Epidemiological investigation of fluoroquinolone resistance in infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

The incidence of infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) has increased markedly in recent years. Treatment is difficult because of frequent multidrug resistance. Although fluoroquinolones offer effective therapy for ESBL-EK infections, their usefulness is threatened by increasing fluoroquinolone resistance. To identify risk factors for fluoroquinolone resistance in ESBL-EK infections, a case-control study of all patients with ESBL-EK infections from 1 June 1997 through 30 September 1998 was conducted. Of 77 ESBL-EK infections, 43 (55.8%) were resistant to fluoroquinolones. Independent risk factors for fluoroquinolone resistance were fluoroquinolone use (odds ratio [OR], 11.20; 95% confidence interval [CI], 1.99-63.19), aminoglycoside use (OR, 5.83; 95% CI, 1.12-30.43), and long-term care facility residence (OR, 3.39; 95% CI, 1.06-10.83). The genotypes of fluoroquinolone-resistant ESBL-EK isolates were closely related. Efforts should be directed at modification of these risk factors to preserve the utility of fluoroquinolones in the treatment of ESBL-EK infections.     

Risk factors for fluoroquinolone resistance in nosocomial Escherichia coli and Klebsiella pneumoniae infections

BACKGROUND: The incidence of fluoroquinolone (FQ) resistance has increased markedly in recent years. Even in the common nosocomial pathogens Escherichia coli and Klebsiella pneumoniae, in which the emergence of FQ resistance was believed to be unlikely, increasing resistance to these agents has been noted. Risk factors for FQ resistance in these pathogens remain unknown. Although FQs are important components of the present antimicrobial arsenal, their continued usefulness is threatened by rising FQ resistance. OBJECTIVE: To identify risk factors for nosocomial FQ resistance. METHODS: A case-control study of hospitalized patients with infections due to FQ-resistant and FQ-susceptible E coli and K pneumoniae occurring between January 1, 1998, and June 30, 1999. RESULTS: We included 123 patients with nosocomial FQ-resistant infections and 70 randomly selected patients with nosocomial FQ-susceptible infections. Independent risk factors (adjusted odds ratio [95% confidence interval]) for FQ resistance were (1) recent FQ use (5.25 [1.81-15.26]); (2) residence in a long-term care facility (3.65 [1.64-8.15]); (3) recent aminoglycoside use (8.86 [1.71-45.99]); and (4) older age (1.03 [1.01-1.06]). CONCLUSIONS: Recent FQ use, residence in a long-term care facility, recent aminoglycoside use, and older age were all noted to be independent risk factors for FQ resistance among patients with nosocomial E coli and K pneumoniae infections. Efforts should be directed at recognition and modification of these risk factors to curb the rise in FQ resistance and preserve the utility of these agents in the treatment of common nosocomial gram-negative infections.     

Clinical outcomes of spontaneous bacterial peritonitis due to extended-spectrum beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae: a retrospective cohort study

Purpose

The aim of this study was to (1) evaluate the clinical outcomes of spontaneous bacterial peritonitis (SBP) due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae (EK) and (2) investigate the relationship between the adequacy of initial antibiotic treatments and patient outcomes.

Methods

We conducted a retrospective cohort study of cirrhotic patients with SBP caused by EK. We evaluated the 30-day mortality rate and used Cox proportional hazard models to identify risk factors for mortality.

Results

Between January 2006 and December 2012, a total of 231 episodes of SBP due to EK were recorded. Among them, 52 were caused by ESBL-producing EK (ESBL-EK). The 30-day mortality rate was significantly higher in patients with SBP due to ESBL-EK than in those with non-ESBL-producing EK (non-ESBL-EK) (34.6 vs. 18.4 %, respectively; p = 0.013). Multivariate analysis revealed that ESBL production [adjusted HR (aHR) 1.82, 95 % confidence interval (CI) 1.00–3.31], nosocomial infection (aHR 2.24, 95 % CI 1.26–3.95), septic shock (aHR 4.84, 95 % CI 2.70–8.65), higher Child-Pugh score (aHR 1.57, 95 % CI 1.28–1.92), and higher Charlson comorbidity index (aHR 1.37, 95 % CI 1.15–1.64) were independent risk factors for 30-day mortality in the total cohort. When we analyzed patients with SBP due to ESBL-EK separately, septic shock (aHR 3.64, 95 % CI 1.40–9.77), accompanying bacteremia (aHR 3.71, 95 % CI 1.37–10.08), and hepatocellular carcinoma (aHR 3.21, 95 % CI 1.20–8.56) were independent risk factors.

