In vitro activity of isepamicin and other aminoglycosides against clinical isolates of Gram-negative bacteria causing nosocomial bloodstream infections.

BACKGROUND AND PURPOSE: Isepamicin is a newly introduced aminoglycoside in Taiwan. Since in vitro data for isepamicin against nosocomial Gram-negative bloodstream infection from Taiwan are limited, we compared the activity of isepamicin, amikacin, gentamicin and tobramycin against nosocomial Gram-negative blood isolates. METHODS: A total of 247 non-duplicate nosocomial blood isolates of Gram-negative bacteria collected between January 2003 and December 2003 in a major teaching hospital in Taiwan were tested for their in vitro susceptibilities to gentamicin, tobramycin, amikacin, and isepamicin using the agar dilution method. The isolates included Escherichia coli (31 isolates), Klebsiella pneumoniae (31), Enterobacter cloacae (30), Serratia marcescens (31), Morganella morganii (21), Citrobacter freundii (10), Pseudomonas aeruginosa (31), Acinetobacter baumannii (31), and Stenotrophomonas maltophilia (31). RESULTS: Overall, isepamicin had high antibacterial activity against the tested Gram-negative bacteria. For the 154 Enterobacteriaceae isolates, isepamicin had the lowest minimum concentration inhibiting 90% of isolates (MIC90) among the tested drugs, while its resistance rate (3.9%) was equal to that of amikacin (3.9%) and lower than those of tobramycin (18.2%) and gentamicin (21.4%). For the 93 of non-fermentative Gram-negative bacilli isolates, isepamicin had the lowest MIC90, and a resistance rate (23.7%) lower than those of amikacin (27.9%), tobramycin (38.7%) and gentamicin (40.9%). CONCLUSIONS: The in vitro activity of isepamicin against Gram-negative bacteria isolates was equal or similar to amikacin and superior to other tested aminoglycosides. In view of its potential for less nephrotoxicity and ototoxicity than other aminoglycosides, isepamicin is a drug of choice for the empirical treatment of nosocomial infections caused by Gram-negative bacteria.     

Antimicrobial susceptibility of multidrug-resistant Gram negative bacteria to fosfomycin

We evaluated the antimicrobial activity of fosfomycin against a randomly selected sample of 30 Klebsiella pneumoniae, 30 Pseudomonas aeruginosa, and 30 Acinetobacter baumannii multidrug-resistant, clinical isolates from patients in a general tertiary care hospital in Athens, Greece. Standard laboratory methods were used for susceptibility testing to commonly used antibiotics and the detection of extended-spectrum-beta-lactamase (ESBL) and metallo-beta-lactamase (MBL) production. The minimum inhibitory concentration (MIC) of fosfomycin for each isolate was determined by the agar dilution method. All K. pneumoniae isolates were both ESBL and MBL producers; all P. aeruginosa isolates were ESBL producers. The K. pneumoniae strains had fosfomycin MICs distributed across a range of 8-64 microg/ml; MIC(50) was 16 microg/ml and MIC(90) 32 microg/ml. The fosfomycin MICs of the P. aeruginosa strains had a distribution across a range of 4 to over 512 microg/ml; MIC(50) was 32 microg/ml and MIC(90) 128 microg/ml. The fosfomycin MICs of the A. baumannii strains had a distribution across a range of 64 to over 512 microg/ml; MIC(50) was 256 microg/ml and MIC(90) more than 512 microg/ml. Although standardized fosfomycin MIC interpretative breakpoints for the species studied are lacking, the findings of our study support the idea that fosfomycin may be further investigated as one among a decreasing list of therapeutic options for the treatment of infections due to multidrug-resistant strains of, primarily, K. pneumoniae and, secondly, P. aeruginosa.     

