P C Appelbaum

..001). The phenotype of strains was associated with their sequence type. Our results demonstrate a clonal shift in CA-MRSA in Dallas children from 1999 to 2002...

..The treatment options available for these infections are now severely compromised and thus new classes of antimicrobial agents effective against MRSA, VISA and VRSA are urgently required...

..Azithromycin selected resistant clones in three of the five parents tested. Amoxicillin-clavulanate and cefuroxime did not yield resistant clones after 50 days...

..PVL(-)/SCC type II/agr type II strains, although rare, were consistently present in the community throughout the study period...

..aureus population. Therefore, an epidemiologically and genetically diverse collection of S. aureus strains was used to determine the range of aureolysin (aur) gene polymorphism...

..Gatifloxacin and moxifloxacin were the most active quinolones tested, while the MICs of the beta-lactams rose with those of penicillin G. LBM415 at two times the MIC was bactericidal (99.9% killing) against six strains after 24 h...

..Overall, WCK 771 was potent both in vivo and in vitro against quinolone-susceptible, but not quinolone-resistant, S. pneumoniae, regardless of penicillin susceptibility...

..Ceftobiprole is refractory to the development of endogenous resistance both in vitro and in vivo. The additional activity of ceftobiprole against MRSA strains makes it a potentially important addition to currently available agents...

..4 to 3.1 h, 0 to 1.8 h, and 0 to 0.9 h, respectively. The PA-SMEs (0.4 times the MIC) for pneumococci, staphylococci, and enterococci were 4.8 to >10.3 h, 1.5 to 9.6 h, and 3.8 to >10.7 h, respectively...

..Efforts should be made to prevent pneumococcal infections in high-risk patients through vaccination...

..Repeat testing showed a false-positivity rate of only 15 of the original 87 isolates by plate screening...

..Rapid identification of patients harbouring VRSA, VISA or hVISA as well as prompt isolation and adherence to infection control protocols are paramount in controlling the dissemination of these pathogens...

..Tigecycline also yielded a low frequency of resistance in single-step tests compared to all beta-lactams, macrolides/ketolides, and quinolones tested...

..Vancomycin nonsusceptibility in S. aureus is on the increase, further complicating therapy...

..These developments are of great concern, and every effort should be made to prevent further development and spread of vancomycin resistance in staphylococci...

..DX-619 has potent in vitro activity against staphylococci, including methicillin-, ciprofloxacin-, and vancomycin-resistant strains...

..Misuse of potent new agents will, however, result in the inevitable development of resistance to these agents; responsible use of potent new agents is required to prevent continuation of this vicious cycle...

..The improved potency, broad spectrum of activity and proven clinical and bacteriological efficacy and safety profile should make it a useful agent in the 21st century battle against community-acquired LRTIs...

..All quinolones tested selected for resistance; judicious use and proper dosing will be necessary to avoid resistance selection of newer broad-spectrum fluoroquinolones...

..125 mg/L [S], 0.25 mg/L [I], 0.5 mg/L [R]). The results indicated that several newly introduced and experimental antimicrobials have potential for the treatment of infections caused by resistant strains of S. pneumoniae...

..Telithromycin and RU 64399 were equally active against macrolide-susceptible (MICs, 0.008 to 0.06 microg/ml) and -resistant S. pyogenes isolates, but HMR 3787 had lower MICs for ermB strains...

..3%) or to a mef(A)-encoded efflux pump (25.7%). One strain had alterations of both 23S rRNA (A2058G Escherichia coli numbering) and ribosomal protein L22 (G95D)...

..With the continuing rise in resistance, judicious use of oral antimicrobial agents is necessary in all age groups...

..5 h. The mean pneumococcal PAEs were 1.7 h, ranging between 1.0 and 2.5 h. The staphylococcal and pneumococcal postantibiotic sub-MIC effects at 0.4 times the MIC ranged from 3.0 to >12.0 h and 1.9 to >12.0 h, respectively...

..Prudent use of all antimicrobials is essential to decrease the emergence of strains resistant to these agents...

