Multicentre evaluation of the in vitro activity of linezolid in the Western Pacific

Multiresistance to antimicrobial agents is common in staphylococci and pneumococci isolates in the Western Pacific region. The activity of linezolid, a new oxazolidinone, was evaluated against a spectrum of Gram-positive species collected in the region. Eighteen laboratories from six countries in the Western Pacific examined the linezolid susceptibility of 2143 clinical isolates of Staphylococcus aureus, coagulase-negative staphylococci (CoNS) and Enterococcus spp. using broth microdilution or disc diffusion methodology. For Streptococcus pneumoniae (n = 351) and other streptococci (n = 83), Etest (AB Biodisk, Solna, Sweden) strips were used. Results were compared with other common and important antimicrobials. Linezolid-resistant strains were not detected among streptococci or staphylococci, including a significant proportion of S. aureus strains that were multiresistant. Almost all enterococci, including 14 vancomycin-resistant Enterococcus faecium, were linezolid susceptible. A small proportion of enterococci (0.8%) were intermediate to linezolid, and one strain of Enterococcus faecalis had a zone diameter of 20 mm (resistant). The linezolid MIC ranges (MIC(90)) of those strains tested by broth microdilution or Etest were: 1-4 mg/L (2 mg/L) for S. aureus, 0.5-4 mg/L (2 mg/L) for CoNS, 0.5-4 mg/L (2 mg/L) for Enterococcus spp., 0.12-2 mg/L (1 mg/L) for S. pneumoniae and 0.25-2 mg/L (1 mg/L) for Streptococcus spp. There was no difference in linezolid susceptibility between countries or between multiresistant and susceptible strains of each species monitored.     

In vitro activity of linezolid against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae.

We report the activity of the new oxazolidinone antimicrobial agent linezolid against 37 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes), 26 clinical isolates of methicillin-resistant S. aureus and 20 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci were inhibited by < or = 4 ug/ml of linezolid. All isolates of methicillin-resistant S. aureus were inhibited by < or = 8 ug/ml of linezolid. All isolates of penicillin-resistant S. pneumoniae were inhibited by < or = 2 ug/ml of linezolid. Linezolid inhibits strains of multidrug resistant Gram-positive cocci in vitro at concentrations < or = 8 ug/ml.     

In vitro activity of a new cephalosporin,RWJ-54428, against streptococci,enterococci and staphylococci,including glycopeptide-intermediate Staphylococcus aureus

The need for new antimicrobial agents with activity against Gram-positive organisms has become increasingly important because of emerging resistance. We compared the activity of a new b-lactam antimicrobial agent, RWJ-54428 (MC-02 479), with representatives of other classes of antimicrobial agents against 76 Staphylococcus aureus (including four glycopeptide- intermediate strains), 50 coagulase-negative staphylococci, 20 Enterococcus faecalis, 20 Enterococcus faecium, 10 Enterococcus gallinarum/Enterococcus casseliflavus, 54 Streptococcus pneumoniae and 22 viridans streptococcal isolates. The MIC(90) of RWJ-54,428 was < or = 2 mg/L for all groups of bacteria tested except E. faecium. The activity against four strains of glycopeptide-intermediate S. aureus was similar to that for other methicillin-resistant S. aureus isolates (range 0.5-2.0 mg/L).     

