Spectrum and potency of dalbavancin tested against 3322 Gram-positive cocci isolated in the United States Surveillance Program (2004)

Dalbavancin is an injectable, next generation lipoglycopeptide with an extended serum elimination half-life. Once-weekly dosing has been successful for treatment of skin and skin structure (SSSI) and catheter-related bloodstream infections (CR-BSI). Concurrent with clinical trails, dalbavancin resistance surveillance was initiated in 2003, and results are reported here for the 2004 United States (USA) component. A total of 3322 Gram-positive cocci were tested by reference broth microdilution methods. Organism species tested included: Staphylococcus aureus (2102; 49% oxacillin-resistant), coagulase-negative staphylococci (CoNS; 255, 82% oxacillin-resistant), beta-hemolytic streptococci (241), viridans group streptococci (46), and Streptococcus pneumoniae (678). Dalbavancin (MIC90,0.06-0.12 microg/mL) was comparable in spectrum, but superior in potency to vancomycin (MIC90,1-2 microg/mL) against staphylococci. Dalbavancin MIC90 values against the tested streptococci was 0.03 microg/mL. Dalbavancin was more active against tested SSTI pathogens than comparator agents having complete susceptibility rates (100.0%) similar to vancomycin. Vancomycin, (16- to 32-fold), linezolid (8- to 32-fold), daptomycin (4- to 32-fold), and quinupristin/dalfopristin (4- to 32-fold) were less active than dalbavancin. In conclusion, dalbavancin exhibited greater potency than comparison glycopeptides or lipopeptides, streptogramin combinations, and oxazolidinones against Gram-positive pathogens associated with SSSI or CR-BSI. Dalbavancin wild-type MIC distributions remain unchanged compared with prior sampled years (2002-2003) in the USA.     

Worldwide assessment of dalbavancin activity and spectrum against over 6,000 clinical isolates

Continuing emergence of new antimicrobial resistance mechanisms and the increased frequency of existing resistances, requires the development of alternative antimicrobial agents. Dalbavancin is an amide glycopeptide derivative with a markedly extended serum elimination half-life. Dalbavancin and selected comparators were tested against 6,339 recent clinical isolates (2002) from the Americas and Europe using reference susceptibility testing methods. The general characteristics of this Gram-positive organism collection were: oxacillin (OXA)-resistant Staphylococcus aureus (ORSA) at 39% of strains; vancomycin-resistant enterococci (VRE) at 10%; and penicillin-nonsusceptible pneumococci at 28%. The overall distribution of dalbavancin minimum inhibitory concentration (MIC) values ranged from < or = 0.015 to > 32 microg/ml, but > 99% of MIC results were at < or =1 microg/ml. S. aureus and coagulase-negative staphylococci were extremely susceptible to dalbavancin (MIC90, 0.06 microg/ml) despite resistance patterns to other agents. Dalbavancin was the most potent compound (by weight) against vancomycin-susceptible Enterococcus faecalis and E. faecium (MIC90, 0.06 and 0.12 microg/ml, respectively); however, VRE strains showed decreased dalbavancin susceptibility (MIC50, 4 or 8 microg/ml). All streptococcal isolates were inhibited at < or =0.25 microg/ml of dalbavancin. This reported dalbavancin activity indicates that the new glycopeptide has significant activity, superior to available agents in the class, and a potency that was uniform across geographically sampled organisms. Some VRE were inhibited by very low dalbavancin concentrations (< or = 1 microg/ml; Van B phenotypes). Further clinical development seems warranted for this once-weekly administered agent.     

Microbiologic characterization of isolates from a dalbavancin clinical trial for catheter-related bloodstream infections

Dalbavancin, a new-generation semisynthetic lipoglycopeptide in phase 3 clinical development, has been documented to be more active than vancomycin or teicoplanin against Gram-positive bacteria, including multidrug-resistant strains, by in vitro testing and in animal models. The human pharmacokinetics of dalbavancin predicts efficacy at weekly dosing intervals. In a phase 2 open-label clinical trial, dalbavancin exhibited superiority when compared with vancomycin against catheter-related bloodstream infection (CR-BSI). The majority of pathogens identified in this study as in clinical practice were coagulase-negative staphylococci (CoNS), necessitating rigorous characterization of duplicate isolates to rule out contaminants and to validate cases for study evaluations. At follow-up for the intent-to-treat population, overall pathogen eradication was 92.3% for dalbavancin and 75.9% for vancomycin. We describe the details of organisms isolated, their epidemiologic/genetic characterization, susceptibility patterns against glycopeptides, and the eradication rates by organism group. In conclusion, dalbavancin was active against all isolated pathogens associated with CR-BSI (CoNS, Staphylococcus aureus and Enterococcus faecalis; all MIC results, < or = 0.25 microg/mL) and achieved significant (P < 0.05) clinical success when compared with vancomycin.     

