The inhibition of neutrophil antibacterial activity by ultra-high molecular weight polyethylene particles.

Following infection, bacterial killing by polymorphonuclear leukocytes (neutrophils) is the main host defense against bacteria. Our hypothesis is that particles of ultra-high molecular weight polyethylene (UHMWP) may impair local neutrophil function and consequently reduce neutrophil bacterial killing. To determine how the in vitro phagocytic-bactericidal activity of neutrophils was affected by exposure to wear particles, tests were run comparing the effects of different particle composition, and different concentrations and sizes of UHMWP particles. There was a significant correlation between the number of particles and the decrease in neutrophil bactericidal activity (p<0.01), and the greatest effect was obtained with a concentration of 10(7) UHMWP/ml. There was a significant decrease in neutrophil bactericidal activity by incubation with particles of 0.1-5 microm (p<0.01), but not with larger size. The results suggest that neutrophil functional defects triggered by the presence of UHMWP particles may potentially contribute to the susceptibility of loose implants to bacterial infections

Trends in the treatment of orthopaedic prosthetic infections

The most commonly used therapy for prosthetic joint infection is a two-stage prosthetic exchange separated by 6 weeks of intravenous antibiotic therapy. This often results in long periods of hospitalization, morbidity, severe functional impairment and sometimes increased mortality. Therefore novel and challenging therapeutic approaches have been attempted, particularly in hip prosthetic infection. This includes, whenever possible, according to the type of microorganism, antibacterial susceptibility and clinical presentation (including age and comorbidities): (i) less aggressive surgical techniques (debridement and prosthesis retention, or re-implantation with a single-stage exchange arthroplasty); and (ii) antibiotic combinations active against biofilm-associated bacteria, including rifampicin (particularly with quinolones) with excellent bio-availability which allow prolonged and efficient oral therap

The discriminatory power of MALDI-TOF mass spectrometry to differentiate between isogenic teicoplanin-susceptible and teicoplanin-resistant strains of methicillin-resistant Staphylococcus aureus

To explore the discriminatory power of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for detecting subtle differences in isogenic isolates, we tested isogenic strains of Staphylococcus aureus differing in their expression of resistance to methicillin or teicoplanin. More important changes in MALDI-TOF MS spectra were found with strains differing in methicillin than in teicoplanin resistance. In comparison, very minor or no changes were recorded in pulsed-field gel electrophoresis profiles or peptidoglycan muropeptide digest patterns of these strains, respectively. MALDI-TOF MS might be useful to detect subtle strain-specific differences in ionizable components released from bacterial surfaces and not from their peptidoglycan networ

Pathogenesis of Foreign Body Infection: Description and Characteristics of an Animal Model

An animal model involving the subcutaneous implantation of tissue cages into guinea pigs and subsequent infection with Staphylococcus aureus was used to study factors pertinent to foreign body infection. Whereas 108 colony-forming units (cfu) of S. aureus strain Wood 46 did not produce any abscesses in the absence of foreign material, 102 cfu was sufficient to infect 95% of the tissue cages despite the presence of polymorphonuclear leukocytes (PMNLs) in sterile tissue cage fluid. Opsonization of S. aureus by tissue cage fluid was adequate during the first hour of infection, but opsonic coating of the organisms decreased at 20 hr after the induction of infection. PMNLs from sterile tissue cage fluid showed decreased phagocytic and bactericidal activities when compared with PMNLs from either blood or peritoneal exudate obtained after short- or long-term stimulation (P < 0.001

The safety and efficacy of high-dose daptomycin combined with rifampicin for the treatment of Gram-positive osteoarticular infections

