Extracellular DNA Impedes the Transport of Vancomycin in Staphylococcus epidermidis Biofilms Preexposed to Subinhibitory Concentrations of Vancomycin

Staphylococcus epidermidis biofilm formation is responsible for the persistence of orthopedic implant infections. Previous studies have shown that exposure of S. epidermidis biofilms to sub-MICs of antibiotics induced an increased level of biofilm persistence. BODIPY FL-vancomycin (a fluorescent vancomycin conjugate) and confocal microscopy were used to show that the penetration of vancomycin through sub-MIC-vancomycin-treated S. epidermidis biofilms was impeded compared to that of control, untreated biofilms. Further experiments showed an increase in the extracellular DNA (eDNA) concentration in biofilms preexposed to sub-MIC vancomycin, suggesting a potential role for eDNA in the hindrance of vancomycin activity. Exogenously added, S. epidermidis DNA increased the planktonic vancomycin MIC and protected biofilm cells from lethal vancomycin concentrations. Finally, isothermal titration calorimetry (ITC) revealed that the binding constant of DNA and vancomycin was 100-fold higher than the previously reported binding constant of vancomycin and its intended cellular d-Ala-d-Ala peptide target. This study provides an explanation of the eDNA-based mechanism of antibiotic tolerance in sub-MIC-vancomycin-treated S. epidermidis biofilms, which might be an important factor for the persistence of biofilm infections.     

Antimicrobial resistance and persistence of Staphylococcus epidermidis clones in a Brazilian university hospital

Oxacillin is an alternative for the treatment of Staphylococcus spp. infections; however, resistance to this drug has become a major problem over recent decades. The main objective of this study was to epidemiologically characterize coagulase-negative staphylococci (CoNS) strains recovered from blood of patients hospitalized in a Brazilian teaching hospital. Oxacillin resistance was analyzed in 160 strains isolated from blood culture samples by phenotypic methods, detection of the mecA gene, and determination of intermediate sensitivity to vancomycin on brain heart infusion agar supplemented with 4 and 6 μg/mL vancomycin. In addition, characterization of the epidemiological profile by staphylococcal cassette chromosome mec (SCCmec) typing and clonal analysis by pulsed-field gel electrophoresis (PFGE) were performed. The mecA gene was detected in 72.5% of the isolates. Methicillin-resistant CoNS isolates exhibited the highest minimum inhibitory concentrations and multiresistance when compared to methicillin-susceptible CoNS strains. Typing classified 32.8% of the isolates as SCCmec I and 50% as SCCmec III. PFGE typing of the SCCmec III Staphylococcus epidermidis isolates identified 6 clones disseminated in different wards that persisted from 2002 to 2009. The high oxacillin resistance rates found in this study and clonal dissemination in different wards highlight the importance of good practices in nosocomial infection control and of the rational use of antibiotic therapy in order to prevent the dissemination of these clones.     

Characterization and monitoring of linezolid-resistant clinical isolates of Staphylococcus epidermidis in an intensive care unit 4 years after an outbreak of infection by cfr-mediated linezolid-resistant Staphylococcus aureus

Resistance to linezolid is emerging among Staphylococcus epidermidis isolates. During the 4 years following an outbreak of cfr-mediated linezolid-resistant S. aureus in our intensive care unit in 2008, we analyzed the clinical context and characterized the resistance mechanisms of 100 linezolid-resistant strains of S. epidermidis. The prevalence of the cfr gene in our strains reached 50% alone or in combination with other mechanisms. The mutation G2576T in domain V was found in 22% of strains, and both the cfr gene and G2576T in 44%. We also found an association between the cfr gene and mutations in the ribosomal protein L3. All 3 mechanisms co-occurred in 1 strain. MICs in combinations rose to >256 μg/mL. 58% of colonized patients, and 90% of infected patients had previously received linezolid for at last 10 days. Vancomycin was the main antibiotic in these infections, most of which were bacteremia. We found a high prevalence of the cfr gene in our clinical S. epidermidis isolates after the 2008 outbreak, despite having implemented isolation and control measures. The potential transmissibility of this agent, even without prior exposure to linezolid, can have serious epidemiological repercussions.     

