In vitro activity of ABT-773, telithromycin and eight other antimicrobials against erythromycin-resistant Streptococcus pneumoniae respiratory isolates of children

The activity of the ketolide ABT-773 against 180 erythromycin-resistant Streptococcus pneumoniae obtained from children was compared with telithromycin, azithromycin, clarithromyin, roxithromycin, clindamycin, penicillin, levofloxacin and gatifloxacin. Ketolide MICs were all ≤1 mg/l, with ABT-773 being the most potent of all drugs tested. MIC₉₀s for macrolides and azithromycin in mefE+ isolates were 16–32 compared with >128 mg/l for ermB+ isolates. ABT-773 and telithromycin MIC₉₀s for mefE+ isolates were 0.125 and 0.5, compared with 0.032 and 0.016 mg/l for ermB+ isolates and 0.5 and 1 mg/l, respectively, for isolates containing both genes. Clindamycin was active against mefE+ but not ermB+ isolates. 155 isolates were resistant to penicillin. All fluoroquinolone MICs were <1 mg/l. Further studies of ketolides for treatment of paediatric S. pneumoniae infections are warranted.     

Comparative antimicrobial activity of ABT-773, a novel ketolide, tested against drug-resistant Gram-positive cocci and Haemophilus influenzae

The antimicrobial activity of ABT-773, a novel ketolide, was tested against 618 Gram-positive strains collected from various surveillance programmes between 1997 and 2000. ABT-773 has potent activity against Streptococcus pneumoniae (MIC₉₀, ≤0.03–0.12 mg/l), β-haemolytic streptococci (MIC₉₀, ≤0.03 mg/l) and viridans group streptococci (MIC₉₀, ≤0.03 mg/l), including erythromycin-resistant strains. In contrast, ABT-773 was less active against erythromycin-resistant Staphylococcus aureus (31% susceptible at ≤0.25 mg/l), coagulase-negative staphylococci (41% susceptible) and enterococci (30% susceptible). Haemophilus influenzae (MIC_90, 4 mg/l) was less inhibited by the two ketolides tested, and ABT-773 was generally two- to fourfold more potent than telithromycin. The ketolides appear to have potential clinical use against some Gram-positive species resistant to macrolides.     

Comparative antimicrobial activity of ABT-773, a novel ketolide, tested against drug-resistant Gram-positive cocci and Haemophilus influenzae

The antimicrobial activity of ABT-773, a novel ketolide, was tested against 618 Gram-positive strains collected from various surveillance programmes between 1997 and 2000. ABT-773 has potent activity against Streptococcus pneumoniae (MIC₉₀, ≤0.03–0.12 mg/l), β-haemolytic streptococci (MIC₉₀, ≤0.03 mg/l) and viridans group streptococci (MIC₉₀, ≤0.03 mg/l), including erythromycin-resistant strains. In contrast, ABT-773 was less active against erythromycin-resistant Staphylococcus aureus (31% susceptible at ≤0.25 mg/l), coagulase-negative staphylococci (41% susceptible) and enterococci (30% susceptible). Haemophilus influenzae (MIC_90, 4 mg/l) was less inhibited by the two ketolides tested, and ABT-773 was generally two- to fourfold more potent than telithromycin. The ketolides appear to have potential clinical use against some Gram-positive species resistant to macrolides.     

Susceptibility of Streptococcus pneumoniae to penicillin, azithromycin and telithromycin (PROTEKT 1999-2003)

Isolates of Streptococcus pneumoniae collected over the first 4 years of the PROTEKT study were tested for susceptibility to penicillin, azithromycin and telithromycin. A total of 20 750 isolates were collected from 39 countries. Penicillin non-susceptibility rates were stable over the study period; overall, 21.8% of isolates were resistant. Azithromycin resistance increased from 31.0% in Year 1 to 36.3% in Year 4. Resistance rates for penicillin and azithromycin varied between countries and were highest in France, Spain, South Africa, USA and the Far East. Multidrug resistance in S. pneumoniae did not change significantly over the 4 years, with an overall rate of 38.6%. Telithromycin retained good activity against S. pneumoniae (0.1% of isolates resistant), including multidrug-resistant isolates.     

