Biomedical subjects

P Vaudaux

Publications and source records attributed to P Vaudaux.

At least 19 recordsLinked to original sources

PubMed2000

Identification of plasma proteins adsorbed on hemodialysis tubing that promote Staphylococcus aureus adhesion.

Risk factors for Staphylococcus aureus infections in patients undergoing hemodialysis include underlying disease, material-induced host defects, and the presence of vascular access catheters. To determine the specific contribution of various potentially adsorbed plasma components in promoting S aureus adhesion to shunt tubing during chronic hemodialysis, we quantified their respective amounts by Western immunoblotting and densitometry and estimated their individual adhesion-promoting activities with specific adhesion-modified bacterial mutants. Fibrinogen, which was the only component consistently present in tubing protein extracts from all patients, was adsorbed in significantly higher amounts on predialyzer than on postdialyzer tubing segments. In contrast, fibronectin and von Willebrand factor were irregularly present in patients' tubing, whereas vitronectin or thrombospondin remained undetectable in all samples. The contribution of fibrinogen in promoting S aureus attachment to hemodialysis tubing was demonstrated by (1) the significantly lower adhesion of a cIfA mutant of strain Newman compared with its parent; (2) the increased attachment of strain 8325-4 after complementation with the cloned cIfA gene on the multicopy plasmid pCF4; and (3) the general tendency for strains Newman and 8325-4(pCF4) to express higher attachment on predialyzer compared with postdialyzer tubing segments in relationship with the higher content of fibrinogen on the former material. However, the specific S aureus attachment-promoting activity of both prefilter and postfilter tubing-adsorbed fibrinogen were much lower than that of the native in vitro-adsorbed protein and may reflect masking or inactivation of the in vivo-adsorbed protein by unknown mechanisms.

Adsorption↗

PubMed1999

Vitronectin interaction with glycosaminoglycans. Kinetics, structural determinants, and role in binding to endothelial cells.

Vitronectin (VN) is a high affinity heparin-binding protein. The physiological role of this binding has hitherto received little attention, and its molecular determinants are subject to controversy. In this study, we characterized vitronectin interaction with heparin, heparin analogues, bacterial extracts, and cell surface glycosaminoglycans. As assessed by (i) fluorescence assays, (ii) precipitation with heparin-Sepharose beads, or (iii) Western blotting with antibodies against VN(347-361) (the heparin-binding site), we demonstrate an exposure of the VN heparin-binding site in multimeric but not monomeric vitronectin. Through its heparin-binding site, vitronectin also bound other glycosaminoglycans and Staphylococcus aureus extracts. The kinetics of heparin binding to vitronectin were complex. After a fast association phase (tau = 0.3 s), a slow conversion of an unstable to a stable heparin-vitronectin complex (tau = 180 s) occurred. Heparin binding kinetics and transition to a stable complex were mimicked by VN(347-361), demonstrating that this area is the fully functional heparin-binding site of vitronectin. Multimeric vitronectin bound to endothelial cells. This binding was blocked by soluble heparin and was not observed when endothelial cells were pretreated with glycosaminoglycan-removing enzymes. Glycosaminoglycan-dependent interaction of endothelial cells with multimeric vitronectin might be a relevant mechanism for removal of multimeric vitronectin from plasma. Conversion of an unstable to a stable glycosaminoglycan-vitronectin complex is likely to be relevant for association with endothelial cells under flow conditions.

Cells, Cultured↗

PubMed1999

Bloodstream infections caused by small-colony variants of coagulase-negative staphylococci following pacemaker implantation.

Small-colony variants (SCVs) of Staphylococcus aureus cause persistent and relapsing infections. Relatively little is known regarding infections caused by SCVs of coagulase-negative staphylococci. We report two cases of pacemaker electrode infections due to SCVs of Staphylococcus epidermidis and Staphylococcus capitis. Sequence analysis of a portion of the 16S rRNA gene (16S rDNA) confirmed the identity of the staphylococcal species as S. capitis and S. epidermidis. Isolates from cultures of blood obtained over at least a 2-week interval were compared by pulsed-field gel electrophoresis and found to be clonal even though the colony morphology was very different. Analysis for auxotrophism revealed hemin dependencies for all isolated SCVs. The two cases have several clinical and laboratory characteristics (which are also seen with S. aureus SCV infections) and strongly suggest that SCVs of coagulase-negative staphylococci must be actively sought, because they grow very slowly and can be easily missed.