Doripenem vs meropenem against Pseudomonas and Acinetobacter

Recently, doripenem has been approved for the treatment of nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP). The E-test was performed to determine the MICs of doripenem and meropenem in 203 endotracheal aspirate isolates that consisted of 140 Acinetobacter calcoaceticus-Acinetobacter baumannii complexes and 63 Pseudomonas aeruginosa. Doripenem showed minimum concentration necessary for inhibition of 50% (MIC 50 ) of P. aeruginosa isolates at 0.38 mg/L which is several times (84.2 times) lower than the corresponding MIC 50 value of >32 mg/L for meropenem. The MIC 50 and MIC 90 were similar for both the drugs against A. baumannii. Thus, P. aeruginosa was consistently more susceptible than the A. baumannii.     

Activity of polymyxin B and the novel polymyxin analogue CB-182,804 against contemporary Gram-negative pathogens in New York City

Multidrug-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa have become common in many regions, often requiring therapy with colistin or polymyxin B. An increase in resistance to these agents would render many infections untreatable. We tested the activity of polymyxin B and the novel polymyxin analogue CB-182,804 against over 5,000 recent Gram-negative clinical isolates from New York City, a region with a high prevalence of multiresistant strains. Over 96% of Escherichia coli, K. pneumoniae, A. baumannii, and P. aeruginosa were susceptible to polymyxin B; only 76% of Enterobacter spp. was susceptible. The MICs of CB-182,804 were generally two-fold higher than polymyxin B and cross-resistance was observed. The addition of rifampin resulted in synergistic inhibition and bactericidal activity in time kill studies, and restored activity against all polymyxin-resistant strains. The synergistic effect of the combination with rifampin was most pronounced against A. baumannii strains, and was slightly greater with CB-182,804 than with polymyxin B against K. pneumoniae and Enterobacter spp. Despite considerable usage of polymyxin B and colistin in this region, polymyxin B retains excellent activity against most Gram-negative isolates. CB-182,804 shows similar activity, particularly when combined with rifampin. The clinical utility of CB-182,804 remains to be determined.     

In vitro activities of tigecycline, ertapenem, isepamicin, and other antimicrobial agents against clinically isolated organisms in Taiwan

This study evaluated the in vitro activities of tigecycline, ertapenem, isepamicin, and other comparators against 861 bacterial isolates recovered from patients treated in three major teaching hospitals in 2003. MICs to antimicrobial agents were determined by the agar dilution method. High rates of oxacillin resistance (58%) in Staphylococcus aureus (60 isolates), and vancomycin resistance (21%) and quinupristin-dalfopristin non-susceptibility (39%) in Enterococcus faecium (34 isolates) were found. Carbapenems had excellent in vitro activities (>or=98% susceptibility) against the 419 isolates of Enterobacteriaceae, with the MIC(50) and MIC(90) of imipenem, meropenem, and ertapenem being 0.25 and 4 mg/L, 0.03 and 0.12 mg/L, and 0.03 and 0.5 mg/L, respectively. For, Pseudomonas aeruginosa (74 isolates) and Burkholderia cepacia (21 isolates), meropenem (MIC(90), 0.25, 2, and 4 mg/L, respectively) had better in vitro activities than imipenem (MIC(90), 8, 4, and 32 mg/L, respectively) and ertapenem (MIC(90), 0.5, >32, and 32 mg/L, respectively). Isepamicin had a similar activity with amikacin against all Enterobacteriaceae, Pseudomonas aeruginosa, B. cepacia, and Acinetobacter baumannii, except for C. freundii isolates in which isepamicin had an eight-fold activity better than amikacin. Tigecycline had excellent in vitro activities against all isolates tested (MIC(90), 相似文献   

2008～2010年我院下呼吸道感染革兰氏阴性杆菌的耐药分析

了解我院2008～2010年医院下呼吸道感染主要病原菌的分布及其耐药性,为临床合理使用抗生素提供依据.回顾性调查下呼吸道感染者中的2555株革兰阴性杆菌的菌种分布及耐药性.分离菌株用全自动微生物鉴定仪进行菌株鉴定和药敏试验.结果表明:连续三年分离率居前五位的革兰氏阴性杆菌为:铜绿假单胞菌、鲍曼不动杆菌、肺炎克雷伯菌、大...     

