Comparative evaluation of cefazolin and clindamycin in the treatment of experimental Staphylococcus aureus osteomyelitis in rabbits

Mader, Jon T.; Adams, Kenneth R.; Morrison, L T

doi:10.1128/aac.33.10.1760

Cited by 36 publications

(20 citation statements)

References 23 publications

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“…Many osteomyelitis studies with animal models reported animal weights [24][25][26] In our present study, rats in the sham, VO, VHB, and VOHB groups gained weight and rats in the control and V groups lost weight, consistent with similar reports in the literature.…”

Section: Discussionsupporting

confidence: 94%

Evaluation and Comparison of the Effects of Hyperbaric Oxygen and Ozonized Oxygen as Adjuvant Treatments in an Experimental Osteomyelitis Model

Oğuz

Ekinci

Eroğlu

et al. 2011

Journal of Surgical Research

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Section: Discussionsupporting

confidence: 94%

Evaluation and Comparison of the Effects of Hyperbaric Oxygen and Ozonized Oxygen as Adjuvant Treatments in an Experimental Osteomyelitis Model

Oğuz

Ekinci

Eroğlu

et al. 2011

Journal of Surgical Research

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“…Recently, it was also shown that the production and expression of PSMs are significantly increased in planktonic S. aureus cultures by subinhibitory concentrations of clindamycin (44,45). Clindamycin achieves high intracellular levels in bones and phagocytic cells and potentiates opsonization and phagocytosis at subinhibitory concentrations (46,47). However, the impact of subinhibitory concentrations of clindamycin on the biofilm formation and matrix composition of clindamycin-sensitive S. aureus has not been investigated so far.…”

mentioning

confidence: 99%

Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin

Schilcher

Andreoni

Haunreiter

et al. 2016

Antimicrob Agents Chemother

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Staphylococcus aureus biofilms are extremely difficult to treat. They provide a protected niche for the bacteria, rendering them highly recalcitrant toward host defenses as well as antibiotic treatment. Bacteria within a biofilm are shielded from the immune system by the formation of an extracellular polymeric matrix, composed of polysaccharides, extracellular DNA (eDNA), and proteins. Many antibiotics do not readily penetrate biofilms, resulting in the presence of subinhibitory concentrations of antibiotics. Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B ( B ) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB. Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections. Staphylococcus aureus is a major cause of both health care-related and community-associated (CA) infections. The Grampositive human-pathogenic bacterium produces and secretes a range of toxins and enzymes leading to acute infections such as bacteremia and skin abscesses (1, 2). In addition, most S. aureus strains are capable of biofilm formation and can persist in host tissues such as the bone, leading to chronic osteomyelitis, or on implanted medical devices such as vascular catheters, vascular grafts, heart valves, and prosthetic joints (3-5). Biofilm-associated infections are extremely difficult to treat, and these chronic or relapsing infections typically require prolonged antibiotic treatment or removal of the device (6-8). Antibiotic resistance of bacteria within a biofilm may result from slow growth, phenotypic heterogeneity, persister cell formation, and inactivation or reduced penetration of the antibiotic (9, 10). Diffusion of the antibiotic through biofilm cell clusters is dependent on the thickness and the composition of the extracellular polymeric matrix (9, 11). The slow transport within biofilms suggests that the bacteria may encounter subinhibitory concentrations of antibiotics. Previous studies have shown that low doses of different antibiotics trigger biofilm formation (12, 13) and lead to dramatic alterations in bacterial gene expression in S. aureus (14).Biofilm formation proceeds in at least three phases: initial attachment, biofilm maturation, and dispersal (15, 16). Initial surface attachment is dependent on bacterial surface molecules such as the S. aureus murein hydrolase AtlA, teichoic acids, and fibronectin-binding proteins (FnBPs) (17)(18)(19)(20). After attachment to the surface, the bacteria multiply and produce the extracellular...

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“…Although its efficacy has been established in several experimental models [9,10], only a few series on the clindamycin treatment of human bone and joint infections have been reported [11][12][13]. The current recommendation for the dosage of oral clindamycin is 150-300 mg every 6 h for moderately severe infection and 300-450 mg every 6 h for severe infection [14].…”

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis

Bouazza

Pestre

Jullien

et al. 2012

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Clindamycin pharmacokinetics have been studied in adult patients. Rifampicin co-administration could decrease clindamycin exposure. WHAT THIS STUDY ADDS• This clindamycin population analysis in patients with osteomyelitis provides useful insight into the fate of this drug and shows that clindamycin clearance increases with body weight. Moreover, this study shows a potential effect of combined rifampicin on clindamycin clearance and addresses sub-therapeutic clindamycin concentrations in heavier patients. AIMSThis study was performed to describe clindamycin, administered either orally or intravenously, concentration-time courses to patients with osteomyelitis, to study the effects of different covariates on clindamycin pharmacokinetics and to simulate an optimized administration scheme. METHODSClindamycin concentrations were measured in 50 patients. A total of 122 plasma concentrations were available (58 from oral administration and 64 from i.v. infusion). A population pharmacokinetic model was developed with MONOLIX 4 software. RESULTSA one compartment model adequately described the data. Clindamycin clearance increased significantly with body weight (BW). The typical population estimates (interindividual variability) for clearance, volume of distribution and absorption rate constant were 16.2 l h -1 (0.39), 70.2 l and 0.92 h -1, respectively. The bioavailability of the oral form was estimated to be 87.6%. According to BW, theoretical doses needed to reach a Cmin of 2 mg l -1 were then calculated. CONCLUSIONSThe current recommendation of 600 mg three times daily seems to be effective up to 75 kg but the dose should be raised to 900 mg three times daily thereafter. These assumptions should be prospectively confirmed.

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Comparative evaluation of cefazolin and clindamycin in the treatment of experimental Staphylococcus aureus osteomyelitis in rabbits

Cited by 36 publications

References 23 publications

Evaluation and Comparison of the Effects of Hyperbaric Oxygen and Ozonized Oxygen as Adjuvant Treatments in an Experimental Osteomyelitis Model

Evaluation and Comparison of the Effects of Hyperbaric Oxygen and Ozonized Oxygen as Adjuvant Treatments in an Experimental Osteomyelitis Model

Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin

Population pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis

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