What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol,ciprofloxacin, colistin,fosfomycin, minocycline,nitrofurantoin, temocillin and tigecycline

Carbapenem-resistant Enterobacteriaceae present an increasing and diverse problem, including strains of multiple species with metallo-β-lactamases (IMP, NDM or VIM) and non-metallo (KPC and OXA-48) enzymes as well as those combining an extended-spectrum β-lactamase (ESBL) or AmpC enzyme with porin loss. Most strains, except those with OXA-48 alone, are broadly resistant to β-lactams and have multiple aminoglycoside-modifying enzymes; those with NDM-1 carbapenemase typically also have 16S rRNA methylases, conferring complete aminoglycoside resistance. In this study, the activity of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline was evaluated against 81 carbapenem-resistant Enterobacteriaceae isolates from the UK. Testing was performed by the Clinical and Laboratory Standards Institute (CLSI) agar dilution method. Chloramphenicol, ciprofloxacin and nitrofurantoin inhibited <25% of the isolates at the breakpoint, whereas colistin was active against 75/81 isolates (92.6%), the exceptions being four Klebsiella pneumoniae and Enterobacter cloacae isolates along with members of inherently resistant genera. Fosfomycin was active against 49/81 isolates (60.5%), including 7/7 Escherichia coli, 16/20 Enterobacter and Citrobacter spp., but only 25/52 Klebsiella spp. Tigecycline was active against 38/81 isolates (46.9%) and was intermediate against another 27 (33.3%), with resistance scattered amongst K. pneumoniae and Enterobacter spp. The activity of colistin, fosfomycin and tigecycline was unrelated to the isolates' carbapenem resistance mechanisms. Temocillin was fully active [minimum inhibitory concentration (MIC) ≤8 mg/L] against only 4/81 isolates (4.9%), but inhibited a further 22 isolates (27.2%) at the British Society for Antimicrobial Chemotherapy (BSAC) urinary breakpoint (32 mg/L), predominantly comprising those isolates with combinations of impermeability and an ESBL or AmpC enzyme, along with 6/11 isolates producing KPC carbapenemases. Studies with transconjugants and transformants confirmed the small effect of KPC enzymes against temocillin, whereas OXA-48 and NDM-1 conferred clear resistance.     

Identification and molecular characterisation of New Delhi metallo-β-lactamase-1 (NDM-1)- and NDM-6-producing Enterobacteriaceae from New Zealand hospitals

The global spread of New Delhi metallo-β-lactamase (NDM) is of significant public health concern. This study sought to determine whether bla(NDM) was present in Enterobacteriaceae isolates displaying resistance to carbapenems that were submitted to the National Antibiotic Reference Laboratory, Institute of Environmental Science and Research (Porirua, New Zealand) during 2009 and 2010. Isolates were tested for the presence of β-lactamase genes and 16S rRNA methylase genes by polymerase chain reaction (PCR) and sequencing. Plasmid transfer studies were undertaken on isolates found to be harbouring bla(NDM). Molecular typing was performed by multilocus sequence typing (MLST). The bla(NDM-1) gene was identified in four Enterobacteriaceae isolates (two Escherichia coli, one Klebsiella pneumoniae and one Proteus mirabilis) from four patients in New Zealand hospitals in 2009 and 2010. In addition, the bla(NDM-6) gene, which differed from bla(NDM-1) by a point mutation at position 698 (C→T), was also identified in an E. coli isolate from the same patient who harboured the bla(NDM-1)-positive P. mirabilis. All four patients had recently been hospitalised or received health care in India. Four of the isolates also produced a CTX-M-15 extended-spectrum β-lactamase and/or plasmid-mediated AmpC β-lactamase, and all five isolates harboured the plasmid-mediated 16S rRNA methylase rmtC gene. The E. coli types were diverse by MLST, and the K. pneumoniae isolate belonged to the internationally disseminated sequence type 11 (ST11) clone. These findings further illustrate the diversity of phenotypic and genotypic features found in association with bla(NDM), in addition to documenting the international spread of this resistance mechanism, notably into a country with historically low rates of antimicrobial resistance.     