In vitro activity of dalbavancin and telavancin against staphylococci and streptococci isolated from patients in Canadian hospitals: results of the CANWARD 2007-2009 study

Two novel lipoglycopeptides, dalbavancin and telavancin, and relevant comparative agents were tested for in vitro activity against clinical isolates of staphylococci and streptococci collected in the cross-Canada surveillance study, CANWARD, in 2007-2009. The rank order of potency (based on MIC(90) [μg/mL], i.e., the concentration of antimicrobial agent required to inhibit the growth of 90% of isolates tested) of glycopeptides against both Staphylococcus aureus and Staphylococcus epidermidis was dalbavancin (0.06 μg/mL) >telavancin (0.5 μg/mL) > vancomycin (1-2 μg/mL); concurrent susceptibility or resistance to oxacillin in staphylococci did not affect potency of glycopeptides. Dalbavancin and telavancin also demonstrated potent activity against Streptococcus pneumoniae, including penicillin-resistant isolates (MIC(90), ≤ 0.03 μg/mL; ≤ 0.06 μg/mL), and Streptococcus pyogenes (≤ 0.03 μg/mL; 0.06 μg/mL). Based on their robust in vitro activities, dalbavancin and telavancin have the potential to treat Gram-positive infections caused by methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae.     

Glycopeptide resistance vanA operons in Paenibacillus strains isolated from soil

The sequence and gene organization of the van operons in vancomycin (MIC of >256 microg/ml)- and teicoplanin (MIC of > or =32 microg/ml)-resistant Paenibacillus thiaminolyticus PT-2B1 and Paenibacillus apiarius PA-B2B isolated from soil were determined. Both operons had regulatory (vanR and vanS), resistance (vanH, vanA, and vanX), and accessory (vanY, vanZ, and vanW) genes homologous to the corresponding genes in enterococcal vanA and vanB operons. The vanA(PT) operon in P. thiaminolyticus PT-2B1 had the same gene organization as that of vanA operons whereas vanA(PA) in P. apiarius PA-B2B resembled vanB operons due to the presence of vanW upstream from the vanHAX cluster but was closer to vanA operons in sequence. Reference P. apiarius strains NRRL B-4299 and NRRL B-4188 were found to harbor operons indistinguishable from vanA(PA) by PCR mapping, restriction fragment length polymorphism, and partial sequencing, suggesting that this operon was species specific. As in enterococci, resistance was inducible by glycopeptides and associated with the synthesis of pentadepsipeptide peptidoglycan precursors ending in D-Ala-D-Lac, as demonstrated by D,D-dipeptidase activities, high-pressure liquid chromatography, and mass spectrometry. The precursors differed from those in enterococci by the presence of diaminopimelic acid instead of lysine in the peptide chain. Altogether, the results are compatible with the notion that van operons in soil Paenibacillus strains and in enterococci have evolved from a common ancestor.     

Antimicrobial susceptibility of 3931 organisms isolated from intensive care units in Canada: Canadian National Intensive Care Unit Study, 2005/2006