Inhibitory and bactericidal activities of gemifloxacin and other antimicrobials against Mycoplasma pneumoniae

The MIC of gemifloxacin was compared with that of sparfloxacin, levofloxacin, moxifloxacin, gatifloxacin, ciprofloxacin, doxycycline, erythromycin, azithromycin and clarithromycin using 97 clinical isolates of Mycoplasma pneumoniae. MBCs of fluoroquinolones were determined for a subgroup of 12 isolates. Macrolides were the most potent agents with MIC₉₀s for all drugs 0.001 mg/l. The doxycycline MIC₉₀ was 0.5 mg/l. Gemifloxacin MICs ranged from 0.001 to 0.25 mg/l. The gemifloxacin MIC₉₀ (0.125 mg/l) was equivalent to moxifloxacin and gatifloxacin, was 2-fold lower than sparfloxacin, 8-fold lower than levofloxacin and 32-fold lower than ciprofloxacin. MBCs for gemifloxacin were predominantly within 2–4 times the corresponding MIC values, indicating a bactericidal effect.     

In vitro activity of garenoxacin against recent clinical isolates of Chlamydia pneumoniae

The in vitro activities of garenoxacin, a novel des-F (6)-quinolone, levofloxacin, moxifloxacin and clarithromycin were tested against 30 recent clinical isolates of Chlamydia pneumoniae. The minimal inhibitory concentration (MIC) at which 90% of the isolates were inhibited and the minimal bactericidal concentration (MBC) at which 90% of the isolates were killed by garenoxacin for C. pneumoniae was 0.03 mg/l (range 0.015–0.03 mg/l).     

Activity of telithromycin against erythromycin-susceptible and -resistant Streptococcus pneumoniae isolates from adults with invasive infections

A telithromycin (TEL) kill-kinetics study was conducted with 120 clinically significant Streptococcus pneumoniae isolates (60 susceptible and 60 highly resistant to erythromycin). Time–kill curves were performed using different antibiotic concentrations. The minimum inhibitory concentrations (MICs) of TEL were low for both erythromycin-susceptible (MIC ≤ 0.016 mg/L) and erythromycin-resistant strains (MIC ≤ 0.25 mg/L). TEL showed 99.9% killing of all erythromycin resistant strains at 18–24 h of incubation. Even for strains with erythromycin MICs ≥ 64.0 mg/L, TEL was uniformly bactericidal at 0.25 mg/L.     

甲磺酸左氧氟沙星对耐青霉素肺炎链球菌的体外抗菌活性

目的 观察甲磺酸左氧氮沙星对耐青霉素肺炎链球菌(PRSP)的药敏及疗效。方法 对6株临床分离的耐青霉素肺炎链球菌，采用E—test方法，测定甲磺酸左氧氮沙星等6种抗生素的抗菌活性。同时观察甲磺酸左氧氮沙星单药治疗取SP临床疗效及不良反应。结果6株取SP均为低耐药菌株，对甲磺酸左氧氮沙星敏感。6例患者经治疗后，5例痊愈，l例显效，无明显副反应发生。结论 甲磺酸左氧氮沙星可有效治疗耐青霉素肺炎链球菌性肺炎。     

社区呼吸道感染中肺炎链球菌对常用抗菌药物敏感性

目的了解社区获得性呼吸道感染中肺炎链球菌对常用抗菌药物的体外抗菌活性。方法先用做肺炎链球菌鉴定粗筛,后用全自动细菌分析系统的革兰阳性菌鉴定卡和单克隆乳胶试剂做肺炎链球菌的最终鉴定,药物敏感性试验用微量稀释方法测定其最低抑菌浓度。结果在1997-11~1998-04,1999-11~2000-04和2001-11~2002-04 3个阶段共收集肺炎链球菌271株。在这3个阶段,肺炎链球菌分别为83,101,87株;对青霉素不敏感率分别为9.6%,8.9%和16%,对青霉素耐药率分别为1.2%,2%和8%;对大环类脂类抗生素的敏感性分别为28.9%,39.6%和18.4%。肺炎链球菌对克拉霉素显示高水平耐药。阿其霉素和克拉霉素的交叉耐药率可达98.4%。对左氧氟沙星的耐药率分别为1.2%,6.9%和1.2%; 对复方新诺明的耐药率分别为30.1%,62.4%和66.7%;多重耐药的肺炎链球菌分别为2.4%,3.0%和6.9%。在多重耐药的肺炎链球菌中,以阿齐霉素、复方新诺明和青霉素模式为主,占72.7%(8/11),同时有80%(8/10)对青霉素耐药的肺炎链球菌发生多重耐药;肺炎链球菌对万古霉素未见有耐药株。结论对青霉素耐药的肺炎链球菌有逐年上升的趋势,定期进行细菌耐药性的监测,有助于合理应用抗菌药物。     

Linezolid, levofloxacin, and vancomycin against vancomycin-tolerant and fluoroquinolone-resistant Streptococcus pneumoniae in an in vitro pharmacodynamic model