Conclusions

Both 7- and 30-day mortalities for SBP due to ESBL-EK were significantly higher than for SBP due to non-ESBL-EK. Initial antibiotic choice was not associated with poor clinical outcomes in patients with SBP due to ESBL-EK.     

肺炎克雷伯菌的耐药现状及危险因素分析

目的本研究通过对我院分离的肺炎克雷伯菌进行标本来源、临床分布以及药敏分析,了解肺炎克雷伯菌的流行学特征、临床状况、耐药现状和危险因素。方法采用法国生物梅里埃公司生产的VITEK-2全自动细菌鉴定及药敏分析仪,对分离的肺炎克雷伯菌进行鉴定和药敏分析;采用回顾性研究,通过对我院肺炎克雷伯菌产ESBLs菌组与非产ESBLs菌组在年龄、住院时间、大型手术、介入性诊疗和侵入性操作等因素的对比分析,了解我院产ESBLs肺炎克雷伯菌的危险因素。结果临床分离的588株肺炎克雷伯菌,痰的检出率最高,占54.08%,其次为血液和中段尿;临床分布以ICU、神经外科、老年病科、呼吸、消化内科及儿科为主;通过单因素方差分析和多因素Logistic回归分析结果显示,导尿及留置导尿、三代头孢的使用、大型手术为我院产ESBLs肺炎克雷伯菌感染的独立的危险因素。结论我院肺炎克雷伯菌感染普遍存在,肺炎克雷伯菌的耐药性严重,提示在今后的诊疗过程中,要针对危险因素,积极采取相关措施,防止多重耐药菌株的产生,控制和降低院内感染的发生率。     

耐碳青霉烯肺炎克雷伯菌感染的危险因素及耐药机制的研究

目的 探讨耐碳青霉烯肺炎克雷伯菌感染的危险因素及耐药机制.方法 对我院2018年6月1日-2019年5月31日57例耐碳青霉烯肺炎克雷伯菌(CRKP)感染患者和70例碳青霉烯敏感肺炎克雷伯菌(CSKP)感染患者进行回顾性分析.结果 CRKP感染患者主要分布在呼吸科31.6％(18/57)、神经内科21.1％(12/57...     

Plasmid-mediated Extended-spectrum beta-Lactamases in Organisms Other Than Klebsiella pneumoniae and Escherichia coli: A Hidden Reservoir of Transferable Resistance Genes

Conclusions Resistance due to AmpC β-lactamases and ESBLs in gramnegative bacillary pathogens is a growing and important problem and is tied to extensive use of extended-spectrum cephalosporins The emergence of these β-lactamases is then amplified by spread of resistant clones or resistant genes among patients within institutions or among patients who move between institutions within a region. Genes encoding β-lactamases are frequently linked to resistance genes for other classes of antibiotics. Thus, use of any one class of antibiotic may select for emergence of resistance to another. Treatment of infections caused by these multidrug-resistant pathogens is often problematic. One strategy to circumvent β-lactamase production has been use of β-lactam/β-lactamase inhibitor combinations, but AmpC β-lactamases and hyperproduction of ESBLs evade this therapeutic strategy. Use of carbapenems and cefepime, which are the most stable of all β-lactam antibiotics to hydrolysis by ESBLs and AmpC β-lactamases, can be expected eventually to select for emergence of resistance to these drugs as well. Traditional isolation precautions that include use of gloves and gown have been shown to be effective during contact with the patient infected or colonized with ESBLproducing K. pneumoniae or E. coli. However, if infection control efforts are directed only at those isolates that the laboratory is capable of identifying as ESBL-producers, the presence in an institutional setting of undetected plasmidencoded ESBLs in Enterobacteriaceae, other than K. pneumoniae and E. coli, will likely be an epidemiologic hazard. A patient infected with these organisms is a hidden reservoir of plasmid-encoded resistance genes that can spread among different species of Enterobacteriaceae. Development of rapid assays to detect the presence of these resistance genes would be a major asset. Control measures that may be effective include early detection of ESBLs in any Enterobacteriaceae, especially Enterobacter species or P. aeruginosa; universal glove use and hand hygiene; cohorting of colonized or infected patients; implementation of control measures simultaneously in all health care facilities linked by patient transfers; and of greatest importance, control of unnecessary and inappropriate antibiotic use.     

