The prevalence of multiple drug resistance Escherichia coli and Klebsiella pneumoniae isolated from patients with urinary tract infections

BackgroundUrinary tract infections (UTIs) and bacterial resistance to antibiotics is global health problem and a threat to public health in many countries.AimsThe study aimed to determine the prevalence of MDR Escherichia coli and Klebsiella pneumoniae in UTI patients.Materials & methodsThe midstream urine samples of 120 patients were collected and cultured as described by the protocols at the respective sample collection sites on MacConkey Blood agar. Samples were tested by using the fully automated VITEK 2 Compact system for Gram‐negative identification and detection of antimicrobial susceptibility of microorganisms.ResultsThe most prevalent pathogen was E. coli, which was found in 82 (68.3%) urine samples, followed by K. pneumonia, found in 38 (31.7%) urine samples. As far as antibiotic resistance is concerned, E. coli isolates were found to be highly resistant for ceftriaxone (89.0% of the isolates), ampicillin (86.6%), levofloxacin (82.9%), cefotaxime (79.3%), aztreonam (74.4%), ceftazidime (68.3%) and gentamicin, piperacillin, and trimethoprim‐sulfamethoxazole, 54.9 and 53.7%, respectively. The E. coli isolates were found to be relatively less resistant to imipenem (2.4%), cefepime (34.1%), and ciprofloxacin (35.4%). For K. pneumonia isolates, high resistance rates were observed for piperacillin (81.6%), levofloxacin (78.9%), ampicillin (76.3%), cefotaxime (73.7%), trimethoprim‐sulfamethoxazole (71.1%), ceftazidime (65.8%), gentamicin (63.2%), cefepime (50.0%), and aztreonam (44.7%). However, moderate resistance rates were detected for these were found to be less resistant for imipenem (13.2%), ceftriaxone (31.6%), and ciprofloxacin (36.8%).Conclusion E. coli and K. pneumoniae from the clinical isolates displayed high resistance to many antibiotics in UTI patients.     

Occurrence of single-point gyrA mutations among ciprofloxacin-susceptible Escherichia coli isolates causing urinary tract infections in Latin America

To detect if isolates susceptible to quinolones already carry mutations in the gyrA and parC genes, we selected 12 ciprofloxacin-susceptible Escherichia coli strains collected from patients with urinary tract infections in Latin America in 1998, as part of ongoing SENTRY Antimicrobial Surveillance Program. The isolates studied exhibited minimal inhibitory concentrations (MICs) for ciprofloxacin between < or = 0.015 microg/mL and 0.5 microg/mL. The molecular characterization of quinolone resistance was determinated by amplification of the gyrA and parC by PCR followed by sequencing of the respective amplicons. We observed that E. coli isolates exhibiting MIC, < or = 0.06 microg/mL for ciprofloxacin did not show mutations in either topoisomerase. On the other hand, all isolates with MIC between 0.12 microg/mL and 0.5 microg/mL demonstrated single mutation in the gyrA gene. The most frequent mutation occurred at position 83, where the amino acid serine was replaced by leucine. No mutations in the parC gene were observed. To preserve the potency and prevent the development of resistance, we suggest that quinolone usage should be rational, especially in the treatment of urinary tract infections, and in the prophylaxis of immunosupressed patient populations.     

Mutation rate and evolution of fluoroquinolone resistance in Escherichia coli isolates from patients with urinary tract infections

Escherichia coli strains from patients with uncomplicated urinary tract infections were examined by DNA sequencing for fluoroquinolone resistance-associated mutations in six genes: gyrA, gyrB, parC, parE, marOR, and acrR. The 54 strains analyzed had a susceptibility range distributed across 15 dilutions of the fluoroquinolone MICs. There was a correlation between the fluoroquinolone MIC and the number of resistance mutations that a strain carried, with resistant strains having mutations in two to five of these genes. Most resistant strains carried two mutations in gyrA and one mutation in parC. In addition, many resistant strains had mutations in parE, marOR, and/or acrR. No (resistance) mutation was found in gyrB. Thus, the evolution of fluoroquinolone resistance involves the accumulation of multiple mutations in several genes. The spontaneous mutation rate in these clinical strains varied by 2 orders of magnitude. A high mutation rate correlated strongly with a clinical resistance phenotype. This correlation suggests that an increased general mutation rate may play a significant role in the development of high-level resistance to fluoroquinolones by increasing the rate of accumulation of rare new mutations.     

