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Prospective study using standardized methodology for antimicrobial susceptibility of gram-positive cocci isolated from the Puerto Rico Medical Center.

The Gram-positive cocci (GPC), Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium, have become important causes of community and nosocomial-acquired infections. The prevalence of multiple resistant isolates to standard antimicrobial drugs has significantly increased over the past decades. Few prospective studies have been performed in Puerto Rico (PR) concerning the GPC antimicrobial susceptibilities pattern. The purpose of this study was to evaluate the in vitro susceptibility of GPC clinical isolates from PR to selected standard antibiotics and to the new antimicrobial agents, linezolid (LZ), quinupristin/dalfopristin (Q/D) and gemifloxacin (GM). The in vitro susceptibility utilizing disk diffusion and Etest methods to selected antibiotics was determined for a total of 429 isolates obtained during a period of 5 months from the Puerto Rico Medical Center Bacteriology Laboratory. The distribution of GPC collected was as follows: 213 S. aureus isolates, 162 E. faecalis, 16 E. faecium and 38 S. pneumoniae. The results of the susceptibility test demonstrated: 1) that in S. aureus, 100% of the isolates were susceptible to vancomycin (VAN), LZ and Q/D; 93% to GM; and 61% to methicillin/oxacillin; 2) in S. pneumoniae, 100% were susceptible to LN and GM; 87% to Q/D; and 53% to penicillin; 3) in E. faecalis, 99% were susceptible to ampicillin; 93% to LZ; 79% to GM; 78.6% to VAN; and 0% to Q/D. Sixty eight and 66% of the E. faecalis isolates were susceptible to gentamicin and streptomycin respectively; and 4) in E. faecium, 100% were susceptible to LZ; 94% to Q/D; 69% to GM; 37.5% to VAN and 20% to ampicillin. In E. faecium isolates, 50% and 31% were susceptible to gentamicin and streptomycin, respectively. Of the vancomycin resistant enterococci, 88.9% and 21% of E. faecium and faecalis showed VanA phenotypic resistance, respectively. These results show that there is a significant degree of antimicrobial resistance in GPC, including 38% methicillin resistance in S. aureus, a near 50% penicillin resistant S. pneumoniae, and a significant resistance of enterococcal species to VAN. The new agents, LZ, Q/D and GM, proved to be effective against both, S. aureus and S. pneumoniae. For E. faecium, both, LZ and Q/D were active, while for E. faecalis, only LZ showed consistent activity.

Gram-Positive Cocci↗

[Antibiotic resistance of enterococci in Germany].

BACKGROUND: The resistance of enterococci against various antimicrobial substances including vancomycin has increased markedly. Since 1989 in the USA in particular high resistance rates against vancomycin have been observed but very few surveillance have been published in Europe. Therefore, we conducted a multicenter study in Germany to obtain information about the incidence and distribution of vancomycin and/or high-level aminoglycoside-resistant enterococci. METHODS: A total of 2046 enterococcal isolates were identified and susceptibility-testing was performed according to international guidelines. RESULTS: A total number of 90.5% of the enterococcal isolates were identified as Enterococcus faecalis and 7.8% was Enterococcus faecium. Resistance against ampicillin was detected in 56.6% of the Enterococcus faecium isolates, however, in only one Enterococcus faecalis isolate. High-level resistance against gentamycin or streptomycin was observed in 7.3% and 24.8% of the isolates, respectively. Twelve isolates showed resistance against vancomycin, however, cross resistance with teicoplanin was found in only two isolates. CONCLUSION: The rate of resistance of enterococci in Germany is still considerably lower than in the United States. Previous vancomycin therapy has been implemented as a risk factor for colonization or infection with vancomycin-resistant enterococci. Continued vigilance, decreased use of vancomycin and strict enforcement of infection control measures are appropriate measures to control the growing problem of resistant enterococci.

Ampicillin Resistance↗

The association between antecedent vancomycin treatment and hospital-acquired vancomycin-resistant enterococci: a meta-analysis.

