Application of a Rat Osteomyelitis Model to Comparein Vivoandin Vitrothe Antibiotic Efficacy against Bacteria with High Capacity to Form Biofilms

Gracia, Elena; Laclériga, Antonio; Monzón, Marta; Leiva, José; Oteiza, Concepción; Amorena, B.

doi:10.1006/jsre.1998.5416

Cited by 59 publications

(55 citation statements)

References 44 publications

(64 reference statements)

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“…Analogous observations were made in our previous mixed-model study [24]. The simplified animal model described in this work may represent a tool for studying chronic S. aureus biofilm infections.…”

supporting

confidence: 78%

mentioning

confidence: 99%

“…There are also mixed-models, involving the use of both a pre-colonized material and a bacterial suspension [4,24], which intend to reproduce the clinical use of infected implants and bacterial suspensions of washing solutions at surgery and systemic infections. In some of these models the number of bacteria used in the inoculated biofilms can be as high as 10' [24]. These rnodels main issue when applied for comparative studies on antibiotic therapy, is that the biofilm formation needs to be guaranteed in the animal before treatment and that the biofilms found in the different animals need to have a similar formation process and cell number.…”

mentioning

confidence: 99%

“…These requirements cannot be met in many cases due to the pathogenic and invasive characteristics of the bacterial strains used, heterogeneity of biofilm formation, or spilling of bacterial suspension, thus indicating the need to develop new models. In our previous study [24], a mixed-model was used which fulfilled most of these prerequisites and appeared to guarantee chronic infection at the implant site and surrounding bone in untreated animals. However, in that model it was difficult to distinguish the effect attributable to the biofilm formed on the implant from that of the inoculated bacterial suspension.…”

mentioning

confidence: 99%

“…The aim of this work is to determine whether an osteomyelitis infection can be successfully reproduced in rats using implants pre-colonized with only lo6 cells of a highly adherent slime-producing (SP) S. urnreus isolate in the absence of bacterial suspension inoculum at the site of surgery, and investigate whether the relative antibiotic efficacy found in this model corresponds to that found in an in vitro biofilm test [1,24] and in a mixed in vivo model [24]. This work intends to provide tools to study osteomyelitis and antibiotic treatments against S. urnreus biofilm bacteria.…”

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confidence: 99%

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A simple infection model using pre‐colonized implants to reproduce rat chronic Staphylococcus aureus osteomyelitis and study antibiotic treatment

Monzón

García-Álvare

Laclériga

et al. 2001

Journal Orthopaedic Research

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E.YOJJO~ S L. CEEI-Arcig6n, Z~i r t r g o~u , SpuiiiAccepted 5 December 2000Institutr oJ Agrohiotcclinolog!., 31006 Pumplonu, Spain AbstractSrq~phploroccus (iureiis biofilms formed on medical implants represent a serious problem, being difficult to eradicate with antibiotic therapy and leading to chronic infections. Simplified in vivo andl in vitro antibiotic susceptibility assays using biofilm bacteria are needed. In this work. a novel chronic osteomyelitis infection model was developed in rats in the absence of bacterial suspension, requiring the use of only lo6 bacteria in biofilms at the site of surgery, with a full success in reproducing infection. Stainless-steel implants pre-colonized for 12 h with a highly adherent S. ciurrus isolate were introduced into the rat tibiae. In animals not submitted to antibiotic treatment, infection was found in the implants and spread to bone in all cases, indicating the high efficacy of the model to reproduce osteomyelitis. The effect of a 21-day treatment with cefuroxime, vancomycin, tobramycin or ciprofloxacin on infection was studied in this model 42 days after surgery. Bone colonization WRS inhibited by vancomycin and cefuroxime. Cefuroxime (the most efficient antibiotic, able to sterilize 1 out of 8 implants) reduced the number of bacteria in biofilms adhered to implants at a higher extent than vancomycin, trobramyciri and ciprofloxacin. Analogous observations were made in this work in vivo and in vitro on the relative antibiotic efficacy against S. CIUWUS biofilm bacteria, suggesting the usefulness of both tests as a potential tool to study antibiotic suceptibility, and the need for new antimicrobials against these bacteria.