尿路感染大肠埃希菌临床分布及耐药性分析

目的了解尿路感染大肠埃希菌的耐药现状,为临床合理使用抗菌药物提供试验依据。方法对该院泌尿系感染者分离出348株病原菌进行鉴定和体外药物敏感试验,采用法国生物梅里埃公司ATB鉴定系统对菌株进行鉴定,采用纸片扩散法(K-B)进行抗菌药敏感性试验。结果医院尿路感染标本分离的大肠埃希菌对常用抗菌药物表现出不同程度的耐药性,大肠埃希菌对碳青霉烯类抗菌药物亚胺培南和美洛培南敏感率为100.0%;对氨苄西林、头孢唑林、头孢呋辛和哌拉西林耐药率较高;对氟喹诺酮类抗菌药物环丙沙星、左氧氟沙星耐药率也大于60.0%。结论大肠埃希菌耐药率呈逐年上升趋势;临床应该重视病原菌的培养和药物敏感试验,根据药敏结果合理应用抗菌药物。     

Spread of R-plasmids among Escherichia coli causing urinary tract infections.

The incidence of multiple-antibiotic resistance among Escherichia coli isolated from urinary tract infections at Charing Cross Hospital, London, increased over the last 10 years, and its distribution was related to O-type. Among strains of the eight O-types most frequently causing such infections at this hospital, O4, O9, and O18 had a high incidence of multiple resistance (35, 22, and 19%, respectively); O2 and O6 had a intermediate incidence (14 and 11%, respectively); and O7, O1, and O75 had a low incidence (8, 6, and less than 3%, respectively). This nonrandom distribution appears to be a consequence of unequal plasmid recipient ability. After overnight mating with antibiotic-resistant donors, R-plasmid infection frequencies among antibiotic-sensitive urinary tract isolates differed by up to 10(5)-fold, and such differences were correlated with the variation in the incidence of antibiotic resistance among the O-types. The inherent differences in the ability to achieve significant R-plasmid spread, which appear to be determined by the host, not the plasmid, may be compounded in some cases by the inhibition of potential mating partners by colicin production.     

Escherichia coli mutators present an enhanced risk for emergence of antibiotic resistance during urinary tract infections

Mutators may present an enhanced risk for the emergence of antibiotic resistance in bacteria during chemotherapy. Using Escherichia coli mutators as a model, we evaluated their ability to develop resistance to antibiotics routinely used for the treatment of urinary tract infections (UTIs). Under conditions that simulate therapeutic drug concentrations in humans, low-level resistance to trimethoprim, gentamicin, and cefotaxime emerged more frequently in mutators than normal strains. Resistance to trimethoprim in both cell types arose from a single point mutation in folA (Ile94-->Leu) and cefotaxime resistance resulted from loss of outer membrane porin OmpF. The mechanisms of gentamicin resistance could not be defined, but resistance did not result from mutations in ribosomal protein L6 (rplF). Although similar mechanisms of low-level antibiotic resistance probably arise in these strains, mutators are a risk factor because the increased generation of mutants with low-level resistance enhances the opportunity for subsequent emergence of high-level resistance.     

Non-hospital antimicrobial usage and resistance in community-acquired Escherichia coli urinary tract infection

OBJECTIVES: To investigate the correlation between non-hospital antimicrobial consumption and resistance. METHODS: Information on the non-hospital sales of antimicrobials from 14 European countries in 1997 and 2000 was compared with the antimicrobial resistance profiles of Escherichia coli isolated from women with community-acquired urinary tract infection in the same countries in 1999/2000. RESULTS: There was no statistically significant correlation between the consumption of and resistance to co-amoxiclav, cefadroxil, fosfomycin, mecillinam, sulfamethoxazole, trimethoprim or trimethoprim-sulfamethoxazole. On the other hand, there were statistically significant correlations between consumption of broad-spectrum penicillins and quinolones in 1997 and 2000 and resistance to ciprofloxacin (P range 0.0005-0.0045) and nalidixic acid (P range 0.0013-0.0049). Total antimicrobial consumption in 1997 was significantly correlated to ciprofloxacin (P=0.0009) and nalidixic acid (P=0.0018) resistance, and there were significant relationships between quinolone consumption in both years and resistance to gentamicin (P range 0.0029-0.0043) and nitrofurantoin (P range 0.0003-0.0007). E. coli with multiple antimicrobial resistance were significantly more common in countries with high total antimicrobial consumption. CONCLUSIONS: Owing to the frequent presence of many possible confounding factors, antimicrobial resistance to one drug does not always correlate well to the consumption of the same drug or closely related drugs. This study showed that the degree of antimicrobial consumption was significantly correlated to the incidence of multidrug-resistant E. coli.     