BACKGROUND: The association between vancomycin hydrochloride treatment and vancomycin-resistant enterococci (VRE) has been investigated in numerous studies with variable results. OBJECTIVES: To conduct a meta-analysis to estimate the magnitude of the association between vancomycin treatment and individual risk of VRE and to identify study characteristics that accounted for heterogeneity in study results. METHODS: Studies were identified using MEDLINE with index terms "Enterococcus," "Enterococcus faecalis," or "Enterococcus faecium" and "vancomycin," "drug resistance," "drug resistance, microbial," or "drug resistance, multiple or risk factors." Reports from conferences and reference lists of recent reviews were used. A total of 420 published reports and 98 conference reports were reviewed; 20 studies described in 15 published reports were included in the analysis. We recorded study period, hospital setting, case and control definitions, length of hospital stay, method of adjustment for differences in length of stay, and data on treatment with vancomycin. The odds ratio (OR) of vancomycin treatment provided the measure of association analyzed. A random-effects model was used to estimate the pooled OR. RESULTS: When results from all 20 studies were combined, the pooled OR was 4.5 (95% confidence interval, 3.0-6.9), but the test for heterogeneity was highly significant (P<.001). The 5 studies that used patients with vancomycin-susceptible enterococci as controls found a stronger association (pooled OR, 10.7; 95% confidence interval, 4.8-23.8) than the 15 studies that used controls who had no VRE isolated (pooled OR, 2.7; 95% confidence interval, 2.0-3.8). After restricting the analysis to the latter studies only, no heterogeneity was evident in the unadjusted study results. Patients with VRE had stayed in the hospital much longer than control patients. Studies that adjusted for this difference found only a small and nonsignificant association between vancomycin treatment and VRE (pooled OR, 1.4; 95% confidence interval, 0.74-2.60). We also detected publication bias, favoring report of studies that found a large measure of association. CONCLUSIONS: The reported strong association between vancomycin treatment and hospital-acquired VRE results from the selection of the reference group, confounding by duration of hospitalization, and publication bias. Studies that accounted for these factors found only a small and nonsignificant association.

Adult↗

The in vitro activity of flomoxef compared to four other cephalosporins and imipenem.

The antibacterial activity of the oxacephalosporin flomoxef was evaluated in comparison to cefpirome, cefuzoname, cefotaxime, ceftazidime, and imipenem against fresh clinical isolates. Flomoxef is an antibiotic with strong antibacterial activity against staphylococci including methicillin-resistant strains and streptococci with the exception of Enterococcus faecalis and Enterococcus faecium. It is very active against gram-negative cocci and rods including gram-positive and gram-negative anaerobes. Against Pseudomonas sp. flomoxef has no activity.

Cephalosporins↗

Evaluation of the Vitek 2 system for rapid identification of clinical isolates of gram-negative bacilli and members of the family Streptococcaceae.

Accuracy of the Vitek 2 automated system (bioMérieux Vitek, USA) for rapid identification of bacteria was evaluated using a collection of 858 epidemiologically unrelated gram-negative and 99 gram-positive clinical isolates. Isolates were tested after subculturing to ensure purity. Conventional agar-based biochemical tests (Steers replicator) were used as a reference method of identification. Gram-negative bacteria were identified to the species level with 95.3% accuracy by the system ( Enterobacteriaceae, 95.9%; and non- Enterobacteriaceae, 92.5%), and gram-positive isolates with 72% accuracy. Although Vitek 2 identified routine clinical isolates of gram-negative bacilli and Enterococcus faecalis and Enterococcus faecium reliably, rapidly, and reproducibly, improvement is required in the identification of less common species of enterococci and viridans group streptococci.

Automation↗

Survey of the susceptibility of urinary isolates to antibacterial agents in 2003.