Comparative analysis of antimicrobial susceptibility among organisms from France, Germany, Italy, Spain and the UK as part of the tigecycline evaluation and surveillance trial.

As part of the tigecycline evaluation and surveillance trial (TEST), bacterial isolates were collected from 39 centres in France, Germany, Italy, Spain and the UK between January 2004 and August 2006. Antimicrobial susceptibilities were determined according to CLSI guidelines. Italy had the highest rate of methicillin-resistant Staphylococcus aureus (36.4%), and was the only country to report vancomycin-resistant Enterococcus faecalis (8.6%). Tigecycline was the only agent to which all Gram-positive isolates were susceptible. For many of the Gram-negative organisms collected, antimicrobial susceptibilities were lowest among isolates from Italy and highest among isolates from Spain. The notable exception was Acinetobacter baumannii, where the poorest susceptibility profile was among isolates from Spain. For A. baumannii, MIC(90)s of imipenem varied from 1 mg/L for isolates in France and Germany to > or =32 mg/L for isolates from Italy and Spain. Tigecycline was the only agent to maintain an MIC(90) of < or =1 mg/L against isolates from all five countries. The in-vitro activity of tigecycline against both Gram-positive and Gram-negative isolates may make it valuable in the treatment of hospital infections, including those caused by otherwise antimicrobial-resistant organisms.     

Detection of carbapenemase-producing Acinetobacter baumannii in a hospital

Acinetobacter baumannii strains resistant to both imipenem (IPM) and ceftazidime (CAZ) were isolated from 1994 through 1996 at Gunma University Hospital. Nine isolates from different inpatients were examined for carbapenem-hydrolyzing activity and for the carbapemase gene bla(IMP) by the PCR method. All nine isolates were carbapenemase-producing strains that hydrolyzed IPM and that harbored bla(IMP). The bla(IMP) gene was transmissible by conjugation to an IPM-susceptible recipient strain of A. baumannii and conferred resistance to IPM, CAZ, cefotaxime (CTX), ampicillin (AMP), and piperacillin (PIP). Either intermediate or high-level resistance to amikacin (AMK) was transferred from two and five strains, respectively, concomitantly with bla(IMP), and gentamicin (GEN) resistance was also transferred in one instance of high-level AMK resistance. Comparative examination of clinical isolates for resistance patterns to nine drugs, IPM, CAZ, CTX, aztreonam, AMP, PIP, AMK, GEN, and norfloxacin, in addition to pulsed-field gel electrophoresis patterns with NotI-digested genomic DNA, confirmed nosocomial transmission of infections involving carbapenemase-producing A. baumannii strains.     

Antimicrobial activity of doripenem (S-4661): a global surveillance report (2003)

The spectrum of activity and potency of doripenem, a broad-spectrum parenteral carbapenem currently in clinical development, was evaluated using 16 008 clinical bacterial isolates collected as part of an international surveillance project during 2003. Using reference broth microdilution methods, doripenem was found to be highly active against oxacillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci (2705 and 297 isolates, respectively; MIC90s 0.06 mg/L), with a potency greater than that of other carbapenem antibiotics. Against enterococci (1474 isolates), with the exception of Enterococcus faecium, doripenem displayed modest activity (MIC50 4). Doripenem was among the most potent agents tested against Streptococcus pneumoniae, viridans group streptococci and beta-haemolytic streptococci (885, 140 and 397 isolates; MIC(90)s 0.5, 0.5 and 0.03 mg/L, respectively). For Enterobacteriaceae (> 6200 isolates), doripenem was four- to 32-fold more active than imipenem against wild-type isolates (MIC90s 0.03-0.5 mg/L). MIC90s for confirmed extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae (121 and 155 isolates; 0.06 and 0.12 mg/L, respectively) were two-fold higher than for wild-type isolates. Doripenem was also active against Citrobacter spp., Enterobacter spp. and Serratia spp. (MIC90s 0.06-0.25 mg/L), including ceftazidime-resistant isolates. Doripenem and meropenem were the most active agents among all beta-lactams against Pseudomonas aeruginosa (829 isolates; MIC50/90s 0.5/8 and 0.5/16 mg/L, respectively), whereas doripenem and imipenem were the most active agents against Acinetobacter spp. (155 isolates; MIC50/90s 0.5/4 and 相似文献   