STUDY OBJECTIVE: To compare the pharmacodynamic profiles of linezolid, levofloxacin, and vancomycin against clinical strains of Streptococcus pneumoniae, including vancomycin-tolerant and fluoroquinolone-resistant isolates. DESIGN: In vitro pharmacodynamic model. SETTING: Biosafety level 2, university research laboratory. BACTERIAL STRAINS: Ciprofloxacin-susceptible (79), ciprofloxacin-resistant (R921), and vancomycin-tolerant (P9802-020) clinical strains of S. pneumoniae. INTERVENTION: An in vitro pharmacodynamic model was used to simulate standard dosing regimens of linezolid, levofloxacin, and vancomycin against the isolates 79, R921, and P9802-020. MEASUREMENTS AND MAIN RESULTS: Bacterial density was profiled over 48 hours. Minimum inhibitory concentrations (MICs) for linezolid, levofloxacin, and vancomycin, respectively were 1, 1, 0.5 microg/ml for isolate 79; 1, 4, 0.5 microg/ml for R921; and 0.5, 0.5, 0.5 microg/ml for P9802-020. Vancomycin minimum bactericidal concentration (MBC) values varied across large ranges for the tested strains. Linezolid achieved 99.9% kill against 79 and R921 by 24 and 28 hours, respectively. Levofloxacin achieved 99.9% kill against 79 and P9802-020 by 28 and 4 hours, respectively. Vancomycin achieved 99.9% kill against 79 and R921 by 8 and 24 hours, respectively. Levofloxacin did not demonstrate activity against R921 at the 48-hour end point. Minimal kill (< 2 log) at 48 hours was noted for vancomycin and linezolid against P9802-020. Conclusion. Vancomycin tolerance appeared to be more reliably characterized by persistent viability in time-kill analyses than by MBC:MIC ratios. Vancomycin exhibited bactericidal activity against the non-vancomycin-tolerant strains of S. pneumoniae. Linezolid exhibited both bactericidal and bacteriostatic activity against all three strains tested, whereas levofloxacin demonstrated bactericidal activity against the fluoroquinolone-susceptible isolates. Further investigation of treatment alternatives for infections due to vancomycin-tolerant S. pneumoniae are needed.     

阿莫西林与红霉素对肺炎链球菌的体外抗菌效果

目的研究阿莫西林(β内酰胺类抗生素)和红霉素(大环内酯类抗生素)联合应用体外对肺炎链球菌的相互作用,并验证红霉素对肺炎链球菌的杀菌作用。方法用琼脂平板二倍稀释法测定阿莫西林和红霉素对肺炎链球菌的最低抑菌浓度(MIC),用影印培养法测定最低杀菌浓度(MBC)。用棋盘微量稀释法和时间-杀菌曲线分析测定两药对肺炎链球菌的联合作用效果。结果阿莫西林对44株菌株的MIC为≤0.004～2mg·L-1,MBC≤0.004～4mg·L-1;红霉素对其的MIC值为0.008～≥256mg·L-1,MBC为0.016～≥256mg·L-1。阿莫西林的MBC/MIC为1～2;红霉素的MBC/MIC的为1～4。对阿莫西林和红霉素均敏感的肺炎链球菌株联合用药时,大部分菌株较单用时相同或略下降,其FICI在1～2。结论红霉素在体外对肺炎链球菌有杀菌作用;与阿莫西林体外联合应用时,阿莫西林杀菌效果不会被减弱。     

Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae isolates from Crete, Greece

Susceptibility to 14 antibiotics was determined for 125 clinical isolates of Streptococcus pneumoniae collected over a 3-year period in Crete, Greece. Twenty-three isolates (18.4%) showed intermediate resistance and 15 (12%) high-level resistance to penicillin. Erythromycin, chloramphenicol, tetracycline, trimethoprim-sulphamethoxazole and sparfloxacin resistance rates were 16.8, 10.4, 19.2, 24.8 and 9.6%, respectively. Multiple resistance was observed in 22 strains. Vancomycin and levofloxacin were the most active agents tested. The most prevalent serotype among penicillin-susceptible pneumococci was 14, followed by 9, 7 and 1, while among penicillin-intermediate or -resistant strains serotype 23 was predominant followed by 19 and 9. These results show that as well as a high level of penicillin resistance in this region, some strains are also resistant to other antibiotics and may show multi-drug resistance.     