..9 to 1.6 h. The mean PA-SMEs (0.4 times the MIC) for pneumococci, staphylococci, and enterococci were 3.0 to >10 h, 1.8 to >10.7 h, and 5.8 h, respectively, while those for E. coli and P. aeruginosa were 7.6 and 4.4 h, respectively...

..Although all quinolones selected, to a greater or lesser degree, for resistant clones with mutations usually in parC or gyrA, BMS-284756 tended to select for resistant clones at a lower rate than other quinolones studied...

..Ribosomal methylation was the most prevalent resistance mechanism among all resistant strains, except in Sofia, where the prevalence of the efflux mechanism was higher...

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..Overall, WCK 771 was the most potent quinolone tested against the staphylococci tested, regardless of quinolone susceptibility...

..All isolates were positive for lytA. The primers were useful for screening for Streptococcus pneumoniae and beta-lactam resistance, and for detection of common macrolide resistance determinants...

..125-64/0.125-64; piperacillin/tazobactam, 0.06-2/0.125-8. Bacteriostatic levels were within two dilutions of broth MICs. By this time-kill method, trovafloxacin had the lowest bacteriostatic concentrations of all compounds tested...

..125 and 1; clindamycin, 0.25 and 8; metronidazole, 1 and 4; gatifloxacin, 0.5 and 4; and moxifloxacin, 0.5 and 2, respectively. Ranbezolid had very good in vitro activity against both gram-negative and -positive anaerobes...

..0-8.0 mg/L), except for two strains without efflux systems (0.0125-0.5 mg/L) and two with efflux systems and ribosomal protein mutations (> 64.0 mg/L), and were bactericidal against eight to ten strains tested at 2 x MIC after 24 h...

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..Clearly, reassessment of current prescribing practices is critical if antibiotic efficacy is to be preserved and the risk for selection of resistance minimized in the new millennium...

..001), thus representing a lower selective pressure for proliferation of resistant mutants. Only moxifloxacin gave a 50% MPC (MPC50) value (1 microg/ml) within the susceptible range...

..Telithromycin at < or =0.5 microg/ml was active against 99.8% of S. pneumoniae isolates tested and may be useful for the treatment of respiratory tract infections caused by macrolide-resistant S. pneumoniae isolates...

..influenzae or M. catarrhalis clones with elevated ceftobiprole MICs is quite low...

..5 x 10(-7) for GW 773546, GW 708408, and telithromycin for macrolide-susceptible strains and 1.1 x 10(-7) to >4.3 x 10(-3) for resistant strains. The postantibiotic effects of GW 773546, GW 708408, and telithromycin were 2.4 to 9.8 h...

..This in vitro mutation study demonstrates a clear distinction between the low frequency of development of resistance with ceftriaxone exposure as opposed to the high frequency with quinolone exposure...

..The broad-spectrum activity of the 3 quinolones suggests potential use in therapy of infections caused by nonfermenters; monobactams should be reserved for infections caused by P. aeruginosa and possibly Acinetobacter spp...

..4 times the MIC) were 2.5 to 6.7 h, 2.9 to >0.0 h, and 7.9 to >10.3 h, respectively. The PA-SMEs were longer than the PAEs, suggesting that sub-MIC levels extend the PAE of ceftaroline against gram-positive cocci...

..aureus (IC(50), 0.01 to 1 microg/ml) with up to 256-fold-higher affinity than those of other agents. Ceftaroline demonstrated very good PBP affinity against all S. aureus and S. pneumoniae strains tested, including resistant isolates...

..All strains were also susceptible to vancomycin, linezolid, ranbezolid, daptomycin, oritavancin, and quinupristin-dalfopristin. LBM415 at the MIC was bacteriostatic after 24 h...

..6 to 6.9 h), and 6.4 h (range, 3.8 to 9.7 h), respectively. The results of in vitro studies obtained with both novel macrolides were similar to those obtained with telithromycin and better than those obtained with older macrolides...

..The macrolides azithromycin and clarithromycin were active against penicillin-susceptible and penicillin-intermediate pneumococci and M catarrhalis; they were inactive against H influenzae and penicillin-resistant pneumococci...

..For all strains, MICs of vancomycin, linezolid, ranbezolid, oritavancin, daptomycin, and quinupristin-dalfopristin were </=4.0 microg/ml. Dalbavancin was bactericidal at four times the MIC against all six strains tested...

