Three hundred and forty eight critically-ill patients with a documented Gram-negative infection were randomized to receive amikacin once- (od) or twice-daily (bd). The amikacin was given by slow intravenous injection in a daily dose of 20 mg/kg in patients under the age of one year (paediatric group) and 15 mg/kg in patients over the age of one year (adult group). Paediatric and adult patients on the od regimen received a loading dose of 25 and 20 mg/kg respectively. The dosages were subsequently adjusted to achieve desirable blood levels. Patients received other antibiotics as clinically indicated. Forty-eight patients were withdrawn from the study due to death or azotaemia occurring in the first 72 h. One hundred and fifty five patients (76 paediatric) received an od dose and 145 (65 paediatric) received a bd dose. The clinical cure rate was 83% in the od group compared to 66% in the bd group (P = 0.001). The bacteriological cure rate was 81% in the od group compared to 58% in the bd group (P = 0.005). In the paediatric sub-group the cure rate was higher with the od regimen (P = 0.002) but this difference was not statistically significant in the adult patients (P = 0.1). The serum creatinine rose in 35% of patients in the bd group compared to 21% in the od group (P = 0.05). Although audiometry was not performed there was no clinical evidence of ototoxicity in any of the patients. In conclusion od amikacin dosing resulted in a higher cure and less nephrotoxicity than conventional bd dosing.

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We aimed to assess the pharmacokinetics of vancomycin in critically ill infants, and to evaluate the standard recommended dose oJ 10 mglkg 6 hourly. All infanfs admitted to the Baragwanath Hospital fCU who had arterial lines in situ, and for whom vancomycin 10 mg/kg 6 hourly was prescrib"ed for an infectiVe insult and who had parental consent, were included in the study. Vancomycin was infused over 60 minutes. Serum samples were taken immediately before the dose and at 30, 60, 120 and 300 minutes after the end of the vancomycin infusion, on days 2 and 8 of therapy. Extrapolated peak concentration (Cmax), trough concentration (Cm in), apparent volume of distribution (Vd), elimination half-life (tOe!) and clearance (CL) were determined for each patient. Day 2 values were compared with those of day 8. Day 2 serum concentrations were assayed on 20 patients and day 8 concentrations in 15. The mean vancomycin Vd on day 2 (0.81I1kg) was significantly (P=0.007) larger than that on day 8 (0.44 IIkg). The change in Vd resulted in a significant change in mean Cmax (29.1 vs 35.5 p.g/ml) (P=0.02) and mean tOe! (5.3 vs 3.4h) (P=O.OI) over the treatment period. Critically ill infants displayed a large initial volume of distribution which probably resulted from aggressive fluid resuscitation. This also results in a large variation in other pharmacokinetic parameters, namely Cmax and tOe!' Although the routine monitoring of vancomycin serum concentrations remain controversial, we feel that in view of these large pharmacokinetic variations, the critically ill infant is a specific group where monitoring of vancomycin serum levels is indicated.

The pharmacokinetics of 400 mg of ciprofloxacin given intravenously (i.v.) every 8 h (q8h) in severely septic adults was documented in a multidisciplinary, tertiary referral intensive care unit (ICU). Sixteen evaluable patients (three pharmacokinetic profiles) without renal dysfunction and with severe sepsis were studied. Ciprofloxacin at a dosage of 400 mg given i.v. q8h was administered over 1 h. Plasma samples for assay (high-pressure liquid chromatography) were taken at timed intervals (preinfusion, at the end of infusion, and at 1, 2, 3, 5, and 7 h postinfusion) for first-dose kinetics (day 0 [D0]), D2, and between D6 and D8. All pharmacokinetic variables were calculated by noncompartmental methods. Standard intensive care was provided. Peak ciprofloxacin concentrations were as follows: D0, 6.01 ± 1.93 mg/liter; D2, 6.68 ± 2.01 mg/liter; and D6 to D8 6.45 ± 1.54 mg/liter. Trough levels were as follows: D0, 0.6 ± 0.5 mg/liter; D2, 0.7 ± 0.4 mg/liter; and D6 to D8 0.6 ± 0.4 mg/liter. The areas under the concentration curves (8 h) were as follows: D0, 13.3 ± 3.8 mg · h/liter; D2, 16.8 ± 5.4 mg · h/liter; and D6 to D8, 15.5 ± 4.7 mg · h/liter. No drug-related serious adverse events occurred. For 17 of 18 patients enrolled in the study, the causative organisms were susceptible to ciprofloxacin. One patient developed renal failure (non-drug related) after the administration of three doses of ciprofloxacin. One patient was infected with ciprofloxacin-resistant organisms on enrollment. Nine of 16 evaluable patients had clinical cures, and 8 had bacteriological cures. One patient developed a ciprofloxacin-resistant superinfection. In two patients the clinical course was indeterminate. Two bacteriological failures occurred. We conclude that in critically ill adults ciprofloxacin at a dosage of 400 mg given i.v. q8h is safe. Its pharmacokinetic profile provides bactericidal activity against most organisms encountered in an ICU. Except for some initial accumulation on D2, no further accumulation occurred in patients without renal failure. Ciprofloxacin should be administered i.v. at a dosage of 400 mg q8h for severe sepsis.

Background: Studies have been done to determine the level of burnout in anaesthesiology internationally, but not in South Africa. Method: The Maslach Burnout Inventory-Human Services Survey was used to assess the level of burnout. The primary objectives were to estimate the level of burnout among doctors working in the Department of Anaesthesiology at the University of the Witwatersrand (Wits doctors) and to estimate the level of burnout among private anaesthetist attending an anaesthetic symposium (Private doctors). Results: High levels of burnout were identified in 21.0% of Wits doctors. Higher burnout scores were noted in female doctors (p = 0.49), less years of anaesthetic experience (p = 0.37), doctors of younger age (p = 0.07), registrars (p = 0.22) and writing examinations within three months of completing the survey (p = 0.15), but none where statistically significant. High levels of burnout were identified in 8.1% of Private doctors Conclusion: High levels of burnout were identified, especially, among anaesthetists working in the academic hospitals affiliated to Wits.

Background and objectives. Hospital-acquired infections (HAIs) are largely preventable through risk analysis and modification of practice. Anaesthetic practice plays a limited role in the prevention of HAIs, although laryngoscope use and decontamination is an area of concern. We aimed to assess the level of microbial contamination of re-usable laryngoscope blades at a public hospital in South Africa. Setting. The theatre complex of a secondary-level public hospital in Johannesburg. Methods. Blades from two different theatres were sampled twice daily, using a standardised technique, over a 2-week period. Samples were quantitatively assessed for microbial contamination, and stratified by area on blade, theatre and time using Fisher's exact test. Results. A contamination rate of 57.3% (63/110) was found, with high-level contamination accounting for 22.2% of these. Common commensals were the most frequently isolated micro-organisms (79.1%), but important hospital pathogens such as Enterobacter species and Acinetobacter baumannii were isolated from blades with high-level contamination. No significant difference in the level of microbial contamination by area on blade, theatre or time was found (p<0.05). Conclusions. A combination of sub-optimal decontamination and improper handling of laryngoscopes after decontamination results in significant microbial contamination of re-usable laryngoscope blades. There is an urgent need to review protocols and policies surrounding the use of these blades.

There was no accumulation of drug even after 7 days of administration. Our C(max) and AUC were lower than that achieved in a similar adult pharmacokinetic study. To achieve end points of area under the inhibitory curve (AUIC) of 100-150 mg/h per l, 10 mg/kg ciprofloxacin eight hourly would be required for some resistant ICU organisms.

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