Comparative activity of linezolid and other new agents against methicillin-resistant Staphylococcus aureus and teicoplanin-intermediate coagulase-negative staphylococci.

The activity of linezolid was determined against 225 recently isolated methicillin-resistant Staphylococcus aureus (MRSA) and 20 methicillin-resistant coagulase-negative staphylococci (CoNS) with decreased levels of susceptibility to teicoplanin. Linezolid activity was compared with other new agents (quinupristin-dalfopristin, trovafloxacin, moxifloxacin, levofloxacin and telithromycin) and six other antimicrobials (erythromycin, clindamycin, gentamicin, vancomycin, teicoplanin and rifampicin). The in vitro activity of linezolid was similar to that of vancomycin. Linezolid inhibited all MRSA strains at between 0.1 and 2 mg/L and all CoNS strains tested at between 0.2 and 0.5 mg/L. These results suggest that linezolid would be useful for the treatment of infections involving these organisms.     

Quinupristin-dalfopristin resistance among gram-positive bacteria in Taiwan

To understand quinupristin-dalfopristin resistance among clinical isolates of gram-positive bacteria in Taiwan, where this agent is not yet available for clinical use, we evaluated 1,287 nonduplicate isolates recovered from January 1996 to December 1999 for in vitro susceptibility to quinupristin-dalfopristin and other newer antimicrobial agents. All methicillin-susceptible Staphylococcus aureus (MSSA) isolates were susceptible to quinupristin-dalfopristin. High rates of nonsusceptibility to quinupristin-dalfopristin (MICs, >/=2 microg/ml) were demonstrated for the following organisms: methicillin-resistant S. aureus (MRSA) (31%), coagulase-negative staphylococci (CoNS) (16%), Streptococcus pneumoniae (8%), viridans group streptococci (51%), vancomycin-susceptible enterococci (85%), vancomycin-resistant Enterococcus faecalis (100%), vancomycin-resistant Enterococcus faecium (66%), Leuconostoc spp. (100%), Lactobacillus spp. (50%), and Pediococcus spp. (87%). All isolates of MSSA, MRSA, S. pneumoniae, and viridans group streptococci were susceptible to vancomycin and teicoplanin. The rates of nonsusceptibility to vancomycin and teicoplanin were 5 and 7%, respectively, for CoNS, ranging from 12 and 18% for S. simulans to 0 and 0% for S. cohnii and S. auricularis. Moxifloxacin and trovafloxacin had good activities against these isolates except for ciprofloxacin-resistant vancomycin-resistant enterococci and methicillin-resistant staphylococci. In Taiwan, virginiamycin has been used in animal husbandry for more than 20 years, which may contribute to the high rates of quinupristin-dalfopristin resistance.     

Comparative activities of daptomycin and several agents against staphylococcal blood isolates. Glycopeptide tolerance

The activity of daptomycin was evaluated against 702 staphylococcal blood isolates (316 methicillin-susceptible Staphylococcus aureus, 187 methicillin-resistant S. aureus [MRSA], and 199 coagulase-negative staphylococci [CoNS]) collected in 41 Spanish hospitals. Glycopeptide tolerance and the incidence of heterogeneous glycopeptide-intermediate (hGISA) isolates were also examined. Vancomycin MICs determined by the Etest were compared with those obtained by the reference broth microdilution method. Daptomycin exhibited good activity, and only 2 isolates were nonsusceptible to this antibiotic. Resistance to linezolid was observed in 2 MRSA isolates and in 16 CoNS. The cfr gene was detected in 7 of these 18 isolates. Vancomycin and teicoplanin tolerance was 9.6% and 21.9%, respectively, in MRSA isolates. We detected the hGISA phenotype in 5.8% of MRSA isolates. Vancomycin MICs by the Etest were slightly higher than those obtained by broth microdilution. Daptomycin retained activity against isolates that were not susceptible to linezolid, teicoplanin, or quinupristin-dalfopristin.     