In 2003, 826 uropathogenic strains were obtained from the urine of our patients. We assessed their activities to antibacterial agents based on the minimal inhibitory concentration (MIC) breakpoints recommended by the National Committee for Clinical Standards (NCCLS). Methicillin-resistant strains accounted for about 70% of Staphylococcus aureus and Staphylococcus epidermidis. The most common gram-positive species was Enterococcus faecalis (15.6%). Enterococcus faecium was the most resistant of the enterococcal species, and the rate of susceptibility to beta-lactams (BLs), fluoroquinolones (FQs), and tetracyclines (TCs) was 0%, 6%, and less than 18%, respectively. Escherichia coli accounted for over 50% of the gram-negative bacilli. The proportion of FQ-resistant or intermediate strains was over 20%, and four of these strains (1.1%) were suspected of producing extended-spectrum beta-lactamase (ESBL). All the ESBL-producing strains (ESBLs) possess resistance to FQs. Over 95% of Klebsiella pneumoniae was susceptible to all agents. The distribution of antimicrobial activity against Pseudomonas aeruginosa indicated a decrease in the number of multidrug-resistant strains and an increase in strains susceptible to all agents. Some differences existed in the resistance to antibacterial agents among Proteus species. No ESBL-producing or multidrug-resistant strain was isolated from Serratia marcescens. This survey suggests that serious clinical problems will result from the increasing number of enterococcal species with multidrug resistance in gram-positive cocci, and isolates of ESBL-producing or FQs-resistant strains in gram-negative bacilli.

Anti-Bacterial Agents↗

Characterization and partial purification of a bacteriocin produced by Leuconostoc carnosum LA44A.

Twenty Leuconostoc strains isolated from vacuum packaged Vienna-type sausages were screened for antagonistic activity against various Gram-positive organisms (including Listeria spp.). One of the three strains exhibiting inhibitory activity was chosen for further investigation. This strain was identified as Leuc. carnosum and the inhibitory substance produced was named carnosin. Carnosin was inactivated by trypsin but not by catalase or other non-proteolytic enzymes tested. Carnosin retained activity after heating at 100 degrees C for 20 min, whereas heating at 121 degrees C for 15 min resulted in complete loss of activity. Carnosin was active at pH values ranging from 2 to 9. Carnosin activity was not detectable until cells were in the late log-phase of growth. At low temperatures (4 degrees C), higher cell densities were required before carnosin activity could be detected. Carnosin was active against various lactic acid bacteria, Enterococcus faecalis and Enterococcus faecium and against Listeria spp. Difficulties in purification were reduced by growing Leuc. carnosum in a modified MRS medium, having 50% of the normal peptone concentration and no Tween or meat extract. Sodium dodecyl sulphate polyacrylamide gel electrophoresis of partially purified carnosin indicated that it has a molecular mass between 2510 and 6000 Da. Yet, retention of activity after exhaustive dialysis suggested a molecular mass > 14kDa. It is hypothesized that carnosin forms large active complexes which can be dissociated to small (active) components.

Bacteriocins↗

In vitro activity of sparfloxacin and clinafloxacin against multidrug-resistant enterococci.

We evaluated the in vitro susceptibility of 140 clinical enterococcal isolates to the quinolones sparfloxacin and clinafloxacin. Isolates included Enterococcus faecalis (107), Enterococcus faecium (29), Enterococcus raffinosus (3), and one Enterococcus gallinarum. There were 111 isolates that showed high-level [minimum inhibitory concentrations (MICs) > or = 2000 micrograms/ml] resistance to gentamicin and were resistant to high levels of all other aminoglycosides; five isolates produced beta-lactamase; 21 isolates were resistant (MIC > or = 16 micrograms/ml) to ampicillin and were not beta-lactamase producers; and 13 strains were resistant (MIC > or = 32 micrograms/ml) to vancomycin. Most strains were susceptible to low concentrations of sparfloxacin and clinafloxacin, with MIC90S of 0.6 microgram/ml and 0.5 micrograms/ml, respectively. There were no inoculum effects. Time-kill experiments were performed with 22 strains; using 2 x MIC at 24 h, a > or = 2 log10 reduction in growth was observed with sparfloxacin and clinafloxacin for 14 and 17 strains, respectively. Time-kill synergism experiments were performed with 15 strains lacking high-level aminoglycoside resistance. In vitro bacterial synergism with the combination of sparfloxacin or clinafloxacin with streptomycin or gentamicin was observed for five and 12 isolates, respectively. The bactericidal activity of sparfloxacin and clinafloxacin suggest that these antibiotics may prove useful for therapy of multidrug resistant enterococci.

Anti-Infective Agents↗

Beta-nitrostyrene derivatives as potential antibacterial agents: a structure-property-activity relationship study.

