablets in the treatment of oropharyngeal candidiasis. PATIENTS AND METHODS: This was a prospective randomized, third-party-blind, multicenter trial conducted at 12 centers in the United States. One hundred seventy-nine HIV-positive patients with mycologically documented oropharyngeal candidiasis were treated with itraconazole oral solution 200 mg/ day for 7 or 14 days, or fluconazole tablets 100 mg/day for 14 days. Severity of disease was scored clinically before treatment and at clinical evaluations on days 3, 7, 14, 21, 35, and 42. Semi-quantitative cultures of mouth washings were also obtained on these days. RESULTS: Both 14-day and 7-day regimens of itraconazole oral solution were equivalent to fluconazole for most efficacy parameters. The clinical response rate was 97% after 14 days of itraconazole and 87% after 14 days of fluconazole. Itraconazole oral solution given for 7 days was also equivalent to fluconazole treatment for 14 days. Approximately one half of patients in all three groups relapsed by 1 month after completion of treatment. There were few adverse reactions to either drug. CONCLUSION: Itraconazole oral solution is well tolerated and offers an alternative at least as effective as fluconazole in the treatment of oropharyngeal candidiasis.

Syndromic approach to detection of gonococcal and chlamydial infections among female sex workers in two Philippine cities.

BACKGROUND: In many developing countries, STD control efforts often involve registration and periodic examinations of female sex workers (FSW). Non-availability of sensitive and specific diagnostic tests frequently constrain this approach. METHODS: A model for detection of Chlamydia trachomatis or Neisseria gonorrhoeae in FSW on the basis of risk assessment and examination was developed from data gathered in Manila and evaluated in a second city (Cebu) in the Republic of the Philippines. RESULTS: Gonococcal or chlamydial cervical infection was found in 23.3% of FSW in Manila and 37.0% in Cebu. Unregistered and younger FSW had greatest risk of chlamydial infection and/or gonorrhoea in both cities. In Manila, where gynaecologists performed the pelvic examinations, signs of cervical mucopus or cervical motion, uterine or cervical motion tenderness in women under < 25 years old or unregistered had positive predictive value (PPV) of 0.60 and sensitivity of 42.1% for cervical infection. In Cebu, where women were not examined by gynaecologists, the same model had high PPV, but a sensitivity of only 12.3%. CONCLUSIONS: Experience and training of clinicians undoubtedly can influence the yield of examination in syndromic management of cervical infection. Nevertheless, inexpensive and diagnostic tests are needed for detection of cervical infection in this population.

Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group.

BACKGROUND: Treatment with low-dose amphotericin B (0.4 mg per kilogram of body weight per day) or oral azole therapy in patients with the acquired immunodeficiency syndrome (AIDS) and cryptococcal meningitis has been associated with high mortality and low rates of cerebrospinal fluid sterilization. METHODS: In a double-blind multicenter trial we randomly assigned patients with a first episode of AIDS-associated cryptococcal meningitis to treatment with higher-dose amphotericin B (0.7 mg per kilogram per day) with or without flucytosine (100 mg per kilogram per day) for two weeks (step one), followed by eight weeks of treatment with itraconazole (400 mg per day) or fluconazole (400 mg per day) (step two). Treatment was considered successful if cerebrospinal fluid cultures were negative at 2 and 10 weeks or if the patient was clinically stable at 2 weeks and asymptomatic at 10 weeks. RESULTS: At two weeks, the cerebrospinal fluid cultures were negative in 60 percent of the 202 patients receiving amphotericin B plus flucytosine and in 51 percent of the 179 receiving amphotericin B alone (P=0.06). Elevated intracranial pressure was associated with death in 13 of 14 patients during step one. The clinical outcome did not differ significantly between the two groups. Seventy-two percent of the 151 fluconazole recipients and 60 percent of the 155 itraconazole recipients had negative cultures at 10 weeks (95 percent confidence interval for the difference in percentages, -100 to 21). The proportion of patients who had clinical responses was similar with fluconazole (68 percent) and itraconazole (70 percent). Overall mortality was 5.5 percent in the first two weeks and 3.9 percent in the next eight weeks, with no significant difference between the groups. In a multivariate analysis, the addition of flucytosine during the initial two weeks and treatment with fluconazole for the next eight weeks were independently associated with cerebrospinal fluid sterilization. CONCLUSIONS: For the initial treatment of AIDS-associated cryptococcal meningitis, the use of higher-dose amphotericin B plus flucytosine is associated with an increased rate of cerebrospinal fluid sterilization and decreased mortality at two weeks, as compared with regimens used in previous studies. Although consolidation therapy with fluconazole is associated with a higher rate of cerebrospinal fluid sterilization, itraconazole may be a suitable alternative for patients unable to take fluconazole.