北京协和医院内科住院患者细菌耐药性监测

  目的  了解北京协和医院内科住院患者临床分离细菌的分布及对抗菌药物的耐药性。  方法  收集2011年1月1日至2012年12月31日北京协和医院内科临床分离的2767株非重复细菌, 采用纸片扩散法或自动化仪器法进行药敏试验, 按美国临床实验室标准化研究所2012年版标准判读药敏结果, 采用WHONET 5.6软件进行数据分析。  结果  2767株非重复细菌中10种最常见的细菌依次为铜绿假单胞菌(11.5%)、大肠埃希菌(11.2%)、金黄色葡萄球菌(10.1%)、肺炎克雷伯菌(9.7%)、鲍曼不动杆菌(9.4%)、凝固酶阴性葡萄球菌(5.0%)、阴沟肠杆菌(4.1%)、粪肠球菌(3.8%)、嗜麦芽窄食单胞菌(3.6%)和屎肠球菌(3.4%), 其中革兰阴性菌占65.3%(1807株), 革兰阳性菌占34.7%(960株)。耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus, MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(methicillin-resistant coagulase negative Staphylococcus, MRCNS)的检出率分别为33.8%(94/278)和75.8%(222/293)。MRS葡萄球菌(MRSA和MRCNS)对β内酰胺类和其他抗菌药物的耐药率明显高于MSS葡萄球菌[甲氧西林敏感金黄色葡萄球菌(methicillin-susceptible Staphylococcus aureus, MSSA)和甲氧西林敏感凝固酶阴性葡萄球菌(methicillin-susceptive coagulase-negative Staphylococcus, MSCNS)]。MRSA中87.2%菌株对磺胺甲噁唑-甲氧苄啶敏感, MRCNS中84.2%菌株对利福平敏感。未发现对万古霉素、替考拉宁和利奈唑胺耐药的葡萄球菌。粪肠球菌对大多数抗菌药物的耐药率明显低于屎肠球菌, 后者对氯霉素的耐药率仅为4.7%。分别发现2株和8株万古霉素耐药的粪肠球菌和屎肠球菌, 根据表型推测为VanA和VanB型耐药; 未发现对利奈唑胺耐药的肠球菌。产超广谱β-内酰胺酶(extended spectrum β-lactamases, ESBLs)的大肠埃希菌、克雷伯菌属细菌(肺炎克雷伯菌和产酸克雷伯菌)和奇异变形杆菌的检出率分别为66.5%、32.6%和30.5%, 产ESBLs菌株的耐药率明显高于非产ESBLs菌株。肠杆菌科细菌对碳青霉烯类抗菌药物仍高度敏感, 总耐药率0.9%~2.9%。泛耐药肺炎克雷伯菌的检出率为0.4%(1/267)。铜绿假单胞菌对亚胺培南和美罗培南的耐药率分别为23.4%和17.4%, 对阿米卡星的耐药率最低(6.6%); 鲍曼不动杆菌对上述两种抗菌药物的耐药率分别为56.8%和57.5%, 对头孢哌酮-舒巴坦和米诺环素的耐药率最低(42.1%和24.0%)。泛耐药鲍曼不动杆菌和铜绿假单胞菌的检出率分别为35.9%和1.6%。流感嗜血杆菌β-内酰胺酶的检出率为19.4%。肺炎链球菌对红霉素和克林霉素的耐药率>94%。  结论  定期进行耐药性监测有助于了解细菌耐药性变迁, 可为临床经验用药提供依据。     

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.     

康替唑胺体外抗菌作用研究

目的 评价唑烷酮类新药康替唑胺对临床分离菌的体外抗菌作用.方法 收集全国19所医院1321株的临床分离菌,以琼脂对倍稀释法测定康替唑胺对分离菌的最低抑菌浓度(MIC)并与有关抗菌药物进行比较,测定康替唑胺的杀菌活性、抗菌药物后效应(PAE)以及不同培养条件对康替唑胺抗菌作用的影响.结果 康替唑胺对革兰阳性菌中葡萄球菌...     

Linezolid for the treatment of resistant gram-positive cocci

OBJECTIVE: To provide a comprehensive review of linezolid, the first of a new class of antibiotics, the oxazolidinones. Therapeutic issues regarding the emergence of multidrug-resistant bacteria and a brief history of the oxazolidinones are also discussed. DATA SOURCES: A MEDLINE search (1966-March 2001) was conducted to identify pertinent literature, including preclinical trials, clinical trials, and reviews. Unpublished clinical data, adverse effects, and dosing information were abstracted from product labeling. STUDY SELECTION: Clinical efficacy data were extracted from clinical trials, case reports, and abstracts that mentioned linezolid. Additional information concerning antibiotic resistance, the oxazolidinones, in vitro susceptibility and the pharmacokinetic profile of linezolid also was reviewed. DATA SYNTHESIS: Linezolid exhibits activity against many gram-positive organisms, including vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and penicillin-resistant Streptococcus pneumoniae. Linezolid inhibits bacterial protein synthesis at an early step in translation and is rapidly and completely absorbed from the gastrointestinal tract following oral administration. Efficacy has been demonstrated in a number of unpublished clinical trials in adults with pneumonia, skin and skin structure infections, and vancomycin-resistant E. faecium infections. The adverse effect profile is similar to that of comparator agents (beta-lactams, clarithrornycin, vancomycin). CONCLUSIONS: Linezolid is the first oral antimicrobial agent approved for the treatment of vancomycin-resistant enterococci. Since the oxazoildinones have a unique mechanism of action and expanded spectrum of activity against virulent and highly resistant gram positive pathogens, linezolid is a valuable alternative to currently available treatment options. Clinical trials evaluating linezolid and other oxazolidinones for antibiotic-resistant gram-positive infections, as well as comparator studies comparing linezolid with other candidate drugs, such as quinupristin/dalfopristin and choramphenicol, will further define the role of linezolid.     