Identification of methicillin-resistant isolates of Staphylococcus aureus and coagulase-negative staphylococci responsible for bloodstream infections with the Phoenix system

We evaluated the reliability of the new Phoenix system (Becton Dickinson Microbiology Systems, Sparks, Md.) in species-level identification and detection of oxacillin (methicillin) resistance among 493 staphylococcal isolates (Staphylococcus aureus, n = 223; coagulase-negative staphylococci, CoNS, n = 270) recovered from patients with bacteremia. Identification results were concordant with those of the ID 32 STAPH system (bioMérieux, Marcy l'Etoile, France) for 100% of S. aureus (223/223) and 97.4% (263/270) of CoNS isolates. For S. aureus isolates, Phoenix oxacillin-susceptibility results fully concurred with those of mecA polymerase chain reaction (PCR) (reference method): 96 mecA-positive isolates identified as resistant, 127 mecA-negative strains as susceptible. Two of the 210 mecA-positive CoNS isolates were misclassified as susceptible by the Phoenix (sensitivity 99%, positive predictive value 97.6%). Five of 60 mecA-negative CoNS isolates were classified as resistant by the Phoenix (specificity 91.7%; negative predictive value 96.5%). The Phoenix system can provide accurate and reliable identification of methicillin-resistant staphylococci responsible for bloodstream infections.     

Gentamicin- and methicillin-resistant Staphylococcus aureus: in vitro susceptibility to antimicrobial drugs

Thirteen nosocomially significant, gentamicin- and methicillin-resistant (GRMR) Staphylococcus aureus isolates, all of phage group III/M (lysotype 42E/47/53/54/75/77/83A/84/85/94/96), were uniformly resistant against augmentin, erythromycin, fosfomycin, gentamicin, methicillin, oxacillin, penicillin G, tetracycline, and tobramycin, but differed in susceptibility to cefamandole, ciprofloxacin, clindamycin, imipenem, josamycin, the synthetic chinolone Ro 23-6240, and ofloxacin. All isolates were susceptible to chloramphenicol, coumermycin, fusidic acid, novobiocin, rifampin, teicoplanin, trimethoprim-sulfamethoxazole (cotrimoxazole), and vancomycin. One isolate was of intermediate susceptibility to netilmicin. On a weight-for-weight basis, the 7 most active drugs were rifampin, coumermycin, cotrimoxazole, novobiocin, teicoplanin, fusidic acid, and vancomycin (in decreasing order) in terms of minimal inhibitory concentrations. With regard to minimal bactericidal concentrations, coumermycin, rifampin, vancomycin, teicoplanin, cotrimoxazole, ofloxacin, and ciprofloxacin (in decreasing order) were the 7 most potent antimicrobial drugs. Freshly defibrinated human blood [65% (v/v)] combined with chloramphenicol and rifampin, respectively, resulted in a weak additive effect (time kill curves). Indifferent effects were observed following combination of blood with ciprofloxacin, cotrimoxazole, coumermycin, fusidic acid, imipenem, netilmicin, novobiocin, ofloxacin, compound Ro 23-6240, teicoplanin, and vancomycin. Rifampin combined with novobiocin, teicoplanin, and vancomycin, respectively, in the presence of 65% (v/v) human blood, resulted in an additive effect. Combinations of rifampin with 9 other antimicrobial drugs in blood yielded essentially indifferent effects.     

一种PCR检测耐甲氧西林金黄色葡萄球菌株新方法的建立

目的建立一种PCR检测耐甲氧西林金黄色葡萄球菌株新方法。方法收集2016年1月至2018年12月入住本院ICU的重症患者的脓液、分泌物、血液等标本中分离培养病原菌株,共43个样本,且均为初次分离所得。以mecA基因检测呈阳性为"金标准",对样本分别进行实时荧光PCR检测和纸片扩散法检测。结果实时荧光PCR方法检测法准确度高于头孢西丁及苯唑西林纸片扩散法;所有耐甲氧西林葡萄球菌对青霉素和苯唑西林药耐药性最强,对红霉素和克林霉素次之,对万古霉素、利奈唑胺、替加环素、利福平均表现为敏感,对四环素、庆大霉素等具备一定的敏感性。结论新建立的荧光PCR检测法相比头孢西丁纸片扩散法和苯唑西林纸片扩散法不仅准确度高,而且特异性好,能够准确检测出耐甲氧西林金黄色葡萄球菌。     

In vitro activities of ramoplanin, selected glycopeptides, fluoroquinolones, and other antibiotics against clinical bloodstream isolates of gram-positive cocci.

