A comparison of teicoplanin versus cephradine plus metronidazole in the prophylaxis of post-operative infection in vascular surgery.

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.

Ultrasound-guided unilateral neck exploration for sporadic primary hyperparathyroidism: is it worthwhile?

The role of preoperative localisation tests before initial neck exploration for primary hyperparathyroidism (PHP) remains controversial, as does the optimal surgical approach. We report our experience with preoperative ultrasound (US) and the operative management of sporadic PHP between 1990 and 1995. Preoperative US was carried out by an experienced radiologist. Three surgeons adopted a policy of 'selective' US-guided unilateral neck exploration (UNE); the fourth surgeon performed routine bilateral neck exploration (BNE). There were 72 patients: 26 men and 46 women, with a mean age of 57.4 +/- 12.5 years (range 21-80 years). All patients underwent initial neck exploration for 'sporadic' PHP, of whom 63 had preoperative US. This was positive in 52 patients; 27 of whom underwent a UNE, 23 had a BNE, and two patients had a UNE converted to a BNE. Patients with 'negative' US (n = 11), and those receiving no preoperative localisation test (n = 90) underwent a BNE. The sensitivity, specificity and accuracy of US were 80% (52/65), 100% (61/61), and 90% (113/126), respectively. Comparable success rates were achieved (BNE: 97% (33/34) vs UNE: 93% (27/29), P < 0.05), with very low morbidity. Failures with the scan-guided UNE were caused by missed contralateral adenomas. An experienced radiologist and a low incidence of multiglandular disease (MGD) are essential prerequisites for the scan-guided unilateral approach. An experienced surgeon, on the other hand, is the only prerequisite for the 'gold standard' bilateral approach.

Teicoplanin vs cephradine and metronidazole in the prophylaxis of sepsis following vascular surgery: an interim analysis of an ongoing trial.

This paper presents further preliminary results of a trial of the prophylaxis of sepsis in 165 patients undergoing vascular surgery. The efficacy and safety of a single dose of teicoplanin was examined and compared with three doses of cephradine plus metronidazole. No significant differences were detected in the prophylactic efficacy in either group. The first interim report indicated abnormalities in liver function, maximum at 7 days, in both groups. These findings are confirmed in this second interim report. Raised levels of GGT and alkaline phosphatase are more prominent in patients receiving teicoplanin. Liver function improved by 28 days, however, suggesting that any abnormality is transient.

A comparison of teicoplanin vs. cephradine and metronidazole in surgical prophylaxis: an interim analysis.

The preliminary results of a trial to examine and compare the safety, tolerability and efficacy of a single dose of teicoplanin with three doses of cephradine combined with metronidazole are presented in a series of 113 patients undergoing elective vascular surgery. There were no obvious differences in the infection rates and sepsis indicators in either group. Neither drug regimen produced any evidence of renal or hepatic damage, though the levels of three hepatocellular enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl-transferase (GGT), were seen to be transiently elevated, peaking 7 days post-operatively. The trial continues.

Teicoplanin: Part 1. An evaluation of the concentrations seen in serum and the subcutaneous fat of the relatively ischaemic lower limb following a single intravenous bolus.

Teicoplanin is a new antibiotic currently undergoing clinical evaluation. Consecutive patients undergoing elective vascular surgery (n = 28) were randomised to receive a single intravenous bolus of 400 mg teicoplanin 1, 3, 6 or 12 h prior to surgery as prophylaxis against Gram-positive infection. Serum and fat antibiotic levels were measured and found to exceed the established MICs for common staphylococcal and streptococcal infections for at least 12 h following administration. This suggests that teicoplanin would be a useful choice of antibiotic in the prophylaxis and treatment of appropriate infections in elective surgery. By extrapolation, teicoplanin would also be of use in the prophylaxis and treatment of suitable infections seen in traumatised patients.

Teicoplanin: Part 2. Evaluation of its use in the biliary system.

Teicoplanin is a new antibiotic currently undergoing extensive investigation to evaluate its potential use in the prophylaxis and treatment of appropriate infection. To ascertain its penetration into the biliary system, 24 patients undergoing elective cholecystectomy were randomised to receive an intravenous bolus of 400 mg teicoplanin 1, 3, 6 or 12 h prior to surgery. During the operation, blood, gall bladder bile and tissue and common bile duct bile were removed for teicoplanin estimation. The results show that teicoplanin penetrates well into the gall bladder wall and bile, though less well into common bile duct bile. These results show that teicoplanin would seem to be a suitable antibiotic for the treatment of biliary infections that are known to be sensitive to the antibiotic.

A study of fucidin uptake in ischaemic tissues.

Twenty-five patients undergoing vascular surgery were given Fucidin 500 mg t.d.s. for the 3 days prior to surgery. Serum and fat levels obtained at the time of surgery show that the antibiotic is well absorbed and penetrates relatively ischaemic tissues. The levels obtained greatly exceed the MIC for Staphylococcus aureus.

A review of antibiotic prophylaxis for open fractures.

A review of the literature strongly supports the use of antibiotic prophylaxis in open fracture management. Because of their broad spectrum of activity, cephalosporins are the drugs of choice in cases of orthopaedic trauma. The extent of the injury determines the appropriate agent and the length of time it should be given. Patients with Type 1 or Type 2 fractures require only brief treatment (one preoperative and two postoperative doses) with an agent that has good antistaphylococci activity. Cephalothin, cefazolin, cefamandole or cefuroxime are recommended. Type 3 fractures present a much greater problem because of the risk of gram-negative infection. The marked activity of cefuroxime, cefamandole, and cefotaxime against these organisms recommends their use in such cases. Combination regimens with aminoglycosides require further study to define added efficacy and to define appropriate dosing regimens. We advocate that antibiotic prophylaxis should be given as soon as possible to all patients with open fractures and Type 3 fractures, and that prophylaxis should continue until 48 hours after adequate soft tissue coverage is achieved.