We tested the in vitro activity of 15 antimicrobials against Gram-positive cocci and 12 antimicrobials against Gram-negative bacilli versus 3931 isolates (20 most common organisms) obtained between September 1, 2005, and June 30, 2006, from 19 intensive care units (ICUs) across Canada. The most active (based upon MIC only) agents against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis were dalbavancin, daptomycin, linezolid, tigecycline, and vancomycin with MIC(90) (microg/mL) of 0.06 and < or =0.03, 0.25 and 0.12, 2 and 1, 0.5 and 0.5, and 1 and 2, respectively. The most active agents against vancomycin-resistant enterococci were daptomycin, linezolid, and tigecycline with MIC(90) (microg/mL) of 1, 4, and 0.12, respectively. The most active agents against Escherichia coli were amikacin, cefepime, meropenem, piperacillin/tazobactam, and tigecycline with MIC(90) (microg/mL) of 4, < or =1, < or =0.12, 8, and 0.5, respectively. The most active agents against extended-spectrum beta-lactamase-producing E. coli were meropenem and tigecycline with MIC(90) (microg/mL) of < or =0.12 and 1, respectively. The most active agents against Pseudomonas aeruginosa were amikacin, cefepime, meropenem, and piperacillin/tazobactam with MIC(90) (microg/mL) of 16, 32, 16, and 64, respectively. The most active agents against Stenotrophomonas maltophilia were tigecycline and trimethoprim/sulfamethoxazole with MIC(90) (microg/mL) of 4 and 4, respectively. The most active agents against Acinetobacter baumannii were fluoroquinolones (e.g., levofloxacin), meropenem, and tigecycline with MIC(90) (microg/mL) of 0.5, 1, and 2, respectively. In conclusion, the most active agents versus Gram-positive cocci and Gram-negative bacilli obtained from Canadian ICUs were daptomycin, linezolid, tigecycline, dalbavancin and amikacin, cefepime, meropenem, piperacillin/tazobactam, and tigecycline (not P. aeruginosa), respectively.     

Comparative in-vitro activity of LY146032 a new peptolide, with vancomycin and eight other agents against gram-positive organisms

The in-vitro activity of LY146032, a new biosynthetic peptolide antibiotic, was compared with vancomycin and eight other antibiotics against 190 Gram-positive bacteria. Organisms tested included streptomycin-susceptible and resistant enterococci, nafcillin-susceptible and resistant Staphylococcus aureus, and nafcillin-susceptible and resistant Staph. epidermidis. LY146032 had excellent in-vitro inhibitory and bactericidal activity against nafcillin-susceptible and resistant staphylococci (MIC90 less than or equal to 0.5 mg/l) and against enterococci (MIC90 less than or equal to 2.0 mg/l). LY146032 was more active than vancomycin against the majority of isolated tested. With the exception of trimethoprim-sulphamethoxazole, LY146032 was the most active agent in vitro against enterococci, and was the most active against nafcillin-resistant staphylococci. LY146032 and vancomycin showed a marked increase in MIC when the inoculum was increased from 10(5) to 10(7) cfu/ml. LY146032 and vancomycin were bactericidal at concentrations within two dilutions of the MIC for staphylococci. LY146032 was bactericidal at less than or equal to 8 mg/l for all enterococcal isolates tested.     

Comprehensive update of dalbavancin activity when tested against uncommonly isolated streptococci, Corynebacterium spp., Listeria monocytogenes, and Micrococcus spp. (1357 strains)

Dalbavancin is an investigational lipoglycopeptide having an extended serum elimination half-life allowing once-weekly dosing. Data from testing 1357 strains of uncommonly isolated species expand the dalbavancin spectrum details as follows (MIC_50/90): β-haemolytic streptococcal serogroups C, F, and G (≤0.03/≤0.03 μg/mL), 7 viridans group of streptococci (≤0.03/≤0.03–0.06 μg/mL), 5 Corynebacterium spp. (0.06/0.12 μg/mL), Listeria monocytogenes (0.06/0.12 μg/mL), and Micrococcus spp. (≤0.03/≤0.03 μg/mL). Among all reported isolates, 99.8% of tested strains were inhibited at dalbavancin MIC values at ≤0.12 μg/mL. Dalbavancin remains very potent against rarer Gram-positive pathogens, using in vitro test experience with organisms cultured through 2011.     