The susceptibilities of 316 gram-positive bacteremic isolates to ramoplanin, vancomycin, and teicoplanin and seven other antibiotics were tested. Ramoplanin demonstrated MICs of < or = 0.25 microgram/ml for at least 99% of Staphylococcus aureus isolates and 100% of coagulase-negative staphylococci tested. For both oxacillin-susceptible and oxacillin-resistant S. aureus and coagulase-negative staphylococci, the activity of ramoplanin surpassed those of both vancomycin and teicoplanin. Ramoplanin and teicoplanin had comparable activities against enterococci and Streptococcus pneumoniae and were superior to vancomycin.     

In vitro activity of RP 59500, a semisynthetic injectable pristinamycin, against staphylococci, streptococci, and enterococci.

The in vitro activity of RP 59500, a semisynthetic pristinamycin, was compared with the activities of vancomycin, oxacillin, ampicillin, gentamicin, ciprofloxacin, and rifampin against five Staphylococcus species, five Streptococcus species, and four Enterococcus species. For staphylococci, MICs were 0.13 to 1 microgram/ml and the MICs for 90% of the strains tested (MIC90s) were 0.13 to 0.5 microgram/ml; there were no differences between oxacillin-susceptible and -resistant strains. For streptococci, MICs were 0.03 to 4 micrograms/ml and MIC90s were 0.25 to 2 micrograms/ml; viridans group streptococci were the least susceptible streptococci. For enterococci, MICs were 0.25 to 32 micrograms/ml and MIC90s were 2 to 4 micrograms/ml; Enterococcus faecalis was the least susceptible. Vancomycin was the only comparative drug with consistent activity against all species of gram-positive cocci. With RP 59500, raising the inoculum 100-fold, lowering the pH of cation-adjusted Mueller-Hinton broth to 5.5, or omitting cation supplementation had little effect on MICs, but 50% serum increased MICs 2 to 4 dilution steps. The differences between MBCs and MICs were greater for staphylococci and enterococci than for streptococci. Time-kill studies with 24 strains indicated that RP 59500 concentrations 2-, 4-, and 16-fold greater than the MICs usually killed bacteria of each species at similar rates; reductions in CFU per milliliter were less than those observed with oxacillin or vancomycin against staphylococci and less than those observed with ampicillin against enterococci. RP 59500 antagonized the bactericidal activities of oxacillin and gentamicin against Staphylococcus aureus ATCC 29213 and that of ampicillin against E. faecalis ATCC 29212. Against the latter, combination with gentamicin was indifferent. RP 59500 has a broad spectrum of in vitro activity against gram-positive cocci; combining it with other drugs is not advantageous.     

2008年中国十二家教学医院革兰阳性球菌耐药性研究

目的 调查2008年我国革兰阳性球菌临床分离株的耐药性.方法 收集2008年6至12月12家教学医院临床分离的1171株非重复革兰阳性球菌.采用琼脂稀释法测定抗菌药物的MIC值.结果 金黄色葡萄球菌和凝同酶阴性葡萄球菌中耐苯唑西林菌株分别占49.9%(232/465)和74.0%(179/242);不J司地区MRSA发生率在33.3%～65.0%之间;不同标本MRSA分离率分别为:呼吸道标本71.1%(108/152),血液标本48.3%(28/58),脓、伤口和无菌体液标本36.0%(68/189).MRSA对复方磺胺和氯霉素的敏感率为81.5%(183/232)和89.7%(208/232);对喹诺酮类、庆大霉素、红霉素、克林霉素、四环素和利福平的敏感率为3.9%～35.0%;未发现对替考拉宁、万古霉素和利奈唑胺耐药的葡萄球菌.共发现3株VRE;粪肠球菌和屎肠球菌对利奈唑胺的敏感率分别为96.2%(101/105)和97.0%(130/134),对高浓度庆大霉素耐药率分别为48.6%(51/105)和75.4%(101/134);粪肠球菌对氯霉素和四环素的敏感率低于屎肠球菌,但对其他所测试抗菌药物均有较高的敏感性;屎肠球菌对除糖肽类抗菌药及利奈唑胺以外的其他所测抗菌药物的敏感率均较低.225株PISP分离率为24.9%(56/225),未发现PRSP.≤3岁儿童组肺炎链球菌中PNSSP分离率为36.6%(15/41),其他年龄组患者中PNSSP分离率为15.4%～26.6%.青霉素敏感的肺炎球菌(PSSP)对头孢丙烯、头孢呋辛和头孢克罗敏感率分别为67.5%(114/169)、66.3%(112/169)和61.5%(104/169),而PISP对这3种药物均耐药;所测225株肺炎链球菌对万古霉素、替考拉宁和利奈唑胺高度敏感,对加替沙星、左氧氟沙星和莫西沙星的敏感率分别为96.9%,97.8%和98.2%,对头孢曲松、氯霉素和阿莫西林/克拉维酸的敏感率分别为81.3%、77.3%和68.0%,对大环内酯类、复方磺胺和四环素的敏感率为11.6%～23.6%.结论 我国VRE发生率低,而葡萄球菌中苯唑西林耐药菌株分离率高.≤3岁儿童组PNSSP分离率高于其他年龄组.替考拉宁、万古霉素和利奈唑胺对葡萄球菌、粪肠球菌、屎肠球菌和肺炎链球菌具有很好的抗菌活性.     

