A total of 272 patients were enrolled into this prospective, unblinded, randomized comparison of single-dose
teicoplanin vs three doses of
cephradine plus
metronidazole as prophylaxis for
vascular surgery at St James's and Seacroft Hospitals, Leeds, UK. In all, 71.3% of patients (194/272) were enrolled at St James's University Hospital. Patients received either a single dose of
teicoplanin, 6 mg/kg i.v., or
cephradine, 1 g i.v. with
metronidazole, 1 g rectally, at induction of anaesthesia followed by two further 1 g doses of
cephradine and
metronidazole 8 and 16 hours later. There were 136 patients in each treatment group. The most common operations were femoropopliteal grafts (96) and
aortic aneurysm repairs (47). In the 'intention-to-treat' analysis, primary
wound infections were seen in 4.4% of patients (6/136) receiving
teicoplanin and 5.9% of patients (8/136) receiving
cephradine plus
metronidazole (95% CI -6.7%, +3.8%). Other disturbances to wound healing occurred in 23 patients (11 in the
teicoplanin and 12 in the
cephradine plus
metronidazole group). Secondary
respiratory tract infections occurred in 17 patients (8 receiving
teicoplanin and 9 receiving
cephradine plus
metronidazole). In the evaluable patients analysis, primary
wound infections occurred in 3.5% of patients (4/114) receiving
teicoplanin and 5.1% of patients (6/117) receiving
cephradine plus
metronidazole. Staphylococcus aureus and Proteus sp. were the most common pathogens in primary
wound infections. Despite the absence of Gram-negative cover in the
teicoplanin group, Gram-negative
infections occurred more often in the
cephradine plus
metronidazole group. Surgery of the lower extremities carried the highest risk of post-operative
infection. Rates of
infection were significantly higher at Seacroft Hospital (P = 0.001), and significantly higher for
cephradine plus
metronidazole between the two hospitals (P = 0.0008). Adverse events occurred in 40 patients receiving
teicoplanin (29.4%) and 39 patients receiving
cephradine plus
metronidazole (28.7%). In 19 patients receiving
teicoplanin (14%) and 15 receiving
cephradine plus
metronidazole (11%) these events were considered to be related to the study drugs. The most often reported events were
infections,
cardiac events and vascular phenomena (haematoma or emboli). Marked changes in haematological parameters and liver function tests were noted seven days after operation in patients in each treatment group, but these resolved quickly as the effects of the operation subsided. ESR remained elevated in both groups at the six-month follow-up assessment. It is concluded from this two-centre study that a single dose of
teicoplanin shows similar efficacy to a three-dose regimen of
cephradine plus
metronidazole as prophylaxis for
wound infection in
vascular surgery. Both regimens were well tolerated, and there was an equal incidence of adverse events in the two regimens, which reflected the poor general health status of this elderly study population.