Activity of tigecycline alone and in combination with colistin and meropenem against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae strains by time-kill assay

Antibiotic combinations including tigecycline have not been studied against Klebsiella pneumoniae carbapenemase (KPC)-producing pathogens. Tigecycline alone and combined with colistin and meropenem was tested against eight genetically unrelated KPC-producing clinical strains of Enterobacteriaceae (four K. pneumoniae, two Escherichia coli, one Enterobacter cloacae and one Serratia marcescens) by time-kill assay. Tigecycline displayed a concentration-independent bacteriostatic activity in seven strains and bactericidal activity in one strain. Colistin showed bactericidal activity at 4× the minimum inhibitory concentration (MIC) in three strains and was bacteriostatic for the remaining strains and concentrations. Meropenem was bactericidal in three strains and bacteriostatic in five strains. The tigecycline+meropenem combination was not bactericidal against the four K. pneumoniae strains and was non-synergistic against all eight strains. Tigecycline+colistin was bactericidal against all strains at most time intervals and concentrations and was also synergistic at 1× and 2× MIC against most strains up to 4-8h and at 4× MIC up to 24 h against all strains. These findings suggest that, at most drug concentrations, tigecycline, colistin and meropenem as single agents do not exhibit efficient bactericidal activity against most of the KPC-producing strains. Tigecycline alone might be a therapeutic option for infections caused by KPC-producers when bacteriostatic activity is adequate or combined with colistin when bactericidal activity is necessary. Additional in vivo tests are warranted to assess better the killing kinetics of tigecycline combinations against KPC-producers.     

30株CRE临床感染特点及blaNDM-1基因检出情况分析

目的 了解我院2013年4月-2014年3月临床分离的30株耐碳青霉烯类肠杆菌科(carbapenem-resistant Enterobacteriaceae, CRE)菌株blaNDM-1基因型检出情况,感染患者的临床特征,以及对常用抗菌药物的耐药特点。方法 临床分离菌株由美国BD公司生产的Phoenix-100全自动细菌鉴定/药敏系统进行菌株鉴定和药敏试验。改良Hodge试验检测产碳青霉烯酶,EDTA协同试验筛查金属β-内酰胺酶。利用特异性引物进行blaNDM-1基因PCR扩增,采用双脱氧末端终止法进行DNA测序,所测序列与GenBank基因库中的已知序列进行BLAST比对。结果 (1)菌株分布情况：我院2013年4月-2014年3月临床标本中分离出对碳青霉烯类抗生素耐药肠杆菌科细菌共30株,其中肺炎克雷伯菌16株,占53.3%;阴沟肠杆菌12株,占40.0%;布氏柠檬酸杆菌和弗氏柠檬酸杆菌各1株,blaNDM-1基因确证,共有5株为产NDM-1酶菌株,5株菌包括肺炎克雷伯菌2株,阴沟肠杆菌2株,布氏柠檬酸杆菌1株,这些细菌来自不同的科室,但主要分布在重症医学科 (15/30, 50.0%),神经内科重症病房(8/30, 26.7%)。标本主要来源于痰(20/30, 66.7%),其次为尿液(5/30, 16.7%),血液4株(13.3%),引流液1株(3.3%)。5株产NDM-1酶菌株分离自4例患者,3株分离自患者尿液标本,2株分离自患者痰标本;感染患者平均年龄为73岁,平均住院时间10个月,2例死亡。(2)药物敏感性试验结果：30株CRE对碳青霉烯类抗生素亚胺培南和美罗培南的耐药率分别为100%和86.7%,对其他β-内酰胺类抗生素耐药率均为100%;对氯霉素、庆大霉素、左氧氟沙星、环丙沙星的耐药率在76.7%~93.3%之间;对多黏菌素和替加环素敏感率高达100%,其次为复方磺胺甲噁唑和阿米卡星,敏感率分别为66.7%和46.7%。5株产NDM-1酶菌株对多黏菌素和替加环素均敏感,3株对复方磺胺甲噁唑敏感,2株对阿米卡星敏感;而对β-内酰胺类抗生素以及喹诺酮类、氯霉素类等均耐药。结论 我院流行的CRE菌株主要分离自重症医学科和神经内科重症病房患者,对多种抗生素呈高度耐药,其中产NDM-1酶菌株主要来自长期住院的高龄患者,且死亡率较高,应对其感染的风险因素进行调查,并有针对性的采取感染预防措施进行防控。     

Efficacy of tigecycline/colistin combination in a pneumonia model caused by extensively drug-resistant Acinetobacter baumannii