Extended-spectrum beta-lactamase (ESBL) produced by Escherichia coli and Klebsiella pneumoniae isolated from Teikyo University Hospital--the second report

We studied the high-level resistant to cefotaxime (CTX, MIC > or = 512 micrograms/ml) clinical isolates of Escherichia coli and Klebsiella pneumoniae in Teikyo University Hospital. The CTX-resistance could be transferred to E. coli K-12 chi 1037 or ML4903 strains from 30 of the 33 isolates by conjugation at a frequency of 10(-4). When the hydrolysis rate of benzylpenicillin was 100%, the beta-lactamases which were extracted from the transconjugants hydrolyzed CTX, CAZ and AZT at the rate of 38-95%, 0-8.6% and 0-56%, respectively. These results demonstrate that these enzymes should be categorized into ESBL. The nucleotide sequence of CTX-resistant gene was identified to that of the CTX-M2 gene which was first described in Argentina. It was found to have 99.9% homology to Toho-1 gene in Japan and 99.6% homology to CMY-2 gene. Using a PCR methods for the detection of one of ESBL gene such as CTX-M2, Toho-1 or CMY-2, the DNA was amplified from all strains (11 isolates of E. coli and 21 isolates of K. pneumoniae).     

Extended-spectrum beta-lactamase (ESBL) produced by Escherichia coli and Klebsiella pneumoniae isolated from Teikyou University Hospital--the first report

We studied the cefotaxime (CTX)-resistant (MIC > or = 32 micrograms/ml) clinical isolates of E. coli and K. pneumoniae in Teikyo University Hospital from 1990 to 1996. The incidence of CTX-resistant isolates was 0.4% (6/1,282) in E. coli and 0.6% (7/1,044) in K. pneumoniae, in 1990. In 1995, the incidence of CTX-resistance increased to 1.7% (50/2,910) in E. coli (p = 0.0013) and 7.2% (144/1,996) in K. pneumoniae (p < 0.0001). These species have been detected in the stool (86 isolates), urine (59 isolates), sputum (15 isolates), pus (15 isolates), throat (10 isolates) and others (12 isolates) in 1995. MIC50 of ampicillin (ABPC), ABPC with clavlanic acid (CVA) 5 micrograms/ml, piperacillin (PIPC), PIPC with CVA 5 micrograms/ml, ceftazidime, CTX, ceftizoxime, cefpodoxime, cefepime, aztreonam, cefmetazole, latamoxef, and imipenem used against 33 isolates (11 isolates of E. coli, 22 isolates of K. pneumoniae), which were detected in 1996-1997, was > 512 micrograms/ml, 8 micrograms/ml, > 512 micrograms/ml, 8 micrograms/ml, 4 micrograms/ml, > 512 micrograms/ml, 16 micrograms/ml, > 512 micrograms/ml, 256 micrograms/ml, 32 micrograms/ml, 2 micrograms/ml, 0.25 microgram/ml and 0.25 microgram/ml, respectively. This susceptibility pattern were very similar to the Toho-1 type beta-lactamases producing strains.     