Bacteremia↗

PubMed1999

Inhibition by heparin and derivatized dextrans of Staphylococcus epidermidis adhesion to in vitro fibronectin-coated or explanted polymer surfaces.

The ability of Staphylococcus aureus to recognize several extracellular matrix or plasma proteins (e.g., fibrinogen, fibronectin, and collagen) promotes bacterial attachment to artificial surfaces. Whereas most S. aureus clinical isolates elaborate a wide repertoire of bacterial surface receptors' called adhesins, exhibiting specific binding of individual host proteins, S. epidermidis is lacking most of such protein adhesins. To document the interactions between S. epidermidis and various surface-adsorbed proteins, we first compared promotion of bacterial attachment by seven purified human proteins immobilized onto poly(methyl methacrylate) (PMMA) coverslips. Only two of them, namely fibronectin and fibrinogen, exhibited adhesion-promoting activities. In the presence of native heparin or two functionalized dextrans (CMDBS for Carboxy Methyl, Benzylamide sulfonate/sulfate), a dose-dependent inhibition of S. epidermidis adhesion to fibronectin-coated, but not to fibrinogen-coated surfaces was observed. The inhibitory effects of each CMDBS were much stronger than that of native heparin. In contrast, a control highly negatively charged, dextran exclusively substituted with carboxy methyl groups exerted no inhibition on S. epidermidis adhesion. To evaluate how CMDBS could interfere with S. epidermidis attachment to coverslips coated in vivo with extracellular matrix components, we also tested PMMA surfaces retrieved from tissue cages subcutaneously implanted in guinea pigs. Each CMDBS, but not heparin, strongly inhibited S. epidermidis adhesion to explanted coverslips, even in the presence of tissue cage fluid. In conclusion, fibronectin plays an important role in promoting S. epidermidis attachment to implanted biomaterials. Furthermore, S. epidermidis adhesion to fibronectin-coated or implanted biomaterials can be efficiently blocked in vitro by CMDBS.

Animals↗

PubMed1998

Role of plasma and extracellular matrix proteins in the physiopathology of foreign body infections.

Foreign body implants are highly susceptible to microorganism infection. The infectious agents may be of low pathogenicity (such as S. epidermidis) or involve more virulent strains (such as S. aureus). The common denominator for the three main elements that play a role in the physiopathology of such infections (bacteria, neutrophils, and different biomaterials) are host proteins deposited over the surface of the devices immediately after their implantation. These proteins modulate that host cells response but can also promote Staphylococcus adhesion to the biomaterial. Neutrophils and other cells such as fibroblasts adhere to several extracellular matrix proteins such as fibronectin, fibrinogen, collagen, vitronectin, via specific cell surface receptor. The evolution of the technology and the increasing numbers of long-term artificial implants require a better understanding of fundamental mechanisms of foreign body infections to reduce their incidence and optimize their treatment.

Bacterial Adhesion↗

PubMed1998

Clumping factor B (ClfB), a new surface-located fibrinogen-binding adhesin of Staphylococcus aureus.

The surface-located fibrinogen-binding protein (clumping factor; ClfA) of Staphylococcus aureus has an unusual dipeptide repeat linking the ligand binding domain to the wall-anchored region. Southern blotting experiments revealed several other loci in the S. aureus Newman genome that hybridized to a probe comprising DNA encoding the dipeptide repeat. One of these loci is analysed here. It also encodes a fibrinogen-binding protein, which we have called ClfB. The overall organization of ClfB is very similar to that of ClfA, and the proteins have considerable sequence identity in the signal sequence and wall attachment domains. However, the A regions are only 26% identical. Recombinant biotinylated ClfB protein bound to fibrinogen in Western ligand blots. ClfB reacted with the alpha- and beta-chains of fibrinogen in the ligand blots in contrast to ClfA, which binds exclusively to the gamma-chain. Analysis of proteins released from the cell wall of S. aureus Newman by Western immunoblotting using antibody raised against the recombinant A region of ClfB identified a 124 kDa protein as the clfB gene product. This protein was detectable only on cells that were grown to the early exponential phase. It was absent from cells from late exponential phase or stationary phase cultures. Using a clfB mutant isolated by allelic replacement alone and in combination with a clfA mutation, the ClfB protein was shown to promote (i) clumping of exponential-phase cells in a solution of fibrinogen, (ii) adherence of exponential-phase bacteria to immobilized fibrinogen in vitro, and (iii) bacterial adherence to ex vivo human haemodialysis tubing, suggesting that it could contribute to the pathogenicity of biomaterial-related infections. However, in wild-type exponential-phase S. aureus Newman cultures, ClfB activity was masked by the ClfA protein, and it did not contribute at all to interactions of cells from stationary-phase cultures with fibrinogen. ClfB-dependent bacterial adherence to immobilized fibrinogen was inhibited by millimolar concentrations of Ca2+ and Mn2+, which indicates that, like ClfA, ligand binding by ClfB is regulated by a low-affinity inhibitory cation binding site.