Due to increasing drug resistance, available antimicrobial options are limited in the treatment of Acinetobacter baumannii infections. Particularly in cases caused by extensively drug-resistant (XDR) A. baumannii, combination regimens must also be taken into consideration. In this study, the efficacies of tigecycline, colistin and tigecycline/colistin combination on bacterial counts in lung tissue were investigated in a rat pneumonia model. One A. baumannii strain resistant to all antimicrobial agents except tigecycline and colistin was selected for the study. In vivo studies revealed a >3log reduction in bacterial counts in the tigecycline, colistin and combination groups at 24h and 48h compared with the control group. No significant differences were determined between colistin, tigecycline and combination groups (P>0.05). On the other hand, differences between treatment groups and the control group were statistically significant (P=0.01). A greater reduction in bacterial counts was observed at 48h compared with 24h in the tigecycline group than in the colistin group (P=0.038 and P=0.139, respectively); the most significant decrease between 24h and 48h was observed in the combination group (P=0.014). Despite detection of in vitro synergistic activity in this study, no statistically significant differences were found between colistin, tigecycline and combination treatments in terms of efficacy on bacterial counts in lung tissue. In the treatment of infections with a high mortality rate such as pneumonia caused by XDR A. baumannii, combining tigecycline with colistin during the first 48h and continuing treatment with one of these agents seems a rational approach.     

儿童心脏术后下呼吸道分离菌的分布及耐药性分析

目的 回顾性分析心血管病医院儿童心脏术后下呼吸道分离菌的分布及其耐药特点,为临床治疗提供用药参考。方法 对2014年1月1日-2016年12月31日术后送检的痰标本进行培养,对分离出的致病菌做鉴定及药敏实验。结果 共分离出762株致病菌,革兰阴性菌占69.29%,革兰阳性菌占21.65%,真菌占7.87%,排名前5位的细菌为铜绿假单胞菌(138株)、大肠埃希菌(95株)、肺炎克雷伯菌(95株)、金黄色葡萄球菌(66株)和肺炎链球菌(64株)。药敏结果显示非发酵菌对氨基糖苷类的耐药率为0.72%~8.57%但对碳青霉烯类≥40%;肺炎克雷伯菌对碳青霉烯类的耐药率为16.13%~24.21%,远高于大肠埃希菌和阴沟肠杆菌的0~2.44%;阴沟肠杆菌的整体耐药率低于大肠埃希菌和肺炎克雷伯菌;金黄色葡萄球菌中MRSA占29.23%,其对青霉素的耐药率为98.41%,对万古霉素、利奈唑胺、替加环素的耐药率为0;肺炎链球菌对青霉素的耐药率为14.06%,对万古霉素、利奈唑胺的耐药率为0。结论 儿童心脏术后下呼吸道分离菌以革兰阴性菌为主;碳青霉烯类抗生素对非发酵菌的高耐药率值得高度重视;肺炎克雷伯菌对碳青霉烯类抗生素的耐药率有上升趋势。     

Effectiveness of a double-carbapenem combinations against carbapenem-resistant Gram-negative bacteria

The emergence of carbapenem-resistant organisms posed considerable threat to global health while only limited treatment options are available and led to efforts to discover a novel way to treat them. To evaluate in vitro synergistic activity of meropenem plus ertapenem, a total of 203 carbapenem-resistant strains, collected from 12 provinces and municipalities in China, were examined with a dual carbapenem combination therapy. The statistical software R was used for analysis. Two hundred and one (201) of carbapenem-resistant strains mainly produced four types of carbapenemase: KPC-2 (n = 142, 69.95%), OXA-232 (n = 7, 3.45%), NDM (n = 38, 18.72%; 36 NDM-1, 1 NDM-4, 1 NDM-5), and IMP (n = 15, 7.39%; 1 IMP-26, 10 IMP-30, 4 IMP-4). Fifty-one out of two hundred and three (51/203 or 25.12%) of the examined strains showed a synergistic effect for the meropenem plus ertapenem combination throughout the checkerboard method, while only three isolates showed potential clinically relevant synergy (3/203, 1.48%). An additive effect was observed in 55/203 (27.09%) of the examined strains. Ninety-seven of the examined isolates (47.78%) showed fractional inhibitory concentration (FIC) greater or equal to 2 (indicating antagonism). The synergistic activity of meropenem plus ertapenem combination suggests this combination can be a possible way to treat the infection caused by the carbapenem-resistant organisms, especially for IMP or NDM producer with a lesser minimum inhibitory concentration (MIC) and the infected individual who was not recommended to use colistin or tigecycline.     