Comparison of Escherichia coli and Klebsiella pneumoniae liver abscesses

BACKGROUND: Escherichia coli and Klebsiella pneumoniae are the most common causative pathogens of pyogenic liver abscesses. The objective of this study was to compare outcome between patients with liver abscesses due to E coli and those with liver abscesses caused by K pneumoniae; we also aimed to identify separately the predictors of mortality in the 2 groups. METHODS: We conducted a retrospective study of 202 patients who presented with pyogenic liver abscesses caused by either E coli or K pneumoniae from July 2000 to June 2005. Outcome of the patients was analyzed by exact logistic regression with adjustment for baseline and clinical covariates. Significant predictors of mortality in the E coli and the K pneumoniae groups were investigated by multivariate analysis of demographic and clinical variables in each group. RESULTS: Of the 202 patients (128 men and 74 women; age range, 19 to 89 years), pyogenic liver abscess was due to E coli infection in 55 patients and K pneumoniae in 147 patients. In contrast to patients with K pneumoniae, patients with E coli liver abscess were more likely to be older and female, have a biliary abnormality or malignancy, pleural effusion, polymicrobial infection with anaerobic or multi-drug-resistant organisms, a higher APACHE II score, and to have been treated initially with ineffective antibiotics; they were also less likely to have diabetes mellitus. The cause of K pneumoniae liver abscess was often cryptogenic. The sensitivity, specificity, positive predictive value, and likelihood ratio of the presence of biliary disorders and coexisting malignancy as a predictive parameter of E coli liver abscess were 25%, 96%, 67%, and 5.45/1, respectively. The sensitivity, specificity, positive predictive value, and likelihood ratio of the presence of diabetes mellitus with an abscess of cryptogenic origin as a predictive parameter of K pneumoniae liver abscess were 39%, 84%, 81%, and 2.36/1, respectively. There was no significant difference in mortality between patients with E coli and those with K pneumoniae infections (26% vs 4%; adjusted OR, 4.2; 95% CI, 0.63 to 27; P = 0.105). However, for patients with liver abscess caused by E coli, the APACHE II score at admission (OR, 1.7; 95% CI, 1.1 to 2.6; P = 0.021), malignancy (OR, 26; 95% CI, 1.8 to 370; P = 0.016), and right-lobe abscess (OR, 0.0029; 95% CI, 0.00010 to 0.15; P = 0.004) were significant predictors of death, whereas uremia (OR, 52; 95% CI, 3.5 to 750; P = 0.004) and multi-drug-resistant isolates (OR, 26; 95% CI, 2.3 to 290; P = 0.009) were significant predictors of death in the K pneumoniae group. CONCLUSIONS: A higher APACHE II score at admission and a higher frequency of coexisting malignancy may have contributed to the higher, although not significant, mortality rate in patients with liver abscess caused by E coli infection. Clinicians should begin with broad antibiotic coverage such as a second-generation cephalosporin and an aminoglycoside with metronidazole when treating liver abscesses with E coli as the likely pathogen due to the high frequency of multi-drug-resistant isolates among E coli isolates.     

产超广谱β内酰胺酶菌株中质粒头孢菌素酶的研究

目的 调查产超广谱β内酰胺酶(ESBLs)的大肠埃希菌和肺炎克雷伯菌中质粒头孢菌素酶(AmpC酶)的发生率及其基因型。方法 收集北京朝阳医院2001年1～12月头孢西丁耐药的产ESBLs的24株大肠埃希菌、8株肺炎克雷伯菌,采用等电聚焦电泳测定β内酰胺酶的等电点;接合试验证实酶基因有无可转移性;脉冲场凝胶电泳(PFGE)确定耐药株的亲缘关系;对AmpC酶基因进行多重PCR及序列分析确定其基因型。结果 2001年北京朝阳医院ESBLs的发生率,大肠埃希菌为16.8％(49／292),肺炎克雷伯菌为160.5％(35／212);ESBLs株中质粒AmpC酶的发生率,大肠埃希菌为2．0％(1／49),肺炎克雷伯菌为17．1％(6／35)。这7株菌均产生DHA-1型AmpC酶;1株肺炎克雷伯菌可将头孢西丁耐药性传给受菌体。该7株菌都产TEM-1酶、5株产CTX-M-3型ESBL、2株产SHV-12型ESBL;该7株菌携带质粒2～5个,且都有约33～36kb的大质粒。PFGE发现这7株菌来自多个不同的克隆株。结论 北京朝阳医院ESBL阳性的大肠埃希菌和肺炎克雷伯菌中,有7株既产DHA-1型质粒AmpC酶,又产CTX-M-3或SHV-12 ESBL。这7株菌来自多个不同的克隆株。     