Convenient test using a combination of chelating agents for detection of metallo-beta-lactamases in the clinical laboratory

Although transmissible metallo-beta-lactamases (MBLs) are a serious threat to beta-lactam antibiotic therapy, the CLSI currently does not recommend testing methods for the detection of MBLs. The aim of this study was to evaluate the capability of double-disk tests (DDTs) by using disks containing a combination of the chelators 2-mercaptopropionic acid (MPA) and Tris-EDTA (TE) to detect MBLs. Sixteen isolates (4 Acinetobacter baumannii isolates, 6 Pseudomonas aeruginosa isolates, 1 Serratia marcescens isolate, 1 Aeromonas hydrophila isolate, 1 Aeromonas veronii isolate, 2 Chryseobacterium meningosepticum isolates, and 1 Stenotrophomonas maltophilia isolate) producing IMP-1, IMP-1-like, IMP-18, GIM-1, SPM-1, VIM-2, VIM-2-like, and chromosomal MBLs and 20 isolates (7 Klebsiella pneumoniae isolates, 3 Escherichia coli isolates, 5 Enterobacter cloacae isolates, 2 S. marcescens isolates, 1 Proteus mirabilis isolate, and 2 A. baumannii isolates) producing non-MBL carbapenemases, AmpC beta-lactamases, and extended-spectrum beta-lactamases were tested. The DDT method was evaluated by using four types of chelator disks (TE, high-strength TE, MPA, and TE plus 20 microl of MPA [at various concentrations]) and the beta-lactams imipenem (IPM), meropenem (MEM), ertapenem (ERT), and ceftazidime (CAZ). DDTs with IPM and a TE disk supplemented with 1:320 MPA detected all MBLs and yielded no false-positive results. Some, but not all, MBL producers were detected in IPM-based tests involving the single chelator TE or MPA alone or by ERT- or CAZ-based tests. IPM-based tests with MPA concentrations other than 1:320 and all MEM-based tests had suboptimal sensitivities or specificities. DDT with IPM and a TE disk supplemented with 20 microl of 1:320 MPA appears to be convenient for the detection of MBLs in the clinical laboratory.     

Time-kill synergy tests of tigecycline combined with imipenem, amikacin, and ciprofloxacin against clinical isolates of multidrug-resistant Klebsiella pneumoniae and Escherichia coli

This study evaluated the activity of tigecycline combined with imipenem, amikacin, and ciprofloxacin against clinical isolates of multidrug-resistant Klebsiella pneumoniae and Escherichia coli co-producing extended-spectrum β-lactamases and acquired AmpC β-lactamases. Broth microdilution tests were performed for cefotaxime, ceftazidime, cefepime, imipenem, amikacin, ciprofloxacin, and tigecycline. Time-kill synergy studies were tested for tigecycline plus imipenem, tigecycline plus amikacin, and tigecycline plus ciprofloxacin. Imipenem (MIC(90) = 1 μg/ml for both K. pneumoniae and E. coli) and tigecycline (MIC(90) = 2 μg/ml for K. pneumoniae and 1 μg/ml for E. coli) were the most potent agents. Combination studies with tigecycline plus imipenem resulted in synergy against 18 K. pneumoniae and 3 E. coli isolates; tigecycline plus amikacin yielded synergy against 8 K. pneumoniae and 3 E. coli isolates; tigecycline plus ciprofloxacin yielded synergy against 7 K. pneumoniae and 2 E. coli isolates. No antagonism was observed with any combination. In the present study, imipenem, amikacin, and ciprofloxacin led to indifferent and some synergistic effects in combination with tigecycline, and none of them demonstrated antagonistic effects.     