Real-time PCR assay allows detection of the New Delhi metallo-β-lactamase (NDM-1)-encoding gene in France

In this study, we report the development of a rapid real-time polymerase chain reaction (PCR) assay with TaqMan probe to detect the New Delhi metallo-β-lactamase (NDM-1)-encoding gene directly from bacterial isolates. The specificity of the assay was verified in silico as well as with a large panel of 84 clinically relevant bacteria, including the Klebsiella pneumoniae NCTC 13443 NDM-1-positive reference strain. Using this assay retrospectively on a local series of 44 K. pneumoniae isolates from Marseille Hospitals (France), it was possible to detect and identify an NDM-1-producing K. pneumoniae strain isolated from bronchoalveolar lavage in April 2010 from a French patient repatriated from India after a motorbike accident. Standard PCR amplification and sequencing of the entire NDM-1 gene from this isolate was also performed and the amino acid sequence showed 100% homology with the NDM-1 protein from the K. pneumoniae reference strain. We believe that this real-time PCR assay would be a powerful tool that could be added to other molecular detection assays such as detection of KPC- or OXA-encoding genes for rapid screening and/or identification of carbapenem-resistant bacterial isolates from patients returning from the Asian continent that could be implemented in a point-of-care strategy.     

Regional variations in multidrug resistance among Enterobacteriaceae in the USA and comparative activity of tigecycline, a new glycylcycline antimicrobial

We report here on the activity of tigecycline and comparators against multidrug-resistant (resistant to >or=3 antimicrobial classes; MDR) Enterobacteriaceae from the USA collected between January 2004 and January 2006 as part of the Tigecycline Evaluation and Surveillance Trial (TEST). Nationally, 131 (5.9%) Escherichia coli, 174 (10.1%) Klebsiella pneumoniae, 4 (1.2%) Klebsiella oxytoca, 24 (4.9%) Enterobacter aerogenes, 126 (9.5%) Enterobacter cloacae and 20 (2.6%) Serratia marcescens isolates were MDR. Four isolates (two K. pneumoniae and two E. cloacae) were resistant to nine antimicrobials. Tigecycline performed well against MDR E. coli (MIC(90) 0.5 microg/mL, 0% resistant) and K. pneumoniae (MIC(90) 4 microg/mL, 9.2% resistant). A MIC(90) of 8 microg/mL was reported for tigecycline against the other MDR organisms studied here, notably lower than those of most comparators.     

In vitro activity of cefepime, imipenem, tigecycline, and gentamicin, alone and in combination, against extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli

STUDY OBJECTIVE: To evaluate the activity of cefepime, imipenem, tigecycline, and gentamicin, alone and in combination, against extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae and Escherichia coli. DESIGN: In vitro susceptibility and time-kill analysis. SETTING: University-affiliated research laboratory. ISOLATES: Ten K. pneumoniae and 10 E. coli clinical strains known to produce ESBL. MEASUREMENTS AND MAIN RESULTS: Minimum inhibitory concentration (MIC) testing was performed at 5.5 and 7.0 log(10) colony-forming units (cfu)/ml. Time-kill studies were performed over 24 hours with a high inoculum of 7.0 log(10) cfu/ml for cefepime, imipenem, tigecycline, and gentamicin at 1 times MIC. Combination studies were tested for cefepime plus tigecycline, cefepime plus imipenem, imipenem plus tigecycline, and for adjunctive gentamicin with cefepime, imipenem, or tigecycline. At the high inoculum, the MIC ranges for cefepime, imipenem, tigecycline, and gentamicin were 0.25-256 (MIC for 90% of tested strains [MIC(90)] = 32), 0.125-2 (MIC(90) = 1), 0.25-16 (MIC(90) = 4), and 0.25-4 mg/L (MIC(90) = 1), respectively, for all isolates. At the higher inoculum, MICs shifted for cefepime, imipenem, and tigecycline. Change in log(10) cfu/ml from baseline to 24 hours for cefepime, imipenem, and tigecycline alone ranged from 4.85-0.71, 5-4.22, and 3.5-1.01, respectively, for all isolates. Bactericidal activity was observed for cefepime alone (10 [50%] of 20 isolates), imipenem alone (20 [100%] of 20), and tigecycline alone (3 [15%] of 20). Combination studies with cefepime plus tigecycline resulted in synergy against 4 (20%) of 20 isolates. Combination studies with gentamicin resulted in synergy against 6 isolates (30%) with cefepime and 4 isolates (20%) with tigecycline. No synergy was observed with imipenem combinations. No antagonism was observed. With the exception of cefepime, correlations were observed between MIC and terminal densities for studied agents. CONCLUSIONS: Cefepime exhibited bactericidal activity but was unrelated to susceptibility. Tigecycline exhibited predictable bacteriostatic activity and synergy in combination against a subset of study isolates. Imipenem exhibited predictable bactericidal activity against all isolates. The utility of combination regimens with novel agents requires further exploration.     