产超广谱β-内酰胺酶大肠埃希菌和肺炎克雷伯菌的分布及耐药性分析

目的了解医院产超广谱β-内酰胺酶（ESBLs）大肠埃希菌和肺炎克雷伯菌的分布及耐药性特点。方法对我院2004年7月～2006年7月间各类临床标本分离出的大肠埃希菌307株和肺炎克雷伯菌202株，用CLSI／NCCLS推荐的表型确证法检测其ESBLs，采用K-B纸片琼脂扩散法进行药敏试验，分析产ESBLs菌株的分布及耐药性。结果大肠埃希菌和肺炎克雷伯菌产ESBLS菌株的检出率分别为38．4％（118／307）和31．7％（64／202），主要分布于尿和痰、咽拭子中，病区主要集中于肺科、神经外科、感染科、泌尿外科、ICU室。产ESBLs菌株对亚胺培南和美罗培南呈高度敏感，对哌托西林／三唑巴坦、头孢哌酮／舒巴坦、头孢西丁耐药率较低，对其他抗菌药物均出现较高耐药。结论产ESBLS的大肠埃希菌和肺炎克雷伯菌分布在不同病区的不同标本中，碳青霉烯类抗生素亚胺培南和美罗培南是治疗产ESBLS菌株感染的较佳药物。     

Klebsiella pneumoniae carriage in low-income countries: antimicrobial resistance,genomic diversity and risk factors

ABSTRACT

Background

Klebsiella pneumoniae

(hereafter, Kp) is a major public health threat responsible for high levels of multidrug resistant (MDR) human infections. Besides, Kp also causes severe infections in the community, especially in Asia and Africa. Although most Kp infections are caused by endogenous intestinal carriage, little is known about the prevalence and microbiological characteristics of Kp in asymptomatic human carriage, and attached risk factors including environmental sources exposure.     

Prevalent phenotypes and antibiotic resistance in Escherichia coli and Klebsiella pneumoniae at an Indian tertiary care hospital: plasmid-mediated cefoxitin resistance.

BACKGROUND: The beta-lactam antibiotics, in combination with aminoglycosides, are among the most widely prescribed antibiotics. However, because of extensive and unnecessary use, resistance to these drugs continues to increase. In recent years, resistance in the Indian bacterial population has increased markedly, the majority showing complex mechanisms. Due to increased transcontinental movement of the human population, it would be wise to know the prevalence and resistance complexity of these strains, well in advance, in order to formulate a policy for empirical therapy. METHODS: One hundred and eighty-one isolates of Escherichia coli and 61 isolates of Klebsiella pneumoniae obtained from 2655 non-repeat samples of pus (912) and urine (1743) were studied, and their resistance rates and patterns were noted. The isolates were analyzed for prevalent aminoglycoside and cephalosporin resistance phenotypes and for the presence of extended spectrum beta-lactamase (ESBL) and AmpC enzymes by spot-inoculation and modified three-dimensional tests developed in our laboratory. Fourteen isolates of E. coli and six of K. pneumoniae, resistant to all of the antibiotics tested, were selected for plasmid screening, curing, and transconjugation experiments, and for comparative evaluation of the double disk synergy test (DDST) and modified three-dimensional test (TDT) for detection of beta-lactamases. RESULTS: Urinary E. coli isolates showed maximum susceptibility to amikacin (57.1%), followed by tobramycin (38.5%) and gentamicin (31.9%). Eighteen (19.8%) isolates were susceptible to cefotaxime, whereas 11 (12.1%) were susceptible to ceftriaxone. The K. pneumoniae isolates from urine samples showed maximum susceptibility to tobramycin (63.6%) followed by amikacin (54.5%). Of the K. pneumoniae isolates, 31.8% were susceptible to cefotaxime and 13.6% were susceptible to ceftriaxone. A more or less similar trend of antibiotic susceptibility was noted in E. coli and K. pneumoniae isolates from pus samples. Twenty-six (14.4%) E. coli and 15 (24.6%) K. pneumoniae isolates were found to be ESBL-producers by NCCLS-ESBL phenotypic confirmatory test. Eighteen (9.9%) E. coli and 19 (31.1%) K. pneumoniae isolates were found to be AmpC enzyme-producers by our modified TDT. The simultaneous occurrence of ESBL and AmpC enzymes was noted in 7.7% and 9.8% isolates of E. coli and K. pneumoniae, respectively. CONCLUSIONS: The prevalence of multidrug-resistant bacterial isolates is quite high in our bacterial population. On comparative evaluation of DDST and TDT in resistant isolates, TDT was found to be the better method, detecting ESBLs in 80% of isolates compared to 15% with DDST. A 19.9-kb plasmid was consistently present in all the screened isolates of E. coli and K. pneumoniae, and was inferred to encode cefoxitin and tetracycline resistance based on curing and transconjugation experiments.     