Purpose: Treatment of Gram-positive osteoarticular infections requires an adequate surgical approach combined with intensive antimicrobial therapy. The aim of this study was to evaluate the safety and efficacy of a combined regimen of high-dose daptomycin and rifampicin, in patients with various types of Gram-positive osteoarticular infections. Methods: This single centre, non-comparative, prospective study evaluated the safety and efficacy of a combined regimen of intravenous daptomycin (8mg/kg/day) and oral rifampicin (600mg/day) in patients with Gram-positive osteoarticular infections, with a minimal follow-up of oneyear. Creatine phosphokinase, transaminases, bilirubinaemia, and serum creatinine, were measured at baseline and regular intervals. Results: The median daily doses of daptomycin and rifampicin, administered for a median duration of 21 (range, 10-122) days to 16 patients (median age, 63.5years; 11 males, five females) presenting with staphylococcal (n = 15) or streptococcal (n = 1) osteoarticular infections, were 8.15 (range, 6.6-8.9) mg/kg/day and 600 (range, 600-900) mg/day, respectively. The combined regimen of daptomycin and rifampicin was well tolerated by all except one patient, without requiring treatment adjustment or discontinuation. One patient developed allergic responses probably due to rifampicin after 42days. Fifteen (94%) patients showed favourable clinical and microbiological outcomes. Conclusions: The combined regimen of high-dose daptomycin and rifampicin was well tolerated and may provide a useful alternative to standard glycopeptide therapy for Gram-positive osteoarticular infection

Role of Bacterial Exopolymers and Host Factors on Adherence and Phagocytosis of Staphylococcus aureus in Foreign Body Infection

Using a previously developed guinea pig model of foreign body infection, we examined ultrastructural and functional surface alterations of Staphylococcus aureus strain Wood 46 during the early phase of infection. Exopolymer-free bacteria were prepared and inoculated into subcutaneously implanted tissue cages. After three hours, the bacteria showed abundant capsular and intercellular exopolymers, which were visualized by transmission electron microscopy. Exopolymers were also produced by S. aureus exposed in vitro to fluid from the tissue cage. In contrast, human serum albumin prevented exopolymer production by S. aureus. The influence of exopolymers on the susceptibility of S. aureus to ingestion and phagocytic killing by neutrophils was tested in vitro and found to be negligible. Furthermore, adherence of S. aureus to fibronectin-coated surfaces was unaffected by the presence or absence of exopolymers. Thus, in our experimental model, exopolymers are produced early during the onset of infection, but they have little impact on adherence and phagocytosi

Host-Bacteria Interactions in Foreign Body Infections

Persistent staphylococcal infections are a major medical problem, especially when they occur on implanted materials or intravascular catheters. This review describes some of the recently discovered molecular mechanisms of Staphylococcus aureus attachment to host proteins coating biomedical implants. These interactions involve specific surface proteins, called bacterial adhesins, that recognize specific domains of host proteins deposited on indwelling devices, such as fibronectin, fibrinogen, or fibrin. Elucidation of molecular mechanisms of S aureus adhesion to the different host proteins may lead to the development of specific inhibitors blocking attachment of S aureus, which may decrease the risk of bacterial colonization of indwelling device

Effect of Vancomycin Therapy for Osteomyelitis on Colonization by Methicillin-Resistant Staphylococcus aureus: Lack of Emergence of Glycopeptide Resistance

Abstract Background: In treating orthopedic infections, the long-term impact of vancomycin therapy on colonization by methicillin-resistant Staphylococcus aureus (MRSA) and the emergence of vancomycin-intermediate S. aureus is unknown. Design: Prospective surveillance of the effect of long-term vancomycin therapy on colonization by MRSA and the emergence of vancomycin-intermediate S. aureus. Methods: Thirty-four patients with MRSA osteomyelitis that was microbiologically documented were longitudinally observed for the emergence of vancomycin-intermediate S. aureus at 3 body sites (wound, anterior nares, and groin) during the initial period of vancomycin therapy and at the 2-month follow-up. Twenty patients received the standard dose (20 mg/kg/d) for 34 ± 6 days and 14 patients received a high dose (40 mg/kg/d) of vancomycin for 37 ± 9 days. Results: During vancomycin treatment, global MRSA carriage (all body sites) fell from 100% to 25% in the group of patients receiving the standard dose of vancomycin, and from 100% to 40% in the group receiving the high dose. During the 2-month follow-up period after vancomycin therapy, global MRSA carriage increased from 25% to 55% in the group receiving the standard dose and decreased from 43% to 36% in the group receiving the high dose. Conclusion: Therapy with a high dose of vancomycin contributes to the sustained eradication of MRSA carriage without promoting the emergence of glycopeptide resistanc