Linezolid surveillance program results for 2008 (LEADER Program for 2008)

The LEADER Program was initiated in 2004 and monitors emerging linezolid resistance in sampled US medical centers. This report summarizes the data obtained in 2008, the 5th consecutive year. A total of 57 institutions participated in 2008 representing all 9 US census regions with 100 target organisms per site (6113 isolates, 101.9% compliance to protocol design). The organisms tested by reference broth microdilution methods were Staphylococcus aureus (3156), coagulase-negative staphylococci (CoNS; 856), enterococci (901), Streptococcus pneumoniae (619), and viridans group (223) or β-hemolytic streptococci (358); also, D-test was used to determine inducible clindamycin resistance in Staphylococcus aureus. Linezolid remained very potent against all sampled species with MIC₉₀ results ranging from 1 μg/mL (streptococci and CoNS) to 2 μg/mL (Staphylococcus aureus and enterococci). Only 0.36% of sampled strains were nonsusceptible to linezolid, a slight decrease from 0.45% and 0.44% in 2006 and 2007, respectively. The nonsusceptible strains (22) were Staphylococcus aureus (3), CoNS (14), and Enterococcus faecium (5) each with defined target mutations (G2576T in 19 strains; T2504A in 1 strain), mobile cfr element (1 strain Staphylococcus epidermidis with an identical pulsed-field gel electrophoresis pattern to a cfr-positive Staphylococcus epidermidis isolated from the same center in LEADER 2007), or an unknown (1 strain) mechanism. The mobile cfr resistance found in a Staphylococcus aureus strain in 2007 was not observed in 2008. In conclusion, linezolid activity sampled by the 5th year of this LEADER Program showed sustained potency and spectrum (99.64% susceptibility levels). The nonsusceptible strain isolation rates remained stable and the plasmid-mediated ribosomal-based resistance mechanism that emerged in Staphylococcus aureus and Staphylococcus epidermidis strains in 2007 showed no evidence of dissemination or increased prevalence. However, there was evidence of cfr persistence with the S. epidermidis strain. The LEADER Program continues to be an effective and sensitive surveillance tool to detect and monitor novel oxazolidinone resistance phenotypes and genotypes.     

金黄色葡萄球菌生物膜产生及相关毒力因子研究

目的 金黄色葡萄球菌引起的感染遍及临床各科,人体各部位。对临床分离的金黄色葡萄球菌进行生物膜、生物膜相关因子及毒力因子检测；方法 刚果红培养基法进行生物膜筛选；用电子显微镜观察生物膜的形成；用PCR方法检测生物膜相关基因及毒力因子。结果 100株金黄色葡萄球菌中,63株产生生物膜,产生物膜率达63.0％,均产生与生物膜高度相关的icaA基因、icaD基因；还可产生ebh、sea、seb、pvl、hla、fnbA 等毒力因子；产生物膜的菌中MRSA菌株占51.2%,MSSA占48.8%；结论 产生物膜的金黄色葡萄球菌已经成为医院感染的致病因素之一,常产生各种毒力因子。     

Efficacy of vancomycin and daptomycin against Staphylococcus aureus isolates collected over 29 years

We investigated vancomycin and daptomycin efficacy for Staphylococcus aureus isolates at our institution by testing 221 methicillin-sensitive and 299 methicillin-resistant isolates recovered from serious infections between 1979 and 2007 using a microdilution method. The MIC₉₀'s for vancomycin remained constant at 2 μg/mL for methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). For MSSA, the geometric mean vancomycin MICs remained at 1.1 μg/mL but varied from 1.1 to 1.7 for MRSA. Tolerance to vancomycin was seen in 6.5% of MRSA and 10.5% of MSSA. Daptomycin MIC₉₀'s remained at ≤1 μg/mL, and the daptomycin concentration at which 90% of the strains were killed (MBC₉₀) remained at 2 μg/ml. Over 29 years, no trend was detected in vancomycin or daptomycin susceptibilities. Daptomycin had excellent inhibitory and bactericidal activities against all strains throughout the years. Although vancomycin's inhibitory activity was consistent over time, vancomycin-tolerant strains whose presence was not predicted by their MIC were found.     