对临床分离的大肠埃希杆菌和肺炎克雷伯菌耐药状况分析

目的：调查和分析上海市杨浦区市东医院临床分离的大肠埃希杆菌和肺炎克雷伯菌分布特征与药敏结果。方法：收集本院2010年临床送检标本所分离的大肠埃希杆菌和肺炎克雷伯菌药敏资料,用WHONET 5.5软件进行数据分析。结果：共获得大肠埃希杆菌696株和肺炎克雷伯菌409株,在菌株总数中排名第一和第三。大肠埃希杆菌检出率较高的科室为普外科（20.3%）、急诊科（14.1%）、风湿肾病科（12.6%）,主要分离自尿（46.3%）、脓液（11.6%）和痰（10.8%）等标本。肺炎克雷伯菌检出率较高的科室为急诊科（17.6%）、呼吸科（14.2%）、肿瘤内科（11.7%）,主要分离自痰（40.8%）、咽拭子（26.4%）和尿（9.5%）等标本。大肠埃希杆菌和肺炎克雷伯菌中产超广谱β-内酰胺酶（ESBLs）菌株检出率分别为56.0%和17.1%,两者的检出率之间具有显著性差异（P〈0.01）,产ESBLs菌株的耐药率明显高于非产ESBLs菌株。结论：本院大肠埃希杆菌和肺炎克雷伯菌在泌尿系统、呼吸系统疾病高发的科室分离率高,其耐药率水平主要受产ESBLs菌株的影响。     

Extended-spectrum beta-lactamases: frequency, risk factors, and outcomes.

STUDY OBJECTIVE: To determine epidemiologic factors of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae in a nonoutbreak setting. DESIGN: Retrospective analysis. SETTING: University teaching hospital. PATIENTS: Fifty-seven patients with cultures of presumed ESBL-producing (i.e., ceftazidime-resistant) E. coli or K. pneumoniae. INTERVENTIONS: To determine overall frequency, institutional antibiograms from 1991-1999 were examined for percentage of isolates with ceftazidime resistance. Medical records from January 1997-June 2000 were reviewed for patient demographics, comorbidities, culture site, antimicrobial therapy, and clinical and microbiologic outcomes. MEASUREMENTS AND MAIN RESULTS: From 1991-1999, frequency increased from undetectable to 4% for ceftazidime-resistant E. coli and from 2% to 6% for ceftazidime-resistant K. pneumoniae. Seventy-one isolates were identified in the 57 patients with presumed ESBL-producing E. coli or K. pneumonia. Fifty-one isolates (72%) were E. coli, with urine the primary site of infection (62%). Eighty-six percent of patients had known risk factors for infection due to ESBL-producing organisms, including hospitalization (37 patients) and residence in long-term care facilities (12 patients). However, in 14% (8 patients), the infection was community acquired in patients who resided at home. CONCLUSION: In addition to known populations at risk, ambulatory patients with chronic conditions represent another patient population that may harbor ESBL-producing organisms.     

Prevalence of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in an urban hospital in Dhaka, Bangladesh

The prevalence of extended-spectrum beta-lactamases (ESBL)-producing organisms in an urban hospital in Dhaka City was assessed over a 10-month period. A double disk test was performed to detect ESBL-producing Escherichia coli and Klebsiella pneumoniae. 43.2% and 39.5% of E. coli and K. pneumoniae had ESBL phenotypes, respectively. The combination of augmentin with ceftazidime detected the most ESBL-producing E. coli (39.5%) while augmentin with ceftriaxone was the best combination for the detection of ESBL (31.6%) in K. pneumoniae.     