Adhesins, Bacterial↗

PubMed1997

Influence of surface treatments developed for oral implants on the physical and biological properties of titanium. (I) Surface characterization.

We present an investigation of the physico-chemical surface properties of commercially pure titanium coverslips which were submitted to various treatments designed to optimize their topography in view of application in oral implantology. The surface microroughness, chemical composition and water wettability were analyzed on titanium coverslips prepared by mechanical polishing, acid attack in HCl/H2SO4, after mechanical polishing or sandblasting, and titanium plasma-spray. The chemical composition has been measured by Auger electron spectroscopy. The treatments have no major influence on the surface chemical composition and all the samples display a composition approaching that of TiO2 with minor amounts of carbon, sulfur, silicon and calcium as impurities. The roughness has been measured by scanning force microscopy on an area of 20 microns x 20 microns on each sample. Polished titanium is smooth (peak-to-valley roughness 81 nm), whereas the acid-attacked surfaces exhibit a micro-roughness in the microns range (2100 nm for polished and acid attacked; 3600 nm for sandblasted and acid attacked) which is quite reproducible over large areas of the sample. The acid attacked samples present a subsurface layer which contains hydrogen below the native passivating oxide layer. Water wettability measurement shows that all surfaces are hydrophobic with a slightly higher contact angle for the acid attacked surfaces. The different treatments analyzed in this study essentially influence the surface roughness by preserving the chemical composition and the wettability properties of titanium native oxide surface layer.

Dental Polishing↗

PubMed1997

Influence of surface treatments developed for oral implants on the physical and biological properties of titanium. (II) Adsorption isotherms and biological activity of immobilized fibronectin.

The influence of titanium surface properties on in vitro adsorption isotherms of fibronectin, promotion of Staphylococcus aureus adhesion, and binding of a monoclonal antibody to the cell-binding domain of fibronectin was examined. Treatments producing different surface roughness were applied to a single side of commercially pure titanium coverslips, which was either mechanically polished (P), or polished and then acid attacked with H2SO4/HCl (PA), or sandblasted and then acid attacked (SLA), whereas the untreated side was blocked by an albumin coating layer. Incubation of the coverslips with concentrations of soluble 3H-labelled fibronectin increasing from 1 to 16 micrograms/ml led to the saturation of all surfaces with immobilized protein from 4 to 16 micrograms/ml. Promotion of S. aureus adhesion by fibronectin adsorbed on all surfaces and binding of the monoclonal antibody to its cell-binding domain was to some extent proportional to the amount of immobilized protein but also showed some minor differences between surfaces. More important material-related differences were observed when fibronectin adsorption isotherms were expressed as a function of the effective, roughness-corrected surface area, yielding amounts of immobilized fibronectin on the rough PA and SLA titanium surfaces which were 50% lower than those adsorbed on either smooth P or polymethylmethacrylate coverslips used as controls. In conclusion, surface treatments increasing the surface roughness of titanium do not increase, but may partly decrease in vitro adsorption of fibronectin. Despite adsorbing different amounts of fibronectin, both rough and smooth titanium surfaces promote normal expression of 2 major functional domains of this protein.

Adsorption↗

PubMed1997

The dipeptide repeat region of the fibrinogen-binding protein (clumping factor) is required for functional expression of the fibrinogen-binding domain on the Staphylococcus aureus cell surface.