48株儿童侵袭性肺炎链球菌血清型分布

目的了解南京地区临床分离的侵袭性肺炎链球菌血清型分布情况。方法用荚膜肿胀实结果检测2007年1月-2010年12月临床分离的48株侵袭性肺炎链球菌的血清型别。结果 48株侵袭性肺炎链球菌常见的血清型别为19F(27.1%)、19A(22.8%)、14(18.7%)和9v(8.3%),有2株用丹麦抗血清无法确定血清型。结论南京地区儿童临床分离的侵袭性肺炎链球菌的常见血清型为19F、19A、14和9v,与其它地区报道有一定差别。     

In vitro activity of ertapenem (MK-0826) against multi-drug resistant Streptococcus pneumoniae compared with 13 other antimicrobials

We tested ertapenem (MK-0826), a new carbapenem, and 13 other antimicrobials by microbroth dilution against 102 isolates of Streptococcus pneumoniae, selected to include organisms resistant to a variety of drug classes. Ertapenem MICs ranged from < or =0.008 to 4 mg/l, MIC(50)=0.5 mg/l, and MIC(90)=2 mg/l. Based on MIC(90), ertapenem potency was 4-fold greater than cefuroxime, 2-fold greater than amoxycillin/clavulanate, =penicillin, 2-fold less than meropenem and ceftriaxone, and 4-fold less than imipenem. Other drug classes including macrolides, tetracycline and fluoroquinolones were less potent overall than the carbapenems. Linezolid (MIC(90)=1 mg/l) was the only agent tested for which all isolates were fully susceptible. Activity of ertapenem decreased as MICs to penicillins, cephalosporins, other carbapenems and macrolides increased. Isolates resistant to clindamycin, tetracycline or fluoroquinolones showed no obvious decrease in ertapenem activity when compared with susceptible isolates with the majority of isolates resistant to these drug classes inhibited by ertapenem at concentrations less than 1 mg/l. Ertapenem may prove useful as an alternative to ceftriaxone and other agents in the treatment of community-acquired pneumonia (CAP) due to S. pneumoniae, including infections caused by organisms with reduced susceptibilities to other antimicrobial agents.     

In vitro activity of telithromycin compared with macrolides and fluoroquinolones against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis

The in vitro activity of telithromycin was compared with erythromycin A, azithromycin, clarithromycin, moxifloxacin, gemifloxacin, levofloxacin, ciprofloxacin, penicillin G, ampicillin, cefuroxime and ceftriaxone against 336 consecutive strains (83 Streptococcus pneumoniae, 168 Haemophilus influenzae and 85 Moraxella catarrhalis) isolated from patients with community-acquired respiratory tract infections. Telithromycin (MIC(90), 0.008 mg/l) was the most active drug against S. pneumoniae. Telithromycin was also highly active against M. catarrhalis (MIC(90), 0.06 mg/l), but less active against H. influenzae (MIC(90), 4 mg/l).     

Assessment of the efficacy of telithromycin simulating human exposures against S. pneumoniae with ribosomal mutations in a murine pneumonia model

Telithromycin (TEL) is a ketolide antimicrobial agent with in vitro activity against Streptococcus pneumoniae (SPN), including macrolide resistant strains. The purpose of this study was to assess the efficacy of TEL against clinical SPN isolates with various genotypic mutations including the newly recognized ribosomal mutations. Pneumonia was induced in either immunocompetent and immunosuppressed mice. Six isolates were included in the study and all were resistant to azithromycin (AZI) by MIC testing. Three oral regimens of TEL were chosen to simulate the human pharmacokinetic (PK) exposures observed in young healthy, healthy elderly (≥65 years), and infected subjects. An additional group was given AZI in human simulated doses. Bacterial density in lung was determined after each treatment. Telithromycin administered simulating infected patients showed greater efficacy (i.e., change in log CFU) than the azithromycin treated group for all isolates except P1660008. The immune system was responsible for increased efficacy (ranging from 45–146%) for all but one of the telithromycin treatment regimens. Unlike other isolates studied in this in vivo model, P1660008 displayed a highly variable response to therapy, such that the reductions in CFU were not consistent with the microbiological and PK profiles of either compound. For all other isolates, the activity of AZI was comparable with untreated controls. Human simulated exposures of TEL displayed 0.5–3.4 log kill in vivo despite the ribosomal mutations studied. These data support the in vivo efficacy of TEL against a variety of genotypic resistance profiles observed in pneumococci, however, additional studies are required to fully characterize the killing profile of the compound against these recently determined ribosomal mutations.     