葡萄球菌生物膜的形成及影响因素

目的了解临床标本中葡萄球菌形成生物膜的状况，及葡萄糖、乙醇、氯化钠对生物膜形成的影响。方法采用刚果红、微量平板法检测生物膜形成及葡萄糖、乙醇、氯化钠对生物膜形成的影响。结果刚果红法检测金黄色葡萄球菌(金葡菌)、凝固酶阴性葡萄球菌(CNS)生物膜阳性率分别为26．2％和12．7％；生物膜半定量法，金葡菌：普通肉汤、0．25％葡萄糖、2％、4％乙醇、2％、4％氯化钠阳性率分别为14．7％、29．6％、32．7％、19．6％、13．1％和14．6％；CNS分别为13．9％、27．8％、26．5％、18．5％和21．5％。结论临床标本葡萄球菌相当一部分能产生生物膜，葡萄糖、乙醇能促进生物膜形成。     

Antimicrobial susceptibility and biofilm formation of Staphylococcus epidermidis small colony variants associated with prosthetic joint infection

We determined the frequency of isolation of non-aureus staphylococcal small colony variants (SCVs) from 31 patients with staphylococcal prosthetic joint infection (PJI) and described the antimicrobial susceptibility, auxotrophy, and biofilm-forming capacity of these SCVs. Eleven non-aureus SCVs were recovered, all of which were Staphylococcus epidermidis, and none of which was auxotrophic for hemin, menadione, or thymidine. Aminoglycoside resistance was detected in 5. Two were proficient, and 7 were poor, biofilm formers. With passage on antimicrobial free media, we observed a fluctuating phenotype in 3 isolates. We also noted a difference in antimicrobial susceptibility of different morphology isolates recovered from the same joints despite similar pulsed-field gel electrophoresis patterns. Our findings suggest S. epidermidis SCVs are common in PJI, and while they have a similar appearance to S. aureus SCVs, they do not necessarily share such characteristics as aminoglycoside resistance; auxotrophy for hemin, menadione, or thymidine; or enhanced biofilm formation. We also underscore the importance of antimicrobial susceptibility testing of all morphologies of isolates recovered from PJI.     

A comparative study of antibodies against proteins extracted from staphylococcal biofilm for the diagnosis of orthopedic prosthesis–related infections in an animal model and in humans

Staphylococcus aureus and Staphylococcus epidermidis are the microorganisms most frequently seen in periprosthetic infections (PPI) with the capacity of forming biofilm. To find potential antigens for the diagnosis of PPI, the immunogenicity of protein components in biofilm from a model biofilm-positive strain (S. epidermidis RP62A) was investigated. A guinea pig animal model of PPI was developed and sera were obtained. Sera of patients with PPI and those of controls were also collected. Data generated with an enzyme-linked immunosorbent assay showed that there were significantly higher levels of anti-extracellular protein IgG in sera of infected animals than in controls. We also found significantly higher anti-extracellular protein IgG levels in infected patients, compared to the controls; however, receiver operating characteristic curves did not aid in diagnosing PPI.     

Staphylococcus haemolyticus disseminated among neonates with bacteremia in a neonatal intensive care unit in Rio de Janeiro,Brazil

Oxacillin-resistant Staphylococcus haemolyticus (ORSH) was found as the most prevalent (77.5%) species of coagulase-negative staphylococci associated with bacteremia in neonates making use of intravenous catheters in an intensive care unit of a Brazilian teaching hospital. Thirty-one blood isolates were confirmed as S. haemolyticus by sequencing of the 16S and clustered in 6 pulsed-field gel electrophoresis types (with 58% of the strains belonging to 2 predominant types B and D). S. haemolyticus was mostly oxacillin-resistant (90.3%) displaying multiresistance profiles (70.4%). However, the mecA gene was undetected in 22.6% strains. ORSH exhibited slime production on Congo-Red agar (67.7%), adherence to polystyrene (96.7%), and glass (87%) surfaces. Interestingly, ica-operon was detected in 58% strains, mostly belonging to the B, D, and F genotypes, which is a significantly higher percentage when compared to other studies conducted at different parts of the globe. Data indicated that ica operon and biofilm-forming ORSH are endemic in Brazilian nosocomial environment.     

