The penetrability of cephazolin into the subcutaneous fat and skeletal muscle of ischaemic lower limbs with atherosclerotic disease.

Seventeen patients with atherosclerotic disease, who were undergoing arterial reconstruction or amputation of the lower limb, had 2 g cephazolin injected per-operatively in two equal doses by intramuscular and intravenous routes. Samples of subcutaneous fat and skeletal muscle from the ischaemic leg, and serum were collected during the operation for assay of cephazolin content. The mean cephazolin levels in the serum, skeletal muscle and subcutaneous fat were found to be well above the minimum inhibitory concentrations required for most important Gram-positive and Gram-negative pathogens.

A study on tissue concentrations of cephradine achieved in patients with peripheral vascular disease.

The levels of cephradine were measured in serum, voluntary muscle and subcutaneous fat samples collected from 30 patients during surgical operations for peripheral vascular disease. Cephradine 2 g was administered in two equal doses by intramuscular and intravenous routes before each operation. The mean levels found in the serum and muscle were well above the minimum inhibitory concentrations required for most important Gram-positive and Gram-negative pathogens, in contrast to the relatively low mean level found in subcutaneous fat.

Evaluation of tissue levels of cefamandole in severely ischaemic lower limbs using two regimens of dosage.

Cefamandole levels were measured in peripheral blood, and in skeletal muscle and subcutaneous fat samples taken from 20 patients during amputation of the leg for severe ischemia. Tissue samples were taken from both proximal and distal levels in the amputated limb. Cefamandole was administered as either a 2 g intravenous bolus given with induction of anaesthesia, or a combination of 1 g intramuscularly with the premedication plus 1 g intravenously with anaesthetic induction. Levels of cefamandole in serum and proximal muscle and fat samples were well above the minimum inhibitory concentrations required for most Gram-positive and Gram-negative organisms. Cefamandole levels in more distal samples were somewhat lower but still achieved therapeutic levels in most cases. Higher tissue levels of cefamandole were achieved when 2 g were given intravenously as a bolus.

Peroperative cephradine concentrations in the gall bladder wall and bile.

Cephradine levels were assayed in serum, gall bladder wall and bile sampled from the gall bladder and common bile duct in 24 patients undergoing elective cholecystectomy. Cephradine was administered either as 1 g given intravenously at the time of anaesthetic induction, or as three 6-hourly doses of 0.5 g taken orally during the pre-operation day followed by 1 g intramuscularly with the premedication. Adequate antibacterial levels of cephradine were achieved in all serum samples, 8 of 9 samples of choledochal bile, 6 of 12 samples of cholecystic bile and all 12 samples of gall bladder wall in the group receiving a single intravenous dose, compared to only 4 of 12 serum samples, 6 of 11 choledochal bile samples, 6 of 10 cholecystic bile samples, and only 3 of 12 samples of gall bladder wall in the group receiving oral cephradine. Therefore, cephradine given as a 1 g bolus intravenously with anaesthetic induction provides satisfactory concentrations for antibacterial prophylaxis during gall bladder surgery but a regimen of oral and intramuscular dosage was found to be unsatisfactory.

Tissue levels of cephradine in ischaemic limbs following a single intravenous injection.

A single dose of 2g cephradine was administered intravenously at the time of anaesthetic induction to 20 patients with occlusive arterial disease. Concentrations of cephradine were measured in serum, subcutaneous fat from the groins of 10 patients underdoing arterial reconstruction and in the subcutaneous fat and skeletal muscle of 10 legs amputated for severe arterial ischaemia. Concentrations of cephradine were adequate for antibacterial prophylaxis at the time of operation in all serum samples, 9 out of 10 samples of subcutaneous fat from reconstruction cases, all muscle and 8 of 10 fat samples from the level of section of amputated limbs, and in 8 of 10 muscle and fat samples from the distal parts of amputated limbs. These results confirm that a single intravenous dose of 2 g cephradine given with anaesthetic provides adequate serum and tissue concentrations for antibacterial prophylaxis during vascular surgery.

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.

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.

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.

Comparison between microscopical examination of unstained deposits of urine and quantitative culture.

Side-room examination of fresh samples of urine was compared with the results of surface viable bacterial counts. Examination of centrifuged deposits of urine for bacterial content was shown to compare very well with subsequent culture results. 87% of infected urines were detected, and only 6% of noninfected urines were wrongly identified. Evaluation of the uncentrifuged samples was less easy. There was poor agreement between the naked eye appearance, the presence of protein, and the pus cell count and the ultimate laboratory bacterial count. Microscopy of urinary sediments after centrifuging is recommended to assist in the rapid diagnosis of urinary tract infections particularly in young children.

The penetration of latamoxef disodium (moxalactam) into the subcutaneous fat and skeletal muscle of ischaemic lower limbs with atherosclerotic disease.

After pre-operative administration of 1 g, latamoxef disodium (moxalactam) levels were measured in peripheral venous blood, skeletal muscle and subcutaneous fat sampled from 29 patients during either arterial reconstruction or amputation undertaken for arterial occlusive disease. Tissue samples were taken from both proximal and distal levels in the amputated limbs. Levels of latamoxef disodium were above the minimum inhibitory concentration required for most commonly encountered Gram-positive and Gram-negative organisms. No patients developed toxicity or superficial wound infection but there was one vascular graft infection by Candida albicans. It has been shown that latamoxef disodium penetrates rapidly into the subcutaneous fat and skeletal muscle of relatively ischaemic limbs, achieving levels inhibitory to many common pathogens.

The concentration of latamoxef achieved in the bile and gallbladder wall of patients with cholecystitis.

This study reports the clinical and pharmacokinetic results following an injection of latamoxef (moxalactam disodium) in patients undergoing cholecystectomy for symptomatic cholelithiasis. Two groups were involved in the study. Group A consisted of 22 patients who received 1 g of intramuscular latamoxef at the time of premedication prior to surgery, and group B consisted of 12 patients each of whom received an intravenous dose of 0.5 g of latamoxef at the time of anaesthetic induction. Latamoxef levels were then measured in peripheral blood, gall bladder bile, common bile duct (CBD) bile and gall bladder wall. Despite a significant difference in the sampling times, inhibitory levels were obtained in the majority of samples in both groups, singularly high levels being assayed in CBD bile. We conclude that an intravenous dosage of latamoxef (0.5 g) given with anaesthetic induction is as effective as 1 g intramuscular dosage given with the pre-medication.