..No mutations in deformylase (def) and formyltransferase (fmt) genes were detected in any of the LBM415-resistant mutants...

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..pneumoniae in Latin American and Caribbean countries, continued surveillance efforts are necessary in order to guide clinical empiric treatment and provide for judicious use of antimicrobial agents...

..1 to 5.0, 1.9 to 2.1, 1.7 to 1.8, 1.0 to 1.7, and 0.7 to 3 h, respectively. The PA-SMEs (four times the MIC) ranged from 6.7 to >11 h for gram-positive organisms and from 2.3 to >11.3 h for gram-negative organisms...

..3%) due to one or several ribosomal mutations. Occasional hypersusceptible strains (1.8%) were found and had no macrolide resistance mechanisms and appeared to be the only truly macrolide-susceptible variants of H. influenzae...

..0 mg/L. Time-kill assays with eight strains demonstrated that daptomycin (2 x MIC) was bactericidal in seven of eight strains tested at 24 h, with >90% killing at 1 h...

..3% of strains. Erm(A) [subclass erm(TR)] was most commonly encountered (60.5%), followed by mef(A) (23.4%) and erm(B) (14.5%). At <0.5 microg/ml, telithromycin was active against 98.5% of the strains tested...

..Ranbezolid was bacteriostatic against pneumococci. Ranbezolid MICs were similar to or lower than those of linezolid. Vancomycin and quinupristin-dalfopristin were also very active...

..From these results we conclude that telithromycin efflux with or without additional ribosomal alterations is present in all H. influenzae strains, except for those for which the telithromycin MICs were very low...

..7 to 5.0 h, 0.7 to 1.8 h, and 1.2 to 6.5 h, respectively. The PA-SME ranges (0.4x MIC) for pneumococci, staphylococci, and enterococci were 5.2 to >8.6 h, 2.1 to 8.3 h, and 4.9 to >10.0 h, respectively...

..7 to >10.7 h, >10.7 to >11.0 h, and >10 to >10.8 h, respectively. The extended PAE of telavancin, together with its long elimination half-life in humans, supports once-daily dosing for this investigational drug...

..The initial isolate was macrolide-susceptible, but the isolates after the treatment were resistant to 14 and 15-membered macrolides and had two amino acid (65WR66) deletions in ribosomal protein L4...

..Single-step mutation studies showed that cefditoren, at the MIC, had the lowest frequency of spontaneous mutants compared with other drugs...

..Faropenem also yielded low rates of spontaneous mutations against all organisms of both species. By comparison, resistant clones were obtained with macrolides, ketolides, and quinolones...

..Multistep resistance selection studies showed that even after 50 consecutive subcultures of 10 strains in the presence of sub-MICs, DC-159a produced only two mutants with maximum MICs of 1 microg/ml...

..influenzae did not rise more than fourfold, in contrast to cefprozil, azithromycin, and clarithromycin, whose MICs rose to variable degrees...

..008 and 16 microg/ml. Azithromycin resistance was found in most species, while most were telithromycin susceptible. Glycopeptides and linezolid were active against viridans group strains but inactive against C. hominis...

..Furthermore, AR-709 was active against strains that were both susceptible and resistant to trimethoprim-sulfamethoxazole...

..MIC increases correlated with changes mostly in the 70GXGXAAXQ77 motif in peptide deformylase. The postantibiotic effect of LBM415 ranged from 0.3 to 1.4 h...

..However induction with vancomycin increased glycopeptide MICs and stabilized the resistance...

..Single-step mutation frequencies for telavancin (<4.0 x 10(-11) to <2.9 x 10(-10) at 2x MIC) were lower than the spontaneous mutation frequencies obtained with the comparators...

..Overall, the MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites...

..CONCLUSION: Mutation in ribosomal protein L22 alone does not confer high-level macrolide resistance unless efflux is present...

..Most methicillin-resistant strains were levofloxacin resistant. CB-181963 was bactericidal against all six methicillin-resistant strains at four times the MIC after 24 h...