Clumping factor of Staphylococcus aureus is a fibrinogen-binding protein that is located on the bacterial cell surface. The protein has an unusual repeat domain (region R) comprising mainly the dipeptide aspartate and serine. To determine if region R has a role in the surface display of the fibrinogen-binding region A domain, deletions lacking the region R encoding region of the clfA gene were generated. To determine the minimum length of region R required for wild-type levels of ClfA expression, variants with truncated region R domains were constructed. S. aureus cells expressing mutated clfA genes were tested for (i) proteins released by lysostaphin treatment that reacted with antisera specific for region A, (ii) clumping in soluble fibrinogen, (iii) adherence to immobilized fibrinogen and (iv) expression of the ClfA antigen on the cell surface by fluorescent activated cell sorting analysis. Each construct expressed three major immunoreactive proteins, two of which were putative N-terminal degradation products. Region R residues greater than 40 were required between region A and W (72 residues between region A and the LPDTG sorting signal) for wild-type levels of clumping in fibrinogen. A stepwise decrease in clumping titre was observed as the distance between region A and LPDTG was decreased from 72 to 4 residues. Similarly, a decrease in binding of anti-ClfA serum and in binding to fibrinogen-coated plastic surfaces was observed with cells expressing ClfA with 40 region R residues or less. Nevertheless, low levels of adherence to fibrinogen and binding to anti-ClfA serum occurred with ClfA derivatives that lacked region R altogether. This indicates that a small proportion of the ClfA molecules are linked to peptidoglycan very close to the cell surface but that residues greater than 72 are needed to allow sufficient ClfA molecules to span the entire cell wall and to display the biologically active A domain in a form that can participate fully in fibrinogen binding.

Binding Sites↗

PubMed1996

Novel animal model for studying the molecular mechanisms of bacterial adhesion to bone-implanted metallic devices: role of fibronectin in Staphylococcus aureus adhesion.

Infection around metallic implants is a rare but severe complication of orthopaedic surgery. A novel animal model mimicking conditions of internal fixation devices was developed to evaluate the role of host proteins adsorbed on metallic devices in promoting adhesion and colonization of the material surfaces by Staphylococcus aureus. Small plates made of pure titanium were either fixed (three screws per plate) onto the iliac bones of guinea pigs or implanted into their subcutaneous space as controls. Five to 6 weeks after surgery, the plates and screws were removed from the previously killed animals, carefully rinsed in buffer, and tested in an in vitro assay of S. aureus adhesion to metallic surfaces. To evaluate the role of fibronectin in staphylococcal adhesion to explanted plates and screws, a mutant of S. aureus that is specifically defictive in fibronectin adhesion due to decreased expression of the fibronectin adhesin was compared with its isogenic parental strain. A significant reduction in adhesion of the fibronectin adhesin-defective mutant compared with the parental strain occurred on both the subcutaneously implanted and bone-implanted metallic plates. The results of this specific biological assay suggest that fibronectin is present on bone-implanted metallic devices and promotes attachment of S. aureus to their surfaces. This novel experimental model should help, to characterize several parameters of bacterial adhesion to metallic orthopaedic devices and to develop novel anti-adhesive strategies for preventing such infections.

Animals↗

PubMed1996

Physical and biological effects of a surface coating procedure on polyurethane catheters.

Central venous catheters are widely used in clinical practice; however, complications such as venous thrombosis or infection are frequent. The physical and biological effects of a coating procedure designed to improve the blood-contacting properties of polyurethane central venous catheters (CVCs) were studied. The surface atomic composition of poly(vinyl pyrrolidone) (PVP)-coated or uncoated Pellethane single lumen CVCs was characterized by electron spectroscopy for chemical analysis (ESCA), which confirmed the presence of an oxygen-rich PVP layer on the former material. Topological analysis of both single and triple lumen CVCs by scanning force microscopy (SFM) revealed a very smooth surface in PVP-coated catheters compared to the more frequent surface irregularities found either in uncoated Pellethane or in four additional randomly selected, commercially available triple lumen polyurethane CVCs. The PVP-coated Pellethane showed a strong reduction in either fibrinogen or fibronectin adsorption compared to all other PVP-free polyurethane CVCs. This decreased protein adsorption led to a proportional reduction in protein-mediated adhesion of either Staphylococcus aureus or Staphylococcus epidermidis and in the binding of a monoclonal antibody directed against the cell-binding domain of fibronectin. Increased surface smoothness and hydrophilic properties of polyurethane CVCs might decrease the risk of bacterial colonization and infection.

