Beatriz Bustamante

Clinical Practice Guidelines for the Management of Sporotrichosis: 2007 Update by the Infectious Diseases Society of America

Guidelines for the management of patients with sporotrichosis were prepared by an Expert Panel of the Infectious Diseases Society of America and replace the guidelines published in 2000. The guidelines are intended for use by internists, pediatricians, family practitioners, and dermatologists. They include evidence-based recommendations for the management of patients with lymphocutaneous, cutaneous, pulmonary, osteoarticular, meningeal, and disseminated sporotrichosis. Recommendations are also provided for the treatment of sporotrichosis in pregnant women and in children.

Antimicrobial activity of selected Peruvian medicinal plants.

The antimicrobial activity of 36 ethanol extracts from 24 plants, all of them currently used in the Peruvian traditional medicine for the treatment of several infectious and inflammatory disorders, was tested by means of the agar-well diffusion assay against four bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) and four fungi (Candida albicans, Trichophyton mentagrophytes, Microsporum gypseum and Sporothrix schenckii). Twenty-five (69%) extracts showed some degree of antimicrobial activity against at least one microorganism. The plants with the greatest antimicrobial activity were Cestrum auriculatum L. Heritier (Solanaceae), Iryanthera lancifolia Ducke Suesseng (Myristicaceae), Lepechinia meyenii (Walp.) Epling (Lamiaceae) and Ophryosporus peruvianus (Gmelin) King & H. Rob. (Asteraceae).

Recombinant Interferon-γlb as Adjunctive Therapy for AIDS-Related Acute Cryptococcal Meningitis

We conducted a phase 2, double-blind, placebo-controlled study to evaluate the safety and antifungal activity of adjuvant recombinant interferon (rIFN)- gamma 1b in patients with acquired immunodeficiency syndrome and acute cryptococcal meningitis. Patients received 100 or 200 microg of rIFN- gamma 1b or placebo, thrice weekly for 10 weeks, plus standard therapy with intravenous amphotericin B, with or without flucytosine, followed by therapy with fluconazole. End points included conversion of cerebrospinal fluid fungal cultures from positive to negative at 2 weeks, resolution of symptoms, and survival. Among 75 patients, 2-week culture conversion occurred in 13% of placebo recipients, 36% of rIFN- gamma 1b (100 microg) recipients, and 32% of rIFN- gamma 1b (200 microg) recipients. There was a trend toward improved combined mycologic and clinical success in rIFN- gamma 1b recipients (26% vs. 8%; P=.078). Therapy with rIFN- gamma 1b was well tolerated, and there was no apparent influence on serial CD4 cell counts and human immunodeficiency virus load measurements. Adjunctive therapy with rIFN- gamma 1b holds promise for patients with acute cryptococcal meningitis and warrants further study.

Sporotrichosis in Peru: Description of an Area of Hyperendemicity

Sporotrichosis is a sporadic and rare mycotic infection in most of the developed world. In many parts of the developing world, sporotrichosis is much more commonly recognized, but epidemiological data are generally lacking from these regions. We report epidemiological, clinical, and treatment data from 238 cases of culture-proven sporotrichosis occurring in a relatively remote area of the south central highlands of Peru that were retrospectively collected during 1995-1997. Most cases (60%) occurred in children aged </=14 years, and the most commonly affected anatomic site was the face. Disease was clinically confined to the skin and subcutaneous tissue in all patients. The incidence of sporotrichosis in this region ranged from 48 to 60 cases per 100,000 persons and was highest among children aged 7-14 years, approaching 1 case per 1000 persons. Sporotrichosis is a significant mycosis in the rural highlands of Peru, with an incidence exceeding those of other invasive mycoses in individuals without human immunodeficiency virus infection.

Interlaboratory variability of caspofungin MICs for Candida spp. using CLSI and EUCAST methods: Should the clinical laboratory Be testing this agent?

