In vivo interactions of continuous flucloxacillin infusion and high-dose oral rifampicin in the serum of 15 patients with bone and soft tissue infections due to Staphylococcus aureus - a methodological and pilot study.

Background: Increased antibiotic resistance against Staphylococcus aureus and low penetration into bone requires regimen optimization of available drugs.

Methods: We evaluate pharmoacokinetic and pharmacodynamic parameters (PK/PD) as well as in vivo interactions of continuous flucloxacillin 12 g/d administration combined with high dose oral rifampicin 600 mg bid in the serum of 15 adult patients with bone and soft tissue infections. We use the patient's own serum directed against his own isolated S.

High prevalence of isolates with reduced glycopeptide susceptibility in persistent or recurrent bloodstream infections due to methicillin-resistant Staphylococcus aureus.

Reduced susceptibility to glycopeptides in methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates is considered a risk factor for failure of glycopeptide therapy. We compared the prevalences of MRSA isolates with reduced glycopeptide susceptibility in patients with versus without persistent or recurrent MRSA bloodstream infections. A retrospective cohort study at the University Hospital of Geneva identified 27 patients with persistent or recurrent clonally related MRSA bacteremic episodes over an 8-year period, which included 208 consecutive nosocomial MRSA bacteremic episodes.

Impact of ciprofloxacin exposure on Staphylococcus aureus genomic alterations linked with emergence of rifampin resistance.

Intensive use of antimicrobial agents in health care settings not only leads to the selection of multiresistant nosocomial isolates of Staphylococcus aureus but may also promote endogenous, resistance-conferring mutations in bacterial genes that encode drug targets. We evaluated the spectrum of rifampin resistance-conferring mutations in cultures of methicillin-susceptible S. aureus (MSSA) or methicillin-resistant S.

Underestimation of vancomycin and teicoplanin MICs by broth microdilution leads to underdetection of glycopeptide-intermediate isolates of Staphylococcus aureus.

Broth microdilution was compared with tube macrodilution and a simplified population analysis agar method for evaluating vancomycin and teicoplanin MICs and detecting glycopeptide-intermediate isolates of Staphylococcus aureus. Modal vancomycin and teicoplanin MICs recorded by tube macrodilution and the agar plate assay, which both used inocula of 10(6) CFU, were significantly higher (2 microg/ml) against a panel of borderline glycopeptide-susceptible and glycopeptide-intermediate methicillin-resistant S. aureus (MRSA) bloodstream isolates compared to broth microdilution (1 microg/ml).

Screening for staphylococcal superantigen genes shows no correlation with the presence or the severity of chronic rhinosinusitis and nasal polyposis.

Background: Staphylococcus aureus secretes numerous exotoxins which may exhibit superantigenic properties. Whereas the virulence of several of them is well documented, their exact biological effects are not fully understood. Exotoxins may influence the immune and inflammatory state of various organs, including the sinonasal mucosa: their possible involvement in chronic rhinosinusitis has been suggested and is one of the main trends in current research.

Comparative activity of oritavancin against meticillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates from Geneva University Hospital.

In this study, we assessed by broth microdilution the in vitro activity of oritavancin, a semisynthetic lipoglycopeptide currently under development, against selected meticillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates (n=56) from Geneva University Hospital, Switzerland, displaying a wide range of vancomycin minimum inhibitory concentrations (MICs) (0.25-4 microg/mL). The MRSA resistance phenotype was confirmed by broth microdilution (oxacillin MIC > or = 4 microg/mL) for all isolates; 89% and 100% of the tested isolates were also resistant to erythromycin and ciprofloxacin, respectively.

Increased uptake and improved intracellular survival of a teicoplanin-resistant mutant of methicillin-resistant Staphylococcus aureus in non-professional phagocytes.

Background/aims: Endogenous development of glycopeptide-intermediate resistance is linked to multiple genetic and phenotypic changes in clinical and laboratory isolates of Staphylococcus aureus. This study evaluated endocytic uptake and intracellular survival of a teicoplanin-resistant derivative of S. aureus in a human epithelial cell line, and compared these to the isogenic teicoplanin-susceptible parent or a spontaneously derived, susceptible revertant.

