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Biomedical subjects

L Ostrosky-Zeichner

Publications and source records attributed to L Ostrosky-Zeichner.

16 recordsLinked to original sources

International, open-label, noncomparative, clinical trial of micafungin alone and in combination for treatment of newly diagnosed and refractory candidemia.

Candida spp. are the fourth leading cause of bloodstream infections, and non-albicans species are increasing in importance. Micafungin is a new echinocandin antifungal agent with excellent in vitro activity against Candida spp. Pediatric, neonatal, and adult patients with new or refractory candidemia were enrolled into this open-label, noncomparative, international study. The initial dose of micafungin was 50 mg/d (1 mg/kg for patients <40 kg) for infections due to C. albicans and 100 mg/d (2 mg/kg for patients <40 kg) for infections due to other species. Dose escalation was allowed. Maximum length of therapy was 42 days. A total of 126 patients were evaluable (received at least five doses of micafungin). Success (complete or partial response) was seen in 83.3% patients overall. Success rates for treatment of infections caused by the most common Candida spp. were as follows: C. albicans 85.1%, C. glabrata 93.8%, C. parapsilosis 86.4%, and C. tropicalis 83.3%. Serious adverse events related to micafungin were uncommon. Micafungin shows promise as a safe and effective agent for the treatment of newly diagnosed and refractory cases of candidemia. Large-scale, randomized, controlled trials are warranted.

Adolescent↗

Quality control and reference guidelines for CLSI broth microdilution susceptibility method (M 38-A document) for amphotericin B, itraconazole, posaconazole, and voriconazole.

Although standard conditions are available for testing the susceptibilities of filamentous fungi to antifungal agents by the Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards) broth microdilution assay, quality control (QC) MIC limits have not been established for any mold-agent combination. This multicenter (eight-center) study documented the reproducibility of tests for one isolate of Paecilomyces variotii ATCC MYA-3630 and 11 other mold isolates (three isolates of Aspergillus fumigatus; two isolates of A. terreus; one isolate each of A. flavus, A. nidulans, Fusarium moniliforme, and F. solani; and two isolates of Scedosporium apiospermum) by the CLSI reference broth microdilution method (M 38-A document). Control limits (amphotericin B, 1 to 4 microg/ml; itraconazole, 0.06 to 0.5 microg/ml; posaconazole, 0.03 to 0.25 microg/ml; voriconazole, 0.015 to 0.12 microg/ml) for the selected QC P. variotii ATCC MYA-3630 were established by the analysis of replicate MIC results. Reference isolates and corresponding MIC ranges were also established for 6 of the 12 molds evaluated. MIC limits were not proposed for the other five molds tested due to low testing reproducibility for these isolates.

Amphotericin B↗

Prophylaxis and treatment of invasive candidiasis in the intensive care setting.

The term "invasive candidiasis" encompasses a group of infections of increasing relevance in the intensive care setting. Prophylaxis is an attractive strategy when dealing with diseases of high prevalence, morbidity, and mortality. The success of prophylaxis is determined by the selection of a population at high risk and the use of the safest and most effective drug. Although risk factors for this disease are known, risk assessment strategies need to be developed to predict a high likelihood of disease so that targeted prophylaxis can be offered. Recent advances in antifungal therapy, such as development of the azoles and echinocandins, have resulted in excellent prophylactic and therapeutic choices for the management of this problem.

Antifungal Agents↗

Voriconazole salvage treatment of invasive candidiasis.

Data on the salvage treatment of invasive candidiasis with voriconazole in 52 patients intolerant of other antifungal agents or with infection refractory to other antifungal agents were analyzed. Patients had received a mean of two previous antifungal agents (range, 1-4 agents), and 83% had received an azole. Manifestations of invasive candidiasis included candidemia (37%), disseminated disease (25%), and infection of other sites (38%). The median duration of voriconazole therapy was 60 days (range, 1-314 days). The overall rate of response was 56% (95%CI, 41-70), with the following response rates observed for individual Candida species: Candida albicans, 44% (20-70); Candida glabrata, 38% (14-68); Candida krusei, 70% (35-93); Candida tropicalis, 67% (30-93); and other Candida spp., 100% (40-100). The response rate in patients who had failed previous azole therapy was 58% (42-73). Common adverse events (~20%) included nausea and emesis, abnormal liver enzymes, and visual disturbances. Serious adverse events occurred in four patients, and nine patients died. Voriconazole has promise as a salvage agent for the treatment of invasive candidiasis, even in the settings of previous azole therapy and infection due to Candida krusei.

