Teicoplanin alone or combined with rifampin compared with vancomycin for prophylaxis and treatment of experimental foreign body infection by methicillin-resistant Staphylococcus aureus

Abstract

The prophylactic and therapeutic activities of teicoplanin were evaluated in two different experimental models of foreign body infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In a guinea pig model of prophylaxis, subcutaneously implanted tissue cages were infected at a >90%6 rate by 102 Bacterial infections of prosthetic devices are a major cause of morbidity and implant failure. Antimicrobial therapy of foreign body infections caused by Staphylococcus aureus is notoriously difficult, and microbial eradication frequently requires the removal of infected materials. An additional serious problem for the therapy of foreign body infections is the increasing incidence of methicillin-resistant strains of S. aureus (MRSA) that frequently express a large number of additional determinants for resistance to several major categories of antistaphylococcal agents. Although vancomycin is the reference antibiotic for treating MRSA infections, its activity against deep-seated infections is not always optimal (30, 32) and frequently requires the parallel administration of other antimicrobial agents such as aminoglycosides or rifampin (18, 49).There are three major concerns about increasing the use of vancomycin. The first one is its narrow toxic to therapeutic ratio involving serious toxic side effects; the second one is the exclusive intravenous route for administration of this agent, thus involving extensive hospital stay and costs; the third one is the growing concern about the possible acquisition of vanco-* Corresponding author. Teicoplanin is a glycopeptide antibiotic with an antibacterial spectrum similar to that of vancomycin (24), but with a much longer half-life and less serious side effects (16,23,43,52). Unlike vancomycin, teicoplanin is well tolerated after intramuscular administration, and its prolonged half-life is suitable for once-daily dosing (43). Several clinical or experimental studies evaluated the efficacy of teicoplanin for treating deepseated staphylococcal infections. Taken together, these different studies have led to discrepant results and controversial interpretations concerning teicoplanin safety and efficacy (see reviews in references 8, 15, and 16). The divergent results of these clinical studies may be explained by significant differences in their design, for example, the choice of open (4, 22, 23, 31, 33, 36, 47) versus comparative (7, 17, 20, 46, 48, 50) trials, and by the wide range of dosage regimens, treatment durations, and antibiotic combinations used by the different investigators.The major objective of our experimental study was to evaluate the efficacy of teicoplanin in two related animal models of foreign body infections caused by an MRSA strain (12, 34). The first of these models (5) was more suitable for assessing the prophylactic activity of teicoplanin on MRSA challenge, whereas the second one (34) evaluated its activity for the treatment of chronic subcutaneous implant-related infections caused by MRSA. In both animal models, teicoplanin was administer...

Implementation of the Masquelet Technique in Complicated Septic Non-union of the Ulna—A Case Report

“…Based on the sensitivities provided by the laboratory cultures, the combination of Teicoplanin and Rifampicin was chosen as an appropriate regimen. This has been widely published and proved to be one of the most effective combinations to treat such infections [12]. However, despite the noticeable clinical improvement and restoration of inflammatory markers to normal ranges within a month, the infection recurred both biochemically and clinically.…”

Comparison of Levofloxacin, Alatrofloxacin, and Vancomycin for Prophylaxis and Treatment of Experimental Foreign-Body-Associated Infection by Methicillin-Resistant Staphylococcus aureus

“…This procedure is used to reduce bacterial clumping and was previously shown to be harmless for ex vivo bacteria regarding their ability to multiply and their susceptibilities to antibiotics (37). To compare the rate of elimination of strain MRGR3 recovered from tissue cage fluids with that of the same strain grown in vitro, tissue cage bacteria were directly exposed to 0.25 g of trovafloxacin per ml in tubes containing 1 ml of either plain MHB or MHB supplemented with 50% pooled tissue cage fluid.…”

“…To evaluate the susceptibility to trovafloxacin of MRSA MRGR3 recovered from infected tissue cage fluids, the bacteria were isolated from the tissue cage fluids by centrifugation and were treated with 0.1% Triton X-100 and sonication to disrupt the host cells, as described previously (37). This procedure is used to reduce bacterial clumping and was previously shown to be harmless for ex vivo bacteria regarding their ability to multiply and their susceptibilities to antibiotics (37).…”

“…To compare the rate of elimination of strain MRGR3 recovered from tissue cage fluids with that of the same strain grown in vitro, tissue cage bacteria were directly exposed to 0.25 g of trovafloxacin per ml in tubes containing 1 ml of either plain MHB or MHB supplemented with 50% pooled tissue cage fluid. To make the comparison with ex vivo bacteria more relevant, bacteria grown in vitro were taken from saline-washed cultures of stationary-phase organisms (37).…”

“…Levofloxacin is the L isomer of ofloxacin and is available both in an oral dosage form and as an intravenous preparation, while alatrofloxacin is the L-Ala-L-Ala prodrug of trovafloxacin used for parenteral administration. We previously showed the usefulness of both guinea pig and rat tissue cage models for evaluating a range of different antimicrobial agents including vancomycin and teicoplanin (37), imipenem (36), and the fluoroquinolones fleroxacin (4,29) and sparfloxacin, temafloxacin, and ciprofloxacin (5), alone or in combination with rifampin (7,29,37), against S. aureus foreign-body-associated infections.…”