Bone and wound fluid concentrations of cephalosporins Oral cefadroxil and parenteral cefuroxime compared in 52 patients with a trochanteric fracture

Nungu, Kitugi Samwel; Larsson, Sune; Wallinder, Lars; Holm, Stig E.

doi:10.3109/17453679508995513

Cited by 11 publications

(5 citation statements)

References 12 publications

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“…total joint arthroplasty 8, 14, 15. Cefuroxime provides a broad spectrum against the most common pathogens,11 is stable against β‐lactamases,11 offers an excellent bone penetration,8, 9, 12, 13 and it is relatively free from serious side‐effects 11. Several studies have highlighted the beneficial outcome of cefuroxime impregnated bone cement as a prophylactic antibiotic regimen in total joint replacement 10, 15–19.…”

Section: Discussionmentioning

confidence: 99%

“…Today, perioperative antibiotic prophylaxis in orthopedic surgery is normally performed for 24 h, starting with an intravenous single‐dose antibiotic administration at time of induction of anesthesia 5, 6. Some authors recommend additional dosages every 4–8 h, if surgery lasts more than 3–4 h or the half‐life of the antibiotic is short,7–9 some perform a prolonged prophylaxis (longer than 24 h), especially when the operating environment is poor 6, 10. The second generation cephalosporin cefuroxime provides an antimicrobial spectrum suitably covering the most important bacteria causing deep infection,11 is stable against β‐lactamases11 and offers a good bone penetration 8, 9, 12, 13.…”

Section: Introductionmentioning

confidence: 99%

“…Some authors recommend additional dosages every 4–8 h, if surgery lasts more than 3–4 h or the half‐life of the antibiotic is short,7–9 some perform a prolonged prophylaxis (longer than 24 h), especially when the operating environment is poor 6, 10. The second generation cephalosporin cefuroxime provides an antimicrobial spectrum suitably covering the most important bacteria causing deep infection,11 is stable against β‐lactamases11 and offers a good bone penetration 8, 9, 12, 13. Therefore, cefuroxime is one of the most frequently used antibiotics for perioperative prophylaxis in orthopedic surgery 8, 14, 15.…”

Section: Introductionmentioning

confidence: 99%

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Effects of cefuroxime on human osteoblasts in vitro

Salzmann

Naal

Knoch

et al. 2007

J Biomedical Materials Res

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The local application of antibiotics in bone cement achieves high local effective antibiotic concentrations. Cefuroxime is widely used for antibiotic prophylaxis in orthopedic surgery, and several reports highlighted a beneficial outcome if cefuroxime-impregnated bone cement was used, but there is a lack of information of direct cefuroxime effects on human bone cells. We, therefore, cultured osteoblasts, previously derived from human trabecular bone specimens and used as a cell-pool further on, with different concentrations of cefuroxime (0-1000 microg/mL) for 24, 48, or 72 h. For reversibility testing, osteoblasts were cultivated for 24 h with cefuroxime followed by 48 h without antibiotics. Cell proliferation (MTT), cytotoxicity (lactate dehydrogenase (LDH)-activity), cell metabolism (alkaline phosphatase (ALP)-activity), and extracellular matrix calcification (Alizarin staining) were assessed after antibiotic treatment. Cefuroxime concentrations of 25-100 microg/mL had little or no effect on cellular proliferation. Proliferation was significantly stimulated at 250 and 1000 microg/mL at each time. LDH-activity significantly increased at the highest concentration of 1000 microg/mL at 72 h. ALP-activity first increased at lower concentrations and then significantly decreased at 1000 microg/mL at 48 and 72 h. Similar to ALP-activity, calcification increased at lower concentrations and was not detectable at 1000 microg/mL. All revealed effects at 24 h were at least partially reversible. In the present study, we demonstrated that cefuroxime at lower concentrations had no inhibiting effects on human osteoblasts. In contrast, higher concentrations significantly altered osteoblastic function. When administered locally in total joint arthroplasty, for example, in antibiotic-impregnated bone cement, cefuroxime might critically impair osteoblastic function and periprosthetic bone metabolism.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of cefuroxime on human osteoblasts in vitro

Salzmann

Naal

Knoch

et al. 2007

J Biomedical Materials Res

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“…The peak concentration of cefadroxil in lung tissue was 54%–69% of the serum value ( Nightingale, 1986 ). The mean value of C bone / C plasma at the same time from administration was 0.3 ( Nungu et al, 1995 ). The peak concentration of cefadroxil in skin blister was 20 mg/L after 3 h. The peak concentration of cefadroxil in serum was 28.4 mg/L after 1.5 h ( Simon et al, 1980 ).…”

Section: Discussionmentioning

confidence: 97%

“…The distribution of cefadroxil in the infected tissue is directly related to its pharmacological effects. Some tissue distribution data in human have been published ( Nightingale, 1986 ; Akimoto et al, 1994 ; Nungu et al, 1995 ). However, they were only the concentration ratios of tissue/serum (plasma) at the peak time or other one time point.…”

Section: Introductionmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Modeling of Cefadroxil in Mouse, Rat, and Human to Predict Concentration–Time Profile at Infected Tissue

Tan

Zhang

Wang³

et al. 2021

Front. Pharmacol.

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The aim of this study was to develop physiologically based pharmacokinetic (PBPK) models capable of simulating cefadroxil concentrations in plasma and tissues in mouse, rat, and human. PBPK models in this study consisted of 14 tissues and 2 blood compartments. They were established using measured tissue to plasma partition coefficient (Kp) in mouse and rat, absolute expression levels of hPEPT1 along the entire length of the human intestine, and the transporter kinetic parameters. The PBPK models also assumed that all the tissues were well-stirred compartments with perfusion rate limitations, and the ratio of the concentration in tissue to the unbound concentration in plasma is identical across species. These PBPK models were validated strictly by a series of observed plasma concentration–time profile data. The average fold error (AFE) and absolute average fold error (AAFE) values were all less than 2. The models’ rationality and accuracy were further demonstrated by the almost consistent Vss calculated by the PBPK model and noncompartmental method, as well as the good allometric scaling relationship of Vss and CL. The model suggests that hPEPT1 is the major transporter responsible for the oral absorption of cefadroxil in human, and the plasma concentration–time profiles of cefadroxil were not sensitive to dissolution rate faster than T85% = 2 h. The cefadroxil PBPK model in human is reliable and can be used to predict concentration–time profile at infected tissue. It may be useful for dose selection and informative decision-making during clinical trials and dosage form design of cefadroxil and provide a reference for the PBPK model establishment of hPEPT1 substrate.

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Antibiotic prophylaxis for surgery for proximal femoral and other closed long bone fractures

Gillespie

Walenkamp

2001

Cochrane Database of Systematic Reviews

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Bone and wound fluid concentrations of cephalosporins Oral cefadroxil and parenteral cefuroxime compared in 52 patients with a trochanteric fracture

Cited by 11 publications

References 12 publications

Effects of cefuroxime on human osteoblasts in vitro

Effects of cefuroxime on human osteoblasts in vitro

Physiologically Based Pharmacokinetic Modeling of Cefadroxil in Mouse, Rat, and Human to Predict Concentration–Time Profile at Infected Tissue

Antibiotic prophylaxis for surgery for proximal femoral and other closed long bone fractures

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