凝固酶阴性葡萄球菌致病性的鉴定

目的以细菌胞外多糖黏附素（PIA）产生作为毒力指标,鉴定凝固酶阴性葡萄球菌（CNS）的致病性。方法用刚果红琼脂培养法分离CNS,用刚果红-阿里新蓝对PIA进行联合染色,同时,与采自皮肤的CNS样本作阴性对照。结果致病性CNS在刚果红琼脂培养基中菌落呈黑色,阴性对照组的菌落为红色。染色镜下观察,致病性CNS菌体着色较深,菌体表面PIA显深红色;对照组菌体无PIA而为淡红色。结论刚果红琼脂培养法和刚果红-阿里新蓝联合染色,对CNS的分离和PIA的检测有重要意义,能为CNS致病性的确定提供可靠依据。     

Characteristics related to antimicrobial resistance and biofilm formation of widespread methicillin-resistant Staphylococcus epidermidis ST2 and ST23 lineages in Rio de Janeiro hospitals, Brazil

Staphylococcus epidermidis is a leading cause of hospital-acquired infections, mostly associated with the use of medical devices in seriously ill or immunocompromised patients. Currently, the characteristics of methicillin-resistant S. epidermidis (MRSE) isolates from Rio de Janeiro hospitals are unknown. In this study, staphylococcal chromosomal cassette mec (SCCmec) types, antimicrobial susceptibility profiles, biofilm formation genes, and multilocus sequence types (MLST) were investigated in 35 MRSE clinical isolates. The collection of isolates was previously well characterized by pulsed-field gel electrophoresis (PFGE) into 2 main genotypes (A and B, 22 isolates) and 10 sporadic genotypes (13 isolates). MLST revealed a total of 8 different sequence types (STs), but ST2 and ST23, which were icaAB-positive, represented the majority (71.4%) of MRSE isolates tested. Almost all isolates (91.4%) belonged to clonal complex 2. SCCmec types III and IV were identified among 71.4% of the isolates, while the remaining was nontypeable. The predominant MRSE genotypes were defined as SCCmec type III/ST2 (PFGE type A) and SCCmec type IV/ST23 (PFGE type B) isolates, which were both associated with high antimicrobial resistance and presence of biofilm-related genes.     

The emergence of Staphylococcus epidermidis simultaneously nonsusceptible to linezolid and teicoplanin in China

Two linezolid-resistant and teicoplanin-intermediate Staphylococcus epidermidis strains were isolated from blood cultures in China. The 2 S. epidermidis strains were methicillin-resistant and showed multidrug-resistance patterns; in addition, population analysis profiling/area under the curve (PAP/AUC) result showed heterogeneous resistant to vancomycin. Comparing to teicoplanin susceptible strains, the 2 isolates showed reduced autolytic activity. Pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) indicated that the 2 S. epidermidis isolates belonged to the same clone. Furthermore, the cfr gene, a G2576T mutation, and a novel C2146T mutation were detected in the 2 isolates. This was the first report of S. epidermidis simultaneously nonsusceptible to linezolid and teicoplanin in China.     

Methicillin-Resistant Staphylococcus aureus Grown on Vancomycin-Supplemented Screening Agar Displays Enhanced Biofilm Formation

Brain heart infusion agar containing 3 mg/liter vancomycin (BHI-V3) was used to screen for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA). There was markedly greater biofilm formation by isolates that grew on BHI-V3 than by strains that did not grow on BHI-V3. Increased biofilm formation by hVISA may be mediated by FnbA- and polysaccharide intercellular adhesin-dependent pathways, and upregulation of atlA and sarA may also contribute to enhanced biofilm formation by hVISA upon prolonged exposure to vancomycin.     

Identification of staphylococci by Phoenix: validation of a new protocol and comparison with Vitek 2

Because of their frequent isolation in the routine laboratory and their increasing clinical significance, fast and accurate species identification of staphylococci may be required; this can only be achieved by automated systems. A total of 147 clinical isolates (52 Staphylococcus aureus, 50 Staphylococcus epidermidis, and 45 other coagulase-negative staphylococci [CoNS]) were first identified by molecular methodology and then comparatively tested by Vitek 2 (new colorimetric identification card) and Phoenix using the novel 0.25 McFarland and the standard 0.50 McFarland inoculum protocols. All S. aureus isolates were accurately identified. Vitek 2 identified correctly all S. epidermidis and 93.3% of the other CoNS, whereas the respective rates were 86% and 82.2% for Phoenix's standard and 92% and 82.2% for the novel protocol. It appears that both systems provide excellent identification of S. aureus, but Vitek 2 recognizes CoNS species more accurately than Phoenix. The 0.25 McFarland protocol does not improve system performance.     