Risk factors for ciprofloxacin resistance among Escherichia coli strains isolated from community-acquired urinary tract infections in Turkey

OBJECTIVES: To determine the risk factors for community-acquired ciprofloxacin-resistant Escherichia coli urinary tract infection (UTI). METHODS: The study was performed with isolates from community-acquired UTIs collected from 15 centres representing six different geographic regions of Turkey. All microbiological procedures were carried out in a central laboratory. Multivariate analysis was performed for detection of risk factors for resistance. Use of quinolones more than once within the last year, living in a rural area, having a urinary catheter, age >50 and complicated infections were included in the model as variables and logistic regression was performed. RESULTS: A total of 611 gram-negative isolates were studied: 321 were isolated from uncomplicated UTI and 290 were isolated from complicated UTI. E. coli was the causative agent in 90% of the uncomplicated UTIs and in 78% of the complicated UTIs (P < 0.001). Seventeen percent of E. coli strains isolated from uncomplicated cases and 38% of E. coli strains isolated from complicated UTI were found to be resistant to ciprofloxacin. In multivariate analysis, age over 50 [odds ratio (OR): 1.6; confidence interval (CI): 1.08-2.47; P = 0.020], ciprofloxacin use more than once in the last year (OR: 2.8; CI: 1.38-5.47; P = 0.004) and the presence of complicated UTI (OR: 2.4; CI: 1.54-3.61; P < 0.001) were found to be associated with ciprofloxacin resistance. Detection of strains of E. coli producing extended-spectrum beta-lactamase (ESBL) enzymes was two times more common in the patients who received ciprofloxacin than those who did not (15% versus 7.4%). CONCLUSIONS: The increasing prevalence of infections caused by antibiotic-resistant bacteria makes the empirical treatment of UTIs more difficult. One of the important factors contributing to these high resistance rates might be high antibiotic use. Urine culture and antimicrobial susceptibility testing are essential in Turkey for patients with UTI who have risk factors for resistance, such as previous ciprofloxacin use. Fluoroquinolone-sparing agents such as nitrofurantoin and fosfomycin should be evaluated as alternative therapies by further clinical efficacy and safety studies.     

泌尿系感染大肠埃希菌的耐药性分析

目的 了解泌尿系感染的大肠埃希菌对常用抗生素的耐药情况,指导临床合理使用抗生素.方法 应用WHONET5对2005～2006年本院肾内科分离的大肠埃希菌128株的药敏结果进行统计分析.结果 128株大肠埃希菌中产超广谱β-内酰胺酶(ESBLs)占29.7%(38株),对氨苄西林、哌拉西林、头孢唑林、头孢呋辛、头孢曲松、复方新诺明、头孢噻肟、环丙沙星耐药率在76.3%～100.0%,其他被监测抗生素耐药率在50.0%以下;不产ESBLs的占70.3%(90株),除氨苄西林、哌拉西林、复方新诺明、庆大霉素的耐药率达到50.0%以上,其他被监测抗生素耐药率均在50.0%以下.结论 大肠杆菌产与不产ESBLs菌株对抗生素的耐药率存在差异;对于产ESBLs菌株临床可选用碳青霉烯类、氨基苷类和呋喃类;不产ESBLs菌株临床可选用头孢菌素类、硝基呋喃类、氟喹诺酮类抗生素.     

