␤-Lactamase production was investigated in cultures of 25 Klebsiella pneumoniae isolates isolated at a hospital in Durban, South Africa, in 1994 and 1996. Twenty of these isolates gave ceftazidime MIC/ceftazidime plus clavulanate MIC ratios of >8, implying production of extended-spectrum ␤-lactamases (ESBLs), and DNA sequencing identified an ESBL gene (bla TEM-53 ) in a further two isolates. Pulsed-field gel electrophoresis (PFGE) defined 4 distinct strains among the 12 isolates collected in 1994 and 9 distinct strains among the 13 isolates collected in 1996. In three cases, multiple isolates from single patients varied in their PFGE profiles and antibiograms, implying mixed colonization or infection. Isoelectric focusing and DNA hybridization found both TEM and SHV enzymes and their genes in all 25 isolates. Many isolates had multiple identical or different ␤-lactamase gene variants, with at least 84 bla SHV and bla TEM gene copies among the 25 organisms. Sequencing identified the genes for the SHV-1, -2, and -5 enzymes and for four new SHV types (SHV-19, -20, -21, and -22). These new SHV variants had novel mutations remote from sites known to affect catalytic activity. Sequencing also found the genes for TEM-1, TEM-53, and one novel type, TEM-63. All the isolates had multiple and diverse plasmids. These complex and diverse patterns of ESBL production and strain epidemiology are far removed from the concept of an ESBL outbreak and suggest a situation in which ESBL production has become endemic and in which evolution is generating a wide range of enzyme combinations. This complexity and diversity complicates patient management and the design of antibiotic use policies.␤-Lactams are prescribed more often than any other antibiotics. This heavy usage has selected for resistance, which is most often caused by ␤-lactamases (17). Recent concerns have centered on extended-spectrum ␤-lactamases (ESBLs), which are an increasing problem in members of the family Enterobacteriaceae in general and especially in Klebsiella spp.Most ESBLs are variants of the classical TEM and SHV ␤-lactamases, but with one or more amino acid substitutions (22, 25; G. A. Jacoby and K. Bush, Amino acid sequences for TEM, SHV, and OXA extended-spectrum and inhibitor-resistant ␤-lactamases [http://www.lahey.org/studies/webt.htm]). These changes alter the catalytic center, permitting hydrolysis of oxyimino-aminothiazolyl cephalosporins. ESBLs have been reported worldwide, but most studies have examined producers collected in Europe, North America, and Southeast Asia (17, 25), and only a few (2) have examined bacteria collected in Africa (20). To redress this situation, we investigated ␤-lactamase types, including ESBLs, in nosocomial Klebsiella pneumoniae isolates collected at a major teaching hospital in Durban, Kwazulu-Natal, South Africa.Although the primary purpose of the study was identification of the types of enzymes produced in South African isolates, the major finding was the remarkable diversity and complexity of ␤-lactamase and strain ty...

Risk factors associated with PIGE may have a synergistic effect. Bacterial plaque, however, appears the most important determinant of PIGE severity. This latter finding emphasises the importance of instituting a preventive plaque-control programme, particularly in young patients on phenytoin therapy.