Adolescent↗

Differential antifungal activity of isomeric forms of nystatin.

When nystatin is placed in RPMI and other biological fluids, there is loss of pure nystatin, with the development of two distinguishable chromatographic peaks, 1 and 2. Peak 1 appears identical to commercially prepared nystatin. By nuclear magnetic resonance (NMR) and mass spectral analysis, peak 2 appears to be an isomer of peak 1. The isomers are quantitatively and fully interconvertible. Formation of peak 2 is accelerated at a pH of >7.0 and ultimately reaches a near 55:45 (peak 1/peak 2 ratio) mixture. We sought to determine the relative activities of peaks 1 and 2 against Candida spp. Peak 2 consistently showed higher MICs when it was the predominant form during the experiment. Time-kill analyses showed that peak 2 required > or =8 x the concentration of peak 1 to produce a modest and delayed killing effect, which was never of the same magnitude as that produced by peak 1. In both types of assays, the activity of peak 2 corresponded with intra-assay formation of peak 1. Both MIC measurements and time-kill analysis suggest that peak 2 has considerably less activity, if any at all, against Candida spp. Peak 2 may serve as a reservoir for peak 1.

Antifungal Agents↗

Empirical antimicrobial therapy for traveler's diarrhea.

Over 7 million cases of traveler's diarrhea, defined as the passage of > or = 3 unformed stools in a 24-h period, occur each year among visitors to developing countries. Bacterial enteric pathogens are the most common etiologic agents isolated. Preliminary clinical results for patients with diarrhea predominantly caused by Campylobacter species have shown that azithromycin may be an effective alternative to fluoroquinolones for the treatment of traveler's diarrhea.

Anti-Bacterial Agents↗

Epidemiology of nosocomial outbreaks: 14-year experience at a tertiary-care center.

Twelve nosocomial outbreaks over 14 years at a tertiary-care center in Mexico are described. Overall mortality was 25.8%, one half due to pneumonia. The most common organism was Pseudomonas aeruginosa. Incidence was three outbreaks per 10,000 discharges; outbreak-related infections comprised 1.56% of all nosocomial infections. Incidence in the intensive care unit was 10-fold higher.

Cross Infection↗

Cryptococcus neoformans var. gattii among patients with cryptococcal meningitis in Mexico. First observations.

A retrospective study of 20 patients with cryptococcal meningitis and their isolated strains was performed. Cryptococcus neoformans var. neoformans was recovered from 14 (70%) cases, and var. gattii was recovered from six (30%) patients. Twelve patients had AIDS (all carrying var. neoformans), two had other diseases (one with var. neoformans and one var. gattii) and there was no identifiable underlying disease in six (one var. neoformans and five var. gattii). Fourteen patients (11 var. neoformans and three var. gattii) resided in the Mexico City area, where a temperate climate is prevalent, and there were six cases (three var. neoformans and three var. gattii) from states with a tropical/subtropical climate. Although there was no significant statistical difference between the two varieties, the fatal outcome was higher in patients with var. neoformans. The disease caused by var. gattii strains was characterized by a higher opening pressure, more inflamatory changes of CSF and a longer clinical course (delayed clinical and mycological cure). Cryptococcus neoformans var. gattii is a significant cause of cryptococcal meningitis in patients without underlying diseases in Mexico.

AIDS-Related Opportunistic Infections↗

Effects of pentoxifylline or dexamethasone in combination with amphotericin B in experimental murine cerebral cryptococcosis: evidence of neuroexcitatory pathogenic mechanisms.