Susceptibility of gram-positive cocci from 25 UK hospitals to antimicrobial agents including linezolid. The Linezolid Study Group

The prevalence of antibiotic resistance amongst Gram-positive cocci from 25 UK hospitals was studied over an 8 month period in 1999. A total of 3770 isolates were tested by the sentinel laboratories using the Etest; these bacteria comprised 1000 pneumococci, 1005 Staphylococcus aureus, 769 coagulase-negative staphylococci (CNS) and 996 enterococci. To ensure quality, 10% of the isolates were retested centrally, as were any found to express unusual resistance patterns. The prevalence of penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant enterococci and methicillin-resistant S. aureus (MRSA) varied widely amongst the sentinel laboratories. The resistance rates to methicillin among S. aureus and CNS were 19.2 and 38.9%, respectively, with MRSA rates in individual sentinel sites ranging from 0 to 43%. No glycopeptide resistance was seen in S. aureus, but 6.5% of CNS isolates were teicoplanin resistant and 0.5% were vancomycin resistant. Vancomycin resistance was much more frequent among Enterococcus faecium (24.1%) than E. faecalis (0.5%) (P<0.05), with most resistant isolates carrying vanA. The rate of penicillin resistance in pneumococci was 8.9%, and this resistance was predominantly intermediate (7.9%), with only six hospitals reporting isolates with high level resistance. The prevalence of erythromycin resistance among pneumococci was 12.3%, with the majority of resistant isolates having the macrolide efflux mechanism mediated by mefE. All the organisms tested were susceptible to linezolid with MICs in the range 0.12-4 mg/L. The modal MICs of linezolid were 1 mg/L for CNS and pneumococci, and 2 mg/L for S. aureus and enterococci. Linezolid was the most potent agent tested against Gram-positive cocci, including multiresistant strains, and as such may prove a valuable therapeutic option for the management of Gram-positive infections in hospitals.     

In vitro activity of ceftobiprole, linezolid, tigecycline, and 23 other antimicrobial agents against Staphylococcus aureus isolates in China

We investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in China and determined the susceptibility of S. aureus to 26 antimicrobial agents, including ceftobiprole, linezolid, and tigecycline. A total of 798 isolates were collected and tested by agar dilution. The mean prevalence of MRSA was 50.4%, the highest in Shanghai (80.3%), followed by those in Beijing (55.5%) and Shenyang (50.0%). Only 4.2% to 12.6% of MRSA were susceptible to erythromycin, fluoroquinolones, gentamicin, and tetracycline. All isolates were susceptible to teicoplanin, vancomycin, linezolid, tigecycline, and ceftobiprole.     

Comparison of the activities of coumermycin, ciprofloxacin, teicoplanin, and other non-beta-lactam antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus from various geographical locations.

