ABSTRACT
OBJECTIVES: The aim of the present study was to evaluate the effects of delayed antifungal therapy on the outcome of invasive aspergillosis due to Aspergillus fumigatus in experimental models of infection. METHODS: A clinical isolate of A. fumigatus susceptible to amphotericin B (MIC 0.5 mg/L) and micafungin [minimum effective concentration (MEC) 0.03 mg/L] was used in all experiments. Two models of infection were investigated in immunosuppressed mice: disseminated infection and pulmonary infection. Twenty-four hours (early therapy) and 48 h (delayed therapy) post-infection, the mice were given vehicle, liposomal amphotericin B, micafungin or liposomal amphotericin B plus micafungin (combination). Drug efficacy was assessed by either survival or tissue burden experiments. RESULTS: In disseminated infection, any drug regimen given early significantly prolonged survival. When therapy was delayed, only micafungin and the combination were effective. In pulmonary infection, although there was a trend towards a prolongation of survival of mice treated early with liposomal amphotericin B, only the combination was effective. Similarly, when therapy was delayed, only the combination was effective. In disseminated infection, any drug regimen given early was effective at reducing the cfu in kidney tissue. In pulmonary infection, only liposomal amphotericin B and the combination given early were effective at reducing the cfu in lung tissue. Conversely, when therapy was delayed, no regimen was effective at reducing the tissue burden, regardless of the type of infection. CONCLUSIONS: Our data indicate that delayed initiation of antifungal therapy is deleterious in experimental models of invasive aspergillosis. A combination regimen seems to have some advantages over a single-drug approach when the therapy is started late.
Subject(s)
Antifungal Agents/administration & dosage , Invasive Pulmonary Aspergillosis/drug therapy , Time Factors , Amphotericin B/administration & dosage , Amphotericin B/pharmacology , Animals , Antifungal Agents/pharmacology , Aspergillus fumigatus/drug effects , Colony Count, Microbial , Disease Models, Animal , Drug Therapy, Combination , Echinocandins/administration & dosage , Echinocandins/pharmacology , Female , Lipopeptides/administration & dosage , Lipopeptides/pharmacology , Lung/microbiology , Micafungin , Mice , Microbial Sensitivity Tests , Survival Analysis , Treatment OutcomeABSTRACT
Intestinal parasites are a serious problem in developing countries, but should not be underestimated in industrialised countries either. Between January 2006 and December 2011, stool specimens and the scotch tests of 5323 Italian and non Italian patients (adults and children) attending the laboratory of our Infectious Diseases Clinic in a teaching Hospital at Ancona were analyzed specifically for intestinal parasites. The present study shows that, over a six-year period, of a total of 5323 patients 305 harboured at least one species of parasite (5.7%). Among the pathogenic protozoa Giardia lamblia was the most common, the overall prevalence of giardiasis being 1.8 % (99/5323). Helminths were found in 0.9% of the patients (48/5323). In particular, Hymenolepis nana, Strongyloides stercoralis and Trichuris trichiura were most commonly recovered in non-Italian children, suggesting that certain intestinal parasites are restricted to endemic areas in the tropics. Eighteen of the 305 infected patients had more than one parasite in their stools. Our study demonstrates that intestinal parasites must be considered even in industrialised areas and stool examination should be supported by epidemiological data and clinical features.
Subject(s)
Feces/parasitology , Intestinal Diseases, Parasitic/diagnosis , Intestinal Diseases, Parasitic/epidemiology , Adult , Animals , Child , Developed Countries/statistics & numerical data , Developing Countries/statistics & numerical data , Female , Giardia lamblia/isolation & purification , Giardiasis/diagnosis , Giardiasis/epidemiology , Hospitals, University , Humans , Hymenolepiasis/diagnosis , Hymenolepiasis/epidemiology , Hymenolepis nana/isolation & purification , Italy/epidemiology , Male , Prevalence , Strongyloides stercoralis/isolation & purification , Strongyloidiasis/diagnosis , Strongyloidiasis/epidemiology , Trichuriasis/diagnosis , Trichuriasis/epidemiology , Trichuris/isolation & purificationABSTRACT
The effects of caspofungin combined with amphotericin B were investigated with Candida glabrata. Although in vitro experiments showed an indifferent interaction, the combination regimen was the only therapeutic approach yielding organ sterilization in a murine candidemia model.