In a murine model of intracerebral infection by Cryptococcus neoformans the therapeutic effects of pentoxifylline or dexamethasone were studied alone and in combination with amphotericin B. Assessed parameters were mean survival time, brain histopathology index, amounts of glutamate and gamma-aminobutyric acid in the brain, and yeast CFU per brain. Survival increased significantly in mice treated with dexamethasone, amphotericin B, amphotericin B plus dexamethasone, and amphotericin B plus pentoxifylline; the latter had significantly longer survival than other treated groups. Indices of histopathological damage were similar in all treated groups. In infected untreated mice, the amounts of glutamate in the brain were decreased, presumably by depletion. In mice treated with amphotericin B plus dexamethasone, glutamate levels returned to the range of control mice. No differences in the amounts of gamma-aminobutyric acid were found between control and treatment groups. Brain fungal counts were significantly lower in mice treated with amphotericin B, amphotericin B plus dexamethasone, and amphotericin B plus pentoxifylline than in untreated animals. In this model, pentoxifylline in combination with amphotericin B improved survival, decreasing the fungal burden, and has potential as adjuvant therapy in cerebral cryptococcosis.

Amphotericin B↗

Humoral and cellular immune response within the subarachnoid space of patients with neurocysticercosis.

To study the immune response within the subarachnoid space in patients with neurocysticercosis, we measured the cerebrospinal fluid contents of immunoglobulins A, E, G, and M in 38 patients and the contents of the proinflammatory cytokines TNF-alpha, IL-1b, IL-6 and IFN-gamma in 17 patients. The same measurements were made in 30 neurological patients without inflammatory or immune-mediated disorders. Each immunoglobulin and cytokine, including the gender and age of the patient, was compared by multiple regression analysis with the CSF contents of cells, protein and ELISA for cysticercal antigens. A direct correlation was found of IgM with cell content (p < 0.058) and with ELISA values (p < 0.027); of age with protein content (p < 0.006); of IL-6 with protein content (p < 0.018) and of IL-1b with ELISA values (p < 0.004). An inverse correlation was found of glucose with ELISA values (p < 0.008). A complex function of the immune response within the subarachnoid space was observed: mean values of IgG, IgM, IgE and interleukins 1b and 6 were increased, whereas values of IgA, TNF-alpha and IFN-gamma were similar to those of controls.

Antigens, Helminth↗

Bronchoaspiration as a possible cause in a case of tetanus. A reminder on the importance of adulthood immunizations.

Although preventable by immunization tetanus still takes a large death toll, mostly in developing countries, where adult population is often unprotected and opportune medical care unavailable. We present a case of tetanus in an elderly patient with bronchoaspiration pneumonia after a near-drowning incident, in which no objective entry site could be suspected with as much temporal relation as the bronchoaspiration incident. Bronchoaspiration of organic matter and feces provides both a source of the causative agent and an adequate polymicrobial environment for the development of the disease. It is under such conditions that we propose this unusual entry site as the cause of tetanus in our patient. Special emphasis is made on the importance of adulthood immunization programs and how incidents like this one should be taken into account in the overall care provided to the elderly population.

Accidents↗

[Tuberculosis in health personnel: importance of surveillance and control programs].

OBJECTIVE: To describe tuberculosis surveillance results among healthcare workers of a tertiary care center. MATERIAL AND METHODS: All medical records of workers from 1992-1998 were reviewed. Demographics, labor, medical history, previous testing, PPD, booster shots and follow-up were analyzed. Statistical analysis was performed with odds ratios, p-values, and 95% confidence intervals. Subgroup analysis were done with chi 2. Kaplan-Meier estimates were used to analyze times to conversion. RESULTS: Surveillance was done in 1617 workers (68% female and 32% male). Mean age was 26.9 +/- 7.6 (15-68) years. Job positions were 30.5% nurses, 14.6% residents and 14.1% interns. Place of origin was Mexico City in 65.8%. BCG vaccination was present in 71.6% and 15.1% had previous PPD. Admission PPD was positive in 39.6%, negative in 48.3% and 12.1% were lost to follow-up. On negatives, 483 booster shots were applied, and 49 additional positives were found. Follow-up was done in 231 workers, of which 100 (43.3%) converted. The mean time for conversion was 22.8 +/- 12.4 months. The conversion rate at twelve months was 20%. Fifty workers received/accepted isoniazid prophylaxis. CONCLUSIONS: A high percentage of workers were PPD-positive; booster shots allowed the detection of an additional 10%. A high conversion rate underscores the need to organize tuberculosis control programs in Mexico.

Adolescent↗