One hundred clinical isolates of methicillin-resistant (Metr) Staphylococcus aureus from five different geographical origins were tested for their susceptibility to 12 non-beta-lactam antibiotics by the broth microdilution technique recommended by the National Committee for Clinical Laboratory Standards. Coumermycin and rifampin showed the highest activity with of MIC90s of 0.032 micrograms/ml for each compound. No resistance was found to coumermycin, whereas a single Metr S. aureus strain was found to be resistant to rifampin. Ciprofloxacin, vancomycin, and teicoplanin were the next most active compounds with MIC90s of 0.25, 0.5, and 0.5 micrograms/ml, respectively. Norfloxacin was less active, with an MIC90 of 1.0 micrograms/ml. Amikacin was the most active aminoglycoside tested, whereas high levels of resistance were found to tobramycin and gentamicin. Doxycycline and chloramphenicol showed variable results. Geographical variations in results were seen with doxycycline, chloramphenicol, and aminoglycosides. Kill-curve studies showed that coumermycin, ciprofloxacin, teicoplanin, vancomycin, and rifampin were highly bactericidal; more than 90% of the inoculum was killed within 8 h.     

Treatment evaluation of experimental staphylococcal infections: comparison of beta-lactam, lipopeptide, and glycopeptide antimicrobial therapy

LY 146032, teicoplanin, vancomycin, oxacillin, cephalothin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam were studied against six isolates of staphylococci (including both Staphylococcus aureus and coagulase negative staphylococci) using in vivo and in vitro methods. In vitro susceptibility measurements demonstrated that all six isolates were sensitive to LY 146032 and vancomycin and that five of six isolates were sensitive to tiecoplanin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam. Comparison of antimicrobial therapy in an in vivo rabbit model demonstrated that cefoperazone plus sulbactam was active against the greatest number of isolates (five of six) based on a reduction of greater than or equal to 5.0 log10 colony forming units per milliliter (CFU/ml) from growth control at the end of the animal treatment study. Vancomycin and oxacillin were equal in achieving reductions of greater than or equal to 5.0 log10 CFU/ml in four of the six isolates. Comparing each isolate's in vivo outcome to in vitro data shows that in vitro susceptibility tests overpredict the sensitivity of these six isolates to LY 146032 and vancomycin, are variable for teicoplanin, cefamandole, ampicillin plus sulbactam, and cefoperazone plus sulbactam, and underpredict for oxacillin.     

In vitro evaluation of AZD2563, a novel oxazolidinone,against 603 recent staphylococcal isolates

AZD2563, a novel oxazolidinone, and a selection of comparator drugs that included linezolid, erythromycin, clindamycin, quinolones, and gentamicin were tested against 384 Staphylococcus aureus (176 oxacillin-resistant S. aureus [ORSA]) and 219 coagulase-negative staphylococci (CoNS; 162 oxacillin resistant) by reference microdilution (all strains) and agar dilution (30 strains) methods. The following results were noted for AZD2563. (Note that, for comparison only, a breakpoint of < or =4 microg/ml [the breakpoint of linezolid] was used for this study, although a susceptibility breakpoint for AZD2563 has not been determined.) For S. aureus, the MIC at which 50% of the isolates tested are inhibited (MIC(50)) was 1 microg/ml, the MIC(90) was 2 microg/ml, and the percent susceptibility was 100%. For CoNS, the MIC(50) was 0.5 microg/ml, the MIC(90) was 1 microg/ml, and the percent susceptibility was 100%. ORSA and OR-CoNS strains were equally inhibited by AZD2563 and linezolid. AZD2563 demonstrated antistaphylococcal activity comparable to that of linezolid.     

Antimicrobial susceptibility of the pathogens of bacteraemia in the UK and Ireland 2001-2002: the BSAC Bacteraemia Resistance Surveillance Programme