阿洛西林及其它常用抗菌药物对京沪两地898株细菌的体外抗菌活性测定

目的研究阿洛西林及其它8种临床常用抗菌药物对常见病原体的体外抗菌活性。方法采用琼脂稀释法测定阿洛西林、美洛西林、哌拉西林、头孢呋辛、头孢曲松、头孢他啶、头孢哌酮、左氧氟沙星和阿奇霉索9种药物对上海、北京两地898株临床分离细菌的最低抑菌浓度（MIC）。结果阿洛西林对肺炎链球菌、流感嗜血杆菌和甲氧西林敏感的金黄色葡萄球菌（MSSA）的MIC50／MIC90分别为0．06／2、0．06／0．5和2／8，三种细菌对阿洛西林的敏感率均高达100％。粪肠球菌、屎肠球菌、铜绿假单胞菌和不动杆菌对阿洛西林的敏感率分别为91％、13％、68％和38％。阿洛西林分别列于9种受试药物的第一、第一和第三位。大肠埃希菌、肺炎克雷伯菌和阴沟肠杆菌对阿洛西林的敏感率分别为41％、65％和39％，低于第三代头孢菌素但优于美洛西林和哌拉西林。结论阿洛西林的抗菌谱广，对革兰阳性菌、阴性菌均有较为理想的抗菌活性，是目前用于社区及医院感染治疗的重要选择药物之一。     

头孢吡肟对肺炎克雷伯氏菌和大肠埃希氏菌的体外敏感性

目的　评价第四代头孢菌素头孢吡肟对 4 2 6株肺炎克雷伯氏菌和大肠埃希氏菌的体外敏感性。方法　收集 2 0 0 1年 3～ 10月福州地区 4家医院分离的肺炎克雷伯氏菌和大肠埃希氏菌 4 2 6株 ,用 Kirby-Bauer琼脂扩散法作药敏试验 :用表型确认试验检测 ESBL s。结果　 4 2 6株肺炎克雷伯氏菌和大肠埃希氏菌中 ,头孢吡肟的敏感性为 94 .37% ,仅次于亚胺培南 (10 0 % )、头孢哌酮 /舒巴坦 (10 0 % )和哌拉西林 /三唑巴坦(99.5 3% ) ,明显高于青霉素类抗生素哌拉西林 (48.83% )和第二代头孢菌素头孢呋辛 (6 0 .0 9% ) ,也高于第三代头孢菌素头孢曲松 (6 2 .91% )、头孢噻肟 (6 4 .79% )、头孢哌酮 (6 5 .73% )和头孢他啶 (88.2 6 % )。经表型确认试验证实 14 2株 (33.33% )为产超广谱 β-内酰胺酶 (ESBL s)菌 ;头孢吡肟对产 ESBL s菌和非产 ESBL s菌体外敏感性分别为 84 .5 1%、99.30 %。结论　头孢吡肟对肺炎克雷伯氏菌和大肠埃希氏菌的体外抗菌活性高于第三代头孢菌素 ,低于亚胺培南、头孢哌酮 /舒巴坦和哌拉西林 /三唑巴坦 ,头孢吡肟可考虑作为医院内感染的经验性一线用药。     

In vitro activity of linezolid and 12 other antimicrobials against coryneform bacteria

OBJECTIVES: To compare the in vitro activity of linezolid with 12 other antimicrobials against 190 strains of the coryneform bacteria, including 60 strains of C. amycolatum, 30 of C. striatum, 30 of C. jeikeium, 10 of C. urealyticum, 20 of B. casei, 20 of D. hominis and 20 of T. otitidis. METHODS: Minimum inhibitory concentrations (MICs) and time-death curves were carried out according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI). RESULTS: Linezolid was very active against the 130 strains of the Corynebacterium species studied. Only the glycopeptides showed similar efficacy. In contrast, penicillin G, ampicillin, macrolides, lincosamides, fluoroquinolones and aminoglycosides showed generally high MICs. Among the beta-lactams, only imipenem was active against the majority of strains of C. striatum and C. amycolatum, and, approximately half of the C. jeikeium and C. urealyticum isolates. Both Dermabacter hominis and Brevibacterium casei showed marked resistance against most of the antimicrobials tested, while Turicella otitidis only showed high MICs against macrolides and clindamycin. For all of them, linezolid, vancomycin and teicoplanin proved effective. The time-death curves showed linezolid to behave as a bacteriostatic agent (approximately 90% death rate). Such activity was more accentuated for C. amycolatum and C. striatum (reduction of 1.3 and 1.7log(10)CFU/mL, respectively) than for C. jeikeium and C. urealyticum (reduction of 1.0 and 0.8log(10), respectively). CONCLUSIONS: Our results indicate that linezolid is active against coryneform bacteria. The efficacy of linezolid is equal to or even superior to that of the glycopeptides.