Although contraceptives, including emergency contraceptives, are widely available free at public health facilities in South Africa, rates of teenage and unintended pregnancy are high. This paper analyses awareness and utilisation of emergency contraception amongst 193 young women (aged 15-24 years) attending public sector health facilities. Structured interviews were held at 17 and 14 primary health clinics in an urban and a rural area respectively. Respondents were asked about their knowledge of contraceptive methods and use, and specifically about emergency contraceptive utilisation. More sexually active young urban women (76%) were currently using a method of contraception, compared to the young rural women (53%). Only 17% had ever heard of emergency contraception, although significantly more in the urban area (p = 0.005) had heard of it. Only one woman from each site had ever used emergency contraception, although 39% had had unprotected intercourse in the previous year when they did not wish to conceive. Young South African women should be the focus of interventions aimed at improving awareness of the availability of emergency contraception and knowledge about its correct utilisation. RésuméOccasions manquées: ultilisation de la contraception d'urgence par les jeunes femmes sud-africaines. Bien que les contreceptifs, y compris les contraceptifs d'urgence soient généralement disponibles et à titre gratuit dans les établissements de santé publics en Afrique du Sud, les taux de grossesse chez les adolescentes et de grossesses non-voulues sont élevés. Cet article fait une analyse de la conscience et de l'utilisation de la contraception d'urgence chez 193 jeunes femmes (âgées de 15 à 24 ans) qui fréquentent des établissements de santé du secteur public. Des interviews structurées ont eu lieu dans 17 et 14 centres de santé primaires dans un milieu rural et un milieu urbain respectivement. Les répondantes ont répondu aux questions sur leur connaissance des méthodes et de l'utilisation des contraceptifs et surtout sur l'utlisation du contraceptif d'urgence. Il y avaient plus des jeunes femmes rurales sexuellement actives (76%) qui utilisaient actuellement une méthode de contraception comparées aux jeunes femmes rurales (53%). Il n'y avait que 17% qui avaient jamais entendu parler de la contraception d'urgence, bien qu'un nombre plus important dans le milieu urbain (p = 0,005) en aient jamais entendu parler. Il n' y avait qu' une seule femme de chaque milieu qui ait jamais utilisé une contraception d'urgence quoique 39% aient eu des rapports sexuels nonprotégés au cours de l'année précédente, quand elles ne voulaient pas avoir des enfants. Il faut que les interventions qui visent l'amélioration de la conscience concernant la disponibilité de la contraception d'urgence et la connaissance de la bonne utlisation de la contraception soient concentrées sur les jeunes femmes sud-africaines. (Rev Afr Santé Reprod 2004; 8[2]: 137-144)

An open, non-randomized trial of continuous infusion therapy was conducted involving five patients with severe haemophilia A who required factor VIII (FVIII) prophylaxis for elective surgery. This was preceded by a 24-h preoperative pharmacokinetic study to characterize the pharmacokinetic parameters of each individual patient following a bolus dose of the intermediate-purity product. A retrospective matched control group was identified to allow for comparisons of FVIII usage between bolus and continuous infusion administration. A loading dose of FVIII was administered preoperatively, and the continuous infusion was started at the end of surgery and continued for 5 days. The patients' FVIII levels, vital signs, and infusion sites were monitored on a daily basis. The clearance was re-calculated on a daily basis using the FVIII activity of that day to adjust the infusion rate to achieve the desired FVIII level. The mean (CV%) pharmacokinetic parameters estimated preoperatively by noncompartmental analysis were: clearance 3.2 mL kg-1 h-1 (35.5%), volume of distribution 52.1 mL kg-1 (40.2%), mean residence time 17.4 h (23.3%), and half-life 12.7 h (23.6%). A progressive decrease in the clearance of FVIII from a mean of 3.1 mL kg-1 h-1 to 2.0 mL kg-1 h-1 (P = 0.125) over the first 5 days was observed. A therapeutically acceptable level of FVIII was systematically achieved, with the only complication being frequent thrombophlebitis. On average the patients used 19% less FVIII when compared with matched historical controls (P = 0.25). This method was found to be safe and effective in haemophilia A patients undergoing elective surgery procedures.

The influence of various covariates (including weight, race, smoking, gender, age, mild-to-moderate alcohol intake, and body surface area) on the population pharmacokinetic parameters of phenytoin in adult epileptic patients in South Africa was investigated. The parameters were the maximum metabolic rate (Vm) and the Michaelis-Menten (MM) constant (Km) of phenytoin. The study population comprised 332 black and colored epileptic patients (note: "black" refers to indigenous people of South Africa, who speak one of the Bantu languages as their native language; "colored" refers to people considered to be of mixed race, classified as such by the apartheid former government of South Africa). The influence of covariates on Vm and Km estimates was determined using nonlinear mixed-effects modeling (NONMEM). Parameter models describing the factors that could potentially influence Vm and Km were tested using the Michaelis-Menten parallel MM and first-order elimination models, to which 853 steady state dose-to-serum concentration pairs were fitted. The results indicated that body weight, smoking, race, and age (65 years or older), in descending order of importance, significantly influenced Vm (p < 0.05). Although a significant difference (p = 0.03) in Km was found between black and colored patients, incorporating the influence of race in Km in the final regression model did not improve the fit of the model to the data, which indicated that the variability in Km was accounted for by Vm. The scaling factors for smoking, colored patients and age (65 years or older) in Vm were 1.16, 1.10, and 0.88, respectively. These factors should be taken into account when adjusting phenytoin dose.