ABSTRACT Although Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) are available for interpreting echinocandin MICs for Candida spp., epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550 Candida isolates from 17 laboratories (Brazil, Canada, Europe, Mexico, Peru, and the United States), we observed an extraordinary amount of modal variability (wide ranges) among laboratories as well as truncated and bimodal MIC distributions. The species-specific modes across different laboratories ranged from 0.016 to 0.5 μg/ml for C. albicans and C. tropicalis, 0.031 to 0.5 μg/ml for C. glabrata, and 0.063 to 1 μg/ml for C. krusei. Variability was also similar among MIC distributions for C. dubliniensis and C. lusitaniae. The exceptions were C. parapsilosis and C. guilliermondii MIC distributions, where most modes were within one 2-fold dilution of each other. These findings were consistent with available data from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (403 to 2,556 MICs) for C. albicans, C. glabrata, C. krusei, and C. tropicalis. Although many factors (caspofungin powder source, stock solution solvent, powder storage time length and temperature, and MIC determination testing parameters) were examined as a potential cause of such unprecedented variability, a single specific cause was not identified. Therefore, it seems highly likely that the use of the CLSI species-specific caspofungin CBPs could lead to reporting an excessive number of wild-type (WT) isolates (e.g., C. glabrata and C. krusei) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs for Candida is not recommended; micafungin or anidulafungin data could be used instead.

Multilaboratory Study of Epidemiological Cutoff Values for Detection of Resistance in Eight Candida Species to Fluconazole, Posaconazole, and Voriconazole

ABSTRACT Although epidemiological cutoff values (ECVs) have been established for Candida spp. and the triazoles, they are based on MIC data from a single laboratory. We have established ECVs for eight Candida species and fluconazole, posaconazole, and voriconazole based on wild-type (WT) MIC distributions for isolates of C. albicans (n = 11,241 isolates), C. glabrata (7,538), C. parapsilosis (6,023), C. tropicalis (3,748), C. krusei (1,073), C. lusitaniae (574), C. guilliermondii (373), and C. dubliniensis (162). The 24-h CLSI broth microdilution MICs were collated from multiple laboratories (in Canada, Brazil, Europe, Mexico, Peru, and the United States). The ECVs for distributions originating from ≥6 laboratories, which included ≥95% of the modeled WT population, for fluconazole, posaconazole, and voriconazole were, respectively, 0.5, 0.06 and 0.03 μg/ml for C. albicans, 0.5, 0.25, and 0.03 μg/ml for C. dubliniensis, 8, 1, and 0.25 μg/ml for C. glabrata, 8, 0.5, and 0.12 μg/ml for C. guilliermondii, 32, 0.5, and 0.25 μg/ml for C. krusei, 1, 0.06, and 0.06 μg/ml for C. lusitaniae, 1, 0.25, and 0.03 μg/ml for C. parapsilosis, and 1, 0.12, and 0.06 μg/ml for C. tropicalis. The low number of MICs (<100) for other less prevalent species (C. famata, C. kefyr, C. orthopsilosis, C. rugosa) precluded ECV definition, but their MIC distributions are documented. Evaluation of our ECVs for some species/agent combinations using published individual MICs for 136 isolates (harboring mutations in or upregulation of ERG11, MDR1, CDR1, or CDR2) and 64 WT isolates indicated that our ECVs may be useful in distinguishing WT from non-WT isolates.

Epidemiology of Human Sporotrichosis Investigated by Amplified Fragment Length Polymorphism

ABSTRACT Amplified fragment length polymorphism (AFLP) was used to analyze the genetic diversity of Peruvian strains of Sporothrix schenckii and to compare them to a panel of non-Peruvian strains. AFLP analysis suggests that the Peruvian strains can be divided into two homogeneous clusters with no reference to geographical origin or the clinical form of sporotrichosis. The strains from abroad present heterogeneous profiles, with the Bolivian strain and the Colombian strains related to one of the Peruvian population. Sequencing of internal transcribed spacer 2, used to examine the relationships over a longer distance, confirmed the division of Peruvian strains into two populations that can be identified on the basis of a single but specific sequence divergence. This paper introduces automated AFLP analysis as a valuable tool for further investigation of the epidemiology and ecology of S. schenckii.

