HPLC-MS identification and expression of Candida drug-resistance proteins from African HIV-infected patients.

The objective of this study was to elucidate the proteomic mechanisms of drug resistance in HIV-infected African patients. Cell membrane fractions from forty oral Candida isolates isolated from African HIV-positive patients were analysed using HPLC-MS with the aim of identifying proteins associated with their pathogenicity and drug resistance. Heat shock proteins that mediate the fungicidal activity of salivary peptides were found in all tested Candida fractions, with pH-responsive proteins associated with increased pathogenicity only being present in the three most commonly isolated species. ABC multidrug transporter efflux pumps and estrogen binding proteins were only found in C. albicans fractions, while ergosterol biosynthesis proteins were identified in four species. The combination of various adherence, invasion, upregulation and efflux pump mechanisms appear to be instrumental for the Candida host colonization and drug resistance emergence in HIV-infected individuals.

Measuring Streptococcus mutans, Streptococcus sanguinis and Candida albicans biofilm formation using a real-time impedance-based system.

Candida albicans and streptococci are amongst the most common fungal and bacterial organisms present in the oral cavity, with a growing body of evidence implicating C. albicans in increased caries severity and in the formation of the cariogenic biofilm. However, the interactive mechanisms between cariogenic streptococci and Candida are yet to be elucidated. In this study, the real-time biofilm formation of C. albicans, S. mutans and S. sanguinis was assessed individually and in combination using the xCELLigence system, an impedance-based microbial biofilm monitoring system. The impedance signal was the highest for C. albicans, followed by S. mutans and S. sanguinis. Although the streptococcal mixed adhesion was found to follow a similar trend to that of S. sanguinis, the introduction of C. albicans resulted in higher adhesion patterns, with the combined growth of S. sanguinis and C. albicans and the combination of all three species resulting in higher biofilm formation than any of the individual organisms over time. This study, the first to use impedance for real-time monitoring of interkingdom biofilms, adds to the body of evidence that C. albicans and oral streptococcal adhesion are interlinked and suggests that interkingdom interactions induce changes in the oral biofilm dynamics over time.

K21 Compound, a Potent Antifungal Agent: Implications for the Treatment of Fluconazole-Resistant HIV-Associated Candida Species.

Background/Objectives: With mucocutaneous candidiasis being highly prevalent in HIV patients, the emergence of fluconazole-resistant Candida species forms a major challenge in treating and eradicating these infections. The objective of this study was to establish the antifungal activity of K21, a membrane-rupturing antimicrobial compound derived from a silica quaternary ammonium compound (SiQAC) with tetraethoxysilane (TEOS). Methods: The study sample included 81 Candida species of which 9 were type strains and 72 were clinical isolates. Minimum inhibitory concentrations, synergy, fractional inhibitory concentration index (FICI), and time kill assays were determined by broth microdilution. Electron microscopy (EM) was used to determine the qualitative changes brought about after treatment with K21. Results: K21 inhibited the growth of all fluconazole-resistant and susceptible Candida strains with only 2 h of exposure required to effectively kill 99.9% of the inoculum, and a definite synergistic effect was observed with a combination of K21 and fluconazole. EM demonstrated the presence of two forms of extracellular vesicles indicative of biofilm formation and cell lysis. Conclusion: The study established the efficacy of K21 as an antifungal agent and with fluconazole-resistant candidiasis on the increase, the development of K21 can provide a promising alternative to combat acquired drug resistance.

Candida antifungal drug resistance in sub-Saharan African populations: A systematic review.

Background: Candida infections are responsible for increased morbidity and mortality rates in at-risk patients, especially in developing countries where there is limited access to antifungal drugs and a high burden of HIV co-infection.  Objectives: This study aimed to identify antifungal drug resistance patterns within the subcontinent of Africa.  Methods: A literature search was conducted on published studies that employed antifungal susceptibility testing on clinical Candida isolates from sub-Saharan African countries using Pubmed and Google Scholar.  Results: A total of 21 studies from 8 countries constituted this review. Only studies conducted in sub-Saharan Africa and employing antifungal drug susceptibility testing were included. Regional differences in Candida species prevalence and resistance patterns were identified.  Discussion: The outcomes of this review highlight the need for a revision of antifungal therapy guidelines in regions most affected by Candida drug resistance.  Better controls in antimicrobial drug distribution and the implementation of regional antimicrobial susceptibility surveillance programmes are required in order to reduce the high Candida drug resistance levels seen to be emerging in sub-Saharan Africa.