Molecular epidemiology, in 1994, of Neisseria gonorrhoeae in Manila and Cebu City, Republic of the Philippines.

BACKGROUND AND OBJECTIVES: Failure of gonococcal infections to respond to 500 mg of ciprofloxacin or 400 mg of ofloxacin has been reported from Australia, the United Kingdom, and the United States. Recently, high rates of decreased susceptibility to the fluoroquinolones have been detected in penicillinase-producing Neisseria gonorrhoeae in the Republic of the Philippines. GOALS: To assess the diversity of antimicrobial-resistant gonococcal strains isolated from female sex workers in Manila and Cebu City in the Republic of the Philippines in 1994. STUDY DESIGN: Isolates of N. gonorrhoeae isolated from 92 female sex workers in Manila (n = 28) and Cebu City (n = 64), respectively, were characterized by plasmid profile, auxotype/serovar class, and antimicrobial susceptibility profile. RESULTS: Plasmid-mediated resistance to penicillin or tetracycline was identified in 79.3% (73/92) of the isolates: penicillinase-producing N. gonorrhoeae (65/92; 70.7%), tetracycline-resistant N. gonorrhoeae (6/92; 6.5%), and penicillinase-producing/tetracycline-resistant N. gonorrhoeae (1/92; 1.1%). A beta-lactamase plasmid of 3.9 megadaltons was discovered. Of 54.3% (50/92) of strains resistant to nalidixic acid, 84% (42/50) of strains had minimum inhibitory concentrations of > or = 0.125 microgram/ml ciprofloxacin; penicillinase-producing N. gonorrhoeae (possessing the 3.05-, 3.2-, 3.9-, and 4.4-megadalton beta-lactamase plasmids, respectively) accounted for 68% (34/50) of these strains. CONCLUSIONS: In the Republic of the Philippines, gonococcal isolates resistant to penicillin or tetracycline accounted for 85.9% (79/92) of the isolates examined and included strains exhibiting resistance to fluoroquinolones. All gonococcal infections should be treated with antimicrobial therapies known to be active against all gonococcal strains to reduce the spread of strains exhibiting decreased susceptibilities to fluoroquinolones.

PIP: During July-October 1994 in the Philippines, Neisseria gonorrhoeae were isolated from 92 female sex workers in Manila and Cebu City. The purpose was to characterize the gonococcal strains by plasmid content, auxotype, serovar, and antimicrobial susceptibilities in order to examine the diversity of antimicrobial-resistant N gonorrhoeae strains in these sex workers. Penicillinase-producing N gonorrhoeae (PPNG) comprised 70.7% of the isolates. Strains with the 3.2-megadalton (Mda) beta-lactamase plasmid were more common in Cebu City than in Manila (57.8% vs. 28.6%; p = 0.02). They had significantly lower minimum inhibitory concentrations (MICs) to penicillin, tetracycline, ceftriaxone, ciprofloxacin, and erythromycin than did strains with 3.05-, 3.9-, or 4.4-Mda plasmid (p 0.01). One PPNG strain had a previously undescribed 3.9-Mda beta-lactamase plasmid. It also had a 24.5-Mda conjugative plasmid. Only 15.2% of all 92 isolates were susceptible to both penicillin and tetracycline. Tetracycline-resistant N gonorrhoeae (TRNG) comprised 6.5% of the isolates. 1.1% of isolates were resistant to both penicillin and tetracycline. 54.3% of all strains were resistant to nalidixic acid (fluoroquinolone), 84% of which had MICs of at least 0.125 mcg/ml ciprofloxacin. 68% of the nalidixic acid-resistant strains had 4.4 Mda beta-lactamase plasmids. 85.9% of all gonococcal isolates exhibited resistance to penicillin or tetracycline. They also included strains exhibiting resistance to fluoroquninolones. These findings reveal the need for periodic surveillance for resistance in N gonorrhoeae to the antimicrobial agents used for primary gonorrhea therapy in order to improve the treatments of choice.

Malignant otitis externa in AIDS patients: case report and review of the literature.

Malignant otitis externa is a necrotizing infection of the external ear canal and surrounding soft tissue and bone, usually caused by Pseudomonas aeruginosa. The infection classically occurs in diabetic patients, however recently, several patients with the acquired immunodeficiency syndrome (AIDS) have been reported to have malignant otitis externa. A patient with AIDS who had malignant otitis externa with skull base osteomyelitis is presented and reported cases in patients with AIDS are reviewed. Predisposing factors include immunologic abnormalities (notably neutropenia), dermatitis, medications, neoplasm, and iatrogenic procedures, e.g., ear lavage. Treatment of malignant otitis externa has traditionally included anti-pseudomonal cephalosporins/penicillins and aminoglycosides for prolonged durations. Recently, ciprofloxacin has been shown to be effective as an oral regimen. With the increasing number of patients with AIDS being seen in the outpatient clinics, the diagnosis of malignant otitis externa should be considered in any patient with persistent ear pain or otorrhea who does not respond to conventional treatment for external otitis.

