Invasive Pneumococcal Disease in Neonates Prior to Pneumococcal Conjugate Vaccine Use in South Africa: 2003-2008.

Background: Neonatal invasive pneumococcal disease (IPD) in developing countries is poorly described. We provide a baseline description of neonatal IPD in South Africa, before implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2009.

Methods: Data from children (age ≤ 2 years) with IPD (pneumococcus identified from a normally sterile specimen) from January 2003 to December 2008 were extracted from a national laboratory-based surveillance database.

Antimycobacterial, docking and molecular dynamic studies of pentacyclic triterpenes from Buddleja saligna leaves.

Buddleja saligna (family Buddlejaceae) is a medicinal plant endemic to South Africa. Two isomeric pentacyclic triterpenes, oleanolic acid and ursolic acid, were isolated from the leaves of B. saligna using silica gel column chromatography.

Detection of neonatal unit clusters of Candida parapsilosis fungaemia by microsatellite genotyping: Results from laboratory-based sentinel surveillance, South Africa, 2009-2010.

Neonatal candidaemia is a common, deadly and costly hospital-associated disease. To determine the genetic diversity of Candida parapsilosis causing fungaemia in South African neonatal intensive care units (NICUs). From February 2009 through to August 2010, cases of candidaemia were reported through laboratory-based surveillance.

Comparison of species-level identification and antifungal susceptibility results from diagnostic and reference laboratories for bloodstream Candida surveillance isolates, South Africa, 2009-2010.

From February 2009 through August 2010, we compared species-level identification of bloodstream Candida isolates and susceptibility to fluconazole, voriconazole, and caspofungin between diagnostic and reference South African laboratories during national surveillance for candidemia. Diagnostic laboratories identified isolates to genus/species level and performed antifungal susceptibility testing, as indicated. At a reference laboratory, viable Candida isolates were identified to species-level using automated systems, biochemical tests, or DNA sequencing; broth dilution susceptibility testing was performed.

Emergence of azole-resistant Candida parapsilosis causing bloodstream infection: results from laboratory-based sentinel surveillance in South Africa.

Objectives: To compare Candida species distribution and antifungal susceptibility at South African public- and private-sector hospitals.

Methods: From February 2009 through to August 2010, laboratory-based surveillance for candidaemia was undertaken at 11 public-sector hospitals and >85 private-sector hospitals across South Africa. A case was defined as a patient of any age admitted to a sentinel hospital with isolation of Candida species from blood culture.

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.

Comparison of Etests and Vitek 2 ® to broth microdilution for the susceptibility testing of Cryptococcus neoformans.

We determined the susceptibility of 102 clinical isolates Cryptococcus neoformans from Durban, South Africa, to amphotericin B, fluconazole, flucytosine, and voriconazole using broth microdilution (BMD) according to the Clinical and Laboratory Standards Institute M27-A3 document and compared these results with Etest and Vitek 2(®). Essential agreement (EA) of Etest and Vitek 2(®) compared to BMD was determined. Low MICs that were below the epidemiological cutoff values of the 4 antifungal agents tested were demonstrated by all isolates.

Rifampicin mono-resistance in Mycobacterium tuberculosis in KwaZulu-Natal, South Africa: a significant phenomenon in a high prevalence TB-HIV region.

Setting: The dual epidemics of HIV-TB including MDR-TB are major contributors to high morbidity and mortality rates in South Africa. Rifampicin (RIF) resistance is regarded as a proxy for MDR-TB. Currently available molecular assays have the advantage of rapidly detecting resistant strains of MTB, but the GeneXpert does not detect isoniazid (INH) resistance and the GenoTypeMTBDRplus(LPA) assay may underestimate resistance to INH.

Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study.

Background: Tuberculous meningitis (TBM) is difficult to diagnose promptly. The utility of the Xpert MTB/RIF test for the diagnosis of TBM remains unclear, and the effect of host- and sample-related factors on test performance is unknown. This study sought to evaluate the sensitivity and specificity of Xpert MTB/RIF for the diagnosis of TBM.

Clinical and mycological predictors of cryptococcosis-associated immune reconstitution inflammatory syndrome.

Objective: HIV-infected patients with treated cryptococcal meningitis are at risk for further neurological deterioration after commencing combination antiretroviral therapy (cART), mostly because of cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). Identifying predictors of C-IRIS could enable risk stratification.

