Oliverio Welsh

Amikacin alone and in combination with trimethoprim-sulfamethoxazole in the treatment of actinomycotic mycetoma

We report the excellent therapeutic response obtained with amikacin alone and in combination with trimethoprim-sulfamethoxazole in the treatment of 15 patients with actinomycotic mycetoma who had a poor response to the traditional pharmacologic agents and/or in whom important organs such as lungs, spinal cord, and bone were involved. We evaluated the results by clinical, radiologic, and laboratory tests. No important side effects were detected during or after the therapy.

Mycetoma : current concepts in treatment

Mycetoma is a granulomatous infection affecting mainly the feet and lower extremities. It can be caused either by aerobic, branched actinomycetes or by eumycetes. Most cases are found in tropical and subtropical regions. The infection is usually produced by the introduction of the etiologic agents through minor wounds caused by thorns and wood splinters. Clinically the disease begins as small, firm nodules that can enlarge to form extensive lesions with fistulae and abscesses with pus containing granules of the causative microorganisms. Antimicrobials and surgery are used in the management of mycetoma. The actinomycetomas generally respond well to antimicrobials. For eumycetomas, surgery may be required. New therapeutic options for drug-resistant cases are discussed.

In Vitro Activities of DA-7157 and DA-7218 against Mycobacterium tuberculosis and Nocardia brasiliensis

ABSTRACT The in vitro activities of DA-7157, a novel oxazolidinone, against clinical isolates of Nocardia brasiliensis and Mycobacterium tuberculosis were determined. Equal MIC50s and MIC90s (0.25 and 0.5 μg/ml, respectively) were found for susceptible and multidrug-resistant isolates of M. tuberculosis. The N. brasiliensis isolates showed an MIC90 of 1 μg/ml and an MIC50 of 1 μg/ml. The DA-7157 prodrug, DA-7218, exhibited similar MICs for M. tuberculosis but fivefold-higher MICs for N. brasiliensis.

In Vitro and In Vivo Activities of Antimicrobials against Nocardia brasiliensis

ABSTRACT In Mexico mycetomas are mostly produced by Nocardia brasiliensis, which can be isolated from about 86% of cases. In the present work, we determined the sensitivities of 30 N. brasiliensis strains isolated from patients with mycetoma to several groups of antimicrobials. As a first screening step we carried out disk diffusion assays with 44 antimicrobials, including aminoglycosides, cephalosporins, penicillins, quinolones, macrolides, and some others. In these assays we observed that some antimicrobials have an effect on more than 66% of the strains: linezolid, amikacin, gentamicin, isepamicin, netilmicin, tobramycin, minocycline, amoxicillin-clavulanic acid, piperacillin-tazobactam, nitroxolin, and spiramycin. Drug activity was confirmed quantitatively by the broth microdilution method. Amoxicillin-clavulanic acid, linezolid, and amikacin, which have been used to treat patients, were tested in an experimental model of mycetoma in BALB/c mice in order to validate the in vitro results. Linezolid showed the highest activity in vivo, followed by the combination amoxicillin-clavulanic acid and amikacin.

Mycetoma: a unique neglected tropical disease

Mycetoma can be caused by bacteria (actinomycetoma) or fungi (eumycetoma) and typically affects poor communities in remote areas. It is an infection of subcutaneous tissues resulting in mass and sinus formation and a discharge that contains grains. The lesion is usually on the foot but all parts of the body can be affected. The causative microorganisms probably enter the body by a thorn prick or other lesions of the skin. Mycetoma has a worldwide distribution but is restricted to specific climate zones. Microbiological diagnosis and characterisation of the exact organism causing mycetoma is difficult; no reliable serological test exists but molecular techniques to identify relevant antigens have shown promise. Actinomycetoma is treated with courses of antibiotics, which usually include co-trimoxazole and amikacin. Eumycetoma has no acceptable treatment at present; antifungals such as ketoconazole and itraconazole have been used but are unable to eradicate the fungus, need to be given for long periods, and are expensive. Amputations and recurrences in patients with eumycetoma are common.