Gram-negative meningitis associated with transsphenoidal surgery: case reports and review.

We present a systematic review of meningitis associated with transsphenoidal surgery. Patients present within the first 4 days after surgery with symptoms of headache, fever, and confusion. Overt cerebrospinal rhinorrhea or nuchal rigidity at the time of presentation is an infrequent finding. Although postoperative aseptic meningitis may be difficult to distinguish from early bacterial meningitis, the findings of hypoglycorrhachia, pleocytosis, and hyperproteinemia in the setting of fever and neurological deficit strongly suggest bacterial infection. The preponderance of cases of gram-negative meningitis observed in this series and in previous reports related to posttraumatic CSF leaks indicates that empirical regimens should include agents suitable for treating infections caused by nosocomial pathogens. In general, patients with uncomplicated meningitis in this setting can be expected to recover and do well. Questions remain as to the role of prophylactic antibiotics in the development of gram-negative meningitis in the setting of transsphenoidal surgery. A multicenter trial might be better able to define this role.

Staphylococcus aureus pericarditis in HIV-infected patients.

Serious infections caused by Staphylococcus aureus in HIV-infected patients have been reported. Contributing factors in the development of invasive S aureus infections include a high rate of skin and nasal colonization, frequent dermatologic disease, and the use of intravenous catheters. The authors report three cases of S aureus pericarditis in HIV-infected patients. While cases of viral, mycobacterial, and malignant pericardial effusions in HIV-infected patients have been reported, a review of the literature disclosed only three cases of bacterial pericarditis. Despite appropriate antibiotic therapy and drainage, a patient's condition may abruptly deteriorate and progress to tamponade. Early recognition of bacteremia and pericarditis and monitoring for cardiac tamponade, along with aggressive treatment, can result in a favorable outcome, but mortality remains high, particularly when S aureus is the causative agent.

Fascioliasis: case reports and review.

Fasciola hepatica, a zoonotic liver fluke, can cause disease in humans. Fascioliasis, while common in some tropical and developing countries, is uncommon in the United States. We report two cases of fascioliasis that illustrate both the hepatic and biliary stages of the disease. Clinical features and diagnostic aspects including serologic, radiographic, and histopathologic studies are emphasized. Praziquantel was ineffective in treatment of both patients. Bithionol appears to be an effective treatment for fascioliasis.

Direct detection of infectious human immunodeficiency virus type 1 (HIV-1) immune complexes in the sera of HIV-1-infected persons.

The sera of human immunodeficiency virus type 1 (HIV-1)-infected subjects were examined for the presence of infectious HIV-1-antibody complexes by their ability to infect Fc gamma receptor (Fc gamma R)-bearing cells. Infection of Fc gamma R-bearing cells by a serum in which half of the p24 antigen was present in a form of immune complexes was inhibited by aggregated human immunoglobulin. Then in studies on 22 sera, 9 sera produced p24 antigen during 14 days of culture in U937 cells. HIV-1 p24 production was inhibited or delayed by the pretreatment of cells with aggregated human immunoglobulin in 6 of the 9 sera that were infectious. These results may reflect interactions between virus-antibody complexes and Fc gamma R-bearing cells in vivo because serum itself was used as the source of virus and virus-antibody complexes. The results indicate that infectious HIV-1 immune complexes are present in the circulation of HIV-1-infected patients.

Salvage trial of trimetrexate-leucovorin for the treatment of cerebral toxoplasmosis in patients with AIDS.

The clinical efficacy of trimetrexate, a dihydrofolate reductase inhibitor with potent in vitro antitoxoplasma activity, was assessed in 9 sulfonamide-intolerant patients with AIDS and biopsy-proven cerebral toxoplasmosis. The 9 patients were treated for 28-149 days with trimetrexate (30-280 mg/m2/day) plus leucovorin (20-90 mg/m2 every 6 h). Radiographic responses were documented in 8 patients, and clinical responses in 5 patients. Despite continued therapy, all patients deteriorated clinically and radiographically within 13-109 days of their initial improvement. Trimetrexate at very high doses for extended periods was not associated with serious toxicity. Trimetrexate alone had dramatic but transient activity in sulfonamide-intolerant patients and thus is not adequate as single-agent therapy for AIDS-associated toxoplasmosis.