Multi-drug resistant oral Candida species isolated from HIV-positive patients in South Africa and Cameroon.

Candida species are a common cause of infection in immune-compromised HIV-positive individuals, who are usually treated with the antifungal drug, fluconazole, in public hospitals in Africa. However, information about the prevalence of drug resistance to fluconazole and other antifungal agents on Candida species is very limited. This study examined 128 Candida isolates from South Africa and 126 Cameroonian Candida isolates for determination of species prevalence and antifungal drug susceptibility. The isolates were characterized by growth on chromogenic and selective media and by their susceptibility to 9 antifungal drugs tested using the TREK™ YeastOne9 drug panel (Thermo Scientific, USA). Eighty-three percent (82.8%) of South African isolates were Candida albicans (106 isolates), 9.4% were Candida glabrata (12 isolates), and 7.8% were Candida dubliniensis (10 isolates). Of the Cameroonian isolates, 73.02% were C. albicans (92 isolates); 19.05% C. glabrata (24 isolates); 3.2% Candida tropicalis (4 isolates); 2.4% Candida krusei (3 isolates); 1.59% either Candida kefyr, Candida parapsilopsis, or Candida lusitaneae (2 isolates); and 0.79% C. dubliniensis (1 isolate). Widespread C. albicans resistance to azoles was detected phenotypically in both populations. Differences in drug resistance were seen within C. glabrata found in both populations. Echinocandin drugs were more effective on isolates obtained from the Cameroon than in South Africa. A multiple-drug resistant C. dubliniensis strain isolated from the South African samples was inhibited only by 5-flucytosine in vitro on the YO9 panel. Drug resistance among oral Candida species is common among African HIV patients in these 2 countries. Regional surveillance of Candida species drug susceptibility should be undertaken to ensure effective treatment for HIV-positive patients.

Hipertensäo portal: anastomose esplenorrenal dital seletiva; análise de 134 intervençöes / Portal hypertension: distal spleno-renal anastomosis: analysis of 134 surgeries

Foi realizada anastomose esplenorrenal distal seletiva (AERS) em 134 pacientes, em um período de quatro anos, sendo 72 pacientes do sexo masculino e 62 do sexo feminino. Foram operados 30 pacientes em caráter de urgência (na vigência da hemorragia), 70 eletivamente (cessada a crise hemorrágica) e 34 foram submetidos à intervençäo em caráter profilático (näo apresentavam história de sangramento digestivo). A esquistossomose mansoni foi a causa da hipertensäo portal em 90% dos casos e a cirrose foi notada em 4,9%. A endoscopia, realizada na maioria dos pacientes, mostrou correlaçäo entre o calibre das varizes e a hemorragia digestiva. Nenhum dos pacientes endoscopados durante a hemorragia ou operados de urgência apresentou varizes finas. A intensidade da fibrose hepática näo está correlacionada com a hemorragia digestiva. A AERS reduz o tamanho do baço, sendo que em 1/4 dos casos ele se torna impalpável e em outro 1/4 se mantém com a ponta palpável. Näo foi possível realizar a AERS em seis pacientes (4,4% dos casos), sendo os quatro primeiros na fase de adestramento cirúrgico. A mortalidade operatória foi de nove pacientes (6,7%), sendo na urgência, 16,6%; eletiva, 4,2% e profilática, 2,9%. Observamos quatro pacientes com encefalopatia durante o seguimento tardio. Cinco pacientes (4,9%) tiveram recidiva hemorrágica precoce. Apenas observamos uma recidiva tardia até o momento - o seguimento foi de 84,4%. A avaliaçäo da morbidade operatória mostrou os seguintes dados: edema de membros inferiores, icterícia, diástase do músculo retoanterior do abdome, dor no hipocôndrio esquerdo, hepatite, coma, hérnia incisional, ascite quilosa, infecçäo urinária, abscesso subfrênico, trombose veia porta, hipertensäo pulmonar