Pharmacokinetics of ceftriaxone in plasma and bone of patients undergoing hip or knee surgery

Gergs, Ulrich; Clauss, Tobias; Ihlefeld, Dorothea; Weiß, Michael; Pönicke, Klaus; Hofmann, Gunther O.; Neumann, Joachim

doi:10.1111/jphp.12282

Cited by 15 publications

(20 citation statements)

References 27 publications

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“…Further research is needed as to the type of antibiotic prophylaxis (ceftriaxone may not be best14), and whether early vaccination in vaccine-naïve patients with traumatic head injury is required.…”

Section: Discussionmentioning

confidence: 99%

Rapidly fatal pneumococcal meningitis following non-penetrating traumatic brain injury

et al. 2020

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A previously healthy young man presented to hospital with severe traumatic brain injury following a motor vehicle collision. Within 24 hours of admission, and despite antibiotic coverage, he developed a fever. On the second day, the source of infection was discovered to be purulent pneumococcal meningitis. At 48 hours post-accident, he developed brain-stem death without evidence of raised intracranial pressure or trans-tentorial herniation. Initial CT scans of the head were essentially normal, but early repeat scans revealed evidence of pneumocephalus and possible frontal bone fracture. Current recommendations do not make room for targeted antibiotic prophylaxis in traumatic brain injury patients with traumatic skull fracture. We argue that our case demonstrates the need for aggressive targeted antibiotic prophylaxis in the presence of certain features such as frontal or sphenoid bone fracture and pneumocephalus.

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Section: Discussionmentioning

confidence: 99%

Rapidly fatal pneumococcal meningitis following non-penetrating traumatic brain injury

et al. 2020

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“…The level of cefuroxime was monitored by reversed‐phase HPLC. The chromatographic system (nearly identical to that used in our earlier studies) consisted of a reverse phase column Vertex plus Knauer (25DD181SBJ), 25 cm length 4 mm width; Knauer, Berlin, Germany), a degasser (Series 1100, Hewlett Packard; Agilent Technologies, Böblingen, Germany), LS2200 VWR Hitachi, L‐7100 pump Merck‐Hitachi, a detector (series 1050 Hewlett Packard) and the HPLC‐Manager‐Software D‐6000 (Merck‐Hitachi). The column was isocratically eluted with a flow rate of 0.5 ml/min at 30°C.…”

Section: Methodsmentioning

confidence: 99%

“…Nevertheless, hospitals use typically cephalosporins of the first generation like cefazolin (1–2 g) or of the second generation of cephalosporins like cefuroxime (1.5 g) . Alternatively, sometimes ceftriaxone or levofloxacin, clindamycin and vancomycin are employed as prophylactic antibiotics in orthopaedic surgery …”

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics of cefuroxime and uptake into hip and spine bone of patients undergoing orthopaedic surgery

Gergs

Becker

Okoniewski

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives To reduce the incidence of peri-or postoperative infections in orthopaedic surgery, patients are prophylactically treated with antibiotics. Here, we wanted to know whether effective bone and intervertebral disc concentrations of cefuroxime are reached. Methods Patients undergoing surgery of hip (N = 40; 62.5% male) or spine (N = 40; 55% male) were pretreated with 1.5 g of the second-generation cephalosporin cefuroxime before surgery. We studied plasma population kinetics and bone and intervertebral disc (C5/6 till L5/S1) concentrations of cefuroxime using high-performance liquid chromatography. Key findings The plasma kinetics of cefuroxime in 80 patients was analysed using a population approach. The clearance amounted to 7.86 l/h. The peripheral and central volumes of distribution were estimated as 8.45 and 10.4 l, respectively. The concentrations in hip samples amounted to 9.8 AE 0.6 µg/g in cancellous bone and 8.9 AE 0.8 µg/g in cortical bone. Cefuroxime concentrations in vertebral bone and intervertebral discs were calculated as 9.6 AE 1.3 and 8.9 AE 1.1 µg/g, respectively.Conclusion Even if a majority of patients undergoing hip or spine surgery probably achieved adequate concentrations of cefuroxime, not all patients reached bone concentrations of cefuroxime above a recommended breakpoint for susceptible germs at the time of surgery.

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“…9 In brief, bone samples were cleaned free of adhering tissue and rinsed with isotonic sodium chloride solution to remove any remaining blood. 9 In brief, bone samples were cleaned free of adhering tissue and rinsed with isotonic sodium chloride solution to remove any remaining blood.…”

Section: Processing Of Deep-frozen Human Samples For Hplc Measurementmentioning

confidence: 99%

“…Samples were treated similarly to a previous publication from our group. 9 In brief, bone samples were cleaned free of adhering tissue and rinsed with isotonic sodium chloride solution to remove any remaining blood. Frozen tissue was cut into smaller samples in a custom-made dissecting machine.…”

Section: Processing Of Deep-frozen Human Samples For Hplc Measurementmentioning

confidence: 99%

Population Pharmacokinetics of Levofloxacin in Plasma and Bone of Patients Undergoing Hip or Knee Surgery

Gergs

Ihlefeld

Clauss

et al. 2017

Clinical Pharm in Drug Dev

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Patients undergoing hip or knee replacement therapy are routinely pretreated with antibiotics before they enter the operation theater. This treatment intends to reduce the incidence of peri- or postsurgical infections. Here, we calculated the uptake kinetics of levofloxacin into bone to see whether levofloxacin could be obtained from the trabecular and cortical bone and at what time concentrations are sufficiently high to inhibit the usual hospital infections. Patients (n = 42) undergoing routine surgery were treated with 500 mg levofloxacin intravenously immediately prior to the operation. Plasma samples were taken before and at 3 points after termination of drug infusion. After replacement of the bones, extracts were obtained from them. Levofloxacin was quantified using high-performance liquid chromatography. The kinetics of levofloxacin and its distribution into bone were analyzed using a population approach (ADAPT5). Clearance was 14.0 L/h, and distribution volume was 77 L. Bone uptake t½ was calculated as 4.2 and 5.4 hours for cortical bone and trabecular bone, respectively. In knee samples (but not in hip samples), we noted that the cortical bone contained higher levels of levofloxacin than the trabecular bone. From our data, we can conclude that levofloxacin might be useful for prophylactic use in bone surgery.

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Pharmacokinetics of ceftriaxone in plasma and bone of patients undergoing hip or knee surgery

Abstract: Under these experimental conditions, concentrations of ceftriaxone in cancellous and cortical bone should be adequate to protect the patients against usual ceftriaxone-sensitive nosocomial infections and are substantially lower than the plasma concentrations.

Cited by 15 publications

References 27 publications

Rapidly fatal pneumococcal meningitis following non-penetrating traumatic brain injury

Rapidly fatal pneumococcal meningitis following non-penetrating traumatic brain injury

Population pharmacokinetics of cefuroxime and uptake into hip and spine bone of patients undergoing orthopaedic surgery

Population Pharmacokinetics of Levofloxacin in Plasma and Bone of Patients Undergoing Hip or Knee Surgery

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