ABSTRACT
The emergence of Candida spp. with resistance to antifungal molecules, mainly the azole class, is an increasing complication in hospitals around the globe. Aim: In the present research, we evaluated the synergistic effects of ketamine with two azole derivatives, itraconazole and fluconazole, on strains of Candida spp. to fluconazole. Materials & methods: The drug synergy was evaluated by quantifying the fractional inhibitory concentration index and by fluorescence microscopy and flow cytometry techniques. Results: Our achievements showed a synergistic effect between ketamine in addition to the two antifungal agents (fluconazole and itraconazole) against planktonic cells and biofilms of Candida spp. Conclusion: This combination promoted alteration of membrane integrity, generation of reactive oxygen species, damage to and DNA and externalization of phosphatidylserine.
Subject(s)
Antifungal Agents/pharmacology , Candida/drug effects , Fluconazole/pharmacology , Itraconazole/pharmacology , Ketamine/pharmacology , Animals , Biofilms/drug effects , Candida/physiology , Candida albicans/drug effects , Candida albicans/physiology , Cell Survival/drug effects , DNA Damage , DNA Fragmentation , DNA, Fungal/drug effects , Drug Resistance, Fungal , Drug Synergism , L Cells , Membrane Potential, Mitochondrial/drug effects , Mice , Microbial Sensitivity Tests , Microbial Viability , Phosphatidylserines/metabolism , Reactive Oxygen Species/metabolismABSTRACT
Many relapses and deaths resulting from disseminated histoplasmosis (DH) in acquired immunodeficiency syndrome (AIDS) patients have been observed in an endemic area in north-eastern Brazil. The objective of this study was to evaluate the risk factors associated with the clinical outcomes of DH/AIDS coinfection in patients from the state of Ceará, Brazil. A retrospective cohort of AIDS patients, after their hospital discharge due to first DH episode in the period 2002-2008, was followed until December 31, 2010, to investigate the factors associated with relapse and mortality. A total of 145 patients were evaluated in the study. Thirty patients (23.3%) relapsed and the overall mortality was 30.2%. The following variables were significantly (P < 0.05) associated with relapse and overall mortality (univariate analysis): non-adherence to highly active antiretroviral therapy (HAART), irregular use of an antifungal, non-recovery of the CD4+ count and having AIDS before DH; histoplasmosis relapse was also significantly associated with mortality. In the multivariate analysis, non-adherence to HAART was the independent risk factor that was associated with both relapse (Adj OR = 6.28) and overall mortality (Adj OR = 8.03); efavirenz usage was discovered to be significant only for the overall mortality rate (Adj OR = 4.50). Adherence to HAART was the most important variable that influenced the outcomes in this specific population.
Subject(s)
AIDS-Related Opportunistic Infections/mortality , HIV Infections/microbiology , Histoplasmosis/mortality , Histoplasmosis/virology , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/epidemiology , Adult , Antifungal Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , Brazil/epidemiology , Coinfection/epidemiology , Coinfection/microbiology , Coinfection/mortality , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/mortality , Histoplasmosis/drug therapy , Histoplasmosis/epidemiology , Humans , Male , Recurrence , Retrospective Studies , Risk FactorsABSTRACT
The State of Ceará in north-eastern Brazil has one of the highest rates in the world of relapse and death due to disseminated histoplasmosis (DH) in acquired immunodeficiency syndrome (AIDS) patients. The objective of this study is to characterise the relapse and mortality of DH in AIDS cases residents in Ceará. We performed a retrospective analysis of the medical records of AIDS patients who had a first episode of DH from 2002 to 2008. We analysed the outcomes until December 31, 2010. A total of 145 patients participated in the study. The mean clinical follow-up duration was 3.38 years (SD = 2.2; 95% CI = 3.01-3.75). The majority of the subjects were male with a mean age of 35 years (SD = 2.2; 95% CI = 3.01-3.75) and were born in the capital of Ceará. DH was the first manifestation of AIDS in 59% of the patients. The relapse rate was 23.3%, with a disseminated presentation in 90% of these patients. The overall mortality during the study period was 30.2%. The majority of patients who relapsed or died had irregular treatment with antifungals or highly active antiretroviral therapy and did not have active clinical follow-up. High rates of recurrence and mortality were found in AIDS-associated DH in this area of the country.