Global assessment of the antimicrobial activity of polymyxin B against 54 731 clinical isolates of Gram-negative bacilli: report from the SENTRY antimicrobial surveillance programme (2001–2004)

In total, 54 731 Gram-negative bacilli isolated worldwide between 2001 and 2004 from diverse sites of infection were tested for susceptibility to polymyxin B by the broth reference microdilution method, with interpretation of results according to CLSI (formerly NCCLS) guidelines. Polymyxin B showed excellent potency and spectrum against 8705 Pseudomonas aeruginosa and 2621 Acinetobacter spp. isolates (MIC50, < or = 1 mg/L and MIC90, 2 mg/L for both pathogens). Polymyxin B resistance rates were slightly higher for carbapenem-resistant P. aeruginosa (2.7%) and Acinetobacter spp. (2.8%), or multidrug-resistant (MDR) P. aeruginosa (3.3%) and Acinetobacter spp. (3.2%), when compared with the entire group (1.3% for P. aeruginosa and 2.1% for Acinetobacter spp.). Among P. aeruginosa, polymyxin B resistance rates varied from 2.9% in the Asia-Pacific region to only 1.1% in Europe, Latin America and North America, while polymyxin B resistance rates ranged from 2.7% in Europe to 1.7% in North America and Latin America among Acinetobacter spp. Polymyxin B also demonstrated excellent activity (MIC90, < or = 1 mg/L; > 98% susceptible) against Citrobacter spp., Escherichia coli and Klebsiella spp., but activity was more variable against Enterobacter spp. (MIC50, < or = 1 mg/L; 83.3% susceptible) and Stenotrophomonas maltophilia (MIC50, < or = 1 mg/L; 72.4% susceptible), and was very limited (MIC50, > 8 mg/L) against Burkholderia cepacia (11.8% susceptible), Serratia spp. (5.4% susceptible), indole-positive Proteus spp. (1.3% susceptible) and Proteus mirabilis (0.7% susceptible).     

亚胺培南对医院内革兰阴性菌的抗菌活性分析

目的:了解亚胺培南对院内革兰阴性菌的抗菌活性。方法:收集2007年至2011年从临床送检标本中分离出来的革兰阴性菌4264株,采用Vitek 2全自动微生物鉴定分析系统、API系统及K-B法进行培养鉴定和药敏试验。结果:发现亚胺培南总耐药率为25.82%(1101/4264),2007年至2011年的年度耐药率分别为4.23%(8/189),9.23%(35/379),10.12%(49/484),24.12%(179/742)和33.60%(830/2470);耐药菌种分别占总菌种数的28.57%(4/14),40.00%(8/20),31.25%(5/16),36.36%(8/22)和65.71%(23/35)。分离率前10位的是大肠埃希菌、鲍曼不动杆菌、肺炎克雷伯菌、铜绿假单胞菌、阴沟肠杆菌、产气肠杆菌、洋葱伯克霍尔德菌、黏质沙雷菌、产酸克雷伯菌和甲型副伤寒沙门菌,对亚胺培南的耐药率分别为0.82%(9/1097),68.22%(631/925),4.07%(29/713),39.86%(228/572),9.64%(27/280),2.40%(3/125),90.00%(81/90),7.02%(4/57),46.43%(26/56)和0(0/45)。2007年至2011年对亚胺培南的年度耐药率,铜绿假单胞菌为6.25%(1/16),31.25%(5/16),19.57%(9/46),34.48%(40/116)和45.77%(173/378);鲍曼不动杆菌为7.14%(1/14),47.06%(8/17),29.63%(8/27),61.45%(110/179)和73.26%(504/688);阴沟肠杆菌为0(0/10),0(0/26),3.13%(1/32),9.23%(6/65)和13.61%(20/147)。大肠埃希菌、肺炎克雷伯菌、产气肠杆菌、黏质沙雷菌在最近1～2年检出了亚胺培南耐药菌株。结论:亚胺培南是一种有效的抗革兰氏阴性菌药物,但药敏性正在逐年下降,耐药菌种数在增多,耐药率正在逐年上升。     