A multidisciplinary project was developed, combining the synthesis of a series of beta-nitrostyrene derivatives and the determination of their physicochemical parameters (redox potentials, partition coefficients), to the evaluation of the corresponding antibacterial activity. A complete conformational analysis was also performed, in order to get relevant structural information. Subsequently, a structure-property-activity (SPAR) approach was applied, through linear regression analysis, aiming at obtaining a putative correlation between the physicochemical parameters of the compounds investigated and their antibacterial activity (both against standard strains and clinical isolates). The beta-nitrostyrene compounds displayed a lower activity towards all the tested bacteria relative to the beta-methyl-beta-nitrostyrene analogues. This was observed particularly for the 3-hydroxy-4-methoxy-beta-methyl-beta-nitrostyrene (IVb) against the Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium). The SPAR results revealed the existence of a clear correlation between the redox potentials and the antibacterial activity of the series of beta-nitrostyrene derivatives under study.

Anti-Bacterial Agents↗

Activity of daptomycin against multi-resistant Gram-positive bacteria including enterococci and Staphylococcus aureus resistant to linezolid.

The activity of daptomycin was assessed against 545 isolates of Gram-positive bacteria including enterococci, coagulase-positive and -negative staphylococci, beta-haemolytic streptococci, viridans streptococci and coryneforms. The panel of isolates was biased towards those with resistance to first-line antimicrobial agents and included linezolid-resistant enterococci and Staphylococcus aureus. MICs of daptomycin were < or =1mg/l for all the staphylococci, streptococci, and coryneforms, except for two isolates of Corynebacterium aquaticum, for which MICs were 8 mg/l. Daptomycin MICs were < or =2 and < or =4 mg/l for Enterococcus faecalis and Enterococcus faecium, respectively.

Acetamides↗

Enterococcal infections: host response, therapeutic, and prophylactic possibilities.

The emergence of resistance against multiple antibiotics and the increasing frequency with which Enterococcus faecalis and Enterococcus faecium are isolated from hospitalized patients underscore the necessity for a better understanding of the virulence mechanisms of this pathogen and the development of alternatives to current antibiotic treatments. The genetic plasticity of enterococci and their ability to rapidly acquire and/or develop resistance against many clinically important antibiotics and to transfer these resistance determinants to other more pathogenic microorganisms makes the search for alternative treatment and preventive options even more important. A capsular polysaccharide antigen has recently been characterized that is the target of opsonic antibodies. A limited number of clinically relevant serotypes exist, and the development of an enterococcal vaccine based on capsular polysaccharides may improve our ability to prevent and treat these infections. Additional enterococcal surface antigens, including ABC transporter proteins and other virulence factors, such as aggregation substance (AS), may also be useful targets for therapeutic antibodies.

Animals↗

The effect of pH on the inhibition of bacterial growth by physiological concentrations of butyric acid: implications for neonates fed on suckled milk.

Butyric acid is released from milk by pre-intestinal lipases during suckling. It is also known to inhibit bacterial growth. To investigate whether butyric acid may be a significant factor in controlling bacterial growth in the stomach of pre-weaned animals, the ability of butyric acid to inhibit growth of selected bacteria was tested over physiological ranges of pH and butyric acid concentrations. Six enteric and environmental strains of bacteria were used: two strains of Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, Enterococcus faecalis, and Enterococcus casseliflavus. At pH 4.5 and 5.0, the growth of all organisms was significantly inhibited in the presence of butyrate, and in some cases growth was completely arrested. At pH 6.0, butyric acid did not affect bacterial growth until the concentration reached 40 mM. The maximum concentration of butyric acid available in cow's milk after incubation with pre-gastric lipase is approximately 16 mM, which would be sufficient to prevent growth of the organisms tested at pH values occurring in the stomach. Therefore, butyric acid inhibition of bacterial growth may explain in part, the role of pre-intestinal lipases in young animals' natural defenses against bacteria in ingested food prior to weaning.

Animals↗

Results of a multicenter, randomized, open-label efficacy and safety study of two doses of tigecycline for complicated skin and skin-structure infections in hospitalized patients.