Comparison of tigecycline and vancomycin for treatment of experimental foreign-body infection due to methicillin-resistant Staphylococcus aureus.

Twice-daily 7-day regimens of tigecycline (7 mg/kg) and vancomycin (50 mg/kg) were compared in a rat tissue cage model of chronic foreign-body infection due to methicillin (meticillin)-resistant Staphylococcus aureus strain MRGR3. Subcutaneously administered tigecycline reached levels in tissue cage fluid that were nearly equivalent or slightly superior to the antibiotic MIC (0.5 microg/ml) for strain MRGR3.

Identification by genomic and genetic analysis of two new genes playing a key role in intermediate glycopeptide resistance in Staphylococcus aureus.

Endogenous, low-level glycopeptide resistance in Staphylococcus aureus results from multifactorial genetic changes. Comparative genomic hybridization analysis revealed the specific deletion of a 1.8-kb segment encompassing two adjacent open reading frames (ORFs) of unknown function in a teicoplanin-susceptible revertant (strain 14-4rev) compared to the sequence of its isogenic, teicoplanin-resistant parental strain, strain 14-4.

Inactivation of a subpopulation of human neutrophils by exposure to ultrahigh-molecular-weight polyethylene wear debris.

Polymorphonuclear neutrophils, a first line of defence against invading microbial pathogens, may be attracted by inflammatory mediators triggered by ultrahigh-molecular-weight polyethylene (UHMWPE) wear particles released from orthopaedic prostheses. Phagocytosis of UHMWPE particles by neutrophils may indirectly compromise their phagocytic-bactericidal mechanisms, thus enhancing host susceptibility to microbial infections. In an in vitro assay, pre-exposure of purified human neutrophils to UHMWPE micrometre- and submicrometre-sized wear particles interfered with subsequent Staphylococcos aureus uptake in a heterogeneous way, as assessed by a dual label fluorescence microscopic assay that discriminated intracellular rhodamine-labelled UHMWPE particles from fluorescein isothiocyanate-labelled S.

Intracellular residency is frequently associated with recurrent Staphylococcus aureus rhinosinusitis.

Aim: The prevalence of intracellular Staphylococcus aureus organisms in the nasal mucosa of patients with recurrent infectious rhinosinusitis episodes was studied.

Method: Twenty-seven consecutive adult patients who failed medical management of chronic rhinosinusitis (CRS) of multiple origins, associated or not with nasal polyposis, were consecutively enrolled for endonasal sinus surgery (including partial middle turbinectomy, middle antrostomy, ethmoidectomy, sphenoidotomy) and followed for a 12-month post-operative period.

Results: Seventeen of these patients showed the presence of intracellular S.

Transcriptomic and functional analysis of an autolysis-deficient, teicoplanin-resistant derivative of methicillin-resistant Staphylococcus aureus.

The molecular basis of glycopeptide-intermediate S. aureus (GISA) isolates is not well defined though frequently involves phenotypes such as thickened cell walls and decreased autolysis. We have exploited an isogenic pair of teicoplanin-susceptible (strain MRGR3) and teicoplanin-resistant (strain 14-4) methicillin-resistant S.

Evidence of an intracellular reservoir in the nasal mucosa of patients with recurrent Staphylococcus aureus rhinosinusitis.

Severe infections due to Staphylococcus aureus require prolonged therapy for cure, and relapse may occur even years after the first episode. Persistence of S. aureus may be explained, in part, by nasal carriage of S.

Comparative analysis and validation of different assays for glycopeptide susceptibility among methicillin-resistant Staphylococcus aureus strains.

Detection of methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibiting intermediate susceptibility to glycopeptides (GISA) is challenging for clinical microbiology laboratories. We compared three different screening assays for evaluating trends in decreased glycopeptide susceptibility during two periods. Ninety four and ninety five consecutive MRSA blood isolates from 189 bacteremic patients collected during periods A (1989-1994) and B (1999-2001), respectively, were screened in parallel for vancomycin or teicoplanin susceptibility by glycopeptide-containing brain-heart infusion agar (BHIA) tests, Etest MICs performed at a standard (0.

