A cross-sectional study of risk factors for HIV among pregnant women in Guatemala City, Guatemala: lessons for prevention.

Although the Central American HIV epidemic is concentrated in high-risk groups, HIV incidence is increasing in young women. From 2005 to 2007, we conducted a cross-sectional study of pregnant women in a large public hospital and an HIV clinic in Guatemala City to describe risk factors for HIV infection and inform prevention strategies. For 4629 consenting patients, HIV status was laboratory-confirmed and participant characteristics were assessed by interviewer-administered questionnaires. Lifetime number of sexual partners ranged from 1 to 99, with a median (interquartile range) of 1 (1, 2). 2.6% (120) reported exchanging sex for benefits; 0.1% (3) were sex workers, 2.3% (106) had used illegal drugs, 31.1% (1421) planned their pregnancy and 31.8% (1455) experienced abuse. In logistic regression analyses, HIV status was predicted by one variable describing women's behaviour (lifetime sexual partners) and three variables describing partner risks (partner HIV+, migrant worker or suspected unfaithful). Women in our sample exhibited few behavioural risks for HIV but significant vulnerability via partner behaviours. To stem feminization of the epidemic, health authorities should complement existing prevention interventions in high-risk populations with directed efforts towards bridging populations such as migrant workers. We identify four locally adapted HIV prevention strategies.

A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis.

Caspofungin is a new broad-spectrum antifungal drug. A multicenter, double-blind, randomized trial was conducted to assess the efficacy, safety, and tolerability of caspofungin relative to amphotericin B in adults with endoscopically documented symptomatic Candida esophagitis. By use of a modified intent-to-treat analysis, endoscopically verified clinical success was achieved in 74% (95% confidence interval [CI], 59%-86%) and 89% (95% CI, 72%-98%) of patients receiving caspofungin at 50 and 70 mg/day, respectively, and in 63% (95% CI, 49%-76%) of patients given amphotericin B at 0.5 mg/kg/day. Therapy was stopped because of drug-related adverse events in 24% of patients in the amphotericin B group and 4% and 7%, respectively, for the caspofungin groups. This report provides the first demonstration of clinical utility for an echinocandin compound. Caspofungin appeared in this study to be as effective as and better tolerated than amphotericin B for the treatment of esophageal candidiasis.

Availability of HIV care in Central America.

Central America is an area with a growing human immunodeficiency virus (HIV) epidemic, but with marked limitations in its health care infrastructure. Estimated adult HIV infection rates range from 0.20% in Nicaragua to 2.01% in Belize. Hospitals and clinicians with experience in HIV care exist mainly, if not only, in capital cities and principal economic centers. Nationally sponsored social security systems in each country consistently offer a wider range of services than do ministry of health systems. Estimated access to the social security system ranges from 0% in Belize and 10% of the population in Honduras to 95% in Costa Rica. Combination antiretroviral therapy is not available through the ministries of health and zidovudine is only sporadically available for prevention of perinatal transmission. Combination therapy is available through the social security system in the countries of Guatemala, Panama, and Costa Rica only. A wide variety of antiretroviral agents are available through private pharmacies in all countries except Belize. With the exception of Costa Ricans, most people with HIV infection in Central America have limited access to HIV-specific health services and limited or no access to antiretroviral agents.

Clinical efficacy of echinocandin antifungals.

The prevalence of fungal infections has increased significantly over the past few decades. Candida and Aspergillus spp. are the most common fungal pathogens due to recent changes in medical technology. Amphotericin B continues to be the treatment of choice in many severe disseminated mycosis cases, but problems with toxicity, resistance and non-availability of an absorbable oral form are important drawbacks. The azoles offer a less toxic alternative but often they are not as effective as amphotericin B and resistance is an increasing problem. The echinocandins are new active antifungal agents with a novel mechanism of action. During the past year, one agent has been released and two others are undergoing advanced stages of investigation. Although these agents are not the ideal antifungal drug, they do offer new options of therapy.

Safety evaluation of chronic fluconazole therapy. Fluconazole Pan-American Study Group.

The possible adverse effects of chronic, high-dose fluconazole therapy are detailed from analysis of a multicenter, dose-escalating study of the therapy of invasive mycoses. Ninety-three adult patients were studied, 48 of these received > or = 6 months therapy and 20 received > or = 1 year. Fifty-eight patients received > or = 300 mg/day, and 7 received > or = 600 mg/day. One patient received 1,997 g over 86 months. Twenty-seven percent experienced possible symptomatic side effects, which resulted in 2 patients discontinuing therapy, and 42% had asymptomatic laboratory abnormalities, none of which were progressive. Headache, hair loss and anorexia were the most common symptoms experienced (each by 3% of patients), and eosinophilia and aspartate aminotransferase increases were the most common laboratory findings (12 and 10%, respectively). Fluconazole appears well tolerated and safe in these doses and durations.