OBJECTIVES: To describe the current patterns of antimicrobial resistance in the major pathogens of bacteraemia in the UK and Ireland, to highlight any unexpected resistance patterns and to act as a reference baseline for future studies. METHODS: In 2001 and 2002, 5092 blood culture isolates were collected by 29 laboratories distributed across the UK and Ireland. A single central laboratory re-identified the isolates and measured MICs by the BSAC agar dilution method. RESULTS: Oxacillin resistance was found in 42% of Staphylococcus aureus and 76% of coagulase-negative staphylococci. Streptococci were generally susceptible to beta-lactams, but tetracycline resistance was common (except in Streptococcus pneumoniae) and particularly common among group B isolates (82% resistant). Nine percent of S. pneumoniae had reduced susceptibility to penicillin (MICs 0.12-1 mg/L), but none required >/=2 mg/L for inhibition. High-level gentamicin resistance was seen in 43% of Enterococcus faecalis, often in combination with raised ciprofloxacin MICs (>/=32 mg/L), but these isolates remained susceptible to ampicillin and imipenem. Only linezolid and tigecycline showed in vitro potency against a large proportion of Enterococcus faecium. Vancomycin resistance was restricted to enterococci (20% of E. faecium, 3% of E. faecalis) and a single isolate of coagulase-negative staphylococci (0.2%, MIC of 8 mg/L). Escherichia coli isolates were commonly resistant to amoxicillin (56%) and tetracycline (88%) but remained susceptible to ceftazidime, piperacillin/tazobactam and imipenem. Extended-spectrum beta-lactamases were detected in 2% of E. coli (none in 2001, 3.2% in 2002), 5% of Klebsiella spp. and 8% of Enterobacter spp. Resistance rates of Pseudomonas aeruginosa to ciprofloxacin, ceftazidime, gentamicin, imipenem and piperacillin/tazobactam were between 4% and 7%. Among the newly licensed and developmental agents, there was no resistance to linezolid in Gram-positive organisms. Ertapenem had a wide spectrum, covering Enterobacteriaceae, streptococci and oxacillin-susceptible staphylococci. MICs of tigecycline were low for Gram-positive species and Enterobacteriaceae except Proteeae and Enterobacter spp. CONCLUSION: Antimicrobial resistance among major bloodstream pathogens to those antimicrobials often selected for empirical therapy was relatively uncommon in 2001-2002, usually <10%. An important exception was oxacillin resistance in S. aureus.     

铜陵市部分医院细菌耐药性监测与分析

目的了解安徽省铜陵市临床分离菌株耐药状况。方法2007年1～12月铜陵市临床分离菌株用Kirby-Bauer法进行药敏试验。结果1375株细菌中,革兰阳性菌399株,占29．0％;革兰阴性菌976株,占71．0％。耐甲氧西林金黄色葡萄球菌（MRSA）和耐甲氧西林凝固酶阴性葡萄球菌（MRCNS）分别占金黄色葡萄球菌和凝固酶阴性葡萄球菌（CNS）的18．4％和70．0％;MRSA和MRCNS对庆大霉素、环丙沙星、克林霉素和红霉素等均高度耐药,对利福平、氯霉素和呋喃妥因的耐药率均较低,未见耐万古霉素葡萄球菌。粪肠球菌对青霉素、氨苄西林、呋喃妥因、磷霉素和氯霉素的耐药率较低,未见耐万古霉素和替考拉宁粪肠球菌;屎肠球菌对磷霉素和氯霉素耐药率较低,发现2株耐万古霉素屎肠球菌。大肠埃希菌和克雷伯菌属中产超广谱β-内酰胺酶（ESBLs）株分别占49．3％和35．9％,产ESBLs株除对亚胺培南和美罗培南敏感外,对其他20种抗生素的耐药率均较不产ESBLs株高。非发酵菌对碳青霉烯类、头孢哌酮／舒巴坦、哌拉西林／三唑巴坦、头孢他啶、头孢吡肟、阿米卡星、环丙沙星等耐药率较低。结论革兰阳性菌对糖肽类抗生素耐药率低;革兰阴性菌对碳青霉烯类、头孢哌酮／舒巴坦、哌拉西林／三唑巴坦等耐药率低。加强细菌耐药性监测对合理使用抗生素、减少耐药菌株的产生和流行有重要临床指导价值。     

In vitro bactericidal activities of linezolid in combination with vancomycin,gentamicin, ciprofloxacin,fusidic acid,and rifampin against Staphylococcus aureus

The in vitro activities of linezolid were determined alone and in combination with vancomycin, ciprofloxacin, gentamicin, fusidic acid, or rifampin against five methicillin-susceptible Staphylococcus aureus (MSSA) and five methicillin-resistant S. aureus (MRSA) strains. Similar responses were obtained against MSSA and MRSA. When combined with fusidic acid, gentamicin, or rifampin, linezolid prevented selection of resistant mutants but showed no synergy. When linezolid was combined with vancomycin and ciprofloxacin, a slight antagonism was observed. While the combination with linezolid may reduce the emergence of mutants resistant to the associated drugs, the absence of synergy, especially in the case of vancomycin and ciprofloxacin, does not argue in favor of such combinations.     

