Preventing and treating discitis: cephazolin penetration in ovine lumbar intervertebral disc

Abstract

Infection can occur after any spinal procedure that violates the disc and although it is not common, the potential consequences are serious. Treatment of discitis is not always successful and the key to management is prevention. Intradiscal prophylaxis with antibiotic is routinely used in spinal surgery, but there is a limited understanding of how well antibiotics can enter the avascular disc after intravenous injection. An in vivo ovine study to optimise prophylactic and parenteral treatment of discitis is described to assess the effectiveness of cephazolin in preventing and treating infection. The concentration of cephazolin was measured in disc tissue from normal and degenerate sheep discs to determine if cephazolin can enter the disc and if disc degeneration affects antibiotic uptake. Fourteen sheep were deliberately inoculated with bacteria to induce discitis. Eight sheep ("prophylaxis" group) were given either a 0, 1, 2 or 3 g dose of prophylactic cephazolin before inoculation while the remaining sheep ("treatment" group) were treated with cephazolin commencing 7 days after inoculation for 21 days at a dose of 50 mg/kg/day. Histopathology and radiography were used to assess the effect of the different treatments. Cephazolin was given 30 min prior to sacrifice and the intradiscal concentration was measured by biochemistry. In the "prophylaxis" group all doses of antibiotic provided some protection against infection, although it was not dose dependent. In the "treatment" group discitis was confirmed radiologically and histologically in all animals from 2 weeks onwards. Biochemical assay confirmed that antibiotic is distributed throughout the disc but was present in higher concentration in the anulus fibrosus than the nucleus pulposus. This study demonstrated that whilst the incidence of iatrogenic discitis can be reduced by antibiotic prophylaxis, it could not be abolished in all incidences with a broad-spectrum antibiotic such as cephazolin. Furthermore, antibiotics were ineffective at preventing endplate destruction once an intradiscal inoculum was established.

Disc size markedly influences concentration profiles of intravenously administered solutes in the intervertebral disc: a computational study on glucosamine as a model solute

“…4, 5). However, in the larger sheep discs, concentrations of cephazolin (negatively charged) were consistently below therapeutic values [3,4]. While the charge of solutes is clearly important [15,17] negatively charged solutes are not completely excluded from the disc, rather their concentration will be around 30 % lower than the equivalent neutral solutes [32].…”

“…While the charge of solutes is clearly important [15,17] negatively charged solutes are not completely excluded from the disc, rather their concentration will be around 30 % lower than the equivalent neutral solutes [32]. The low concentrations seen in the sheep and even lower concentrations found in human NP [3] are mainly because of disc size rather than solute charge. Transport of agents other than drugs into the disc from the blood supply is now also of interest because of the potential danger arising from injecting directly into the disc itself [26].…”

“…Pharmacokinetics of various solutes have been examined in a wide range of species from animals as large as horses [1,2] to sheep [3,4], dogs [5,6], rabbits [7][8][9] and finally to animals as small as rats and mice [10,11]. Apart from inherent inter-and intra-species differences in cell type, tissue composition and mechanical properties, there is a huge difference between the disc sizes among these species.…”

“…Animal studies are typically used to test and characterize effects of such solutes on disc behavior [3,5]. In a recent study on the transport of solutes into a human lumbar intervertebral disc after intravenous injection, despite identical serum profiles, substantial differences in concentrations across the disc regions were computed when disc geometry was altered only by ±10 and ±20 % [17]; as shown above, size differences between human and animal discs are vastly greater than 20 %.…”

A survey of the “medical” articles in the European Spine Journal, 2006

“…In an experimental study on sheep, Walters et al [28] have assessed the efficacy of cephalozin in preventing and treating infection of the disc. This paper consists of two studies.…”