Diffusion of Cefepime into Cancellous and Cortical Bone Tissue

Breilh, Dominique; Boselli, Emmanuel; Bel, Jean-Christophe; Chassard, D.; Saux, Marie-Claude; Allaouchiche, Bernard

doi:10.1179/joc.2003.15.2.134

Cited by 26 publications

(12 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19 Cefepime appears to remain an excellent option in Gram-negative infections due to relatively low resistance and excellent bone penetration. 20 In our series, the bacterial pathogen profile did not vary in relation to the patient's HIV status. Previous literature identified Staphylococcus aureus as the most common organism causing osteoarticular infections in HIV patients.…”

Section: Discussionmentioning

confidence: 76%

The microbiology of chronic osteomyelitis in a developing world setting

Mthethwa

Marais

2017

SA orthop. j.

View full text Add to dashboard Cite

Objectives: The primary aim of this study was to identify the microorganisms that cause chronic osteomyelitis in a developing world clinical setting and to characterise the antibiotic sensitivity profile of these pathogens. Furthermore, we aimed to determine whether the causative organisms vary in relation to physiological status of the host, the HIV status of the patient or the cause of the infection (post-traumatic, post-operative and haematogenous). Methods:We performed a retrospective review of consecutive adult patients treated curatively for chronic osteomyelitis of long bones, over a two-year period. Patient charts were reviewed and data extracted in respect of patient demographics, the cause of infection, physiological status of the host in accordance with the Cierny and Mader classification, HIV status, surgical treatment strategy and causative organism.Results: A total of 108 organisms were identified in the 60 patients included in the study. Multiple organism were cultures in 45% of patients, a single Gram-positive organism in 22% and a single Gram-negative organism in 26% of patients. In four cases (7%) no causative organism was cultured. The most prevalent organisms were Enterobacteriaceae (34%), Staphylococcus spp. (29%), Pseudomonas aeruginosa (11%), and Enterococcus spp. (9%). Many isolates were found to be resistant to commonly used empirical anti-microbial agents. Seventy per cent of Enterobacteriaceae spp. were resistant to either cefuroxime and/or ampicillin-clavulanic acid. Seventy-seven per cent of Staphylococcus aureus isolates were susceptible to cloxacillin. More than 50% of Pseudomonas aeruginosa strains were resistant to meropenem, imipenem, piperacillin-tazobactam or cefepime. There was a significant association between the aetiology of the infection and the microorganisms involved (p-value < 0.01). The bacterial pathogen profile was, however, not associated with the physiological status of the host (p=0.22) or the HIV status of the patient. Conclusion:While the majority of haematogenous chronic osteomyelitis still involved a solitary Gram-positive organism, the incidence of Gram-negative infections was found to be higher than previously reported. Contiguous chronic osteomyelitis was mostly polymicrobial in nature and solitary infections involving a Gramnegative organism was most common in the post-traumatic group. The bacterial pathogen did not vary in relation to the HIV status of the patient or the physiological status of the host.

show abstract

Section: Discussionmentioning

confidence: 76%

The microbiology of chronic osteomyelitis in a developing world setting

Mthethwa

Marais

2017

SA orthop. j.

View full text Add to dashboard Cite

show abstract

“…94,95 Most beta-lactams, however, manifest bone:serum ratios between 0.1 and 0.3, consistent with their hydrophilic nature. 96-102 Similar variability and point estimates have been found for vancomycin in infected patients, with an average bone:serum ratio of ~0.20.…”

Section: Antimicrobial Pharmacokineticsmentioning

confidence: 87%

Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing

Onufrak

Forrest

González

2016

Clinical Therapeutics

129

104

View full text Add to dashboard Cite

Purpose An understanding of the pharmacokinetic (PK) and pharmacodynamic (PD) principles that determine response to antimicrobial therapy can provide the clinician with better-informed dosing regimens. Factors influential on antibiotic disposition and clinical outcome are presented, with a focus on the primary site of infection. Techniques to better understand antibiotic PK and optimize PD are acknowledged. Methods PubMed (inception – April 2016) was reviewed for relevant publications assessing antimicrobial exposures within different anatomical locations and clinical outcomes for various infection sites. Findings A limited literature base indicates variable penetration of antibiotics to different target sites of infection, with drug solubility and extent of protein binding providing significant PK influences in addition to the major clearing pathway of the agent. PD indices derived from in vitro and animal models determine the optimal magnitude and frequency of dosing regimens for patients. PK/PD modeling and simulation has been shown an efficient means of assessing these PD endpoints against a variety of PK determinants, clarifying the unique effects of infection site and patient characteristics to inform the adequacy of a given antibiotic regimen. Implications Appreciation of the PK properties of an antibiotic and its PD measure of efficacy can maximize the utility of these life-saving drugs. Unfortunately, clinical data remains limited for a number of infection site-antibiotic exposure relationships. Modeling and simulation can bridge preclinical and patient data for the prescription of optimal antibiotic dosing regimens, consistent with the tenets of personalized medicine.

show abstract

“…However, in a pharmacokinetic study of seven patients with external ventricular drains treated with cefepime, modelling predicted that neither cefepime at 2 g q12h or q8h would achieve target levels and only an estimated 7.8% of cefepime penetrated the CSF (albeit with non-inflamed meninges) [46]. Cefepime achieves adequate concentrations in various other body sites, including the gall bladder, pancreas, peritoneum, lung, prostate and bone [47][48][49].…”

Section: Pharmacology Of Cefepimementioning

confidence: 99%