In vitro activity of daptomycin versus linezolid and vancomycin against gram-positive uropathogens and ampicillin against enterococci, causing complicated urinary tract infections

OBJECTIVES: The existing therapeutic options for complicated urinary tract infections (UTI) caused by gram-positive uropathogens are not always optimal. Therefore, newer antimicrobials have to be assessed. METHODS: The antimicrobial activity of daptomycin was tested versus linezolid, vancomycin, and ampicillin (enterococci on ly), against pathogens from three different collections: (1) Uropathogens from hospitalized urological patients with complicated and/or hospital-acquired UTIs of the Urologic Clinic, Hospital St. Elisabeth, Straubing. (2) Uropathogens from a multicenter study comprising 37 urological centers throughout Germany. (3) Methicillin-resistant Staphylococcus aureus (MRSA) isolates of patients and staff within the Hospital St. Elisabeth, Straubing. Genotyping of the latter isolates was performed by pulsed-field gel electrophoresis. The minimal inhibitory concentrations (MIC) of daptomycin, linezolid, vancomycin, and ampicillin (only tested against enterococci) were determined by an agar dilution method using a multipointer with an inoculum of 10(4) CFU per point. RESULTS: For all methicillin-susceptible Staphylococcus aureus (n = 25), MRSA (n = 49), methicillin-susceptible coagulase-negative staphylococci (n = 129), methicillin-resistant coagulase-negative staphylococci (n = 33), for Enterococcus faecalis (n = 289), and for Enterococcus faecium (n = 4) the MICs ranged up to 2 mg/l (daptomycin, linezolid), up to 4 mg/l (vancomycin), and up to 8 mg/l (ampicillin, enterococci only) indicating that all strains were susceptible to the antibiotics tested. CONCLUSIONS: According to the in vitro activity daptomycin may be considered a promising antibacterial agent for the treatment of complicated UTI caused by gram-positive uropathogens. Thus, daptomycin should be evaluated in a clinical study.     

Semisynthetic glycopeptide antibiotics derived from LY264826 active against vancomycin-resistant enterococci.

Certain derivatives of the glycopeptide antibiotic LY264826 with N-alkyl-linked substitutions on the epivancosamine sugar are active against glycopeptide-resistant enterococci. Six compounds representing our most active series were evaluated for activity against antibiotic-resistant, gram-positive pathogens. For Enterococcus faecium and E. faecalis resistant to both vancomycin and teicoplanin, the MICs of the six semisynthetic compounds for 90% of the strains tested were 1 to 4 micrograms/ml, compared with 2,048 micrograms/ml for vancomycin and 256 micrograms/ml for LY264826. For E. faecium and E. faecalis resistant to vancomycin but not teicoplanin, the MICs were 0.016 to 1 micrograms/ml, compared with 64 to 1,024 micrograms/ml for vancomycin. The compounds were highly active against vancomycin-susceptible enterococci and against E. gallinarum and E. casseliflavus and showed some activity against isolates of highly vancomycin-resistant leuconostocs and pediococci. The MICs for 90% of the strains of methicillin-resistant Staphylococcus aureus tested were typically 0.25 to 1 micrograms/ml, compared with 1 microgram/ml for vancomycin. Against methicillin-resistant S. epidermidis MICs ranged from 0.25 to 2 micrograms/ml, compared with 1 to 4 micrograms/ml for vancomycin and 4 to 16 micrograms/ml for teicoplanin. The spectrum of these new compounds included activity against teicoplanin-resistant, coagulase-negative staphylococci. The compounds exhibited exceptional potency against pathogenic streptococci, with MICs of < or = 0.008 microgram/ml against Streptococcus pneumoniae, including penicillin-resistant isolates. In in vivo studies with a mouse infection model, the median effective doses against a challenge by S. aureus, S. pneumoniae, or S. pyogenes were typically 4 to 20 times lower than those of vancomycin. Overall, these new glycopeptides, such as LY307599 and LY333328, show promise for use as agents against resistant enterococci, methicillin-resistant S. aureus, and penicillin-resistant pneumococci.     

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