In vitro activity of BAY 12-8039, a novel 8-methoxyquinolone, compared to activities of six fluoroquinolones against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

The in vitro activity of a novel 8-methoxyquinolone, BAY 12-8039, against recent clinical isolates of Streptococcus pneumoniae (n = 404), Haemophilus influenzae (n = 330), and Moraxella catarrhalis (n = 250) was evaluated. Activity was compared to those of six other fluoroquinolones: ciprofloxacin, clinafloxacin, levofloxacin, ofloxacin, sparfloxacin and trovafloxacin. BAY 12-8039 and clinafloxacin had the highest levels of activity against S. pneumoniae, both with a MIC at which 90% of the isolates were inhibited (MIC90) of 0.06 microg/ml. Trovafloxacin and sparfloxacin were the next most active agents versus S. pneumoniae (MIC90s = 0.12 microg/ml). No differences in activity against penicillin-susceptible, -intermediate, or -resistant strains of S. pneumoniae were noted for any of the fluoroquinolones tested. MIC90s for the seven fluoroquinolones ranged from 0.008 to 0.06 microg/ml versus H. influenzae and from 0.008 to 0.12 microg/ml for M. catarrhalis. The MICs for two strains of S. pneumoniae and one strain of H. influenzae were noted to be higher than those for the general population of organisms for all of the fluoroquinolones tested. Finally, the activity of BAY 12-8039 versus S. pneumoniae was found to be diminished when MIC determinations were performed with incubation of agar dilution plates or broth microdilution trays in 5 to 7% CO2 versus ambient air.     

替加环素对414株需氧革兰阴性和革兰阳性临床分离菌株的体外抗菌活性

目的测定替加环素等15种抗菌药物对我院2004年和2005年临床分离的414株革兰阴性菌和革兰阳性需氧菌的体外抗菌活性。方法采用微量肉汤稀释法测定替加环素等15种抗菌药物对所测菌株的MIC,数据分析采用WHONET5.3软件。结果MRSA对替加环素、利奈唑胺及万古霉素的敏感率均为100%,替加环素对MRSA的MIC90是所测抗菌药物中最低者;万古霉素耐药肠球菌(VRE)对替加环素及利奈唑胺敏感率均为100%,替加环素对所有肠球菌的MIC90分别是利奈唑胺和万古霉素的MIC90的1/8和1/16;替加环素对青霉素中介肺炎链球菌(PISP)的MIC90为0.5mg/L,对青霉素耐药肺炎链球菌(PRSP)的MIC范围是0.25~1mg/L,其他抗菌药物对PISP和PRSP的MIC90是替加环素的1~32倍;替加环素对亚胺培南耐药的鲍曼不动杆菌的MIC范围是其他抗菌药物的1/2~1/64;对铜绿假单胞菌的MIC90是32mg/L;产ESBLs大肠埃希菌和肺炎克雷伯菌对替加环素、美罗培南和亚胺培南敏感率均为100%。结论替加环素对铜绿假单胞菌的抗菌活性较差,对其他需氧革兰阴性杆菌有较好的体外抗菌活性;对需氧革兰阳性球菌的抗菌活性最强。     

Increasing incidence of linezolid-intermediate or -resistant, vancomycin-resistant Enterococcus faecium strains parallels increasing linezolid consumption

Clinical enterococcal resistance to linezolid is defined by the presence of the G2576T mutation. We evaluated the incidence of genetically proven linezolid resistance among vancomycin-resistant Enterococcus faecium strains and linezolid consumption for a possible association. A relationship was found (r(2) = 0.73, P = 0.03) and predicts increasing resistance with current trends of linezolid use.     

In vitro activities of daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin against Staphylococci and Enterococci, including vancomycin- intermediate and -resistant strains

The in vitro activity of daptomycin was compared with those of vancomycin, linezolid, and quinupristin-dalfopristin against a variety (n = 203) of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and S. epidermidis (MRSA and MRSE, respectively), vancomycin-resistant enterococci (VRE), and vancomycin-intermediate S. aureus (VISA). Overall, daptomycin was more active against all organisms tested, except Enterococcus faecium and VISA, against which its activity was similar to that of quinupristin-dalfopristin. In time-kill studies with MRSA, MRSE, VRE, and VISA, daptomycin demonstrated greater bactericidal activity than all other drugs tested, killing > or =3 log CFU/ml by 8 h. Daptomycin may be a potential alternative drug therapy for multidrug-resistant gram-positive organisms and warrants further investigation.     