First report of CTX-M-15 and CTX-M-3 beta-lactamases among clinical isolates of Enterobacteriaceae in Béjaia, Algeria

We assessed the prevalence and phenotypic characteristics of extended-spectrum beta-lactamase producers among 365 clinical isolates of members of the family Enterobacteriaceae recovered from two hospitals in Béjaia, Algeria, between March 2004 and April 2005. Twenty-one strains were resistant to cefotaxime and/or ceftazidime. A double-disk synergy test yielded a positive result in five cases (three Escherichia coli, one Klebsiella pneumoniae and one Enterobacter cloacae). Using polymerase chain reaction and sequencing, the three E. coli isolates and the K. pneumoniae isolate were found to produce extended-spectrum beta-lactamase CTX-M-15 and the E. cloacae isolate produced CTX-M-3. The three CTX-M-15-producing E. coli isolates were not isolated in the same wards, although genotyping by randomly amplified polymorphic DNA analysis revealed that they were clonally related. The bla(CTX-M-15) genes were transferred from E. coli by conjugation, whilst conjugative transfer of bla(CTX-M) genes from K. pneumoniae and E. cloacae was not detectable.     

In vitro activity of tigecycline and comparators against Gram-negative pathogens isolated from blood in Europe (2004-2009)

Here we report on the antimicrobial resistance amongst Gram-negative isolates (excluding Acinetobacter spp.) collected from blood culture sources at European study sites as part of the global Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) from the study start in 2004 until August 2009. All isolates were collected and tested for minimum inhibitory concentrations using Clinical and Laboratory Standards Institute methodology. Over the collection period, extended-spectrum β-lactamase (ESBL) production was recorded in 21.1% of Klebsiella pneumoniae, 2.6% of Klebsiella oxytoca and 11.3% of Escherichia coli, primarily in Croatia, Greece, Hungary, Italy, Poland, Romania and the Slovak Republic. ESBL rates stabilised amongst K. pneumoniae over 2006-2009, but doubled amongst E. coli in 2008-2009. The patterns of antimicrobial resistance changed accordingly for both organisms. Generally, Greece had the highest antimicrobial resistance for K. pneumoniae, Italy for E. coli, Serratia marcescens and Enterobacter spp., and Croatia for Pseudomonas aeruginosa. High resistance rates amongst K. pneumoniae were also seen in Croatia and Italy. Imipenem resistance amongst K. pneumoniae was reported exclusively in Greece (13.8%); amongst other Enterobacteriaceae, imipenem resistance was absent or low. Similarly, meropenem resistance was low amongst the Enterobacteriaceae except K. pneumoniae from Greece (42.6%). Across Europe, the most active antimicrobial agents against the Enterobacteriaceae were tigecycline, amikacin and the carbapenems, each with <10% resistance each year. Against the other antimicrobials, significant increases in non-susceptibility were reported for K. pneumoniae and E. coli, both important causative pathogens of bacteraemia.     

1例泛耐药肺炎克雷伯菌尿源性脓毒症伴血小板减少的给药策略分析

临床药师对1例泛耐药肺炎克雷伯菌尿源性脓毒症伴血小板减少患者进行用药干预,分析替加环素联合黏菌素治疗效果不佳及血小板减少的原因,推荐头孢他啶阿维巴坦单药治疗产肺炎克雷伯菌（KPC）碳青霉烯酶类耐药肺炎克雷伯菌（CRKP）的重症感染,基于患者感染部位、病原菌酶型等,制定抗感染治疗方案后,患者感染指标和血小板逐渐恢复至正常范围,病情好转。     

蒲地蓝消炎口服液联合阿莫西林对肺炎链球菌感染的协同作用

目的阿莫西林(amoxicillin,Amx)具有广谱抗菌作用,蒲地蓝消炎口服液(PDL)具有抗炎、免疫调节和抗菌活性。为了增强抗菌药效、减少Amx的不良反应,本研究对二者联合应用的抗肺炎链球菌感染效果进行了研究。方法以肺炎链球菌滴鼻感染ICR小鼠建立小鼠细菌性肺炎模型;以肺指数、肺组织病理评分、炎症因子表达等作为评价指标,考察PDL和Amx联用对肺炎链球菌感染小鼠肺炎的保护作用。结果PDL液和Amx联用能显著抑制肺炎链球菌引起的小鼠肺炎病变,两药联用对感染小鼠具有协同抗感染作用,其中Amx(每日0.37 g/kg)与PDL(每日5.5 mL/kg)联用的联合指数为0.12,对肺炎的治疗表现为强协同作用,肺指数抑制率达到61.22%,肺指数显著低于模型对照组和单一药物组(P<0.05,P<0.01);Amx(每日0.37 g/kg)与PDL(每日2.75 mL/kg)联用的联合指数为0.57,为协同作用。两药联用能显著抑制感染小鼠体重下降,改善小鼠肺组织病理损伤(P<0.01),同时显著抑制细菌感染诱导的小鼠血清炎症因子白细胞介素-6(IL-6)(P<0.01)、白细胞介素-8小鼠同源物(KC)(P<0.05)、肿瘤坏死因子-α(TNF-α)(P<0.01)、单核细胞趋化蛋白-1(MCP-1)(P<0.01)的表达升高。结论PDL和Amx联用对肺炎链球菌感染小鼠肺炎具有协同治疗作用,在临床上具有重要的应用价值。     