电子鼻检测常见伤口感染细菌实验研究

为了进一步探讨电子鼻用于伤口细菌感染快速筛查的可能性,使用自制电子鼻检测鲍曼不动杆菌、大肠杆菌、肺炎克雷伯杆菌、金黄色葡萄球菌、铜绿假单胞菌的巯基乙酸酯（TH）培养液及纯培养液,经过预处理后,使用支持向量机、BP神经网络、逻辑回归3种算法进行分类。结果显示,使用BP算法,总体识别率可达93%以上。对于单个识别率,检测大肠杆菌、肺炎克雷伯杆菌、金黄色葡萄球菌可达98%以上,检测鲍曼不动杆菌、铜绿假单胞菌可达90%左右,表明电子鼻用于伤口感染细菌的快速检测和识别具有一定的可行性。     

多重耐药革兰阴性杆菌体外联合药效数据库初建

目的研究临床常用抗生素对多重耐药革兰阴性杆菌的协同和相加作用,初步建立体外联合药效数据库。方法选取磷霉素(PHOS)、左氧氟沙星(LEV)、头孢他啶(CAZ)、复方新诺明(SMZ)、哌拉西林/他唑巴坦(TZP)、头孢哌酮/舒巴坦(SCF)和亚胺培南(IMP)7种抗生素,两两组合为21种药物组。经超广谱β-内酰胺酶(ESBLs)和改良碳青霉烯灭活试验(mCIM)确认,172株多重耐药革兰阴性杆菌分为耐碳青霉烯肺炎克雷伯菌(20株,A组)、泛耐药的鲍曼不动杆菌(50株,B组)、产ESBLs的肠杆菌(62株,C组)和耐碳青霉烯的铜绿假单胞菌(40株,D组)4个耐药菌组。棋盘稀释法测定21种药物组对4个耐药菌组的体外联合药效,统计学分析采用Whonet5.6。结果172株待测菌株均对7种抗生素单药耐药。联合药效检测结果显示:4组均未出现拮抗作用;对A组耐药菌呈现协同作用的药物组有10组,部分协同作用的有14组,无相加作用,PHOS+LEV药物组协同百分率最高(30%,6/20);对B组耐药菌呈现协同作用的药物组有12组,部分协同作用的有10组,相加作用的有3组,LEV+SMZ药物组协同作用百分率最高(56%,28/50);对C组耐药菌呈现协同作用的药物组有14组,部分协同作用的有17组,相加作用的有16组,IMP+LEV药物组协同作用百分率最高(30.6%,19/62);对D组耐药菌呈现协同作用的药物组有12组,部分协同作用的有14组,相加作用的有13组,IMP+LEV药物组协同作用百分率最高(20%,8/40)。结论喹诺酮类、碳青霉烯类、磺胺类和磷霉素等药物联合应用,对多重耐药革兰阴性杆菌有较好的协同作用,治疗前行体外联合药效监测,可提高抗生素使用的准确性,临床应用价值较高。     

In vitro activity of tazobactam and piperacillin combination against 224 strains of Pseudomonas aeruginosa according to the production of beta-lactamase]