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confidence: 78%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A simple infection model using pre‐colonized implants to reproduce rat chronic Staphylococcus aureus osteomyelitis and study antibiotic treatment

Monzón

García-Álvare

Laclériga

et al. 2001

Journal Orthopaedic Research

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A new model of implant‐related osteomyelitis in rats

et al. 2003

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Infection related to osteosynthesis often has dramatic consequences for the patient. Prolonged hospitalization with systemic antibiotic therapy, several revision procedures, possible amputation, and even death may occur. To investigate the pathology of infection in orthopedic surgery, a new rat model of implant related osteomyelitis was developed. Three different concentrations (10(6), 10(3), and 10(2) colony-forming units (CFU)/10 microl) of Staphylococcus aureus were inoculated into the tibial medullary cavity with simultaneous insertion of a titanium Kirschner wire. Controls received phosphate-buffered saline (PBS). Each group consisted of 10 animals. Animals were followed for 4 weeks until sacrifice. X-rays of the tibiae were taken weekly, blood counts were analyzed, and body temperature and weight were determined. After sacrifice, infection was evaluated by histological and microbiological investigations. All animals inoculated with Staph. aureus in either concentration developed microbiological, histological, and radiological signs of osteomyelitis in correlation to the amount of inoculated bacteria. X-rays clearly revealed osseous destruction after 14 days with progression of osteomyelitis during the following weeks. CFU/g bone and bone weight after sacrifice showed dependence on the amount of inoculated CFU. The histological results confirmed the radiological findings. No significant changes in blood counts, body weight, and body temperature between the groups could be observed. The results demonstrate that it is possible to develop a model of implant-related osteomyelitis in rats with dependence on the amount of inoculated bacteria. No other promoters of infection besides intramedullary insertion of titanium Kirschner wires were used in this model.

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Efficacy of moxifloxacin compared to teicoplanin in the treatment of implant‐related chronic osteomyelitis in rats

Özturan

Yücel

Koçoğlu

et al. 2010

Journal Orthopaedic Research

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Treatment of implant-related chronic osteomyelitis is often difficult and usually consists of implant removal, extensive surgical debridement, and prolonged antibiotic use. This study was performed to assess the efficacy of moxifloxacin compared to a glycopeptide, teicoplanin in chronic implant-related methicillin-sensitive Staphylococcus aureus (MSSA) osteomyelitis. The left femoral medullar cavities of 60 Wistar male rats were contaminated with 100 l of 10 8 cfu/ml methicillin-sensitive S. aureus (ATCC 29213) and Kirschner wires were placed into the medulla of the femur. After 6 weeks, rats were randomly divided into five groups. In two groups, the Kirschner wires were removed. Experimental groups were as follows: group 1: contaminated, Kirschner wire inside, received teicoplanin; group 2: contaminated, Kirschner wire removed, received teicoplanin; group 3: contaminated, Kirschner wire inside, received moxifloxacin; group 4: contaminated, Kirschner wire removed, received moxifloxacin; group 5: contaminated, Kirschner wire inside, no antibiotics (control group). Groups 1 and 2 received teicoplanin (20 mg/kg once daily), whereas groups 3 and 4 received moxifloxacin (10 mg/kg twice daily) intraperitoneally for 28 days. At the end of the treatment, animals were sacrificed by inhalation anesthesia with ether and femora were retrieved and bacterial counts (cfu/g) were determined. Bacterial counts in all study groups were significantly reduced relative to the control. The decrease of bacterial counts was more prominent in group 4 compared to group 1 (p = 0.001) and group 2 (p = 0.003). Moxifloxacin therapy is an effective alternative to teicoplanin for chronic implant-related MSSA osteomyelitis.

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Application of a Rat Osteomyelitis Model to Comparein Vivoandin Vitrothe Antibiotic Efficacy against Bacteria with High Capacity to Form Biofilms

Cited by 59 publications

References 44 publications

A simple infection model using pre‐colonized implants to reproduce rat chronic Staphylococcus aureus osteomyelitis and study antibiotic treatment

A simple infection model using pre‐colonized implants to reproduce rat chronic Staphylococcus aureus osteomyelitis and study antibiotic treatment

A new model of implant‐related osteomyelitis in rats

Efficacy of moxifloxacin compared to teicoplanin in the treatment of implant‐related chronic osteomyelitis in rats

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