Alterations of susceptibility of Pseudomonas aeruginosa by overproduction of multidrug efflux systems, MexAB-OprM, MexCD-OprJ, and MexXY/OprM to carbapenems: substrate specificities of the efflux systems

Overproduction of multidrug efflux systems MexAB-OprM, MexCD-OprJ, and MexXY/OprM of Pseudomonas aeruginosa caused reduction of susceptibility of the mutant, which lacked AmpC and all three systems to panipenem, meropenem, S4661 and DU6681a; meropenem, S4661 and DU6681a; and BO2727, panipenem, meropenem, S4661 and DU6681a, respectively, but not reduction of the susceptibility to imipenem and biapenem. Thus, we determined substrate specificities of these efflux systems to carbapenems. Received: February 28, 2002 / Accepted: July 5, 2002     

Detection of metallo β-lactamase production and antibiotic resistance with E-test method in pseudomonas,acinetobacter and klebsiella strains,in Turkey

The metallo beta-lactamase (MBL) mediated resistance patterns remain unknown in most countries. We aimed to investigate the existence and antimicrobial resistance of MBL-producing strains among carbapenem-resistant Gram-negative bacteria that were isolated from nosocomial infections in patients in an university hospital in Turkey. Fifteen of 52 Pseudomonas aeruginosa strains (29%), 5 of 24 Acinetobacter baumanii strains (21%), and 2 of 2 Klebsiella pneumoniae strains (100%) were found to be metallo enzyme producers, with the Etest MBL technique. The in vitro antibiotic susceptibility of the MBL-positive organisms was investigated by the Etest method. Of the ten drugs tested, isepamicin was the most active agent against the MBL-producing strains. Overall, the rank order of activity of the ten antibiotics, in terms of the percentages of susceptible strains, was: isepamicin, 73%; ciprofloxacin, 64%; amikacin, 59%; aztreonam, 18%; tobramycin, 18%; meropenem, 14%; cefoperazone-sulbactam, 5%; piperacillin-tazobactam, 0%; ticarcillin-clavulanate, 0%; and cefepim, 0%. The meropenem minimum inhibitory concentrations (MICs) of the metallo enzyme-producing and nonproducing carbapenem-resistant strains were compared, and the MBL-producers were found to have higher meropenem MICs than the nonMBL-producing carbapenem-resistant strains. Early preventive measures should be taken against MBL-producing nosocomial pathogens that are associated with wide spread and high antimicrobial resistance.     

KPC and NDM-1 Genes in Related Enterobacteriaceae Strains and Plasmids from Pakistan and the United States

To characterize the genomic context of New Delhi metallo-β-lactamase-1 (NDM-1) and Klebsiella pneumoniae carbapenemase (KPC), we sequenced 78 Enterobacteriaceae isolates from Pakistan and the United States encoding KPC, NDM-1, or no carbapenemase. High similarities of the results indicate rapid spread of carbapenem resistance between strains, including globally disseminated pathogens.     

Acquisition of the mcr-1 gene by a high-risk clone of KPC-2-producing Klebsiella pneumoniae ST437/CC258, Brazil

We identified one clinical isolate of K. pneumoniae harboring the mcr 1 (plasmid of IncX4 family) and bla_KPC-2 (plasmid of IncFIB family) genes in southern Brazil. These findings highlight that K. pneumoniae isolates carrying both mcr-1 and bla_KPC-2 may emergence as a serious threat to antimicrobial therapy.     

CHROMagar mSuperCARBA and RAPIDEC® Carba NP test for detection of carbapenemase-producing Enterobacteriaceae

A novel chromogenic medium CHROMagar mSuperCARBA was evaluated to detect carbapenem-resistant Gram-negatives. This medium is as sensitive and as specific as the SUPERCARBA medium for detecting KPC, MBL and OXA-48-type producers (100% and 100%, respectively) and is compatible with subsequent testing of carbapenemase activity using the RAPIDEC^® CARBA NP.     

Drug interaction between valproic acid and carbapenems in patients with epileptic seizures

Valproic acid (VPA) is a widely used antiepileptic drug (AED). When carbapenems are concomitantly used with VPA, the serum levels of VPA may decrease and aggravate seizures. The aim of this study was to evaluate the risk factors associated with decreased serum VPA levels and clinical outcome in patients being treated with a combination of carbapenems and VPA. Fifty-four adult patients who were treated with VPA for epileptic seizures concomitant with carbapenems for the treatment of infections were evaluated in this study. Serum VPA levels were measured before and during combination therapy with VPA and carbapenems, and the change in serum VPA levels was calculated. The risk factors related to the decrease in serum VPA levels and clinical outcomes were evaluated. Our results show that VPA concentrations were reduced to subtherapeutic levels after the introduction of carbapenems. The reduction in VPA concentrations was found within 24 hours of the start of treatment with carbapenems. VPA levels continuously declined while the combination of treatments was used, which aggravated epileptic seizures in 48% of the patients. Renal disease and enzyme-inducing AEDs were risk factors that contributed to the severity of reduced serum VPA levels during combined treatment with carbapenems. This study suggests that clinicians need to be aware of the reduction of VPA concentrations to subtherapeutic levels and the aggravation of seizures while patients are treated with a combination of carbapenems and VPA.     

黏质沙雷菌耐药性及碳青霉烯类抗生素耐药机制研究

目的 探讨黏质沙雷菌分离株的整体耐药特点,研究其对碳青霉烯类药物耐药的主要机制.方法 收集2007至2010年从宁波市第一医院不同病区分离(剔除重复菌株)黏质沙雷菌247株,用Vitek2 -Compact及配套革兰阴性杆菌药敏卡(GNS)检测其药敏情况,对筛选出的20株耐碳青霉烯类菌株进行PCR检测其耐药基因.结果 黏质沙雷菌对头孢曲松、氨曲南、环丙沙星的耐药率较高,分别为70.4％( 174/247)、64.8％ (160/247)、57.4％ (142/247)；对阿米卡星、庆大霉素、亚胺培南、美罗培南的耐药率较低,分别为:3.5％( 8/229)、5.4％( 13/241)、5.9％(14/237)、8.1％ (20/247).PCR检测20株对碳青霉烯类抗生素耐药的黏质沙雷菌中,1、7、12和16号的AmpC染色体基因表达是阴性参考菌株的98.3、102.3、121.5、87.3倍；共有12株黏质沙雷菌分离株同时携带CTX-M型超广谱β内酰胺酶(ESBLs)和KPC-2型碳青霉烯类酶.黏质沙雷菌所携带的CTX-M以CTX-M1、CTX-M2、CTX-M9为主；2株菌携带有SHV基因；2株菌携带有SME基因；2株菌携带有TEM基因；5株菌膜孔蛋白基因ompC和ompF均缺失；仅1株ompC基因缺失；2株菌ompF基因缺失.结论 黏质沙雷菌对β内酰胺类药物耐药的原因比较复杂,以产β内酰胺酶为主.开展对耐药菌株的进化和多耐药基因的研究,有利于合理应用抗菌药物,降低抗生索对耐药菌的选择压力及控制耐药菌株的蔓延.