Piperacillin (PIP) alone and combined with 4 mg/l, 8 mg/l of tazobactam (TAZ) were tested by MIC determination on Mueller-Hinton agar against 224 clinical strains of P. aeruginosa: "wild type" (BLA-), 32 producing a constitutive cephalosporinase (CEP), 41 producing the PSE-1 type beta-lactamase, 7 PSE-2, 8 PSE-3, 9 PSE-4, 13 TEM-1, 24 TEM-2, 13 OXA-1, 22 OXA-2, 5 OXA-3. The combination with 8 mg/l was more effective than that one with 4 mg/l. Combinations of PIP-TAZ 8 mg/l reduced the MICs of PIP for the resistant strains (MICs greater than 64 mg/l) to the susceptible ot the moderately susceptible range (MICs less than or equal to 64 mg/l) for 31% of the CEP producing strains, 63% of the PSE-1, 15% of the PSE-2, none of the PSE-3, 34% of the PSE-4, 39% of the TEM-1, 30% of the TEM-2, 23% of the OXA-1, 14% of the OXA-2, 27% of the OXA-3, TAZ is the first beta-lactamase inhibitor effective against the constitutive cephalosporinase of P. aeruginosa; it is also very effective against the most frequently found PSE-1 beta-lactamase in P. aeruginosa.     

Comparative in vitro bacteriostatic and bactericidal activity of levofloxacin and ciprofloxacin against urinary tract pathogens determined by MIC,MBC, Time-Kill curves and bactericidal index analysis

The Bactericidal Index is a new way to assess bactericidal activity, representing the total bacterial kill over a drug concentration range. The aim of the study was to compare the in vitro activity of LEV with that of CIP against uropathogens determined by MIC, MBC, time-kill curves and BI analysis. A total of 141 strains [E. coli (EC) n=30; Klebsiella spp n=30; P aeruginosa (PA) n=35; P. mirabilis (PM) n=21; E. cloacae n=25] were preliminarily tested for MIC evaluation. MICs were obtained by 100 l microbroth dilution, followed by whole volume transfer for MBC determination. The time-kill tests were determined with 3 isolates each of EC, PA and PM and the killing monitored over 24h. FQs were added to a final concentration of 0.25, 0.5, 1, 2, 4, 8 and 16xMIC. Aliquots were sub-cultured at intervals. To assess the BI, overnight bacterial cultures were diluted to about 107 CFU/ml and set up containing a range of drug concentrations. MIC values of LEV were slightly higher than CIP; MBC/MIC ratio was in the range 1:1/1:2. LEV showed 99.9% killing after 6h against EC and after 3 h against PA at 1xMIC and after 3h at 2xMIC against PM in contrast with CIP (after 3h at 8xMIC). The BI data showed that FQs became more bactericidal with increasing incubation time and evidenced the enhanced bactericidal potency of LEV. A paradoxical effect was observed for all PA and PM strains, with slower killing at high concentrations of LEV (128 g/ml) at 24h and CIP (4 g/ml) at 3h. CIP was more active in terms of MIC values but LEV exhibited similar or even better bactericidal activity when time-kill curves or BI were compared. Calculation of BI allows the bactericidal activity of drugs, at clinically relevant concentrations, to be readily compared.     

Comparison of in vitro activities of levofloxacin, ciprofloxacin, ceftazidime, cefepime, imipenem, and piperacillin-tazobactam against aerobic bacterial pathogens from patients with nosocomial infections.

BACKGROUND AND PURPOSE: There is a rapid worldwide emergence of multidrug-resistant pathogens, especially in nosocomial isolates. This study compared the in vitro activities of levofloxacin, ciprofloxacin, ceftazidime, cefepime, imipenem, and piperacillin-tazobactam against 208 aerobic bacterial pathogens that caused 197 nosocomial infections in 184 patients. METHODS: Antimicrobial susceptibility was evaluated by E test in accordance with the guidelines of the National Committee for Clinical Laboratory Standards. RESULTS: Most (140/208, 67%) of the isolates were facultative Gram-negative bacilli. Levofloxacin and ciprofloxacin were the most effective (22/22, 100%) against oxacillin-sensitive Staphylococcus aureus. None of the antibiotics tested were found to be effective (0/25) against oxacillin-resistant S. aureus. Of the 11 isolates of Acinetobacter baumannii that were not pandrug-resistant (PDR), only 9 isolates (9/11, 81%) were sensitive to imipenem and 5 isolates (5/11, 45%) were sensitive to levofloxacin, ciprofloxacin, and ceftazidime. Another 22 isolates of A. baumannii that were PDR were completely resistant to all 6 antibiotics. The majority of isolates of Pseudomonas aeruginosa were sensitive to these 6 antimicrobial agents with 10/11 (91%) sensitive to levofloxacin and ciprofloxacin, 9/11 (83%) sensitive to ceftazidime, cefepime and piperacillin-tazobactam, and 8/11 (75%) sensitive to imipenem. CONCLUSIONS: The majority of the bacterial isolates causing nosocomial infections were found to be sensitive to the 6 antibiotics tested. Bacterial isolates of nosocomial infections that were completely resistant to these 6 antibiotics were PDR A. baumannii, PDR P. aeruginosa, and oxacillin-resistant S. aureus. More potent antimicrobial agents are needed to treat infections caused by PDR A. baumannii and PDR P. aeruginosa.     

