Experimental selection of paromomycin and miltefosine resistance in intracellular amastigotes of Leishmania donovani and L. infantum.

Although widespread resistance of Leishmania donovani and L. infantum against miltefosine (MIL) and paromomycin (PMM) has not yet been demonstrated, both run the risk of resistance selection. Unraveling the dynamics and mechanisms of resistance development is key to preserve drug efficacy in the field. In this study, resistance against PMM and MIL was experimentally selected in vitro in intracellular amastigotes of several strains of both species with different antimony susceptibility background. To monitor amastigote susceptibility, microscopic determination of IC50-values and promastigote back-transformation assays were performed. Both techniques were also used to evaluate the susceptibility of field isolates from MIL-relapse patients. PMM-resistance could readily be selected in all species/strains, although promastigotes remained fully PMM-susceptible. Successful MIL-resistance selection was demonstrated only by promastigote back-transformation at increasing MIL-concentrations upon successive selection cycles. Important to note is that amastigotes with the MIL-resistant phenotype could not be visualized after Giemsa staining; hence, MIL-IC50-values showed no shift. The same phenomenon was observed in a set of recent clinical isolates from MIL-relapse patients. This study clearly endorses the need to use intracellular amastigotes for PMM- and MIL-susceptibility testing. When monitoring MIL-resistance, promastigote back-transformation should be used instead of the standard Giemsa staining. In-depth exploration of the mechanistic background of this finding is warranted.

[Non-antibiotic anti-infectious treatments in urology]. / Les médicaments anti-infectieux non antibiotiques en urologie.

OBJECTIVE: To define the terms of use of pesticides, antifungal, antiviral and antiseptic treatments in urology. MATERIALS AND METHODS: A literature search was conducted on MEDLINE for all these treatments used in urology. The molecules were classified by family. Modes of action, indications in urology and adverse effects have been detailed. Authorisation files were consulted and then complemented by a literature analysis. RESULTS: Although parasitic or viral diseases are uncommon in urology, their specific treatment deserves a thorough knowledge of pesticide and antiviral molecules. Antifungal treatments are regularly used in urology with special features to know to improve the efficacy/safety ratio. Antiseptics are used daily in urology and a better understanding of these molecules allows better use. CONCLUSION: Beyond antibiotics, antiviral, antiparasitic and antifungal deserve a thorough knowledge. Antiseptic although used daily have features little known.

[Recommendations of the Infectious Disease Committee of the French Association of Urology. Diagnosis, treatment and monitoring candiduria]. / Recommandations du comité d'infectiologie de l'AFU. Diagnostic, traitement et suivi des candiduries.

The candiduria are frequently encountered in urology. We present the recommendations of the Infectious Diseases Committee of the French Association of Urology for diagnosis, treatment and monitoring of urinary tract infections. C. albicans is the most frequently isolated species, representing 60% of the isolates. Immunosuppression, diabetes mellitus, age extremes of life, the presence of catheters or procedures on the urinary tract are risk factors for Candida urinary tract infection. The candiduria is usually asymptomatic and does not need treatment. Only 4-14% of patients with candiduria have symptoms of urinary infection. It is necessary before choosing candiduria isolated on a first urinalysis to eliminate contamination by conducting a second harvest. In patients surveyed, the removal of the material allows the resolution of the candiduria nearly half the time and represents the first step of management. Oral fluconazole is the recommended treatment for cystitis (400 mg on day 1 and 200 mg daily for 7 to 14 days). In cases of pyelonephritis without associated candidemia, the first-line therapy is fluconazole (3-6 mg/kg/day) for 14 days or amphotericin B at a dose of 0.5 to 0.7 mg/kg/day with or not associated to flucytosine when potentially resistant strain (C. glabrata).

A case of Candida haemulonii osteitis: clinical features, biochemical characteristics, and antifungal resistance profile.

We describe here the first case of osteitis caused by Candida haemulonii in a young immunocompetent patient. This patient presented a history of severe peripheral vascular disease associated with a lack of hygienic conditions as the only risk factors for such an uncommon infection. Clinical signs and histological examination allowed us to determine that it was a C. haemulonii infection and not colonization. The outcome was favourable with oral voriconazole therapy and surgical revascularization. An environmental cause of such infections is most probable, as C. haemulonii has previously been isolated from different non-human sources. Identification methods, results obtained with three in vitro antifungal susceptibility methods and clinical features are reported.

Invasive infections due to Trichoderma species: report of 2 cases, findings of in vitro susceptibility testing, and review of the literature.

Trichoderma species are filamentous fungi that were previously considered to be culture contaminants. We report 2 well-documented cases of invasive Trichoderma infections, and we comprehensively review the literature on this topic. Trichoderma species are mainly responsible for continuous ambulatory peritoneal dialysis-associated peritonitis (7 cases) and invasive infections in immunocompromised patients (9 cases) with a hematologic malignancy or solid-organ transplant. Definitive diagnosis is difficult to achieve because of the lack of specific diagnosis tools. Species identification can benefit from a molecular approach. Trichoderma longibrachiatum is the most common species involved in these infections. Regardless of the type of infection, the prognosis was poor, with 8 deaths among 18 cases. This may be partially because of the resistance of these organisms to the majority of available antifungal agents, including amphotericin B. Trichoderma species now should be added to the growing list of emerging filamentous fungal pathogens.