Nosocomial infection due to Vibrio cholerae in two referral hospitals in Guatemala.

We report nosocomial infection with Vibrio cholerae 01, in four seriously ill individuals and one infant in Guatemala. Nosocomial cholera occurs in developing countries in Latin America and should be suspected in hospitalized patients with diarrhea, especially during community outbreaks, in order to institute appropriate diagnostic, therapeutic, and control measures.

Epidemic gram-negative bacteremia in a neonatal intensive care unit in Guatemala.

BACKGROUND: Nosocomial bloodstream infection is an important cause of morbidity and mortality among neonates. From September 1 through December 5, 1990 (epidemic period), gram-negative bacteremia developed in 26 neonates after their admission to the neonatal intensive care unit (NICU) of Hospital General, a 1000-bed public teaching hospital in Guatemala with a 16-bed NICU. Twenty-three of the 26 patients (88%) died. METHODS: To determine risk factors for and modes of transmission of gram-negative bacteremia in the NICU, we conducted a cohort study of NICU patients who had at least one blood culture drawn at least 24 hours after admission to the NICU and performed a microbiologic investigation in the NICU. RESULTS: The rate of gram-negative bacteremia was significantly higher among patients born at Hospital General, delivered by cesarian section, and exposed to selected intravenous medications and invasive procedures in the NICU during the 3 days before the referent blood culture was obtained. During the epidemic period, the hospital's chlorinated well-water system malfunctioned; chlorine levels were undetectable and tap water samples contained elevated microbial levels, including total and fecal coliform bacteria. Serratia marcescens was identified in 81% of case-patient blood cultures (13/16) available for testing and from 57% of NICU personnel handwashings (4/7). Most S. marcescens blood isolates were serotype O3:H12 (46%) or O14:H12 (31%) and were resistant to ampicillin (100%) and gentamicin (77%), the antimicrobials used routinely in the NICU. CONCLUSIONS: We hypothesize that gram-negative bacteremia occurred after invasive procedures were performed on neonates whose skin became colonized through bathing or from hands of NICU personnel.

A Pan-American 5-year study of fluconazole therapy for deep mycoses in the immunocompetent host. Pan-American Study Group.

Eighty-eight immunocompetent patients with deep mycoses from eight countries were evaluated with the same protocol for efficacy of fluconazole monotherapy. Entry doses were raised from 100 to 400 mg as safety was shown in initial cohorts, and dosages up to 2,400 mg daily and durations up to 44 months were studied. Results were very similar in different countries. Twenty-seven of 28 evaluable patients with paracoccidioidomycosis, 13 of 19 with sporotrichosis, 14 of 16 with coccidioidomycosis, and eight of eight with histoplasmosis demonstrated objective responses to therapy, as did one patient each with zygomycosis and alternariosis. For these patients, relapses have been unusual thus far. In contrast, one patient with chromoblastomycosis responded but relapsed, and six did not respond; one patient with mycetoma responded but relapsed, and two did not respond. The drug was well tolerated by patients, including six who received intravenous therapy. In vitro susceptibility tests suggested that clinical response was correlated with susceptibility but that resistance did not preclude clinical response. Fluconazole therapy appears efficacious for several deep mycoses; dosages of greater than 200 mg daily may be needed for some diseases. The further evaluation of fluconazole for these entities is warranted.

Efficacy of short courses of oral novobiocin-rifampin in eradicating carrier state of methicillin-resistant Staphylococcus aureus and in vitro killing studies of clinical isolates.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial infection problem. Colonization appears to be more common than invasive disease is. Eradication of colonization or the carrier state could limit the spread of MRSA, thus reducing the potential for mortality and morbidity in other patients. The detection of patients with MRSA infection in a rehabilitation ward led to a study of the combination of novobiocin-rifampin in vivo and in vitro. We found that 300 mg of rifampin plus 500 mg of novobiocin orally twice daily for 5 days, in 18 courses of treatment given to 12 patients, resulted in the clearing of MRSA in 79% of the evaluable courses and 81% of the evaluable sites. A second course cleared MRSA from one of the patients with a treatment failure. Side effects were not noted. All 18 pretherapy isolates were susceptible to either drug in vitro, but 1 of 2 posttherapy isolates was rifampin resistant. Timed-kill studies demonstrated that the rate of killing was the same with either drug alone or both drugs together. Pretherapy isolates from treatment successes or failure were killed at the same rate by the drug combination. However, with the rifampin-resistant isolate killing ceased after 48 h. Results of this study suggest that previously untreated patients are likely to have isolates that are susceptible to the combination of drugs and that the combination is commonly effective in eradicating MRSA carriage. Since the regimen is orally administered, and thus convenient, in conjunction with other measures it has the promise of reducing the spread of MRSA in hospitals.