BACKGROUND: Tigecycline is a broad-spectrum glycylcycline antibiotic being investigated for the treatment of serious infections in hospitalized patients. Tigecycline has been shown to be efficacious against serious infections in animals, and preliminary studies in healthy adults have shown that tigecycline has an acceptable tolerability profile. OBJECTIVE: This study compared the clinical and microbiological efficacy, pharmacokinetic properties, and tolerability of 2 doses of tigecycline in hospitalized patients with a complicated skin and skin-structure infection (cSSSI). METHODS: This Phase II, randomized, open-label study was conducted between September 1999 and March 2001 at 14 investigative centers across the United States. Patients were randomized to receive tigecycline 25 or 50 mg IV q12h for 7 to 14 days. The primary efficacy end point was the clinically observed cure rate among clinically evaluable (CE) patients at the test-of-cure visit. Secondary end points were the clinical cure rate at the end of treatment and bacteriologic response in microbiologically evaluable (ME) patients. Also, in vitro tests of susceptibility to tigecycline were performed for selected pathogens known to cause skin infections, including methicillin-resistant and methicillin-susceptible Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, and Enterococcus faecium. Tolerability assessments also were conducted. RESULTS: A total of 160 patients received > or =1 dose of tigecycline; 109 patients were CE, and 91 were ME. The majority of patients (74%) were men, and the mean (SD) age was 49.0 (14.8) years. At the test-of-cure visit, the clinical cure rate in the 25-mg group was 67% (95% CI, 53.3%-79.3%) and in the 50-mg group was 74% (95% CI, 60.3%-85.0%). In the 25-mg group, 56% of the patients had eradication (95% CI, 40.0%-70.4%) of the pathogens compared with 69% (95% CI, 54.2%-82.3%) in the 50-mg group. Values for the minimum concentration of tigecycline that is inhibitory for 90% of all isolates ranged from 0.06 to 0.50 microg/mL for the selected pathogens. Both tigecycline doses were generally well tolerated. Nausea and vomiting were the most common adverse events. CONCLUSIONS: In this study, tigecycline appeared efficacious and showed a favorable pharmacokinetic profile and an acceptable safety profile in the treatment of hospitalized patients with cSSSI. In patients who received 50-mg doses of tigecycline q12h, the clinical cure rates and microbial eradication rates were 74% and 70%, respectively, and were 67% and 56% in patients who received 25-mg doses.

Adolescent↗

The tyrosine decarboxylase operon of Lactobacillus brevis IOEB 9809: characterization and conservation in tyramine-producing bacteria.

Bacterial genes of tyrosine decarboxylases were recently identified. Here we continued the sequencing of the tyrosine decarboxylase locus of Lactobacillus brevis IOEB 9809 and determined a total of 7979 bp. The sequence contained four complete genes encoding a tyrosyl-tRNA synthetase, the tyrosine decarboxylase, a probable tyrosine permease and a Na+/H+ antiporter. Rapid amplification of cDNA ends (RACE) was employed to determine the 5'-end of mRNAs containing the tyrosine decarboxylase gene. It was located only 34-35 nucleotides upstream of the start codon, suggesting that the preceding tyrosyl-tRNA synthetase gene was transcribed separately. In contrast, reverse transcription-polymerase chain reactions (RT-PCRs) carried out with primers designed to amplify regions spanning gene junctions showed that some mRNAs contained the four genes. Homology searches revealed similar clusters of four genes in the genome sequences of Enterococcus faecalis and Enterococcus faecium. Phylogenetic analyses supported the hypothesis that these genes evolved all together. These data suggest that bacterial tyrosine decarboxylases are encoded in an operon containing four genes.

Amino Acid Sequence↗

Clonal dissemination of vancomycin-resistant Enterococci and comparison of susceptibility testing methods.

One hundred fifty clinical isolates of Enterococcus faecalis (88 isolates) and Enterococcus faecium (62 isolates) were tested in vitro for their susceptibility to vancomycin and high-level aminoglycosides (HLA). Remel's Synergy Quad Plates (RSQ) were used as the reference method and compared to Kirby-Bauer disc diffusion test, Vitek GPS-TA card, MicroScan Panel (GP-6), and Etest. Streptomycin susceptibility results for MicroScan GP-6 and RSQ were recorded at 24 and 48 h and all other methods and antibiotics were read at 24 h or less. When compared with the agar screen method, all of the methods demonstrated > 99% agreement. One isolate was falsely sensitive to gentamicin at 24 h, but resistant at 48 h, when tested on both MicroScan and RSQ agar screen. Thirty-nine isolates showed resistance to vancomycin with all methods. These isolates were from three different local hospitals and were identified as E. faecium. Pulse-field gel electrophoresis demonstrated that all of the vancomycin-resistant isolates were derived from the same clone. Of interest is the observation that high-level resistance to aminoglycosides varied between the clonally related isolates.