Growth, Congo Red agar colony morphotypes and antibiotic susceptibility testing of Mycobacterium avium subspecies paratuberculosis

OBJECTIVE: Mycobacterium avium subspecies (subsp.) paratuberculosis (MAP) is the causative agent of Johne's disease in ruminants and has been associated with Crohn's disease in humans. We sought to test growth rates and susceptibilities of various strains of MAP in two available growth media. DESIGN: Paired comparison design. METHODS: Using the BACTEC macrobroth radiometric growth system and Congo Red-staining agar media, we determined inherent differences in growth characteristics of three bovine and two human strains of MAP and compared susceptibility results obtained in each growth system. RESULTS: Significant differences were observed in growth rate as well as mycobactin J dependence between strains and between a laboratory-adapted isolate of the same strain in the macrobroth system. Similarly, colonial morphology and Congo Red staining on agar media were observed. Two strains, one human and one bovine, demonstrated a 100% rough transparent colony with white coloration on Congo Red agar, while one bovine isolate exclusively grew as a smooth opaque colony with red coloration on Congo Red agar. The remaining strains exhibited mixtures of these two colonial morphotypes on agar media. Comparative susceptibility results between the BACTEC radiometric macrobroth method and the agar proportionality method showed good correlation for most antibiotics/inhibitors tested. However, erratic or poor growth in the macrobroth system prevented minimal inhibitory concentration determinations for two bovine strains by this method. CONCLUSION: This study demonstrates the variability in the colonial morphology of MAP on Congo Red agar as well as the correlation of antibiotic susceptibility results between the BACTEC macro broth method and the agar proportionality method. This study also emphasizes the need for the development of improved, standardized culture and susceptibility test methods for MAP.     

In Vitro Studies of Pharmacodynamic Properties of Vancomycin against Staphylococcus aureus and Staphylococcus epidermidis

The bactericidal activities of vancomycin against two reference strains and two clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis were studied with five different concentrations ranging from 2× to 64× the MIC. The decrease in the numbers of CFU at 24 h was at least 3 log₁₀ CFU/ml for all strains. No concentration-dependent killing was observed. The postantibiotic effect (PAE) was determined by obtaining viable counts for two of the reference strains, and the viable counts varied markedly: 1.2 h for S. aureus and 6.0 h for S. epidermidis. The determinations of the PAE, the postantibiotic sub-MIC effect (PA SME), and the sub-MIC effect (SME) for all strains were done with BioScreen C, a computerized incubator for bacteria. The PA SMEs were longer than the SMEs for all strains tested. A newly developed in vitro kinetic model was used to expose the bacteria to continuously decreasing concentrations of vancomycin. A filter prevented the loss of bacteria during the experiments. One reference strain each of S. aureus and S. epidermidis and two clinical isolates of S. aureus were exposed to an initial concentration of 10× the MIC of vancomycin with two different half-lives (t_1/2s): 1 or 5 h. The post-MIC effect (PME) was calculated as the difference in time for the bacteria to grow 1 log₁₀ CFU/ml from the numbers of CFU obtained at the time when the MIC was reached and the corresponding time for an unexposed control culture. The difference in PME between the strains was not as pronounced as that for the PAE. Furthermore, the PME was shorter when a t_1/2 of 5 h (approximate terminal t_1/2 in humans) was used. The PMEs at t_1/2s of 1 and 5 h were 6.5 and 3.6 h, respectively, for S. aureus. The corresponding figures for S. epidermidis were 10.3 and less than 6 h. The shorter PMEs achieved with a t_1/2 of 5 h and the lack of concentration-dependent killing indicate that the time above the MIC is the parameter most important for the efficacy of vancomycin.     