Adsorption↗

PubMed1996

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 devices.

Adhesins, Bacterial↗

PubMed1995

Identification of the ligand-binding domain of the surface-located fibrinogen receptor (clumping factor) of Staphylococcus aureus.

The ability of Staphylococcus aureus to bind to fibrinogen and fibrin is believed to be an important factor in the initiation of foreign-body and wound infections. Recently, we reported the cloning and sequencing of the gene clfA encoding the fibrinogen receptor (clumping factor, ClfA) of S. aureus strain Newman and showed that the gene product was responsible for the clumping of bacteria in soluble fibrinogen and for the adherence of bacteria to solid-phase fibrinogen. This was confirmed here by showing that antibodies raised against purified Region A inhibited both of these properties. Also, immunofluorescent microscopic analysis of wild-type Newman and a clfA::Tn917 mutant of Newman with anti-ClfA Region A sera confirmed that Region A is exposed on the bacterial cell surface. Furthermore, polystyrene beads coated with the Region A protein formed clumps in soluble fibrinogen showing that the ClfA protein alone is sufficient for the clumping phenotype. Western immunoblotting with anti-ClfA Region A antibodies identified the native ClfA receptor as a 185 kDa protein that was released from the cell wall of S. aureus by lysostaphin treatment. A single extensive ligand-binding site was located within Region A of the ClfA protein. Truncated ClfA proteins were expressed in Escherichia coli. Lysates of E. coli and proteins that had been purified by affinity chromatography were tested for (i) their ability to bind fibrinogen in Western ligand blotting experiments, (ii) for their ability to inhibit clumping of bacteria in fibrinogen solution and adherence of bacteria to solid-phase fibrinogen, and (iii) for their ability to neutralize the blocking activity of anti-ClfA Region A antibody. These tests allowed the ligand-binding domain to be localized to a 218-residue segment (residues 332-550) within Region A.

Bacterial Adhesion↗

PubMed1995

Role of Staphylococcus aureus coagulase and clumping factor in pathogenesis of experimental endocarditis.

The pathogenic role of staphylococcal coagulase and clumping factor was investigated in the rat model of endocarditis. The coagulase-producing and clumping factor-producing parent strain Staphylococcus aureus Newman and a series of mutants defective in either coagulase, clumping factor, or both were tested for their ability (i) to attach in vitro to either rat fibrinogen or platelet-fibrin clots and (ii) to produce endocarditis in rats with catheter-induced aortic vegetations. In vitro, the clumping factor-defective mutants were up to 100 times less able than the wild type strain to attach to fibrinogen and also significantly less adherent than the parents to platelet-fibrin clots. Coagulase-defective mutants, in contrast, were not altered in their in vitro adherence phenotype. The rate of in vivo infection was inoculum dependent. Clumping factor-defective mutants produced ca. 50% less endocarditis than the parent organisms when injected at inoculum sizes infecting, respectively, 40 and 80% (ID40 and ID80, respectively) of rats with the wild-type strain. This was a trend at the ID40 but was statistically significant at the ID80 (P < 0.05). Coagulase-defective bacteria were not affected in their infectivity. Complementation of a clumping factor-defective mutant with a copy of the wild-type clumping factor gene restored both its in vitro adherence and its in vivo infectivity. These results show that clumping factor plays a specific role in the pathogenesis of S. aureus endocarditis. Nevertheless, the rate of endocarditis with clumping factor-defective mutants increased with larger inocula, indicating the contribution of additional pathogenic determinants in the infective process.

Animals↗

PubMed1995

Effect of toluene extraction on Biomer surface: I. ESCA, ATR/FTIR, contact angle analysis and biological properties.

