New possibilities for chromoblastomycosis and phaeohyphomycosis treatment: identification of two compounds from the MMV Pathogen Box® that present synergism with itraconazole

BACKGROUND Black fungi of the Herpotrichiellaceae family are agents of chromoblastomycosis and phaeohyphomycosis. There are few therapeutic options for these infections and it is common to associate antifungal drugs in their treatment. OBJECTIVES To investigate the Medicines for Malaria Venture (MMV) Pathogen Box® for possible compounds presenting synergism with antifungal drugs used to treat black fungal infections. METHODS An initial screening of the Pathogen Box® compounds was performed in combination with itraconazole or terbinafine at sub-inhibitory concentrations against Fonsecaea pedrosoi. Hits were further tested against eight Herpotrichiellaceae using the checkerboard method. FINDINGS No synergism was observed with terbinafine. MMV687273 (SQ109) and MMV688415 showed synergism with itraconazole against F. pedrosoi. Synergism of these compounds was confirmed with some black fungi by the checkerboard method. SQ109 and itraconazole presented synergism for Exophiala dermatitidis, F. pedrosoi, F. monophora and F. nubica, with fungicidal activity for F. pedrosoi and F. monophora. MMV688415 presented synergism with itraconazole only for F. pedrosoi, with fungicidal activity. The synergic compounds had high selectivity index values when combined with itraconazole. MAIN CONCLUSIONS These compounds in combination, particularly SQ109, are promising candidates to treat Fonsecaea spp. and E. dermatitidis infections, which account for most cases of chromoblastomycosis and phaeohyphomycosis.

Effect of secondary infection on epithelialisation and total healing of cutaneous leishmaniasis lesions

BACKGROUND Cutaneous leishmaniasis (CL) generally presents with a single or several localised cutaneous ulcers without involvement of mucous membranes. Ulcerated lesions are susceptible to secondary contamination that may slow the healing process. OBJECTIVE This study verified the influence of non-parasitic wound infection on wound closure (epithelialisation) and total healing. METHODS Twenty-five patients with a confirmed diagnosis of CL and ulcerated lesions underwent biopsy of ulcer borders. One direct microbial parameter (germ identification in cultures) and four indirect clinical parameters (secretion, pain, burning sensation, pruritus) were analysed. FINDINGS Biopsies of ten lesions showed secondary infection by one or two microorganisms (Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis, Streptococcus pyogenes and Candida parapsilosis). "Secretion" and "burning sensation" influenced epithelialisation time but not total healing time. Positive detection of germs in the ulcer border and "pain" and "pruritus" revealed no influence on wound closure. CONCLUSIONS Our borderline proof of clinical CL ulcer infection inhibiting CL wound healing supports the need to follow antimicrobial stewardship in CL ulcer management, which was recently proposed for all chronic wounds.

Use of amplified Mycobacterium tuberculosis direct test in respiratory samples from HIV-infected patients in Brazil / Utilização do amplified Mycobacterium tuberculosis direct test em amostras respiratórias de pacientes HIV positivos no Brasil

OBJECTIVE: To compare the accuracy of the amplified Mycobacterium tuberculosis direct (AMTD) test with reference methods for the laboratory diagnosis of tuberculosis in HIV-infected patients. METHODS: This was a study of diagnostic accuracy comparing AMTD test results with those obtained by culture on Löwenstein-Jensen (LJ) medium and by the BACTEC Mycobacteria Growth Indicator Tube 960 (BACTEC MGIT 960) system in respiratory samples analyzed at the Bioassay and Bacteriology Laboratory of the Oswaldo Cruz Foundation Evandro Chagas Clinical Research Institute in the city of Rio de Janeiro, Brazil. RESULTS: We analyzed respiratory samples collected from 118 patients, of whom 88 (74.4%) were male. The mean age was 36.6 ± 10.6 years. Using the AMTD test, the BACTEC MGIT 960 system, and LJ culture, we identified M. tuberculosis complex in 31.0%, 29.7%, and 27.1% of the samples, respectively. In comparison with LJ culture, the AMTD test had a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 89.4%, 75.7%, and 95.0%, respectively, for LJ culture, whereas, in comparison with the BACTEC MGIT 960 system, it showed values of 88.6%, 92.4%, 83.8%, and 94.8%, respectively. CONCLUSIONS: The AMTD test showed good sensitivity and specificity in the population studied, enabling the laboratory detection of M. tuberculosis complex in paucibacillary respiratory specimens. .