四川省细菌耐药监测网2011年川北地区细菌耐药性监测数据分析

目的掌握四川省川北地区医院临床分离细菌对常用抗菌药物的耐药状况。方法按统一监测方案,监测2011年度川北地区3所医院临床分离细菌耐药状况及细菌敏感性。依据2010年临床实验室标准化协会(Clinical and Labora-tory Standards Institute,CLSI)标准,以Whonet 5.5软件进行数据分析。结果 3家医院2011年1～12月各种临床标本中分离菌株共5006株,其中革兰阴性菌4010株,占80.1%;革兰阳性菌996株,占19.9%。最常见的细菌依次为大肠埃希菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和金黄色葡萄球菌。耐甲氧西林金黄色葡萄球菌(Methicillin-resistant Staphylococcus au-reus,MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(Methicillin-resistant coagulase negative Staphylococcus,MRCNS)的检出率分别为18.2%和87.0%,未发现万古霉素、利奈唑胺耐药葡萄球菌。粪肠球菌和屎肠球菌对万古霉素耐药率分别为1.7%和2.6%,未发现利奈唑胺耐药肠球菌。大肠埃希菌及肺炎克雷伯菌产超广谱β-内酰胺酶(Extended Spectrum Beta Lactamas-es,ESBLs)的比率分别为58.2%和27.7%。鲍曼不动杆菌、铜绿假单胞菌对亚胺培南的耐药率分别为43.2%和18.1%;鲍曼不动杆菌耐药率超过铜绿假单胞菌。结论本地区临床分离细菌耐药现象较为普遍,应加强细菌耐药监测管理,及时了解细菌耐药性情况,为临床用药提供依据。     

In Vitro Activities of Six Fluoroquinolones against Canadian Isolates of Vancomycin-sensitive and Vancomycin-resistant Enterococcus species

The in vitro activities of six fluoroquinolones were determined against 1482 Enterococcus species isolates collected as part of a 1996 Canadian surveillance study. Clinafloxacin MIC₉₀s were 4 or 8 μg/mL, trovafloxacin and BAY 12-8039 MIC₉₀s were 8 or 16 μg/mL, sparfloxacin MIC₉₀s were 32 μg/mL, and ciprofloxacin and ofloxacin MIC₉₀s were >32 μg/mL for the vancomycin-sensitive Enterococcus faecalis, vancomycin-sensitive Enterococcus faecium, and vancomycin-resistant E. faecium isolates collected.     

Antimicrobial activities of seven novel tetramethylpiperidine-substituted phenazines against multiple-drug-resistant Gram-positive bacteria

BACKGROUND: A dramatic increase in multiple-drug-resistant (MDR) Gram-positive pathogens has occurred in recent times, leading to increased rates or morbidity and mortality and also associated with high costs for the treatment of these infections. It is clear that there is an urgent need for the development of effective antimicrobial agents. The anti-bacterial activity of seven 2,2,6,6-tetramethylpiperidine (TMP)-substituted phenazines, compared to clofazimine (B663), were tested against 70 clinical isolates of methicillin-resistant Staphylococcus aureus, MDR Streptococcus pneumoniae and resistant Enterococcus sp. METHODS: Standard minimum inhibitory concentration agar dilution susceptibility tests were done on all isolates, including ATCC control strains. RESULTS: All the TMP-substituted phenazines were more active than clofazimine against all isolates tested. Compound B4125 was the most active by inhibiting all growth of the organisms tested, including vancomycin-resistant Enterococcus faecium. CONCLUSION: Clofazimine has been shown to have anti-staphylococcal activity. We demonstrate enhanced anti-bacterial activity of TMP-substituted phenazines against drug-resistant Gram-positive organisms compared to clofazimine.     