Splenic abscess caused by Klebsiella pneumoniae and non-Klebsiella pneumoniae in Taiwan: emphasizing risk factors for acquisition of Klebsiella pneumoniae splenic abscess

Klebsiella pneumoniae was recently reported to be the major pathogen causing pyogenic splenic abscess in Taiwan. To better understand the characteristics of K. pneumoniae splenic abscess, which may be helpful in alerting clinicians to this infection entity when dealing with a suspicious patient, patients hospitalized between January 1981 and December 2002 with the diagnosis of splenic abscess were included in a retrospective study. Among the 38 enrolled patients, 9 (23.7%) suffered from K. pneumoniae splenic abscess. Compared to those with non-K. pneumoniae splenic abscess, patients suffering from splenic abscess caused by K. pneumoniae had a higher prevalence of underlying diabetes mellitus (88.9% vs 37.9%; p = 0.006) and higher incidence of concomitant liver abscess (44.4% vs 0%; p < 0.001) caused by the same pathogen. When dealing with patients suffering from K. pneumoniae splenic abscess, clinicians should work up to exclude a concomitant liver abscess caused by the same pathogen.     

In vitro activity of antimicrobial agents against extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae at a tertiary care center in Lebanon

Looking for therapeutic options, we assessed the minimum inhibitory concentrations (MICs) of 7 antimicrobial agents against extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (n = 58) and Escherichia coli (n = 84) isolates. High rates of susceptibility were shown for both E coli and K pneumoniae against ertapenem (100% for both), piperacillin/tazobactam (83% and 91%, respectively) and amikacin (96% and 82%, respectively). In addition, most K pneumoniae isolates were susceptible to quinolones (72%-75%) and cefepime (88%). However, clinical correlation is warranted.     

耐碳青霉烯类肺炎克雷伯菌血流感染危险因素分析及列线图预测模型构建

[摘要]?目的?探究住院患者发生耐碳青霉烯类肺炎克雷伯菌（carbapenem-resistant Klebsiella pneumoniae, CRKP）血流感染的危险因素,并构建列线图模型。方法?选取2016年1月1日—2021年12月31日我院药学部收治的190例肺炎克雷伯菌（Klebsiella pneumonia, KP）所致血流感染患者作为研究对象,并根据是否耐碳青霉烯类抗菌药物,分为CRKP组（n=40）和碳青霉烯类敏感肺炎克雷伯菌（carbapenem-sensitive Klebsiella pneumonia, CSKP）组（n=150）。Logistic回归模型分析住院患者发生CRKP血流感染的危险因素,并绘制预测CRKP血流感染的列线图模型。使用ROC曲线、校准曲线及Hosmer-Lemeshow（H-L）检验对列线图模型进行验证。结果?感染前1个月内留置导尿管、留置中心静脉导管、使用免疫抑制剂、使用碳青霉烯类抗菌药物以及年龄≥65岁是影响住院患者发生CRKP血流感染的危险因素（P均＜0.05）。对列线图进行验证,校准曲线拟合良好,H-L检验χ2 =7.630,P=0.366,AUC为0.817（95% CI：0.739～0.895）。结论?感染前1个月内留置导尿管、留置中心静脉导管、使用免疫抑制剂、使用碳青霉烯类抗菌药物以及年龄≥65岁是住院患者发生CRKP血流感染的危险因素,据此构建的列线图模型对住院患者发生CRKP所致血流感染有较好预测价值,可为临床医护人员制定个体化防治策略提供参考。