Biomer is a poly(ether-urethane-urea) block copolymer widely used as biomedical devices. Extraction process of this polymer has purified its surface of low molecular weight polyurethane chains and Santowhite Powder additive. ESCA and ATR/FTIR have suggested a homogenization of the polymer by enrichment of the first layers with poly(aminomethacrylate) additive after extraction. Therefore, the surface of the extracted Biomer exhibits a different wettability and biological response. The treatment causes a significant decrease in fibronectin adsorption and induces a reduction in Staphylococcus aureus adhesion.

Adsorption↗

PubMed1994

Aqueous humor penetration of ofloxacin given by various routes.

We studied the aqueous humor penetration of ofloxacin after topical, oral, and intravenous administration in 51 consecutive patients undergoing cataract surgery. Aqueous humor concentration (mean +/- SD) was 0.53 +/- 0.35 mg/l when ofloxacin 0.3% eyedrops were instilled topically six times, one drop every three hours, until 90 minutes preoperatively, and 0.63 +/- 0.29 mg/l (P = .45) when two additional instillations were made, one drop every 30 minutes, until 30 minutes before aqueous humor aspiration. Aqueous humor concentration two hours after a single 200-mg oral dose (0.38 +/- 0.15 mg/l) was significantly lower (P = .048) than that 12 hours after the same oral dose (0.58 +/- 0.24 mg/l). Two hours following an intravenous infusion of 200 mg of ofloxacin, aqueous humor concentration was 0.33 +/- 0.19 mg/l. Our results suggest that therapeutic levels above the minimum inhibitory concentration for many bacteria cultured in endophthalmitis can be achieved in aqueous humor after either topical or oral administration, which indicates that this antibiotic passes easily through the corneal and the blood aqueous barriers.

Administration, Oral↗

PubMed1994

Role of fibronectin in staphylococcal adhesion to metallic surfaces used as models of orthopaedic devices.

Staphylococcal infection of various prosthetic and internal fixation devices is a major complication associated with orthopaedic surgery. This study investigated the role of the host protein fibronectin in promoting adhesion of Staphylococcus aureus and Staphylococcus epidermidis to metallic surfaces representing materials used for orthopaedic devices. Pure human fibronectin was adsorbed in vitro onto coverslips (0.8 x 0.8 cm) of stainless steel, pure titanium, or titanium-aluminum-niobium alloy. In vitro bacterial adhesion was promoted more strongly by the metallic surfaces coated with fibronectin than by albumin-coated controls for two strains of S. aureus and one strain of S. epidermidis. Furthermore, with the fibronectin-coated coverslips, bacterial adhesion to titanium alloy was significantly greater than adhesion to stainless steel. Adhesion of the three staphylococcal strains was promoted more strongly by coverslips explanted from the subcutaneous space of guinea pigs and tested under similar conditions than by albumin-coated controls. Incubation of either in vitro fibronectin-coated or explanted metallic coverslips with anti-fibronectin antibodies produced a significant decrease in staphylococcal adhesion. These results suggest that the presence of fibronectin on the surface of implanted metallic devices is an important determinant of colonization of orthopaedic biomaterials by staphylococci.

Adsorption↗

PubMed1994

Comparative efficacies of imipenem, oxacillin and vancomycin for therapy of chronic foreign body infection due to methicillin-susceptible and -resistant Staphylococcus aureus.

The efficacies of imipenem when directed against methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains of Staphylococcus aureus were compared with those of oxacillin and vancomycin in a subcutaneous rat model, using chronically infected tissue cages. At three weeks after inoculation, stable chronic infections were established with average bacterial counts exceeding 10(6) cfu/mL tissue cage fluid for both strains. Intraperitoneal administration (twice a day for 7 days) of imipenem (80 mg/kg) or oxacillin (200 mg/kg) produced peak levels of 23 or 45 mg/L and through levels of < 0.1 and 5.7 mg/L, respectively. The therapeutic regimens of either imipenem (P < 0.001) or oxacillin (P < 0.02) administered for 7 days led to significant reductions in bacterial counts in the tissue cage fluids of animals chronically infected with MSSA. In contrast, imipenem was not effective against chronic MRSA tissue cage infections, despite the relatively low MIC of the infecting strain and the use of high dose (120 mg/kg) therapy. In-vitro susceptibility testings of MRSA performed before and after imipenem therapy demonstrated the emergence of a highly resistant subpopulation.

Animals↗