Plasma, Bone, Hip Capsule, and Drain Fluid Concentrations of Cephazolin During Total Hip Replacement

Abstract

A rapid intravenous bolus injection of cephazolin (4.0 g) was administered immediately before induction of anaesthesia to seven patients having total hip replacement. The plasma, bone, hip capsule and drain fluid concentrations of cephazolin following rapid intravenous injection of cephazolin were all well above the minimum bactericidal concentration of this antibiotic against a wide range of organisms, in particular, the penicillin resistant Staph. aureus, most Gram negative rods and Bacteroides species that cause postoperative infections in these patients. These results suggest that an intravenous bolus injection of cephazolin (4.0 g) given during induction of general anaesthesia should provide safe, effective prophylactic cover against all the organisms that cause postoperative wound infections in patients who undergo total hip replacement. This pharmacokinetic finding needs to be confirmed in a larger clinical trial of cephazolin. The optimum empirical prophylactic mode of administration of cephazolin that provides high plasma and tissue concentrations during this procedure appears to be a rapid intravenous bolus injection before induction of anaesthesia. The intravenous injections of cephazolin were well tolerated in every patient. No cases of thrombophlebitis occurred and no other side or toxic effects were reported.

Plasma, bone, hip capsule and drain fluid concentrations of ampicillin and flucloxacillin during total hip replacement after intravenous bolus injection of magnapen.

“…The concentrations of ampicillin in many patients samples of cancellous and groundup bone did exceed this value. However, the MIC of cephazolin against this organism is much less (2 ;g/ml) and is well below the tissue concentrations of this antibiotic found in our earlier study of cephazolin (Parsons et al, 1978b). Thus cephazolin would appear on pharmacokinetic grounds to be the drug of choice for post-operative wound infections caused by Klebsiella pneumoniae.…”

“…For the reasons already considered (Parsons et al, 1978a) we do not believe that this wide variation reflects insensitivity of the microbiological assay methods used to measure the antibiotic content of the tissue samples. Other studies (Paddock, Parsons & Vickers, 1977;Parsons, David, Paddock & Stamp, 1978) showed that there is a close correlation and reproducibility between the results of paired split samples that were simultaneously assayed in our unit and the manufacturers' laboratories.…”

“…Possible causes of this phenomenon are discussed in detail elsewhere Parsons et al, 1978a). They include differences in the distribution and penetration of antibiotics between adjacent parts of the same bone fragment, the avidity with which the antibiotic binds to tissue proteins within bone, and the ratio between the amount of protein-free antibiotic in the intravascular Haversian canal systems of bone and that which reaches extravascular (e.g.…”

“…These antibiotics differ from one another chemically, pharmacokinetically and bacteriologically. They include lincomycin (Parsons,10 Beavis, Hossack , cephradine (Parsons et al, 1978a) and cephazolin (Parsons et al, 1978a, b). In view of our earlier experience, we were asked by the manufacturers to evaluate the bone penetration of ampicillin and flucloxacillin after a combined proprietary preparation of these penicillins (Magnapen).…”

Target site antibiotic concentrations in orthopedic/trauma extremity surgery: is prophylactic cefazolin adequately dosed? A systematic review and meta-analysis

“…Parsons et al. (1978) also found higher levels in the hip capsule than in bone with mean concentrations of 35 µg/g (SD 7.2) and 14 (2.3) respectively.…”