Current status and future trends in the diagnosis and treatment of drug-susceptible and multidrug-resistant tuberculosis

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.

New approaches in the diagnosis and treatment of susceptible, multidrug-resistant and extensively drug resistant tuberculosis

Tuberculosis [TB] is killing nearly two million people worldwide every year. The current global burden of TB is mainly due to the expanding human immunodeficiency virus infection and its association with active TB disease and increasing resistance of Mycobacterium tuberculosis strains to most-effective [first-line] anti-TB drugs. Incomplete/ improper treatment of TB patients leads to evolution of drug-resistant M. tuberculosis strains as a result of chromosomal mutations in genes encoding drug targets. Sequential accumulation of mutations in target genes generate multidrug-resistant [resistant atleast to rifampin and isoniazid] M. tuberculosis [MDR-TB] and extensively drug-resistant [additionally resistant to fluoroquinolones and an injectable anti-TB agent] M. tuberculosis [XDR-TB] strains. While proper treatment of susceptible TB has > 95% cure rate, effective treatment of MDR-TB is difficult in developing countries as it is heavily dependent on rapid diagnosis, supervised aggressive therapy with several [5 - 6] expensive, toxic and less efficacious drugs for 18 - 24 months and regular monitoring for bacteriological and clinical improvement. Treatment of XDR-TB is far more difficult even in developed countries. Several anti-TB drugs with novel mechanism of action are under clinical development, which may shorten treatment duration of susceptible TB to around three months and also help in effective treatment of MDR-TB / XDR-TB

Diagnosis of endocarditis caused by Mycobacterium abscessus

We report a fatal case of native valve endocarditis due to Mycobacterium abscessus in a hemodialysis patient. The diagnosis was based on culture isolation of acid-fast bacilli from peripheral blood and a permanent catheter tip, and their identification as M abscessus by a reverse hybridization-based assay and direct DNA sequencing of the 16S-23S internal transcribed spacer region. Rapid diagnosis and combination therapy are essential to minimize mortality due to this pathogen. Although combination therapy was started with clarithromycin and tigecycline, the patient refused to take clarithromycin due to severe abdominal pain. The patient became afebrile after therapy with tigecycline alone although bacteremia persisted. He was discharged against medical advice and readmitted three months later for persistent fever. His blood cultures again yielded M abscessus and a transesophageal echocardiogram showed two mobile vegetations. The patient was noncompliant with therapy and died due to cardiac arrest and multiorgan failure. This report shows that M abscessus should also be considered in the differential diagnosis of infective endocarditis in hemodialysis patients

Phenotypic and molecular characterization of candida dubliniensis isolates from clinical specimens in Kuwait

This study was carried out to characterize Candida dubliniensis using phenotypic and molecular methods and to determine the occurrence of C. dubliniensis in clinical specimens in Kuwait. A total of 880 clinical specimens for isolation of fungi were processed according to standard procedures. Of these, 390 germ-tube-positive clinical isolates of Candida species were examined for rough colonies with hyphal fringes and chlamydospore production on simplified sunflower seed agar for their presumptive phenotypicidentification as C. dubliniensis. The identification of C. dubliniensis isolates was further confirmed by the Vitek 2 yeast identification system, semi-nested [sn] PCR amplification of high-copy rDNA and direct DNA sequencing of the internally transcribed spacer 2 [ITS2] region. Of the 390 isolates of Candida species investigated, 12 were identified as C. dubliniensis, giving an overall occurrence of 3%. All the C. dubliniensis isolates formed rough colonies with hyphal fringes and abundant chlamydospores on sunflower seed agar, did not assimilate trehalose, lactate and alpha -methyl-D-glucoside, and were isolated from human immunodeficiency virus [HIV]-negative patients. Four C. dubliniensis isolates utilized D-xylose. The species-specific primer derived from the ITS2 sequence of C. dubliniensis and used together with the panfungal reverse primer in the reamplification step of the snPCR specifically amplified rDNA from reference and clinical C. dubliniensis isolates and not from C. albicans or other Candida species. The identity of two representative isolates was confirmed by DNA sequencing of the ITS2 region. The identity of 12 C. dubliniensis isolates was first established by phenotypic characteristics and then by snPCR using species-specific primers derived from ITS2 sequences. The recovery of C. dubliniensis from HIV-negative patients from Kuwait reinforces the existing view that this novel yeast species has a worldwide distribution and its occurrence is not restricted to any particular immunocompromised population

Emergence of imipenem resistant pseudomonas aeruginosa in a burns unit in Kuwait

pseudomonas aeruginosa resistant to imipenem with a minimum inhibitory concentration of>16 mg/L emerged during treatment of three patients with this drug in a Burns Unit. This is the first report of emergence of imipenem resistance in Kuwait