产ESBLs大肠埃希菌和肺炎克雷伯菌的耐药性分析

目的了解我院2009年1～12月大肠埃希菌和肺炎克雷伯菌产超广谱β-内酰胺酶（ESBLs）菌株的分布情况及耐药性,指导临床用药。方法采用纸片扩散法（K-B法）和酶抑制剂增强纸片扩散法对396株大肠埃希菌和肺炎克雷伯菌进行检测和分析。结果大肠埃希菌和肺炎克雷伯菌ESBLs的检出率分别为52.7%和35.7%,产ESBLs菌对亚胺培南、哌拉西林/舒巴坦、头孢西丁和阿米卡星的耐药率较低。结论重视产ESBLs菌的检测,应根据药敏试验合理用药,碳青霉烯类、头孢西丁及β-内酰胺酶抑制剂复合物、阿米卡星是目前治疗产ESBLs菌比较理想的抗菌药物。     

血流感染患者产超广谱β-内酰胺酶大肠埃希菌和肺炎克雷伯菌耐药性及危险因素分析

目的 分析血流感染患者产超广谱β-内酰胺酶(ESBLs)大肠埃希菌和肺炎克雷伯菌的耐药性,探讨导致其感染的危险因素及相关预后,为临床治疗和预防提供依据。方法 回顾性分析2014年1月—2018年12月天津市第五中心医院住院的214例产ESBLs大肠埃希菌和肺炎克雷伯菌血流感染患者的临床资料。结果 共收集到菌株214株,其中大肠埃希菌157株,肺炎克雷伯菌57株,产ESBLs菌株的检出率分别为52.2%和24.6%。产ESBLs菌株对青霉素、头孢菌素、氨基糖苷类和喹诺酮类抗菌药物的耐药率显著高于非产ESBLs菌株。多因素回归分析显示,感染前30d使用头孢菌素是产ESBLs菌株感染的危险因素,合并肿瘤性疾病、慢性肝脏疾病、血红蛋白<100g/L、入住ICU是大肠埃希菌和肺炎克雷伯菌血流感染患者死亡的独立危险因素。结论 产ESBLs大肠埃希菌和肺炎克雷伯菌耐药形势严峻,感染前30d使用头孢菌素增加产ESBLs菌株感染的风险,合并肿瘤性疾病、慢性肝脏疾病、血红蛋白<100g/L、入住ICU提示大肠埃希菌和肺炎克雷伯菌血流感染患者预后不佳。     

血流感染患者产超广谱β-内酰胺酶大肠埃希菌和肺炎克雷伯菌耐药性及危险因素分析

目的 分析血流感染患者产超广谱β-内酰胺酶(ESBLs)大肠埃希菌和肺炎克雷伯菌的耐药性,探讨导致其感染的危险因素及相关预后,为临床治疗和预防提供依据。方法 回顾性分析2014年1月—2018年12月天津市第五中心医院住院的214例产ESBLs大肠埃希菌和肺炎克雷伯菌血流感染患者的临床资料。结果 共收集到菌株214株,其中大肠埃希菌157株,肺炎克雷伯菌57株,产ESBLs菌株的检出率分别为52.2%和24.6%。产ESBLs菌株对青霉素、头孢菌素、氨基糖苷类和喹诺酮类抗菌药物的耐药率显著高于非产ESBLs菌株。多因素回归分析显示,感染前30d使用头孢菌素是产ESBLs菌株感染的危险因素,合并肿瘤性疾病、慢性肝脏疾病、血红蛋白<100g/L、入住ICU是大肠埃希菌和肺炎克雷伯菌血流感染患者死亡的独立危险因素。结论