OBJETIVO: Comparar a acurácia do teste amplified Mycobacterium tuberculosis direct (AMTD) com métodos de referência para o diagnóstico laboratorial de tuberculose em pacientes HIV positivos. MÉTODOS: Estudo de acurácia diagnóstica comparando os resultados do teste AMTD com os de cultura em Löwenstein-Jensen (LJ) e de BACTEC Mycobacteria Growth Indicator Tube 960 (sistema BACTEC MGIT 960) em amostras respiratórias analisadas no Laboratório de Bacteriologia e Bioensaios do Instituto de Pesquisa Clínica Evandro Chagas da Fundação Oswaldo Cruz, no Rio de Janeiro (RJ). RESULTADOS: Foram analisadas amostras respiratórias de 118 pacientes, dos quais 88 (74,4%) eram do sexo masculino. A média de idade foi de 36,6 ± 10,6 anos. O complexo M. tuberculosis foi identificado em 31,0%, 29,7% e 27,1% das amostras através do teste AMTD, sistema BACTEC MGIT 960 e LJ, respectivamente. Na comparação com a cultura em LJ, o teste AMTD apresentou sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo de 87,5%, 89,4%, 75,7% e 95,0%, respectivamente, enquanto na comparação com o sistema BACTEC MGIT 960, os valores foram de 88,6%, 92,4%, 83,8% e 94,8%, respectivamente. CONCLUSÕES: O teste AMTD mostrou boa sensibilidade e especificidade na população estudada, possibilitando a detecção laboratorial do complexo M. tuberculosis em espécimes respiratórios paucibacilares. .

Factors associated with epidemic multiresistant Pseudomonas aeruginosa infections in a hospital with AIDS-predominant admissions

INTRODUCTION: Infections caused by multiresistant Pseudomonas aeruginosa (MR-PA) have been associated with persistent infections and high mortality in acquired immunodeficiency syndrome (AIDS) patients. Therefore, understanding the predisposing factors for infection/colonization by this agent is critical for controlling outbreaks caused by MR-PA in settings with AIDS patients. OBJECTIVEAND METHODS: To analyze the presence of factors associated with the acquisition of an epidemic MR-PA strain in a hospital with AIDS-predominant admission. A case-control study was carried out in which cases and controls were gathered from a prospective cohort of all hospitalized patients in an infectious disease hospital during a five-year study period. RESULTS: Multivariate logistic regression analysis demonstrated that enteral nutrition OR = 14.9), parenteral nutrition (OR = 10.7), and use of ciprofloxacin (OR = 8.9) were associated with a significant and independent risk for MR-PA acquisition. CONCLUSIONS: Although cross-colonization was likely responsible for the outbreaks, the use of ciprofloxacin was also an important factor associated with the acquisition of an epidemic MR-PA strain. More studies are necessary to determine whether different types of nutrition could lead to modification of gastrointestinal flora, thereby increasing the risk for infection/colonization by MR-PA in this population.

Outbreaks, persistence, and high mortality rates of multiresistant Pseudomonas aeruginosa infections in a hospital with AIDS-predominant admissions

INTRODUCTION: Authors have reported increased incidence of multiresistant Pseudomonas aeruginosa (MR-PA) infections worldwide over the last decade. Researchers have proposed multifaceted approaches to control MR-PA infections, but none have been reported in the acquired immunodeficiency syndrome (AIDS) setting. OBJECTIVE AND METHODS: Herein we report the impact of a multifaceted intervention for controlling MR-PA over five years in a hospital with AIDS-predominant admissions and describe the clinical characteristics of MR-PA infection in our patient population. The clinical outcomes of infected patients and molecular characteristics of the isolated strains were used as tools for controlling MR-PA infection rates. RESULTS: Significant temporary decrease of new infections was achieved after intervention, although a high level of diagnostic suspicion of nosocomial infection was maintained. We obtained 35 P. aeruginosa isolates with multiresistant profiles from 13 infected and 3 colonized patients and 2 environmental samples. Most of the patients (94 percent) were immunocompromised with AIDS (n = 10) or HTLV-1 infections (n = 5). Of the followed patients, 67 percent had persistent and/or recurrent infections, and 92 percent died. We observed differences in the antibiotic-resistance pattern of MR-PA infection/colonization during two outbreaks, although the genetic profiles of the tested strains were identical. CONCLUSIONS: Therefore, we concluded that early multidisciplinary interventions are essential for reducing the burden caused by this microorganism in patients with AIDS. Prolonged or suppressive antibiotic-based therapy should be considered for MR-PA infections in patients with AIDS because of the persistence characteristic of MR-PA in these patients.

Multidrug-resistant tuberculosis among male inmates in Rio de Janeiro, Brazil

Susceptibility tests to six anti-tuberculosis drugs were performed on fifty-eight M. tuberculosis isolates obtained from tuberculous inmates in the Male Penal Sanatorium, Rio de Janeiro, Brazil. The rate of resistant tuberculosis was higher than observed in the community. The overall resistance rate was 17.2 (per cent) and 3.4 (per cent) of the isolates were multi-drug resistant.