Mycetoma Medical Therapy

Medical treatment of mycetoma depends on its fungal or bacterial etiology. Clinically, these entities share similar features that can confuse diagnosis, causing a lack of therapeutic response due to inappropriate treatment. This review evaluates the response to available antimicrobial agents in actinomycetoma and the current status of antifungal drugs for treatment of eumycetoma.

Dermatophytoses in Monterrey, México

In the present report we reviewed a total of 2397 cases of dermatophytosis from superficial cutaneous lesions between the years 1978 and 1990. The cases included were from the Department of Dermatology at the University Hospital located in the city of Monterrey, México. A total of 726 tinea pedis, 613 tinea unguium, 441 tinea capitis, 395 tinea corporis and 222 tinea cruris cases were observed. The most commonly isolated dermatophyte species was Trichophyton rubrum (45%), followed by Trichophyton mentagrophytes (23.7%), Trichophyton tonsurans (21%), Microsporum canis (7.1%) and Epidermophyton floccosum (2.5%). Less frequently we isolated Microsporum audouinii, Microsporum gypseum, Trichophyton violaceum and Trichophyton verrucosum. Most of the cases were observed in the warmest months of the year (from March to September), and were equally distributed in both genders, except for tinea cruris which was more prevalent in men (3.5 : 1 ratio).

Actinomycetoma and advances in its treatment

Actinomycetoma is a chronic subcutaneous infection caused by aerobic branching actinomycetes. Its clinical features are firm tumefaction of the affected site and the presence of abscesses, nodules, and sinuses that drain a seropurulent exudate containing filamenting granules. The disease is caused by inoculation of the infectious agent through minor trauma in susceptible individuals. Nocardia brasiliensis, Actinomadura madurae, and Streptomyces somaliensis are among the most frequent agents in the Americas. Cellular and humoral immunity have been studied in animal models. Standard therapy for uncomplicated cases is sulfamethoxazole-trimethoprim given for many months. Bone involvement, disseminated cases, and special locations require combined treatment with amikacin and sulfamethoxazole-trimethoprim. Isolated reports include the addition of other antibiotics such as rifampicin, imipenem, or meropenem. When needed, other aminoglycosides can be used. Amoxicillin-clavulanic acid is indicated in specific cases as alternative treatment. Oxazolidinone antibiotics, such as linezolid and other similar compounds (DA-7218 and DA-7157), have been studied in experimental infections in animal models as well as in vitro and ex vivo, with encouraging results.

In Vitro Activity of PNU-100766 (Linezolid), a New Oxazolidinone Antimicrobial, against Nocardia brasiliensis

ABSTRACT The in vitro activity of a novel oxazolidinone, linezolid, was studied by comparing the activity of linezolid with those of amikacin, trimethoprim-sulfamethoxazole, and amoxicillin-clavulanic acid against 25 strains of Nocardia brasiliensis isolated from patients with mycetoma. All N. brasiliensis strains tested were sensitive to linezolid (MIC at which 90% of strains are inhibited [MIC90], 2 μg/ml; MIC50, 1 μg/ml). This antimicrobial might constitute a good alternative for treatment of actinomycetoma.

The Mycetoma Knowledge Gap: Identification of Research Priorities

Mycetoma is a tropical disease which is caused by a taxonomically diverse range of actinomycetes (actinomycetoma) and fungi (eumycetoma). The disease was only recently listed by the World Health Organization (WHO) as a neglected tropical disease (NTD). This recognition is the direct result of a meeting held in Geneva on February 1, 2013, in which experts on the disease from around the world met to identify the key research priorities needed to combat mycetoma. The areas that need to be addressed are highlighted here. The initial priority is to establish the incidence and prevalence of the disease in regions where mycetoma is endemic, prior to determining the primary reservoirs of the predominant causal agents and their mode of transmission to susceptible individuals in order to establish novel interventions that will reduce the impact of the disease on individuals, families, and communities. Critically, economical, reliable, and effective methods are required to achieve early diagnosis of infections and consequential improved therapeutic outcomes. Molecular techniques and serological assays were considered the most promising in the development of novel diagnostic tools to be used in endemic settings. Improved strategies for treating eumycetoma and actinomycetoma are also considered.