Aminoglycosides↗

Antimicrobial activity of imipenem against isolates from complicated urinary tract infections.

Antimicrobial activity of imipenem was measured using 4725 strains isolated from patients with complicated urinary tract infections (CUTIs) between 1988 and 2000. Imipenem was inactive against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, Enterococcus faecium and some non-fermenting Gram-negative rods. Resistant strains (MIC>16 mg/l) were observed in Staphylococcus haemolyticus (22%), Enterococcus faecalis (4%), Enterococcus avium (8%), Serratia marcescens (5%) and Pseudomonas aeruginosa (7%). Although the prevalence of imipenem-resistant strains of S. aureus, S. epidermidis and P. aeruginosa was sporadically high in some years, no steady increase was seen over the period. Resistant strains were rare in other major uropathogenic species. These results suggest that imipenem is still one of the most reliable antimicrobial drugs.

Anti-Bacterial Agents↗

Survival of enterococci during hospital laundry processing.

Much remains to be elucidated about the epidemiology of nosocomial enterococcal infections. Enterococci are, however, known to be relatively thermotolerant, and several studies have shown that under laboratory conditions many strains are able to survive the time/temperature combinations of the UK Department of Health recommendations for the decontamination of used linen (HSG(95)18). We therefore wished to investigate the efficacy of decontamination of enterococci from hospital linen in working hospital laundries. The thermotolerance of 40 strains of Enterococcus faecalis and Enterococcus faecium was first determined. Reduction by a factor of greater than 10(5) was achieved in only two of 40 strains after 3 min at 71 degrees C or 10 min at 65 degrees C, the time/temperature combinations specified by the Department of Health for the disinfection of used linen. During experimental challenge of 10 working hospital laundries, however, we demonstrated successful decontamination of laundry artificially contaminated with enterococci. This was shown to take place during the washing stage. Our study suggests that, despite the relative thermotolerance of enterococci, the time/temperature combinations specified in HSG(95)18 should be adequate for their decontamination in hospital laundries.

Decontamination↗

Susceptibility to quinupristin-dalfopristin and linezolid in 839 clinical isolates of Gram-positive cocci from Norway.

A total of 839 clinical isolates of Gram-positive cocci from Norway including Staphylococcus aureus (n = 214), coagulase negative Staphylococcus spp. (n = 100), Streptococcus pyogenes (n = 99), Streptococcus agalactiae (n = 80), Streptococcus pneumoniae (n = 127), Streptococcus spp. viridans group (n = 70), Enterococcus faecalis (n = 75), and Enterococcus faecium (n = 74), were tested by E-test for susceptibility to a range of antimicrobials including the novel antibiotics quinupristin-dalfopristin and linezolid. Subgroups of oxacillin resistant S. aureus and coagulase negative Staphylococcus spp., penicillin non-susceptible S. pneumoniae and vancomycin resistant Enterococcus spp. were specifically included as they are the intended targets for these new drugs. All isolates were susceptible to linezolid (MIC5o and MIC9o 0.25-2.0 mg/l, MIC range 0.12-2 mg/l). Staphylococcal and streptococcal isolates were also susceptible to quinupristin-dalfopristin except for some intermediately susceptible viridans group isolates (MIC54, and MIC90 0.25-2 mg/l, MIC range 0.125-2 mg/l). Enterococcus faecium (MIC90 = 4.0 mg/l) and Enterococcus faecalis (MIC50 = 8.0 mg/l, MIC90 > or = 32 mg/l) were less susceptible to this substance. There was no linkage between reduced susceptibility to linezolid or quinupristin-dalfopristin and resistance to other classes of antimicrobials. The study demonstrated a high prevalence of in vitro susceptibility to linezolid and quinupristin-dalfopristin, which is necessary for their use in the treatment of infections with resistant Gram-positive pathogens. The results were used to evaluate the appropriateness of breakpoints and to define a baseline for monitoring possible future emergence of resistance to quinupristin-dalfopristin and linezolid in Norway.

Acetamides↗