The resistance ofEscherichia coli strains isolated from community-acquired urinary tract infections

Urinary tract infections (UTIs) are the most common infections caused byEscherichia coli. Most recent research demonstrates that antibiotic resistance has reached a critical point throughout the world, as increased use of antibiotics among nonhospitalized patients encourages the growth of drug-resistant pathogens among that population. The goal of this study was to determine the antimicrobial drug resistance ofE coli strains isolated from community-acquired UTIs in 5 different regions in Turkey. The minimum inhibitory concentrations of ciprofloxacin, gentamicin, sulfamethoxazole, trimethoprim, trimethoprim-sulfamethoxazole, and ampicillin and forE coli were determined with the agar dilution method. Among the 480 strains isolated, 8.3% were resistant to ciprofloxacin, 3.3% to gentamicin, 35.4% to sulfamethoxazole, 33.3% to trimethoprim, 27.9% to trimethoprim-sulfamethoxazole, and 40.8% to ampicillin. These results show that the antibiotics currently most effective againstE coli are ciprofloxacin and gentamicin. Local epidemiologic trends should be considered when prescribing antibacterial therapy. More research in bacterial gene mapping will be necessary to elucidate the influence of regional antimicrobial drug use and resistance in epidemiologic trends among the general population.     

Antibiotic resistance and small R plasmids among Escherichia coli isolates from outpatient urinary tract infections in northern Norway.

Escherichia coli strains from outpatient urinary tract infections in northern Norway over a period of 1 year were examined for resistance to nine commonly used antibiotics. Strains collected during 4.5 months were examined for R plasmid content by using conjugation and in vitro transformation. Of the E. coli strains, 42% were resistant to one or more antibiotics. Resistance was highest to sulfonamide (20.8% of all strains), nitrofurantoin (14.5%), and tetracycline (10.1%), whereas less than 6% of the strains were resistant to ampicillin, carbenicillin, cephalothin, nalidixic acid, or trimethoprim-sulfamethoxazole. No strain was resistant to gentamicin. Tetracycline resistance was more common in men than in women. Resistance to cephalothin, nalidixic acid, and sulfonamide was higher in strains from older people. Resistance to sulfonamide was more frequent in the urban community. These was no seasonal variation in antibiotic resistance, although the incidence of urinary tract infection varied with seasons. Plasmid-determined resistance to ampicillin, streptomycin, sulfonamide, and tetracycline was found. About 18% of the resistant strains from the urban municipality carried R plasmids, most of which were small plasmids mediating resistance to sulfonamide and streptomycin. The overall frequency of resistance in strains collected from rural areas was similar to the urban frequency, but in the rural strains, R plasmids were found in only 5% of the resistant strains.     

Genetic and biochemical characterization of norfloxacin resistance in Escherichia coli.

In Escherichia coli the frequency of spontaneous single-step mutation to high levels of resistance to the newer 4-quinolone agent norfloxacin was confirmed to be over 300-fold lower than that to the older agent nalidixic acid. Serial passage on incremental concentrations of drug was necessary to produce mutants highly resistant to norfloxacin. Genetic analysis of one such highly resistant strain identified two mutations conferring drug resistance. One mutation, nfxA, mapped around 48 min on the E. coli genetic map and was shown to be an allele of gyrA by studies demonstrating an increased drug resistance of DNA gyrase reconstituted with the gyrase A subunit isolated from the mutant strain. These findings also identified the DNA gyrase A subunit as a target of norfloxacin. The second mutation, nfxB, mapped between 20 and 22 min was associated with additional resistances to tetracycline, chloramphenicol, and cefoxitin and with decreases in outer membrane porin protein OmpF. The nfxA and nfxB mutations together accounted for most, but not all, of the norfloxacin resistance phenotype of this strain.     

引起尿路感染的大肠埃希菌的耐药谱分析

目的调查引起患者尿路感染的大肠埃希菌的检出率及其耐药谱,为临床合理应用抗菌药物提供参考。方法收集分离自2014年度本院住院患者的尿培养阳性菌株共488株,采用VITEK2全自动微生物分析仪(法国梅里埃公司)进行菌种鉴定和药敏试验。超广谱β-内酰胺酶(ESBLs)菌的检测则采用美国临床和实验室标准协会(CLSI)推荐的双纸片法确证试验。结果引起尿路感染的488株病原菌中,共检到大肠埃希菌235株(占48.16%,235/488),其中产ESBLs菌株54株(占23.0%,54/235)。亚胺培南、替加环素、阿米卡星、哌拉西林钠/舒巴坦钠、哌拉西林/他唑巴坦对产ESBLs的大肠埃希菌具有较强的抗菌活性;产ESBLs菌株具有多耐药性,对氨苄西林、哌拉西林、头孢唑啉、头孢噻肟、头孢曲松和头孢他啶的耐药率均高于90%,对氨曲南、替卡西林/克拉维酸钾、复方新诺明、环丙沙星、庆大霉素、妥布霉素和左氧氟沙星的耐药率均高于60%,对头孢吡肟、头孢西丁和呋喃妥因的耐药率为分别为53.70%、36.00%和31.48%,其耐药率大多明显高于非产ESBLs菌株(P0.05)。本次研究发现3株耐亚胺培南的大肠埃希菌。结论引起尿路感染的大肠埃希菌的耐药现象严重,尤其是产ESBLs菌株,临床上需及时监测细菌的耐药性变迁,为临床抗感染药物治疗提供参考依据。     