Zyvox Annual Appraisal of Potency and Spectrum Program Results for 2006: an activity and spectrum analysis of linezolid using clinical isolates from 16 countries

The Zyvox Annual Appraisal of Potency and Spectrum Program has completed its fifth year of monitoring for emerging resistance to linezolid and other Gram-positive active agents on the continents of Europe, Asia, Australia, and Latin America. In 2006, 4216 Gram-positive isolates from 16 nations were submitted for analysis from 6 organism groups including Staphylococcus aureus (54.0%), coagulase-negative staphylococci (CoNS) (14.6%), enterococci (10.0%), Streptococcus pneumoniae (9.4%), viridans group streptococci (5.0%), and beta-hemolytic streptococci (7.0%). Linezolid retained potent activity against S. aureus (MIC(50) and MIC(90), 2 microg/mL; 39.8% methicillin resistant) and CoNS (MIC(50) and MIC(90), 1 microg/mL; 74.3% methicillin resistant). Despite endemicity of vancomycin-resistant enterococci (up to 30.0%) in several nations, linezolid inhibited >99% of strains at 相似文献   

Antimicrobial activity of daptomycin against multidrug-resistant Gram-positive strains collected worldwide

Daptomycin is a cyclic lipopeptide recently released for clinical use in the treatment of serious Gram-positive infections in hospitalized patients. We evaluated the in vitro activity of daptomycin tested against recently isolated multidrug-resistant Gram-positive clinical strains. A total of 386 isolates were selected from a large collection of strains from more than 70 centers located in Europe, North America, and South America. The strains were tested by reference broth microdilution methods in Mueller-Hinton broth with 50 mg/L Ca++ against daptomycin. Daptomycin was the most potent compound tested against penicillin-resistant Streptococcus pneumoniae with MIC50/90 values at < or =0.12 and 0.25 microg/mL, respectively. Daptomycin was also highly active against vancomycin-resistant enterococci and staphylococcal strains with various resistance patterns. Enterococcus faecium showed higher daptomycin MIC values (MIC90, 4 microg/mL) when compared to E. faecalis (MIC90, 1 microg/mL). In summary, resistance to vancomycin, teicoplanin, quinupristin/dalfopristin, or penicillin among the Gram-positive isolates did not adversely influence daptomycin activity. Daptomycin showed a significant potency and spectrum against Gram-positive species, including multidrug-resistant strains, and may represent a reasonable therapeutic option for infections caused by these important pathogens.     

Molecular characterization of multidrug-resistant Enterococcus spp. from poultry and dairy farms: detection of virulence and vancomycin resistance gene markers by PCR

Thirty multidrug-resistant Enterococcus spp. strains, including two from the milk of cows with mastitis, nine from chicken litter and 19 from turkey litter, were isolated. Twenty-five were identified by biochemical methods as E. gallinarum and five as E. faecalis. Most of the isolates were resistant to vancomycin, gentamicin, streptomycin, tetracycline, erythromycin, bacitracin, kanamycin and nalidixic acid but sensitive to ciprofloxacin, sulfamethoxazole, chloramphenicol, ampicillin and ofloxacin. Attempts were made by partial amplification of the gene sequences to detect the vancomycin resistance markers vanA (734-bp), vanB (420-bp), vanC1 (531-bp), and vanC2-C3 (673-bp); virulence markers cylA (427-bp) and cylB (225-bp) for enterococcal cytolysin and a biofilm-forming surface protein (Esp). Individual and multiplex-PCR assays for vancomycin resistance markers revealed the vanC1 gene in 22 E. gallinarum strains. None of the remaining isolates including five E. faecalis strains (MIC=2 microg ml(-1)) and three E. gallinarum strains (MIC=8 microg ml(-1)) had any of the van genes tested. Analysis by pulsed-field gel electrophoresis (PFGE) and a comparison of smaI banding profiles showed 11 different patterns. Probing with a DIG-labeled vanC1 PCR product indicated a common 38.0 kb SmaI DNA fragment in all the E. gallinarum strains harboring the vanC1 gene. The genes cylA and cylB were detected only in one clinical E. gallinarum isolate and two quality control clinical strains of E. faecalis (ATCC 51299 and 29212). None of the virulence factors were found in milk or poultry isolates. Intermediate level resistance to vancomycin in enterococci from the US animal farms was predominantly due to the presence of vanC1 gene.     

