Dataset Information

Effect of Vancomycin, Gentamicin and Clindamycin on Cartilage Cells In Vitro.

ABSTRACT:

Background

The treatment of grafts with vancomycin for ligament reconstruction in knee surgery is the current standard. However, high antibiotic concentrations have chondrotoxic effects.

Purpose

To test the chondrotoxicity of clindamycin, gentamicin and vancomycin in comparable concentrations. In vitro and in vivo effective concentrations hugely vary from drug to drug. To allow for comparisons between these three commonly used antibiotics, the concentration ranges frequently used in orthopedic surgical settings were tested.

Study design

Controlled laboratory study.

Methods

Human cartilage from 10 specimens was used to isolate chondrocytes. The chondrocytes were treated with clindamycin (1 mg/mL and 0.5 mg/mL), gentamicin (10 mg/mL and 5 mg/mL) or vancomycin (10 mg/mL and 5 mg/mL), at concentrations used for preoperative infection prophylaxis in ligament surgery. Observations were taken over a period of 7 days. A control of untreated chondrocytes was included. To test the chondrotoxicity, a lactate dehydrogenase (LDH) test and a water-soluble tetrazolium salt (WST-1) assay were performed on days 1, 3 and 7. In addition, microscopic examinations were performed after fluorescence staining of the cells at the same time intervals.

Results

All samples showed a reasonable vitality of the cartilage cells after 72 h. However, clindamycin and gentamicin both showed higher chondrotoxicity in all investigations compared to vancomycin. After a period of 7 days, only chondrocytes treated with vancomycin showed reasonable vitality.

Conclusions

The preoperative treatment of ligament grafts with vancomycin is the most reasonable method for infection prophylaxis, in accordance with the current study results regarding chondrotoxicity; however, clindamycin and gentamicin cover a wider anti-bacterial spectrum.

Clinical relevance

The prophylactic antibiotic treatment of ligament grafts at concentrations of 5 mg/mL or 10 mg/mL vancomycin is justifiable and reasonable. In specific cases, even the use of gentamicin and clindamycin is appropriate.

SUBMITTER: Mayr HO

PROVIDER: S-EPMC10740484 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Effect of Vancomycin, Gentamicin and Clindamycin on Cartilage Cells In Vitro.

Mayr Hermann O HO Regenbrecht Nina N Mayr Moritz Florian MF Riedel Bianca B Hart Melanie L ML Schmal Hagen H Seidenstuecker Michael M

Biomedicines 20231125 12

<h4>Background</h4>The treatment of grafts with vancomycin for ligament reconstruction in knee surgery is the current standard. However, high antibiotic concentrations have chondrotoxic effects.<h4>Purpose</h4>To test the chondrotoxicity of clindamycin, gentamicin and vancomycin in comparable concentrations. In vitro and in vivo effective concentrations hugely vary from drug to drug. To allow for comparisons between these three commonly used antibiotics, the concentration ranges frequently used ...[more]

PMID: 38137364

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Project description:ObjectiveTo describe risk of Clostridium difficile infection associated with clindamycin and acute kidney injury associated with gentamicin during delivery hospitalizations.MethodsWomen admitted for delivery from January 2006 to March 2015 were analyzed using an inpatient administrative database. Primary outcomes were C difficile infection and acute kidney injury. C difficile infection was compared between women receiving clindamycin (with or without other antibiotics) and women receiving antibiotics other than clindamycin. Acute kidney injury was compared between women receiving gentamicin (with or without other antibiotics), women receiving antibiotics other than gentamicin, and women receiving no antibiotics. Unadjusted and adjusted log linear models analyzing the role of patient demographics, mode of delivery, and hospital-level characteristics were created evaluating risk of C difficile infection and acute kidney injury with risk ratios (RRs) and adjusted risk ratios with 99% CIs as measures of association. A sensitivity analysis for gentamicin and acute kidney injury was performed restricted to women with preeclampsia.ResultsOf 5,657,523 women admitted for delivery hospitalization, 266,402 (4.7%) received clindamycin and 165,726 (2.9%) received gentamicin. C difficile infection was diagnosed in 0.04% of women receiving clindamycin. Compared with women receiving other antibiotics, clindamycin was associated with a nearly threefold increased risk of C difficile infection (RR 2.93, 99% CI 2.21-3.90). Acute kidney injury was diagnosed in 0.24% of women receiving gentamicin. Gentamicin was associated with a threefold increased risk of acute kidney injury (RR 3.01, 99% CI 2.62-3.45) compared with women receiving other antibiotics, whereas receipt of no antibiotics was associated with significantly lower risk (RR 0.18, 99% CI 0.15-0.20). In adjusted analyses, these associations retained significance. Significantly increased risk of acute kidney injury was noted for women with preeclampsia receiving gentamicin (RR 2.04, 99% CI 1.64-2.53).ConclusionReceipt of clindamycin was associated with significantly increased likelihood for C difficile infection and receipt of gentamicin with significantly increased likelihood of acute kidney injury, although the absolute risk of these complications was low.

Project description:Population pharmacokinetic (popPK) models are an essential tool when implementing therapeutic drug monitoring (TDM) and to overcome dosing challenges in neonates in clinical practice. Since vancomycin, gentamicin, and amikacin are among the most prescribed antibiotics for the neonatal population, we aimed to characterize the popPK models of these antibiotics and the covariates that may influence the pharmacokinetic parameters in neonates and infants with no previous pathologies. We searched the PubMed, Embase, Web of Science, and Scopus databases and the bibliographies of relevant articles from inception to the beginning of February 2024. The search identified 2064 articles, of which 68 met the inclusion criteria (34 for vancomycin, 21 for gentamicin, 13 for amikacin). A one-compartment popPK model was more frequently used to describe the pharmacokinetics of the three antibiotics (91.2% vancomycin, 76.9% gentamicin, 57.1% amikacin). Pharmacokinetic parameter (mean ± standard deviation) values calculated for a "typical" neonate weighing 3 kg were as follows: clearance (CL) 0.34 ± 0.80 L/h for vancomycin, 0.27 ± 0.49 L/h for gentamicin, and 0.19 ± 0.07 L/h for amikacin; volume of distribution (Vd): 1.75 ± 0.65 L for vancomycin, 1.54 ± 0.53 L for gentamicin, and 1.67 ± 0.27 L for amikacin for one-compartment models. Total body weight, postmenstrual age, and serum creatinine were common predictors (covariates) for describing the variability in CL, whereas only total body weight predominated for Vd. A single universal popPK model for each of the antibiotics reviewed cannot be implemented in the neonatal population because of the significant variability between them. Body weight, renal function, and postmenstrual age are important predictors of CL in the three antibiotics, and total body weight for Vd. TDM represents an essential tool in this population, not only to avoid toxicity but to attain the desired pharmacokinetic/pharmacodynamic index. The characteristics of the neonatal population, coupled with the lack of prospective studies and external validation of most models, indicate a need to continue investigating the pharmacokinetics of these antibiotics in neonates.

Dataset Information

Effect of Vancomycin, Gentamicin and Clindamycin on Cartilage Cells In Vitro.

Background

Purpose

Study design

Methods

Results

Conclusions

Clinical relevance

Publications

Effect of Vancomycin, Gentamicin and Clindamycin on Cartilage Cells In Vitro.

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