Treatment of cutaneous sporotrichosis with one daily dose of potassium iodide

BACKGROUND Recommended treatment for cutaneous sporotrichosis consists of a saturated solution of potassium iodide (SSKI) administered in three daily doses (tid). Because compliance with this regimen has been a problem in our previous experience, we evaluated the use of one daily (qd) full dose of SSKI. METHODS Patients with culture-confirmed cutaneous sporotrichosis were entered in a randomized, nonblinded study to compare the safety and efficacy of qd vs. tid dosage of SSKI. RESULTS Fifty-seven patients were enrolled to receive either qd (29) or tid (28) SSKI. Three (1 in the qd and 2 in the tid group) were not compliant with the assigned regimen. Side effects were common but mild in both treatment groups (61% in the qd and 42% in the tid group, P = 0.17); treatment had to be discontinued because of side effects in 3 cases (2 in the qd and 1 in the tid group). Overall 26 (89.6%) and 25 (89.2%) of the individuals initially assigned to the qd and tid dosing schedule, respectively, were cured by the treatment. No relapse was detected after 45 days of follow-up. CONCLUSION These findings suggest that a single daily full dose of SSKI appears to be appropriate therapy for cutaneous sporotrichosis; further studies with larger numbers of patients are required.

Multicenter Study of Anidulafungin and Micafungin MIC Distributions and Epidemiological Cutoff Values for Eight Candida Species and the CLSI M27-A3 Broth Microdilution Method

ABSTRACT Since epidemiological cutoff values (ECVs) using CLSI MICs from multiple laboratories are not available for Candida spp. and the echinocandins, we established ECVs for anidulafungin and micafungin on the basis of wild-type (WT) MIC distributions (for organisms in a species-drug combination with no detectable acquired resistance mechanisms) for 8,210 Candida albicans, 3,102 C. glabrata, 3,976 C. parapsilosis, 2,042 C. tropicalis, 617 C. krusei, 258 C. lusitaniae, 234 C. guilliermondii, and 131 C. dubliniensis isolates. CLSI broth microdilution MIC data gathered from 15 different laboratories in Canada, Europe, Mexico, Peru, and the United States were aggregated to statistically define ECVs. ECVs encompassing 97.5% of the statistically modeled population for anidulafungin and micafungin were, respectively, 0.12 and 0.03 μg/ml for C. albicans, 0.12 and 0.03 μg/ml for C. glabrata, 8 and 4 μg/ml for C. parapsilosis, 0.12 and 0.06 μg/ml for C. tropicalis, 0.25 and 0.25 μg/ml for C. krusei, 1 and 0.5 μg/ml for C. lusitaniae, 8 and 2 μg/ml for C. guilliermondii, and 0.12 and 0.12 μg/ml for C. dubliniensis. Previously reported single and multicenter ECVs defined in the present study were quite similar or within 1 2-fold dilution of each other. For a collection of 230 WT isolates (no fks mutations) and 51 isolates with fks mutations, the species-specific ECVs for anidulafungin and micafungin correctly classified 47 (92.2%) and 51 (100%) of the fks mutants, respectively, as non-WT strains. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin and micafungin due to fks mutations.

Evaluation of cats as the source of endemic sporotrichosis in Peru

Although contact with domestic cats has been shown to be a risk factor for sporotrichosis in endemic areas, systematic evaluation of apparently unaffected cats as possible reservoirs for infection has not been explored. The goals of this study were to identify the following aspects of sporotrichosis in the endemic area of Abancay, Peru: (i) the overall prevalence of sporotrichosis in the cat population, (ii) the most common site where the fungus can be isolated from these cats, and (iii) whether cats without identifiable skin lesions may be carriers of the fungus in the oral mucosa, nasal mucosa, or nails. One household cat in each of 85 neighborhoods within the endemic area of Abancay, Peru was randomly selected. Oral and nasal swabs, as well as nail clippings were taken from 84 of the cats. In addition, samples from skin lesions that were suspected to be due to sporotrichosis were collected from cats or members of families that owned the pets. Cultures inoculated with two nasal swabs and one set of nail clippings from two different cats yielded Sporothrix schenckii, the identity of which were confirmed by rDNA sequencing. The overall prevalence of Sporothrix schenckii colonization was 2.38% (95% CI 0.41-9.14) in this cat population. None of the skin lesion samples from the cats and only one such sample from a family member were positive for Sporothrix schenckii in culture. These results suggest a role for domestic cats as a possible reservoir for sporotrichosis infection in Abancay.