Phenotypic and genotypic heterogeneity of glycopeptide resistance determinants in gram-positive bacteria

Gram-positive glycopeptide-resistant bacteria isolated in various hospitals in Europe and in the United States between 1986 and 1988 were collected. Three resistance phenotypes could be distinguished. Thirty-one enterococci were highly resistant to vancomycin and teicoplanin. Resistance was transferable to other enterococci by conjugation for 16 of the 22 isolates that were tested. Homology was detected by hybridization between a probe specific for the vanA gene, which encodes an inducible high-level glycopeptide resistance protein in Enterococcus faecium BM4147, and DNA of the 31 clinical isolates and the 16 corresponding transconjugants. This indicates that a single class of resistance determinants accounts for high-level glycopeptide resistance in enterococci. The strains differed in their biotypes and resistance phenotypes and harbored resistance plasmids of various sizes, suggesting that spread of this resistance phenotype is due to dissemination of a gene rather than of a bacterial clone or of a single plasmid. Four enterococcal isolates were resistant to low levels of vancomycin and susceptible to teicoplanin. Twenty-three coagulase-negative staphylococcal isolates were resistant to teicoplanin and susceptible to vancomycin. These two groups of strains did not hybridize with the vanA probe and did not transfer resistance at a detectable frequency. The vanA gene was not detected in the glycopeptide-producing strains of Amycolatopsis orientalis (vancomycin) and Actinoplanes teichomyceticus (teicoplanin) or in various gram-positive bacteria intrinsically resistant to glycopeptides.     

Comparative in vitro activities of AC98-6446, a novel semisynthetic glycopeptide derivative of the natural product mannopeptimycin alpha, and other antimicrobial agents against gram-positive clinical isolates

AC98-6446 is a novel semisynthetic cyclic glycopeptide antibiotic related to the natural product mannopeptimycin alpha (AC98-1). In the present study the activity of AC98-6446 was evaluated against a variety of recent clinical gram-positive pathogens including multiply resistant strains. AC98-6446 demonstrated similar potent activities against methicillin-susceptible and methicillin-resistant staphylococci and glycopeptide-intermediate staphylococcal isolates (MICs at which 90% of isolates are inhibited [MIC(90)s], 0.03 to 0.06 microg/ml). AC98-6446 also demonstrated good activities against both vancomycin-resistant and -susceptible strains of enterococci (MIC(90)s, 0.12 and 0.25 microg/ml, respectively) as well as against streptococcal strains (MIC(90)s, 3 log(10) CFU/ml) of staphylococcal and streptococcal isolates and a marked decrease in the viable counts of most enterococcal strains (from 0.2 to 2.5 log(10) CFU/ml). Unlike vancomycin, which demonstrates time-dependent killing, AC98-6446 demonstrated concentration-dependent killing. The potent activity, novel structure, and bactericidal activity demonstrated by AC98-6446 make it an attractive candidate for further development.     

Dalbavancin and telavancin: novel lipoglycopeptides for the treatment of Gram-positive infections

Two glycopeptide analogues of vancomycin and teicoplanin have been developed with improved pharmacokinetic/pharmacodynamic parameters. Dalbavancin was derived from teicoplanin, and telavancin is a derivative of vancomycin. The half-life of dalbavancin in humans is 147-258 h (6-11 days) allowing for weekly administration. Dalbavancin possesses more potent in vitro activity than vancomycin or teicoplanin. Dalbavancin has been investigated in uncomplicated and complicated skin and skin structure infections (SSSIs) in clinical trials and has demonstrated equivalent or superior (versus vancomycin only) efficacy versus comparators. Telavancin exhibits a dual mechanism of action, low potential for resistance development and is active against resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Clinical trials involving SSSIs have demonstrated equivalent or superior (versus vancomycin for MRSA) efficacy compared with a standard therapy. Both telavancin and dalbavancin show promise as alternative treatments for patients with serious infections caused by resistant Gram-positive pathogens.     

Antipneumococcal activity of dalbavancin compared to other agents

Against 307 pneumococci of various resistotypes, dalbavancin MICs were 0.008 to 0.125 microg/ml. All strains were susceptible to vancomycin, teicoplanin, linezolid, and quinupristin-dalfopristin. Dalbavancin at 2x MIC was bactericidal against all 10 pneumococci tested after 24 h. Vancomycin and teicoplanin killed 10 and 8 strains, respectively, at 2x MIC after 24 h.     

Detection of vancomycin resistant genes vanA and vanB by cycling probe technology.

