The global burden of tuberculosis (TB) is still large. The increasing incidence of drug-resistant, multidrug-resistant (MDR) (resistant to at least rifampicin and isoniazid), and extensively drug-resistant (XDR) (additionally resistant to a fluoroquinolone and kanamycin/amikacin/capreomycin) strains of Mycobacterium tuberculosis and the association of active disease with human immunodeficiency virus coinfection pose a major threat to TB control efforts. The rapid detection of M. tuberculosis strains and drug susceptibility testing (DST) for anti-TB drugs ensure the provision of effective treatment. Rapid molecular diagnostic and DST methods have been developed recently. Treatment of drug-susceptible TB is effective in ≥95% of disease cases; however, supervised therapy for ≥6 months is challenging. Non-adherence to treatment often results in the evolution of drug-resistant strains of M. tuberculosis due to mutations in the genes encoding drug targets. Sequential accumulation of mutations results in the evolution of MDR and XDR strains of M. tuberculosis. Effective treatment of MDR-TB involves therapy with 5-7 less effective, expensive, and toxic second-line and third-line drugs for ≥24 months and is difficult in most developing countries. XDR-TB is generally an untreatable disease in developing countries. Some currently existing drugs and several new drugs with novel modes of action are in various stages of development to shorten the treatment duration of drug-susceptible TB and to improve the outcome of MDR-TB and XDR-TB.
Tuberculosis (TB) is a major infectious disease killing nearly two million people, mostly in developing countries, every year. The increasing incidence of resistance of Mycobacterium tuberculosis strains to the most-effective (first-line) anti-TB drugs is a major factor contributing to the current TB epidemic. Drug-resistant strains have evolved mainly due to incomplete or improper treatment of TB patients. Resistance of M. tuberculosis to anti-TB drugs is caused by chromosomal mutations in genes encoding drug targets. Multidrug-resistant (resistant at least to rifampin and isoniazid) strains of M. tuberculosis (MDR-TB) evolve due to sequential accumulation of mutations in target genes. Emergence and spreading of MDR-TB strains is hampering efforts for the control and management of TB. The MDR-TB is also threatening World Health Organization's target of tuberculosis elimination by 2050. Proper management of MDR-TB relies on early recognition of such patients. Several diagnostic methods, both phenotypic and molecular, have been developed recently for rapid identification of MDR-TB strains from suspected patients and some are also suitable for resource-poor countries. Once identified, successful treatment of MDR-TB requires therapy with several effective drugs some of which are highly toxic, less efficacious and expensive. Minimum treatment duration of 18-24 months is also long, making it difficult for health care providers to ensure adherence to treatment. Successful treatment has been achieved by supervised therapy with appropriate drugs at institutions equipped with facilities for culture, drug susceptibility testing of MDR-TB strains to second-line drugs and regular monitoring of patients for adverse drug reactions and bacteriological and clinical improvement.
Bloodstream infections due to Candida species are important complications in severely ill hospitalized patients. This study presents data on species distribution and antifungal susceptibility profiles of Candida bloodstream isolates obtained from Kuwait during a 10-year period. All the bloodstream isolates were identified to species level by the germ tube test and carbohydrate assimilation profile using the VITEK 2 yeast identification system. Using E-test strips for amphotericin B, fluconazole, 5-flucytosine and voriconazole, MICs were determined on RPMI agar supplemented with 2 % glucose. The MIC breakpoints for resistance were based on Clinical and Laboratory Standards Institute criteria or those published by reference laboratories, and were as follows: amphotericin B, >1 mg ml . In all, 607 bloodstream yeast isolates were obtained over the past 10 years in Kuwait. Candida albicans was the predominant species (39.5 %), followed by Candida parapsilosis (30.6 %), Candida tropicalis (12.4 %), Candida glabrata (5.6 %) and Candida krusei (1.6 %). All C. albicans, C. tropicalis and C. glabrata isolates were susceptible to amphotericin B. Of 186 isolates of C. parapsilosis tested, only four (2 %) exhibited an MIC for amphotericin B of >1 mg ml "1 . Resistance to fluconazole was observed in nine (3.8 %) C. albicans isolates, two (5.8 %) C. glabrata isolates and four (40 %) C. krusei isolates. Resistance to 5-flucytosine was observed in two (0.8 %) C. albicans isolates, seven (9.3 %) C. tropicalis isolates, three (1.6 %) C. parapsilosis isolates and all ten (100 %) C. krusei isolates. All the isolates of C. albicans, C. tropicalis, C. parapsilosis, C. glabrata and C. krusei were susceptible to voriconazole, including those resistant to fluconazole. Although amphotericin B and fluconazole are widely used in clinical practice in Kuwait, resistance to these drugs remained low. INTRODUCTIONCandida species are one of the major causes of nosocomial bloodstream infections worldwide (Jarvis, 1995;. Despite the availability of an expanded antifungal armamentarium, the mortality associated with invasive Candida infections remains high, ranging between 19 and 49 % (Blot et al., 2002;Alonso-Valle et al., 2003;Gudlaugsson et al., 2003;Morgan, 2005). The incidence and associated mortality due to candidaemia can be influenced by several factors including characteristics of the population at risk, standard of the healthcare facilities available, distribution of Candida species and prevalence of resistance (Hobson, 2003;Eggimann et al., 2003). Hence, epidemiological information available for one centre or geographical region may not be applicable to others (Hobson, 2003). The increased isolation rates of non-albicans Candida species and a gradual shift in the antifungal susceptibility profile, especially against azole antifungal agents, have underlined the need to monitor laboratory data for possible emergence of resistance and to select the most appropriate antifungal agent for therapy (Sanglard & Odds, 2002;Eggimann et al., 2003). C...
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