A Phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis.

SETTING: Current treatment for pulmonary tuberculosis (TB) might be shortened by the incorporation of fluoroquinolones (FQs). OBJECTIVES: A Phase II study aimed to assess the sterilising activities of three novel regimens containing FQs before a Phase III trial of a 4-month regimen containing gatifloxacin (GFX). DESIGN: A total of 217 newly diagnosed smear-positive patients were randomly allocated to one of four regimens: isoniazid (INH), pyrazinamide and rifampicin (RMP) with either ethambutol, GFX, moxifloxacin (MFX) or ofloxacin (OFX) for 2 months. At the end of the study, RMP and INH were given for 4 months. The rates of elimination of Mycobacterium tuberculosis were compared in the regimens using non-linear mixed effects modelling of the serial sputum colony counts (SSCC) during the first 8 weeks. RESULTS: After adjustment for covariates, MFX substitution appeared superior during the early phase of a bi-exponential fall in colony counts, but significant and similar acceleration of bacillary elimination during the late phase occurred with both GFX and MFX (P = 0.002). Substitution of OFX had no effect. These findings were supported by estimates of time to conversion, using Cox regression, but there were no significant differences in proportions culture-negative at 8 weeks. CONCLUSIONS: GFX and MFX improve the sterilising activity of regimens and might shorten treatment; their progression into Phase III trials therefore seems warranted.

Superficial incisional infection in arthroplasty of the lower limb. Interobserver reliability of the current diagnostic criteria.

The Department of Health and the Public Health Laboratory Service established the Nosocomial Infection National Surveillance Scheme in order to standardise the collection of information about infections acquired in hospital in the United Kingdom and provide national data with which hospitals could measure their own performance. The definition of superficial incisional infection (skin and subcutaneous tissue), set by the Center for Disease Control (CDC), should meet at least one of the defined criteria which would confirm the diagnosis and determine the need for specific treatment. We have assessed the interobserver reliability of the criteria for superficial incisional infection set by the CDC in our current practice. The incisional site of 50 patients who had an elective primary arthroplasty of the hip or knee was evaluated independently by two orthopaedic clinical research fellows and two orthopaedic ward sisters for the presence or absence of surgical-site infection. Interobserver reliability was assessed by comparison of the criteria for wound infection used by the four observers using kappa reliability coefficients. Our study demonstrated that some of the components of the current CDC criteria were unreliable and we recommend their revision.

Characterization of Intracellular Activity of Antitubercular Constituents the Roots of Euclea natalensis.

Naphthoquinones and triterpenes isolated from the roots of Euclea natalensis. A.DC (Ebenaceae) were evaluated for their inhibitory activity against Mycobacterium tuberculosis.. Crude extract, diospyrin and 7-methyljuglone isolated from the plant, exhibited minimum inhibitory concentrations of 8.0, 8.0, and 0.5 µg ml-1, respectively, against M. tuberculosis. H37 Rv (ATCC 27294), a drug-sensitive strain. Minimum inhibitory concentrations (MICs) of 7- methyljuglone against a panel of clinical pan-sensitive and drug-resistant strains of M. tuberculosis. ranged from 0.32 to 1.25 µg/ml. The concentration of 7-methyljuglone that effected a 90% reduction of growth of M. tuberculosis. Erdman within J774.1 macrophages was 0.57 µg/ml. The superior intracellular and extracellular inhibition of M. tuberculosis. by 7-methyljuglone relative to that of the antituberculosis drugs streptomycin and ethambutol suggests that this compound be considered as a lead for further investigations.

Tuberculosis care in community care organizations in sub-Saharan Africa: practice and potential.

SETTING: Community care organizations in sub-Saharan Africa. OBJECTIVES: To evaluate current tuberculosis (TB) care in community health care organizations in sub-Saharan Africa, to assess their potential contribution to tuberculosis care, and to develop a model for expanded community participation in effective TB control. DESIGN: Quantitative assessment of tuberculosis care and cross-sectional assessment of qualitative measures in 14 community care organizations in Uganda, Zambia, South Africa and Malawi. RESULTS: The community care organizations assessed mainly provided care for human immunodeficiency virus (HIV) and aquired immune deficiency syndrome (AIDS) patients, and received funding from non-governmental organizations. Shortcomings in tuberculosis care included delays in diagnosis (which was often not based on sputum examination), drug shortages, low completion rates, high default rates, inadequate recording, little interaction with government tuberculosis programmes, and inadequate training of staff. However, one organization that provided primarily tuberculosis care and collaborated closely with the district tuberculosis programme and hospital attained a high treatment completion rate. The strong points of the community care organizations that favour a potential role of community participation in tuberculosis care were accessibility and staff motivation. CONCLUSION: Despite most community care organizations' shortcomings in tuberculosis care, they do have the potential to improve the care of tuberculosis patients, thus reducing the load on overstretched health facilities. Their potential impact on tuberculosis control depends on their population coverage and sustainability. HIV/AIDS community care organizations with strengthened management of tuberculosis care could serve as a model for expanded community participation in tuberculosis control. Operational research is needed to assess the feasibility and cost-effectiveness of community-based TB care.