Itraconazole therapy for nonmeningeal coccidioidomycosis: clinical and laboratory observations.

Itraconazole, a new oral triazole antifungal agent, was administered in 75 courses to patients with chronic coccidioidomycosis at dosages of 50 to 400 mg/day for a median duration of 10 months. Assessment of efficacy was made with a standardized scoring system. Responses were seen in 42 of 58 assessable courses (72%). Nonresponse occurred exclusively in patients who had failed previous therapy and was most common in pulmonary disease. Toxicity was minimal at the doses studied. Pharmacokinetic analysis of itraconazole in serum at steady state showed negligible circadian variation; differences in serum concentrations among patients were large. Clinical isolates of Coccidioides immitis showed uniform in vitro susceptibility to itraconazole. Itraconazole shows impressive activity in this series of patients with refractory coccidioidomycosis. Further evaluation of itraconazole in this and in other systemic mycoses is in order.

Efficacy of itraconazole in blastomycosis in a murine model and comparison with ketoconazole.

Mice were infected intranasally with B. dermatitidis yeasts, and after infection treated orally. Itraconazole 50-150 mg/kg/day was protective (prolonged survival) against lethal infection, although the infection was not sterilized. Itraconazole was approximately 3 times as potent as ketoconazole. These results suggest advantages for itraconazole therapy clinically.

Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis.

The pharmacokinetics of fluconazole, a new oral azole, were evaluated in cerebrospinal fluid and sera of eight patients with coccidioidal meningitis. At a dose of 50 mg/day, peak concentrations of 2.5 to 3.5 and 2.0 to 2.3 micrograms/ml occurred at 2 to 6 and 4 to 8 h in serum and cerebrospinal fluid, respectively. At 100 mg/day, peak concentrations of 4.5 to 8.0 and 3.4 to 6.2 micrograms/ml occurred at 2 to 4 and 4 to 12 h, respectively. The mean ratios of the concentration in cerebrospinal fluid to that in serum were 73.8% at 50 mg/day and 88.7% at 100 mg/day. Results suggested that there was a prolonged half-life in both cerebrospinal fluid and serum and that it was slightly longer in the former. Minimal toxicity was noted in 34 patient months of therapy (12 months on 50 mg daily; 22 months on 100 mg daily). After a mean of 4.5 months of therapy, five patients responded to therapy and three were unevaluable. The penetration of fluconazole into cerebrospinal fluid was substantial, toxicity was minimal, and early clinical experience was encouraging. Fluconazole holds promise as the sole or adjunctive therapy for fungal meningitis.

Treatment of mycoses with itraconazole.

The efficacy of itraconazole, a new oral triazole, was evaluated at doses of 50-400 mg/day in 64 courses: 39 with coccidioidomycosis, and 25 with other mycoses. Among patients with coccidioidomycosis, 21 had pulmonary disease; 10, bone and joint; 8, lymphatic; 6, skin and soft tissue; 3, meningeal; and 1, urogenital. After a mean of 7.1 months of treatment, 17 of 27 evaluable courses (63%) have shown a full response; 8 (30%), a partial response; and 2 (7%), no response. Response to treatment was higher in patients with a shorter duration of illness and in patients with no previous treatment. After a mean of 12 months of treatment, two of five responders off therapy have relapsed. In patients with other mycoses, diagnoses include aspergillosis in six patients; histoplasmosis and tinea in three each; alternariosis, candidiasis, cryptococcosis, blastomycosis, and chromomycosis in two each; and pseudallescheriosis in one. After a mean of 9.4 months of treatment, 14 of 23 evaluable patients (61%) have shown a full response; 2 (8%), a partial response; and 7 (30%), no response. All patients with histoplasmosis and blastomycosis have responded to therapy. There are no relapses among five evaluable responders after a mean of 9.2 months off therapy. In 512 patient months of therapy, toxicity has been minimal. Mean serum levels in patients receiving 200 mg twice daily range from 3.9 to 5.9 micrograms/ml for 8 hr after dosing, with a peak at 7 hr and wide interpatient variability. Itraconazole is well tolerated and has continued to demonstrate efficacy in the treatment of a variety of systemic and superficial mycoses.