In vitro and in vivo activities of novel 2-(thiazol-2-ylthio)-1beta-methylcarbapenems with potent activities against multiresistant gram-positive bacteria

SM-197436, SM-232721, and SM-232724 are new 1beta-methylcarbapenems with a unique 4-substituted thiazol-2-ylthio moiety at the C-2 side chain. In agar dilution susceptibility testing these novel carbapenems were active against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) with a MIC(90) of 相似文献   

In-vitro activity of sparfloxacin, a new quinolone antimicrobial agent

The in-vitro activity of sparfloxacin (AT-4140), a new difluorinated quinolone, was compared with those of ciprofloxacin, temafloxacin and selected members of other groups of antimicrobial agents, against 651 recent distinct clinical isolates and strains with known mechanisms of resistance. Three strains of Chlamydia trachomatis were also studied. The MICs for 90% of the Enterobacteriaceae were between 0.06 and 1 mg/l; for Pseudomonas aeruginosa the MIC90 was 2 mg/l. Sparfloxacin was 16-fold more active against Acinetobacter spp. than ciprofloxacin. For Staphylococcus spp., Streptococcus, spp. and Enterococcus faecalis the MIC90 was between 0.25 and 1 mg/l; sparfloxacin was four-fold more active against Str. pneumoniae than ciprofloxacin. Ninety percent of strains of Haemophilus influenzae, Branhamella catarrhalis and Neisseria spp. were inhibited by less than 0.03 mg/l; for Bacteroides fragilis the MIC90 was 1 mg/l. The three strains of Chl. trachomatis were susceptible to 0.06-0.12 mg/l sparfloxacin, which was 16-fold more active than ciprofloxacin. There was cross resistance among the quinolones, but not between the quinolones and other groups of antimicrobials. The protein binding of sparfloxacin was 40% and serum had little effect on its activity.     

In vitro activities of LTX-109, a synthetic antimicrobial peptide, against methicillin-resistant, vancomycin-intermediate, vancomycin-resistant, daptomycin-nonsusceptible, and linezolid-nonsusceptible Staphylococcus aureus

LTX-109 and eight other antimicrobial agents were evaluated against 155 methicillin-resistant Staphylococcus aureus (MRSA) isolates, including strains resistant to vancomycin and strains with decreased susceptibility to daptomycin and linezolid, by microdilution tests to determine MICs. Time-kill assays were performed against representative MRSA, vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus (VRSA) isolates. LTX-109 demonstrated a MIC range of 2 to 4 μg/ml and dose-dependent rapid bactericidal activity against S. aureus. This activity was not influenced by resistance to other antistaphylococcal agents.     

In vitro activities of quinupristin-dalfopristin and cefepime,alone and in combination with various antimicrobials,against multidrug-resistant staphylococci and enterococci in an in vitro pharmacodynamic model

Use of combinations of antimicrobials that together achieve synergistic activities against targeted microorganisms is one potential strategy for overcoming bacterial resistance. As the incidence of infections caused by multidrug-resistant staphylococci and enterococci increases, the importance of devising additional synergistic drug combinations for these bacteria is magnified. We evaluated a number of antimicrobial combinations, with a focus on quinupristin-dalfopristin (Q-D), cefepime, and linezolid, using a previously described in vitro pharmacodynamic model. The combination of Q-D with either linezolid or vancomycin, as well as the combination of cefepime-vancomycin, resulted in enhanced killing (> or =2-log(10) increase in killing versus the most-active single agent) against methicillin-resistant Staphylococcus aureus (MRSA) 494. An improved effect (<2 log(10) kill increase in kill) against MRSA 494 was noted for cefepime plus either Q-D or linezolid, as well as linezolid-vancomycin. Similar relationships were observed for a methicillin-susceptible S. aureus isolate (isolate 1199). Against methicillin-resistant S. epidermidis R444, enhanced killing was achieved with the combination of cefepime-linezolid, while improvement was noted for vancomycin with either cefepime or linezolid. The combination of cefepime and vancomycin also achieved enhanced killing against a glycopeptide-intermediate-susceptible S. aureus isolate (isolate 992). The combination of linezolid and doxycycline achieved an enhanced effect against vancomycin-resistant Enterococcus faecalis (VREFc) and E. faecium. Q-D plus ampicillin or linezolid resulted in similar enhancement of activity against the VREFc isolate. The results of this study suggest a number of novel antimicrobial combinations that may be useful against staphylococci and enterococci. Combination regimens including cefepime, Q-D, and/or linezolid warrant further investigation for the treatment of refractive infections due to multidrug-resistant gram-positive pathogens.     

