Primary Capreomycin Resistance Is Common and Associated With Early Mortality in Patients With Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa.

BACKGROUND: Capreomycin is a key antimycobacterial drug in treatment of extensively drug-resistant tuberculosis (XDR-TB). Drug-susceptibility testing (DST) for capreomycin is not routinely performed in newly diagnosed XDR-TB in South Africa. We performed this study to assess the prevalence, clinical significance, and molecular epidemiology of capreomycin resistance in newly diagnosed patients with XDR-TB in KwaZulu-Natal, South Africa. METHODS: Retrospective cohort study of consecutive patients with XDR-TB admitted to a TB referral hospital without previous XDR-TB treatment. A subset of isolates had extended DST (including capreomycin), mutational analysis, and IS6110 restriction fragment length polymorphism assays. RESULTS: A total of 216 eligible patients with XDR-TB were identified. The majority were treated with capreomycin (72%), were young (median age: 35.5 years), and were female (56%). One hundred five (76%) were HIV+, and 109 (66%) were on antiretroviral therapy. A subset of 52 patients had full DST. A total of 47/52 (90.4%) patients with XDR-TB were capreomycin resistant. Capreomycin-resistant patients experienced worse mortality and culture conversion than capreomycin susceptible, although this difference was not statistically significant. The A1401G mutation in the rrs gene was associated with capreomycin resistance. The majority of capreomycin-resistant strains were F15/LAM4/KZN lineage (80%), and clustering was common in these isolates (92.5%). CONCLUSIONS: Capreomycin resistance is common in patients with XDR-TB in KwaZulu-Natal, is predominantly because of ongoing province-wide transmission of a highly resistant strain, and is associated with high mortality. Capreomycin should be included in routine DST in all patients with XDR-TB. New drug regimens that do not include injectable agents should be operationally tested as empiric treatment in XDR-TB.

Synthesis and antitubercular activity of 2-(substituted phenyl/benzyl-amino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium chlorides.

A series of 2-(substituted phenyl/benzyl-amino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium chlorides 7-13 and 15 was synthesized in their hydrochloride salt form. The title compounds were characterized by FT-IR, NMR ((1)H and (13)C) and elemental analysis. They were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, multidrug resistance tuberculosis and extensively drug resistance tuberculosis by agar diffusion method and tested for the cytotoxic action on peripheral blood mononuclear cells by MTT assay. Among all the tested compounds in the series, compounds 7 and 11 emerged as promising antitubercular agents at 16 µg/mL against multidrug resistance tuberculosis and over 64 µg/mL against extensively drug resistance tuberculosis. The conformational features and supramolecular assembly of the promising compounds 7 and 11 were determined by single crystal X-ray study.

An outbreak of foodborne salmonellosis in rural KwaZulu-Natal, South Africa.

BACKGROUND: Salmonella enterica serotype Enteritidis is a universally recognized cause of foodborne disease. In South Africa, outbreaks of foodborne disease are generally under reported. We investigated the etiology of acute gastroenteritis in 216 patients who presented to a rural hospital in KwaZulu-Natal, South Africa, after consuming a meal at a school function. MATERIALS AND METHODS: Stool specimens from 37 patients, as well as two food samples, were available for microbiological investigation. Similarity between isolates was investigated using phenotypic and genotypic techniques. Phenotypic investigations included morphological, biochemical, and antibiogram profiling. Genotypic relatedness was determined with pulsed-field gel electrophoresis analysis. The available epidemiological data were also described. RESULTS: Salmonella Enteritidis was isolated from 18 patients and 1 food sample. Isolates were phenotypically and genotypically indistinguishable. Epidemiological data suggest a point-source outbreak with a possibility of continued transmission. CONCLUSIONS: The results suggest a foodborne Salmonella Enteritidis outbreak due to contaminated food served at the school function. Epidemiological investigations continue to be extremely difficult in rural areas.

The aetiology of acute community acquired bacterial meningitis in children and adults in Maputo, Mozambique.

BACKGROUND: Community-acquired acute bacterial meningitis is a life-threatening infection and many outbreaks have been reported all around the world. METHODOLOGY: We analysed 330 cerebrospinal fluid (CSF) samples received over a period of eight months from patients older than one month. Microscopy, cultures, identification, and antigen detection were performed for the positive samples. RESULTS: Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type b were isolated in 5.4%, 4.8%, and 3.6% of CSF samples respectively. CONCLUSIONS: Our findings indicate that N. meningitidis is the most common cause of acute bacterial meningitis in Mozambique and that H. influenzae type b was isolated only from children aged younger than six years. This is the first study to provide data on the aetiological agents of acute bacterial meningitis in children and adults in Mozambique.

Intravenous glucose preparation as the source of an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae infections in the neonatal unit of a regional hospital in KwaZulu-Natal.

In the last week of May 2005, staff at Mahatma Gandhi Memorial Hospital in KwaZulu-Natal realised that many babies in the high-care nursery ward had bloodstream infections involving Klebsiella pneumoniae bacteria. Attempts to identify a common source of infection failed. The ward was therefore closed and new babies needing high care were admitted to another empty ward. Despite this, babies still became infected. This resulted in a request for assistance from the Department of Medical Microbiology of the Nelson R Mandela School of Medicine. A search for common factors through case history studies of the 26 infected babies showed that blood cultures of the babies remained positive despite the administration of appropriate antibiotics. Different options that could explain this were investigated. The organism was found in intravenous glucose preparations used for multiple dosing. Unopened vials of the same medication were sterile. The nursery was found to lack proper hand-wash facilities and to be overcrowded and understaffed. Reinforcement of hand hygiene and a ban on the multiple dosing of medicines stopped the outbreak. In conclusion, this outbreak resulted from a combination of factors among which lack of hand hygiene and multiple dosing of an intravenous glucose preparation were most significant.

Lower dose of ciprofloxacin is adequate for the treatment of Neisseria gonorrhoeae in KwaZulu Natal, South Africa.

The response of male gonococcal urethritis to a single 250 mg dose of ciprofloxacin versus 500 mg was studied. Both regimens were given in combination with doxycycline in the context of the local syndromic management protocol. There was no significant difference in response between the regimens, inclusive/exclusive of tetracycline susceptible isolates. One patient in the 250 mg arm failed to respond clinically but was microbiologically cured and four patients in the 500 mg arm failed microbiologically but responded clinically. All four isolates had ciprofloxacin MICs