泌尿系感染病原菌的分布及耐药性分析

目的探讨本地区引起泌尿系感染的病原菌及其耐药性,为临床治疗提供依据。方法用常规方法分离鉴定病原菌,用K-B法进行药物敏感试验。结果302株病原菌中革兰阴性杆菌252株,占83%,主要为大肠埃希菌和肺炎克雷伯菌。革兰阳性球菌38株,占13%。真菌12株,占4%。大肠埃希菌产ESBLs检出率为43.8%,肺炎克雷伯菌产ESBLs检出率为57.1%,耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)的检出率为56.2%,MRSA的检出率为22.2%。结论了解引起泌尿系感染病原菌的分布及耐药性监测,合理使用抗菌药物以减少耐药菌株的产生和医院感染的爆发流行。     

泌尿道来源大肠埃希菌继发血流感染的危险因素分析

目的了解住院患者泌尿道来源大肠埃希菌(ECO)继发血流感染情况,探讨泌尿道来源ECO继发血流感染的危险因素及此种现象的分离率变迁情况,为更好地预防和控制泌尿道来源ECO继发血流感染和流行提供科学依据。方法收集2011~2013年由泌尿道来源ECO继发血流感染的住院患者82例,与同期尿培养为ECO但无血流感染患者82例进行单因素χ2检验及多因素Logistic回归分析。分别计算2011~2013年各年及不同科室泌尿道来源ECO的分离率,绘制成表格进行分析得出分离率变迁情况。结果肾功能不全、尿管留置、发热、尿常规白细胞增多在试验组和阴性组中差异具有统计学意义(P0.05),属于危险因素。其中尿管留置、发热、尿常规白细胞增多具有显著关系,属于独立危险因素。结论泌尿道来源ECO继发血流感染为多因素所致,主要与尿管留置、发热、尿常规白细胞增多有关,对存在上述危险因素的患者应尽量减少侵入性操作(如泌尿插管等),严格无菌及消毒制度,密切关注临床症状及其实验室检查指标。通过分离率的图表发现,泌尿道来源ECO继发血流感染的现象明显升高,并在该院呈扩散趋势。     

Multiclinic comparative study of norfloxacin and trimethoprim-sulfamethoxazole for treatment of urinary tract infections

Three hundred seventy patients with upper or lower urinary tract infections were entered into a multicenter, open comparative study. A total of 190 patients were treated with norfloxacin, and 180 patients were treated with trimethoprim-sulfamethoxazole. The percentage of strains susceptible to norfloxacin (99%) was significantly greater (P less than 0.001) than the percentage of strains susceptible to trimethoprim-sulfamethoxazole (90%). The percentages of patients with bacteriological outcomes of eradication were greater in the norfloxacin group (97%) than in the trimethoprim-sulfamethoxazole group (90%). The difference was significant (P less than 0.05). Seven patients (three treated with norfloxacin, four treated with trimethoprim-sulfamethoxazole) experienced early reinfection. Of 370 patients entered into the study, 20 patients experienced clinical adverse effects that were probably or definitely related to the study drug; 6 patients were in the group that received norfloxacin, and 14 were in the group that received trimethoprim-sulfamethoxazole. Study antimicrobial agents were discontinued because of clinical adverse effects in eight patients (norfloxacin, one patient; trimethoprim-sulfamethoxazole, seven patients). Three patients receiving norfloxacin and four patients receiving trimethoprim-sulfamethoxazole had laboratory adverse effects which were classified as probably or definitely drug related. None of the clinical or laboratory adverse effects was serious.