Monocyte dysfunction in severe trauma: evidence for the role of C5a in deactivation.

Consecutive severely traumatized patients (n = 16) requiring intensive care underwent serial monitoring of complement activation and monocyte migratory function with the chemoattractant activated serum (C5a) and formyl-methionyl-leucyl-phenylalanine (FMLP). Complement was found to be activated, and chemotaxis to C5a was correspondingly depressed maximally at a mean 5 to 7 days after injury (p = less than 0.01). The migratory response to FMLP was within the normal range throughout. Conversely, in a consecutive series of patients undergoing aortoiliac bypass grafting (n = 11), there was no evidence of complement activation, and monocyte migratory function remained normal for both C5a and FMLP. These data suggest that in patients with severe trauma, the activation of complement, particularly the fifth component (C5a), reduces the migratory responsiveness of circulating monocytes to C5a. This reduction in a host-response mechanism may explain the propensity to infection and poor wound healing seen in patients with severe trauma and also indicates that C5a, thought to be the major in vivo chemoattractant for leukocytes, has profound systemic actions.

A rapid method for monocyte isolation and chemotaxis.

A rapid method for isolating human peripheral blood monocytes and studying chemotaxis is described. The cells are isolated at a mean purity of 60% (+/- 10%) using Dextran. T500 sedimentation of whole blood, followed by centrifugation of the leucocyte-rich plasma obtained on a discontinuous Percoll gradient (density 1.067 g/ml). Chemotaxis was performed using a 48-well chamber and the chemoattractants activated serum (C5a) and FMLP and was proven by checkerboard analysis. Using this technique pooled serum was found to be activated by the PVP-coated polycarbonate filter in use, producing the attractant C5a. At high concentrations this produced a chemotactic response identical to zymosan-activated serum (ZAS). This technique requires small volumes of blood (15 ml) and enables monocyte isolation and chemotaxis to be completed in approximately 4 hr using leucocyte preparations in which the monocyte is the predominant cell. It therefore facilitates the sequential investigation of monocyte function in patients.

Suppressed neutrophil oxidative activity in sepsis: a receptor-mediated regulatory response.

We have reported that neutrophils from patients with intraabdominal sepsis show suppressed superoxide production in response to soluble chemoattractants. To determine whether this could be a result of altered receptor function, neutrophil function studies and characterization of receptors were performed upon 22 patients recently operated upon for intraabdominal sepsis. Patient cells showed an absence of subagarose migratory response to activation serum (C5) but intact FMLP response. Superoxide production to FMLP was 5.3 +/- 0.1 nmole FcC compared to 11.2 +/- 0.1 nmole for laboratory normals. Addition of cytochalasin B reversed this. Scatchard analyses of patients' cells showed affinity of 55.5 +/- 0.6 as compared to 36.5 +/- 1.8 for controls. The number of receptors of cell was approximately 55,000 for both controls and patients. Internalization studies revealed significant increase in tritiated-FMLP uptake at room temperature. These results support the hypothesis that superoxide suppression is due to enhanced clearance of stimulant by enhanced internalization of the receptor-ligand complex.

Regulation of monocyte function by complement activation products.

Normal human monocytes, obtained at a mean purity of 60% by Percoll density gradient centrifugation, were found to be chemotactically deactivated to C5a by exposure to low, and biologically significant, concentrations of zymosan-activated serum (ZAS), while retaining their full response to FMLP. C5a was found to be 40X more potent than its metabolite C5adesArg in reducing chemotaxis to activated pooled serum. Conversely, exposure of monocytes to varying concentrations of N-formyl-methionyl-leucyl-phenylalanine (FMLP) decreased chemotaxis to that attractant, though had no effect on chemotaxis to activated serum. Monocytes were also found to actively absorb C5a from solutions of ZAS, rich in C5a. Our data support the concept that monocytes are specifically regulated by C5a and C5adesArg.

Morbidity of simple cholecystectomy and cholecystectomy with transduodenal sphincteroplasty.

Exploration of the common bile duct via transduodenal sphincteroplasty is thorough and provides an opportunity for the natural passage of retained calculi. However, this procedure destroys both the sphincter ampulla and sphincter choledochus, the sequelae of which are unknown. Fifty patients who had a transduodenal sphincteroplasty performed between 1970 and 1980 were randomly selected and compared with 50 patients who only had cholecystectomy. They were all seen in the outpatient department, assessed on a modified Visick scale and had liver function tests performed. There was no statistical difference in the subjective quality of result or in the liver function of the sphincteroplasty group when compared with the cholecystectomy patients, which suggests that destruction of the sphincters does not appear to be harmful to the patient.

Transduodenal sphincteroplasty: an analysis of 118 consecutive cases.

The results of 118 consecutive common bile duct explorations via transduodenal sphincteroplasty are presented and analysed. The operations were performed for suspected choledocholithiasis by one surgeon over a 10-year period. Choledocholithiasis was proved in 22 per cent of the cholecystectomies carried out during this period and tended to present significantly earlier in females, 14.5 per cent presenting before 35 years of age. One hundred and four survivors were traced and 93.5 per cent had achieved a good result at a mean 5-year follow-up.