2015年北京协和医院细菌耐药性监测

目的了解2015年北京协和医院临床分离细菌对抗菌药物的耐药性。方法收集2015年1月1日至12月31日北京协和医院临床分离的5746株非重复细菌,采用纸片扩散法或自动化仪器法进行药敏试验,按美国临床实验室标准化协会2015年版标准判读药敏结果,采用WHONET 5.6软件进行数据分析。结果 5746株非重复细菌中,10种最常见细菌分别为:大肠埃希菌(19.4%)、铜绿假单胞菌(11.3%)、肺炎克雷伯菌(10.9%)、金黄色葡萄球菌(9.8%)、鲍曼不动杆菌(9.6%)、粪肠球菌(6.5%)、B群链球菌(5.1%)、屎肠球菌(4.6%)、凝固酶阴性葡萄球菌(2.7%)、阴沟肠杆菌(2.5%)。其中革兰阴性菌占67.5%,革兰阳性菌占32.5%。耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(methicillin-resistant coagulase-negative Staphylococcus,MRCNS)的检出率分别为22.9%和77.6%。MRSA和MRCNS菌株对β内酰胺类和其他抗菌药物的耐药率明显高于甲氧西林敏感金黄色葡萄球菌(methicillin-susceptible Staphylococcus aureus,MSSA)和甲氧西林敏感凝固酶阴性葡萄球菌(methicillin-susceptible coagulase-negative Staphylococcus,MSCNS)菌株。仍有88.8%的MRSA对磺胺甲噁唑-甲氧苄啶敏感。MRCNS中有81.7%的菌株对利福平敏感。未发现对万古霉素、替考拉宁和利奈唑胺耐药的葡萄球菌。粪肠球菌对大多数抗菌药物(除氯霉素外)的耐药率要明显低于屎肠球菌。两者中均有少数万古霉素耐药株,未发现对利奈唑胺耐药的肠球菌。β溶血链球菌对青霉素的敏感率为90.8%。产超广谱β-内酰胺酶的大肠埃希菌、克雷伯菌属(肺炎克雷伯菌和产酸克雷伯菌)和奇异变形杆菌的检出率分别为52.3%(582/1112)、28.9%(200/692)和26.2%(27/103)。肠杆菌科细菌对碳青霉烯类仍高度敏感,总耐药率≤4.3%。泛耐药肺炎克雷伯菌的检出率为3.0%(19/630)。鲍曼不动杆菌对亚胺培南和美罗培南的耐药率分别为76.5%和74.8%,对头孢哌酮-舒巴坦和米诺环素的耐药率最低,分别为49.8%和21.8%。铜绿假单胞菌对亚胺培南和美罗培南的耐药率分别为16.6%和11.9%,对阿米卡星的耐药率最低(5.2%)。泛耐药鲍曼不动杆菌和铜绿假单胞菌的检出率分别是20.8%(115/553)和1.8%(12/650)。结论细菌耐药性仍对临床构成严重威胁,临床需合理规范应用抗菌药物,避免耐药菌株的广泛传播。     

In vivo activities of U-100592 and U-100766, novel oxazolidinone antimicrobial agents, against experimental bacterial infections.

The Upjohn oxazolidinones, U-100592 and U-100766, are orally bioavailable synthetic antimicrobial agents with spectra of activity against antibiotic-susceptible and -resistant gram-positive pathogens. In several mouse models of methicillin-resistant Staphylococcus aureus infection, U-100592 and U-100766 yielded oral 50% effective doses (ED50) ranging from 1.9 to 8.0 mg/kg of body weight, which compared favorably with vancomycin subcutaneous ED50 values of 1.1 to 4.4 mg/kg. Similarly, both compounds were active versus a Staphylococcus epidermidis experimental systemic infection. U-100592 and U-100766 effectively cured an Enterococcus faecalis systemic infection, with ED50 values of 1.3 and 10.0 mg/kg, and versus a vancomycin-resistant Enterococcus faecium infection in immunocompromised mice, both drugs effected cures at 12.5 and 24.0 mg/kg. Both compounds were exceptionally active in vivo against penicillin- and cephalosporin-resistant Streptococcus pneumoniae, with ED50 values ranging from 1.2 to 11.7 mg/kg in systemic infection models. In soft tissue infection models with S. aureus and E. faecalis, both compounds exhibited acceptable curative activities in the range of 11.0 to 39.0 mg/kg. U-100766 was also very active versus the Bacteroides fragilis soft tissue infection model (ED50 = 46.3 mg/kg). In combination-therapy studies, both U-100592 and U-100766 were indifferent or additive in vivo against a monomicrobic S. aureus infection in combination with other antibiotics active against gram-positive bacteria and combined as readily as vancomycin with gentamicin in the treatment of a polymicrobic S. aureus-Escherichia coli infection. U-100592 and U-100766 are potent oxazolidinones active against antibiotic-susceptible and -resistant gram-positive pathogens in experimental systemic and soft tissue infections.