Epidemiology and molecular characteristics of community-associated methicillin-resistant and methicillin-susceptible Staphylococcus aureus from skin/soft tissue infections in a children's hospital in Beijing,China

To evaluate the epidemiology and molecular features of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and methicillin-sensitive S. aureus (MSSA) from children with skin and soft tissue infections (SSTIs) in Beijing, China, prospective community-acquired S. aureus SSTIs surveillance was conducted at the Beijing Children's Hospital, Beijing, China, for a 12-month period from August 1, 2008, to July 30, 2009. Susceptibility to 12 antimicrobials was determined by the agar dilution method. Genotypic characteristics of CA-MRSA isolates were tested by SCCmec typing, spa typing, and multilocus sequence typing. Panton–Valentine leukocidin gene was detected. Of 1104 cases, 31.8% (351) were community-acquired S. aureus. CA-MRSA accounted for 4% (14) of S. aureus. Among 14 CA-MRSA and 120 MSSA isolates tested, 100% and 91.7% were multidrug resistant, respectively. ST59-MRSA-IVa-t437 (42.9%) was the most common form of CA-MRSA. Spa typing analysis of 120 MSSA isolates was performed, followed by pulsed-field gel electrophoresis and multilocus sequence typing of a selected number of isolates. The most common spa types among MSSA were t084 (8.3%), t091 (5.8%), t034 (5%), t127 (4.2%), t002 (4.2%), and t796 (4.2%). No predominant spa type was seen. Of the MSSA isolates that could be classified into spa-CCs, 15.0% had a genetic background observed in CA-MRSA clones (spa-CC437, spa-CC342, and spa-CC377). Panton-Valentine Leukocidin (PVL)-positive community-acquired S. aureus strains were more commonly associated with skin abscesses than other SSTIs (29.4% versus 5.9%, P < 0.01).In conclusion, CA-MRSA infections are not common among Chinese children with SSTIs. Our findings show that MSSA strains in China have diverse genetic backgrounds.     

Comparison of Sensititre microdilution method to other standard methods for susceptibility testing of coagulase-negative staphylococci from paediatric blood cultures

Susceptibility testing on 60 isolates of Staphylococcus epidermidis and 20 isolates of Staphylococcus hominis was performed using the Sensititre (Trek Diagnostics, Cleveland, OH, USA) method and compared with Vitek-2 automated susceptibility testing (bioMèrieux, Marcy l'Etoile, France), MICE strips for minimum inhibitory concentration determination (Oxoid, Basingstoke, UK), and disc diffusion (MAST, Bootle, UK). The categorical agreement between Vitek and Sensititre was greater than 90% for agents tested against S. epidermidis except for tetracycline (52%) and oxacillin (67%), and for S. hominis, the agreement was greater than 90% except for tetracycline (80%), gentamicin (65%), and oxacillin (75%). The categorical agreement between disc diffusion and Sensititre was greater than 90% for antimicrobials tested against S. epidermidis except for tetracycline (45%), moxifloxacin (70%), clindamycin (88%), and cefoxitin (80%), while against S. hominis, the categorical agreement was greater than 90% for antimicrobials tested except for gentamicin (65%), tetracycline (75%), moxifloxacin (80%), and ciprofloxacin (75%). Categorical agreement between MICE strips and Sensititre for S. epidermidis and S. hominis was greater than 95% for vancomycin and daptomycin. Sensititre method shows good categorical agreement with other standard methods for susceptibility testing of S. hominis and S. epidermidis.     

Update on the telavancin activity tested against European staphylococcal clinical isolates (2009-2010)

This study evaluated telavancin activity against 3868 Staphylococcus aureus and 1003 coagulase-negative staphylococci (CoNS) collected from 33 European hospitals (2009-2010). Studies of telavancin potency included analysis of strains with decreased susceptibility to glycopeptides. Telavancin (MIC_50/90, 0.12/0.25 μg/mL) showed high activity against S. aureus and CoNS, regardless of the stratification analysis performed (year sampled, infection source, or methicillin susceptibility). In addition, telavancin (MIC_50/90, 0.25/0.5 μg/mL) retained activity against S. aureus isolates with higher vancomycin (MIC, 2 μg/mL) or teicoplanin (MIC, 2-8 μg/mL) MIC results. Overall, telavancin exhibited higher potency (at least 2-fold greater) than tested comparators (vancomycin, daptomycin, and linezolid) against European staphylococci. Alongside published clinical data, the telavancin in vitro activity observed against these pathogens supports this drug as an option for treating S. aureus infections in Europe, including those infections caused by strains with decreased susceptibility to vancomycin and/or teicoplanin.