Design: Prospective, longitudinal cohort study for 24 weeks.

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.

A comparative study of amoxicillin, clindamycin and chlorhexidine in the prevention of post-extraction bacteraemia.

We evaluated some of the regimens recommended for the antimicrobial prophylaxis of infective endocarditis prior to dental extraction in 160 patients. Group A patients served as the control group, group B subjects rinsed their mouths with chlorhexidene, group C subjects took 3 g amoxicillin orally and group D patients took 600 mg clindamycin orally. The proportion of patients who had post-extraction bacteraemia in groups A, B, C and D was 35, 40, 7.

An investigation of the frequency of bacteraemia following dental extraction, tooth brushing and chewing.

We conducted a study to determine the frequency of bacteraemias following dental extraction and common oral procedures, namely tooth brushing and chewing, and the relationship between bacteraemia and oral health in black patients. Positive blood cultures were detected in 29.6% of patients after dental extraction, in 10.

Novel polycyclic 'cage'-1,2-diamines as potential anti-tuberculosis agents.

A series of polycyclic 'cage' derivatives of N-geranyl-1,2 diamines were synthesized and screened for their anti-mycobacterial activity against H(37)Rv, multidrug resistant (MDR) and extensively drug-resistant (XDR) strains of tuberculosis. By substituting the adamantyl skeleton of SQ109 with trishomocubanyl (9), oxa-pentacycloundecyl (14, 16), pentacycloundecyl, PCU, (10, 15) and azapentacycloundecyl (22, 23), the effect of other polycyclic "cage" skeletons could be investigated. Compound 9 (trishomocubanyl moiety) proved to be the most active (MICs: 0.

Total synthesis of a depsidomycin analogue by convergent solid-phase peptide synthesis and macrolactonization strategy for antitubercular activity.

Depsidomycin is a cyclic heptadepsi-peptide isolated from the cultured broth of Streptomyces lavendofoliae MI951-62F2. It exhibits significant antimicrobial and immunosuppressive activity. The total synthesis of a depsidomycin analogue in which 1,2-piperazine-3-carboxylic acid was substituted with proline is described.

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.

In vitro antifungal and antibacterial activities of pentacycloundecane tetra-amines.

The antifungal and antimicrobial activities of three pentacycloundecane (PCU) tetra-amine derivatives are reported herein. The in vitro activity of these PCU derivatives against yeasts (Candida albicans and non-albicans species) and filamentous fungi was evaluated using the Clinical and Laboratory Standards Institute (CLSI) M27-A2 and M38-A2 guidelines and the 2H-tetrazolium salt, (MTS) colorimetric method. The minimum inhibitory concentration against most of the tested clinical fungal strains for GKM8 and GKM9 derivatives ranges from 15.

Blood cultures for the diagnosis of multidrug-resistant and extensively drug-resistant tuberculosis among HIV-infected patients from rural South Africa: a cross-sectional study.

Background: The yield of mycobacterial blood cultures for multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) among drug-resistant TB suspects has not been described.

Methods: We performed a retrospective, cross-sectional analysis to determine the yield of mycobacterial blood cultures for MDR-TB and XDR-TB among patients suspected of drug-resistant TB from rural South Africa. Secondary outcomes included risk factors of Mycobacterium tuberculosis bacteremia and the additive yield of mycobacterial blood cultures compared to sputum culture.

Cerebrospinal T-cell responses aid in the diagnosis of tuberculous meningitis in a human immunodeficiency virus- and tuberculosis-endemic population.

Rationale: Current tools for the rapid diagnosis of tuberculous meningitis (TBM) are suboptimal. We evaluated the clinical utility of a quantitative RD-1 IFN-gamma T-cell enzyme-linked immunospot (ELISPOT) assay (T-SPOT.TB), using cerebrospinal fluid cells for the rapid immunodiagnosis of TBM.

Extensively drug-resistant Mycobacterium tuberculosis from aspirates, Rural South Africa.

The yield from aspirating lymph nodes and pleural fluid for diagnosing extensively drug-resistant (XDR) tuberculosis is unknown. Mycobacterium tuberculosis was cultured from lymph node or pleural fluid aspirates of 21 patients; 7 (33%) cultures grew XDR M. tuberculosis.

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.

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.

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.