Fixed dose combinations for tuberculosis: Lessons learned from clinical, formulation and regulatory perspective.

Worldwide, tuberculosis (TB) remains one of the most important communicable diseases in terms of morbidity and mortality. Its control requires multi-drug therapy for at least six months, which could lead to patient non-compliance, failure of therapy and ultimately resulting in the emergence of drug resistance. Fixed dose combinations (FDCs) in TB therapy reduce the number of tablets to be consumed and thereby increase patient compliance with recommended treatment regimens. Thus, FDCs play a significant role in preventing the emergence of drug resistance and successful treatment. However, the quality of FDCs with respect to variable bioavailability and their registration requirements are major hurdles to their implementation in national TB control programs. It is anticipated that a large global market for FDCs will encourage large-scale production and increased competition, which in turn will result in FDCs at affordable prices. The Global Drug Facility (GDF), established by the World Health Organization (WHO), aims to ensure universal uninterrupted access to quality TB drugs for implementation of directly observed treatment short-course (DOTS) in resource-poor countries. In this program, four FDCs were accepted as the drugs of first choice because of their obvious advantages in controlling TB. This demands the necessity of addressing quality and registration requirements of FDCs systematically. In light of this current knowledge on anti-TB FDCs, their dosage, combinations, available clinical studies and the experiences with TB therapy has been discussed in this article, which should serve as lessons for selection of appropriate FDCs for other diseases such as malaria and AIDS.

Bioactive compounds from Lippia javanica and Hoslundia opposita.

Lippia javanica and Hoslundia opposita are aromatic herbs that occur all over Mozambique and are well known for their medicinal properties. A Phytochemical investigation of L. javanica led to the isolation of eight compounds, 4-ethyl-nonacosane (1), (E)-2(3)-tagetenone epoxide (2), myrcenone (3), piperitenone (4), apigenin (5), cirsimaritin (6), 6-methoxyluteolin 4'-methyl ether (7), 6-methoxyluteolin and 3',4',7-trimethyl ether (8). Three known compounds, 5,7-dimethoxy-6-methylflavone (9), hoslunddiol (10) and euscaphic acid (11) were isolated from H. opposita. This is the first report of compounds 1, 2, 5-8 from L. javanica and of compound (9) from H. opposita. The compounds were tested against Mycobacterium tuberculosis and HIV-1 reverse transcriptase for bioactivity. It was found that compounds 2, 4 and 9 inhibited the HIV-1 reverse transcriptase enzyme by 91, 53 and 52%, respectively, at 100 microg mL(-1). Of all the compounds tested against a drug-sensitive strain of M. tuberculosis, euscaphic acid (11) was found to exhibit a minimum inhibitory concentration of 50 microg mL(-1) against this strain.

Videofluoroscopy in the assessment of feeding disorders of children with neurological problems.

A multidisciplinary assessment, including videofluoroscopy, was carried out on 14 children with feeding difficulties associated with neurological problems. Recommendations were made on all aspects of feeding and the trunk position was changed for half of the patients. A later interview with the parents confirmed that the recommendations had been helpful. The optimum trunk position for feeding was determined during videofluoroscopy by positioning the patient in the erect or reclined position, and also by analysis of relative difficulties during the oral and pharyngeal phases of swallowing. Those with difficulties mainly in the oral phase fed best in the reclined position; those with difficulties mainly in the pharyngeal phase fed best in the erect position, particularly if they had upper-oesophageal sphincter spasm in association with a tonic labyrinthine reflex.

The rationale for recommending fixed-dose combination tablets for treatment of tuberculosis.

There is considerable exigency to take all necessary steps to cure tuberculosis cases and prevent further emergence of drug-resistant tuberculosis. The most important of these steps is to ensure that the treatment, particularly of sputum smear-positive cases, is adequate and that patients adhere to their treatment by supervised, direct observation of drug-taking according to the standardized regimens. Use of fixed-dose combinations (FDCs) of tablets against tuberculosis is now being recommended by WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD) as an additional step to ensuring proper treatment. FDCs simplify the prescription of drugs and the management of drug supply, and may also limit the risk of drug-resistant tuberculosis arising as a result of inappropriate drug selection and monotherapy. Only FDCs of proven quality and proven rifampicin bioavailability should be purchased and used. In most situations, blood levels of the drugs are inadequate because of poor drug quality rather than poor absorption. This is true irrespective of the human immunodeficiency virus (HIV) infection status of the tuberculosis patients (other than those with overt acquired immunodeficiency syndrome, with CD4 counts < 200 cells/mm3). Currently, WHO, IUATLD and their partners are developing strategies for ensuring that only quality FDCs are used in tuberculosis programmes. A simplified and effective protocol for assessment of rifampicin bioavailability has been developed, and laboratories are being recruited to form a supranational network for quality assurance of FDCs. Standardization of FDC drug formulations has been proposed, which limits rifampicin-containing preparations to nine (including a four-drug FDC and three paediatric FDCs).