Emergence of multidrug-resistant NDM-1-producing Gram-negative bacteria in Bangladesh

The main objective of this study was to investigate the prevalence of bla (NDM-1) in Gram-negative bacteria in Bangladesh. In October 2010 at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) laboratories, 1,816 consecutive clinical samples were tested for imipenem-resistant Gram-negative organisms. Imipenem-resistant isolates were tested for the bla (NDM-1) gene. Among 403 isolates, 14 (3.5?%) were positive for bla (NDM-1), and the predominant species were Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli. All bla (NDM-1)-positive isolates were resistant to multiple antibiotics. Among β-lactamase genes, bla (CTX-M-1-group) was detected in ten isolates (eight bla (CTX-M-15)), bla (OXA-1-group) in six, bla (TEM) in nine, bla (SHV) in seven, and bla (VIM) and bla (CMY) in two isolates each. The 16S rRNA methylase gene, armA, was detected in five?K. pneumoniae isolates and in one E. coli isolate. rmtB and rmtC were detected in a Citrobacter freundii and two?K. pneumoniae isolates, respectively. qnr genes were detected in two?K. pneumoniae isolates (one qnrB and one qnrS) and in an E. coli isolate (qnrA). Transferable plasmids (60-100?MDa) carrying bla (NDM-1) were detected in 7 of the 11 plasmid-containing isolates. Pulsed-field gel electrophoresis (PFGE) analysis grouped K. pneumoniae isolates into three clusters, while E. coli isolates differed significantly from each other. This study reports that approximately 3.5?% of Gram-negative clinical isolates in Bangladesh are NDM-1-producing.     

Strict anaerobic bacteria: comparative study of various beta-lactam antibiotics in combination with tazobactam or sulbactam]

The minimal inhibitory concentrations of piperacillin (PIP) or cefotaxime (CTX) alone or in combination with tazobactam (TAZ) were determined against 168 anaerobes. All the strains were inhibited by PIP + TAZ, but certain strains resistant to CTX + TAZ were found among B. fragilis, Eubacterium and Peptostreptococcus. The second investigations included 30 strains of Bacteroides fragilis. Concentrations of 2, 4 and 8 mg/l of TAZ and sulbactam (SUL) were combined with piperacillin or cefotaxime. The two beta-lactamase-inhibitors had similar activities when used at 2 or 4 mg/l, but at 8 mg/l TAZ was more active than SUL. All B. fragilis strains were inhibited by PIP + TAZ or PIP + SUL, whereas resistance was observed with CTX + SUL or CTX + TAZ. On the same strains the activities of 6 beta-lactams (PIP, mezlocillin, ticarcillin (TIC), CTX, ceftriaxone and ceftazidime) were determined in combination with either SUL 4 mg/l or TAZ 8 mg/l. Only PIP or TIC + SUL or TAZ were able to inhibit at least 90% of tested strains. No resistance could be detected with PIP + TAZ combination. As conclusion, the two inhibitors when combined with PIP or TIC offered greater activity against both Gram positive or negative anaerobes and PIP + TAZ remained the more potent combination.