..Single-passage selection testing showed low resistance frequencies with CG400549, but multistep analysis showed that CG400549 yielded resistant mutants after 14 to 17 days in all strains tested...

..CEM-101 had low MICs as well as low potential for the selection of resistant mutants, independent of bacterial species or resistance phenotypes in pneumococci and S. pyogenes...

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..The parental ceftaroline MIC for the one K. pneumoniae extended-spectrum β-lactamase-negative isolate tested was 0.5 μg/ml and did not change after 50 daily passages...

..Combinations of ACHN-490 with cefepime, doripenem, imipenem, or piperacillin-tazobactam yielded synergies in ≥70% and ≥80% of strains at 6 and 12 h, respectively, and in ≥68% at 24 h...

..The increase in linezolid-resistant coagulase-negative staphylococci correlated with nosocomial transmission of selected mutated strains in patients who had received linezolid...

..aeruginosa the MPC/MIC ratios were 4 to > or =16. The MPC/MIC ratios for beta-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 microg/ml) than those for ss-lactamase-negative strains...

..016 to 2 microg/ml (parents) to 0.125 to 8 microg/ml (with clones stable after 10 drug-free subcultures). Single-step mutant selection frequencies were similarly low for razupenem and comparators...

..The remaining 14 strains were more heterogeneous and had mutations only in parC and/or parE, and the MICs of quinolones were lower for these strains...

..Fourteen of these 34 organisms were quinolone resistant (levofloxacin MICs of > or =4 microg/ml)...

..5 μg/ml with 91 to 97% protein binding) against all MRSA strains. No antagonism was observed; synergy occurred for one MRSA strain treated with fusidic acid plus tobramycin...

..The daptomycin-nonsusceptible VISA's cell wall demonstrated a reduction in muramic acid O-acetylation, a phenotypic parameter not previously reported for VISA; some isolates also contained a single point mutation in the mprF gene...

..Retapamulin has a low potential for resistance selection in S. pyogenes, with a slow and gradual propensity for resistance development in S. aureus...

..Exposure to DK-507k and sitafloxacin resulted in mutations, mostly in gyrA...

..aureus (including methicillin-resistant and vancomycin-nonsusceptible strains) are inhibited by very low concentrations of retapamulin and that all four testing methods are satisfactory for use for susceptibility testing...

..This article analyses macrolide-resistance mechanisms and their worldwide distributions in S pneumoniae, S pyogenes, and H influenzae...

..The Alexander Project is a continuing surveillance study, begun in 1992, examining the susceptibility of pathogens involved in adult community-acquired respiratory tract infections (CARTI) to a range of antimicrobial agents...

..Single-passage selections showed very low frequencies of resistance to ceftobiprole irrespective of genotype or phenotype; the maximal ceftobiprole MIC of recovered clones was 8 mug/ml...

..Common clones were observed between Europe, Asia, and America. Overall, while serotypes/serogroups of macrolide resistant isolates were limited, multiple PFGE and MLST types were found, with clustering of common clones within countries...

..For clinical and public health reasons, it is essential that microbiology laboratories adequately test for vancomycin-resistance in S. aureus...

..125 mg/L and MIC90s of 1.0 mg/L). Piperacillin-tazobactam, clindamycin and metronidazole were active against most strains, and ceftriaxone was active mainly against beta-lactamase-negative organisms...

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..Daptomycin combined with rifampin yielded synergy in one vancomycin-intermediate S. aureus strain only, and virtually all synergy occurred between daptomycin and gentamicin...

..Time-kill studies of 12 strains showed that HMR 3787, RU 64399, and telithromycin were bactericidal against all strains after 24 h at two times the MIC...

..Erythromycin was bactericidal against all 10 strains with MICs < or= 8 mg/L at 4 x MIC after 24 h...

..The administration of perioperative antibiotics reduced but did not abolish these effects of bacterial contamination of prosthetic vascular grafts...

..After the exposure of one strain of each species to NXL 103 for 10 daily subcultures, the MICs remained within ± 1 dilution...

..These studies have demonstrated the effectiveness of WCK 771, administered orally and parenterally, for the treatment of diverse staphylococcal infections in mice, including those caused by quinolone-resistant strains...