Cycling Probe Technology (CPT) has been used to develop gene-based assays for detection of vancomycin resistance genes vanA and vanB in enterococci (VRE). Cycling Probe Technology utilizes a chimeric DNA-RNA-DNA probe that is cleaved by the enzyme RNase H when hybridized to its complementary DNA target. Conversion of full-length probe into the cleaved probe fragments is the basis for detection and quantification of the CPT reaction. Two gene-specific probes, each one unique to either the vanA or vanB gene, were utilized for development of vanA and vanB CPT assays, respectively. Both vanA and vanB CPT assays were used to determine the presence or absence of the corresponding gene in 440 clinical enterococcal isolates. The presence of vanA and vanB gene sequences was detected in 154 and 131 isolates, respectively. Phenotypic characterization of all isolates was determined through interpretation of conventional susceptibility data obtained with the disk diffusion method. Comparison between disk diffusion characterization and CPT assays revealed 11 discrepant isolates. The identity of these isolates was resolved by polymerase chain reaction (PCR) which confirmed the vanA and vanB CPT assay data. Therefore, compared to conventional phenotyping, both the vanA and vanB CPT assays appeared superior for accurate identification of VanA and VanB isolates.     

A multicenter evaluation of linezolid antimicrobial activity in North America

Overall, 141 centers in North America enrolled in this international surveillance study designed to evaluate the in vitro antimicrobial activity and spectrum of linezolid, a new oxazolidinone. Each participant tested the susceptibility of clinical isolates of staphylococcal species (n = 85) against 12 drugs, and enterococcal species (n = 40) against 6 drugs using reference broth microdilution trays; and of streptococcal species (n = 25) against 6 drugs using Etests (AB BIODISK, Solna, Sweden). Quality control testing was conducted using recommended strains, and verification of resistance to linezolid and select other agents was performed by a regional monitor. Of the 20,161 isolates collected from sites across the United States (US; n = 132) and Canada (n = 9), 18,307 were included in this analysis. Oxacillin resistance occurred in 38.7 and 70.6% of Staphylococcus aureus and coagulase-negative staphylococcal (CoNS) isolates, respectively. Vancomycin resistance was reported in 65.9 and 2.6% of Enterococcus faecium and E. faecalis, respectively. Penicillin resistance occurred in 37.2% of Streptococcus pneumoniae, 17.5% constituting high-level resistance (MIC, > or =2 microg/ml). The MIC(90) for linezolid was 1 microg/ml for streptococci, 2 microg/ml for enterococci and CoNS isolates, and 4 microg/ml for S. aureus. Using the US FDA-recommended susceptible breakpoints for linezolid, there were no confirmed reports of linezolid resistance (i.e., MIC > or =8 microg/ml). The occurrence of linezolid MICs was unimodal and generally varied between, 1-4 microg/ml for staphylococci (94% of recorded results), 1-2 microg/ml for enterococci (93%), and 0.5-1 microg/ml for streptococci (85%). Susceptibility to linezolid was not influenced by susceptibility to other antiicrobials such as vancomycin, beta-lactams or macrolides. Only linezolid was universally active against essentially all tested Gram-positive specimens. The unimodal susceptibility pattern is indicative of excellent and near complete activity against key Gram-positive pathogens including multiply resistant strains, but surveillance for emerging resistances (rare) and the performance of routine susceptibility tests to guide patient therapy seems prudent.     

Dalbavancin is active in vitro against biofilms formed by dalbavancin-susceptible enterococci

We tested the in vitro activity of dalbavancin, vancomycin and daptomycin against 83 enterococcal isolates in planktonic and biofilm states. The MIC₉₀ for vancomycin-susceptible Enterococcus faecalis was 0.125 and 4 μg/mL for dalbavancin and daptomycin, respectively. For vancomycin-resistant Enterococcus faecium, the MIC₉₀ was >16 and 2 μg/mL for dalbavancin and daptomycin, respectively. Dalbavancin minimum biofilm inhibitory concentrations (MBICs) for vancomycin-susceptible and -resistant isolates were ≤0.25 and >16 μg/mL, respectively. The daptomycin MBIC₉₀ for all isolates was 4 μg/mL. For E. faecalis and E. faecium, dalbavancin minimum biofilm bactericidal concentrations (MBBCs) for vancomycin-susceptible and -resistant isolates were ≤4 and >16 μg/mL, respectively, whereas vancomycin MBBCs were >128 μg/mL for all isolates, and daptomycin MBBC₉₀ values for both species were 128 μg/mL. In summary, dalbavancin exhibited in vitro activity against all tested isolates of vancomycin-susceptible, but not against vancomycin-resistant enterococci; activity was observed in both the planktonic and biofilm states.     