Organization of Ca2+ stores in myeloid cells: association of SERCA2b and the type-1 inositol-1,4,5-trisphosphate receptor.

In this study, we have analysed the relationship between Ca2+ pumps and Ins(1,4,5)P3-sensitive Ca2+ channels in myeloid cells. To study whether sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA)-type Ca(2+)-ATPases are responsible for Ca2+ uptake into Ins(1,4,5)P3-sensitive Ca2+ stores, we used the three structurally unrelated inhibitors thapsigargin, 2,5-di-t-butylhydroquinone and cyclopiazonic acid. In HL-60 cells, all three compounds precluded formation of the phosphorylated intermediate of SERCA-type Ca(2+)-ATPases.

Differential effects on neutrophil activation of staurosporin and its protein kinase C-selective derivative cgp 41231.

The relative insensitivity of the chemoattractant-induced respiratory burst to non-specific kinase inhibitors, such as staurosporin, is widely considered as evidence against the involvement of protein kinase C in signal transduction by chemoattractants. In this study we compared the effect on neutrophil activation of the non-specific kinase inhibitor staurosporin with the effect of its protein kinase C-selective derivative cgp 41251. Staurosporin activates secondary granule release by itself and enhances chemoattractant-induced primary granule release; it inhibits superoxide production in response to phorbol esters at low concentrations, but superoxide production in response to chemoattractants only at considerably higher concentrations.

Contribution of tumor necrosis factor to host defense against staphylococci in a guinea pig model of foreign body infections.

The contribution of the cytokine tumor necrosis factor (cachectin; TNF) to host defenses against staphylococcal foreign body infections was studied in vivo. In tissue cages subcutaneously implanted into guinea pigs, progressive infection was initiated by a very low inoculum (100 cfu) of Staphylococcus aureus with a success rate of 100%, as is frequently encountered in related clinical situations. Locally injected autologous bacterial components derived from the cell wall of S.

Successful single-dose prophylaxis of Staphylococcus aureus foreign body infections in guinea pigs by fleroxacin.

Single-dose administration of fleroxacin was evaluated as a means of preventing foreign body infection due to staphylococci. Tissue cages were implanted into guinea pigs and subsequently infected (100% rate) with 10(2) or more CFU of Staphylococcus aureus Wood 46. When a single dose of 30 mg of fleroxacin or vancomycin per kg of body weight was administered intraperitoneally, bactericidal levels of the antimicrobial agent were found in the tissue cage fluid after 3 h (when guinea pigs were inoculated with S.

Host factors selectively increase staphylococcal adherence on inserted catheters: a role for fibronectin and fibrinogen or fibrin.

Intravascular catheters are prone to staphylococcal infections. To study the role in staphylococcal adherence played by fibrinogen or fibrin and fibronectin deposited on inserted catheters, 187 peripheral or central cannulae were prospectively removed from hospitalized patients. Compared with uninserted catheters, which allowed only minimal adherence, previously inserted catheters promoted significant adherence of staphylococcal isolates from patients with intravenous device infection.

Inhibition by immunoglobulins of Staphylococcus aureus adherence to fibronectin-coated foreign surfaces.

Recent data suggest that fibronectin may favor Staphylococcus aureus infection by promoting attachment to either injured tissues or implanted foreign bodies. Using a previously described in vitro assay, we show that promotion of S. aureus adherence by surface-bound fibronectin, adsorbed on polymethylmethacrylate (PMMA) coverslips, is antagonized by antistaphylococcal antibodies present in immunoglobulin G (IgG) purified from human plasma.

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.

Attachment of Staphylococcus aureus to polymethylmethacrylate increases its resistance to phagocytosis in foreign body infection.

The mechanisms responsible for the development of a pyogenic infection (most commonly due to staphylococci) in the vicinity of an implanted foreign body have been studied recently by several investigators. Thus, we have been able to demonstrate that the phagocytic function of residential polymorphonuclear leukocytes (PMN) is deficient in the presence of a foreign body. Others have shown that in the presence of foreign surfaces, microorganisms produce extracellular amorphous material, the pathogenic role of which is still to be defined.