Antimicrobial activity of tigecycline tested against nosocomial bacterial pathogens from patients hospitalized in the intensive care unit

The antimicrobial activity of tigecycline and selected antimicrobials was evaluated against bacterial pathogens isolated from patients hospitalized in intensive care units (ICUs) worldwide. A total of 9093 isolates were consecutively collected in >70 medical centers in North America (4157), South America (1830), Europe (3034), and the Asia-Australia (72) areas. The isolates were collected from the bloodstream (68.5%), respiratory tract (13.6%), skin/soft tissue (5.5%), and urinary tract (2.0%) infections in the 2000-2004 period, and susceptibility was tested by reference broth microdilution methods. The most frequently isolated pathogens were Staphylococcus aureus (32.1%), Enterococcus spp. (13.7%), coagulase-negative staphylococci (CoNS; 13.0%), Pseudomonas aeruginosa (8.4%), and Escherichia coli (7.9%). All Gram-positive pathogens (5665) were inhibited at < or =1 microg/mL of tigecycline. Resistance to oxacillin was detected in 43.5% of Staphylococcus aureus and in 85.0% of CoNS, and resistance to vancomycin was observed in 18.6% of enterococci. Tigecycline was very active against Enterobacteriaceae (1876 strains tested) with an MIC90 of < or =1 microg/mL, except for Serratia spp. (2 microg/mL). Extended-spectrum beta-lactamase (ESBL) phenotype was detected in 10% of E. coli and 31% of Klebsiella spp., whereas 28% of Enterobacter spp. were resistant to ceftazidime (AmpC enzyme production). These resistance phenotypes did not adversely affect tigecycline activity. Tigecycline and trimethoprim/sulfamethoxazole were the most active compounds against Stenotrophomonas maltophilia (MIC90, 2 and 1 microg/mL respectively). Tigecycline was also active against Acinetobacter spp. (MIC90, 1 microg/mL), but P. aeruginosa showed decreased susceptibility to tigecycline (MIC90, 16 microg/mL). In summary, isolates from ICU patients worldwide showed high rates of antimicrobial resistance. The most alarming problems detected were vancomycin resistance among enterococci, ESBL-mediated beta-lactam resistance and fluoroquinolone resistance among Enterobacteriaceae, and carbapenem resistance among P. aeruginosa and Acinetobacter spp. Tigecycline exhibited potent in vitro activity against most of clinically important pathogenic bacteria (except P. aeruginosa) isolated from ICU patients and may represent an excellent option for the treatment of infections in this clinical environment.     

Antimicrobial susceptibility and macrolide resistance genes in Enterococcus faecium with reduced susceptibility to quinupristin-dalfopristin: level of quinupristin-dalfopristin resistance is not dependent on erm(B) attenuator region sequence

Antimicrobial resistance and the mechanisms implicated were studied in 148 clinical Enterococcus faecium isolates with a quinupristin-dalfopristin (Q/D) MIC > or =1 microg/mL. As expected, higher levels of resistance were detected for macrolide antibiotics (94% erythromycin, 100% azithromycin, 100% josamycin). High-level resistance to gentamicin and streptomycin was detected in 18.9% and 66.2% of isolates, respectively, in our series of enterococci. Resistance against tetracycline was found in only 12.8% of the isolates, and 13 isolates were resistant to vancomycin. The dalvabancin MIC(90) for these isolates was >16 microg/mL. Polymerase chain reaction screening for the previously described streptogramin resistance determinants erm(A), erm(B), mefA/E, vat(D), and vat(E) was performed to determine the prevalence of streptogramin resistance mechanisms in these clinical enterococcal isolates. The combination of erm(B) and vat(D) genes encoding resistance to streptogramins was detected in 1 Q/D-resistant E. faecium isolate. A total of 131 Q/D-nonsusceptible enterococci only contained the erm(B) gene. The erm(B) promoter sequence reveals no differences between the strains analyzed, regardless of the Q/D MIC value.