肺炎克雷伯菌（Klebsiella pneumoniae,KP）是临床常见的条件致病菌之一,广泛分布于医院环境中,常易导致呼吸道、泌尿道、腹腔感染以及血流感染。作为碳青霉烯类抗菌药物,亚胺培南对多药耐药的肺炎克雷伯菌所致感染具有很好的疗效。近年来,随着抗菌药物在临床的广泛使用甚至滥用,肺炎克雷伯菌对亚胺培南的耐药性也日趋严重,给临床抗感染治疗带来了更多的困难和挑战。本文就耐亚胺培南肺炎克雷伯菌耐药现状和耐药机制进行简要综述,以期为相关合理用药等提供参考。

Studies from several countries indicate that the incidence and mortality of bloodstream infection (BSI) have been increasing over time. We studied the burden of disease and death related to BSI in a defined geographical area of Mid-Norway, where BSI episodes were prospectively recorded by the same microbiological department during 12 consecutive years. Death from BSI was defined as death within 3002days of BSI detection. Age and sex standardized incidence and mortality rates and case fatality rates were calculated. Between 2002 and 2013, 1995 episodes of BSI in 1719 patients aged 16 to 9902years were included. The overall incidence of BSI was 215 per 100,000 person-years. The incidence increased exponentially with age, particularly in males. The incidence increased from 205 to 223 per 100,000 person-years from 2002–07 to 2008–13.Escherichia coliwas the most frequently isolated infective agent, followed byStreptococcus pneumoniaeandStaphylococcus aureus. The rate ofS. pneumoniaeBSI decreased over time in males (on average by 9.2% annually), but not in females. The total rate of BSI microbes with acquired resistance increased slightly over time, but did not exceed 2 episodes per 100,000 person-years. The mortality of BSI was 32 per 100,000 person-years, higher in males than in females (36 vs. 28 per 100,000 person-years) and was significantly higher in old age, particularly in males. The total BSI mortality was similar in the first and second halves of the study period, but the mortality ofS. pneumoniaeBSI decreased in males (15.0% annually). The crude case fatality decreased from the first to the second half of the study period (17.2% to 13.1%;p65=0.014). The rate of blood culture sampling increased more than twofold during the study period. The mortality of BSI remained stable during 2002–2013. At the same time, BSI incidence increased and case fatality rate decreased, perhaps because an increased rate of blood culture sampling may have led to improved detection of milder BSI episodes. Very low, yet slightly increasing rates of microbes with acquired resistance were observed. The online version of this article (doi:10.1186/s12879-017-2291-2) contains supplementary material, which is available to authorized users.

Abstract BACKGROUND: Across the globe, upper respiratory tract infections (URTIs) are the most prevalent cause of morbidity in childhood. AIMS: The aim of our study is to analyze the incidence and etiology of bacterial URTIs in Bulgarian children, as well as the increasing antimicrobial resistance to the most common etiologic agents over a period of 17 years. STUDY DESIGN: Retrospective study. METHODS: The study material comprised the data from 4768 patients (aged 1-16 years) with URTI during the period from 1998-2014. Specific microbiology agent detection was performed by culture examination. Susceptibilities to the investigated pathogens were determined by the disk diffusion method and minimal inhibitory concentration according to the criteria of the Clinical and Laboratory Standards Institute (CLSI). Polymerase chain reaction was used to detect the presence of 尾-lactam resistance genes. RESULTS: We identified the following as the most common URTI bacterial pathogens: Streptococcus pneumoniae (40.94%), Streptococcus pyogenes (34.16%), Haemophilus influenzae (44.23%), Moraxella catarrhalis (39.19%) and Staphylococcus aureus (23.88%). In more than 70% of cases, a polymicrobial etiology was found. The most commonly affected individuals were pre-school-aged children, which accounted for more than 36% of all patients. During the study period, a dramatic increase in resistance to antibiotic agents was observed. The most frequent types of resistance were the enzymatic inactivation of penicillins and cephalosporins (close to 100% in staphylococci and moraxellae) and inducible macrolide-lincozamide resistance (about 20% of Gram-positive cocci). CONCLUSION: Due to mandatory immunization against pneumococci and H. influenzae in Bulgaria and the vast expanding resistance to the most popular antimicrobial agents changes in the etiology of URTI have recently been noted. Regular analysis of this etiological dynamic and the antimicrobial resistance of respiratory pathogens is important for choosing the correct therapy and successful treatment.

In recent years, the increased use of macrolides was linked with the emergence of resistance Streptococcus pneumoniae worldwide. The main aim of this study was to determine the prevalence of S. pneumoniae resistant to macrolides and to identify the macrolide resistance genotypes among clinical isolates collected in North Lebanon. Disk diffusion susceptibility method was performed for 132 strains of S. pneumoniae isolated over a period of 5 years in North Lebanon. Polymerase Chain Reaction followed by pyrosequencing was carried out for confirmation of phenotypic diagnosis. The macrolide resistance genotypes were also identified by using PCR amplification of genes implicated in this resistance: erm (A), erm (B), erm (C), msr (A), lin (A) and mef (A/E). Macrolide resistance was found in 34.1% of S. pneumoniae isolates. We observed that the cMLS B phenotype (31/45, 68.9%) was the most common in these pneumococci and erm (B) was the most common resistance gene (32/45, 71.1%). This study shows that macrolide resistance in S. pneumoniae in North Lebanon is mainly related to target site modification with predominance of cMLSb phenotype but is also mediated by efflux pumps. lin (A) gene was reported for the first time in one S. pneumoniae strain in combination with erm (B) and mef (A/E) genes.

Abstract We sought to characterize pneumococcal isolates associated with bacteremia, pneumonia and meningitis in cancer patients and to estimate the coverage of the available pneumococcal vaccines. Fifty isolates recovered from 49 patients attending a cancer reference center over a 1-year period were analyzed. The prevalent serotypes were: 23F (12%), 6A (8%), 3, 4, 20, and 23A (6% each). All isolates were susceptible to chloramphenicol, levofloxacin, rifampicin, and vancomycin. Resistance or reduced susceptibility to penicillin made up 14%, and one isolate was also intermediately resistant to ceftriaxone. The three (6%) erythromycin-resistant isolates presented the M or cMLS B phenotypes and harbored the mef(A/E) gene exclusively or along with the erm(B) gene. Twenty-two (44%) isolates were closely related to 11 international clones, being strongly associated with penicillin non-susceptibility. Combined immunization with the 13-valent conjugate and the 23-valent polysaccharide vaccines might contribute to reduce (76%) the burden of the pneumococcal infections in the population investigated. Copyright 脗漏 2016 Elsevier Inc. All rights reserved.

目的：了解山西省儿童医院住院部肺炎链球菌分离株的耐药状况。方法收集2012年1月至2014年12月山西省儿童医院住院患儿各类体液标本中肺炎链球菌分离株，用E－test法和纸片扩散法进行药敏试验，分析肺炎链球菌对主要抗菌药物敏感率及最低抑菌浓度（ MIC）等情况，比较非侵袭性肺炎链球菌耐药性的年度变化及不同标本来源肺炎链球菌的耐药性差异。率的比较采用Fisher确切概率法或χ2检验。结果收集了671株肺炎链球菌，其中非侵袭性分离株607株，非脑脊液侵袭性分离株40株，脑脊液分离株24株。671株肺炎链球菌分离株对抗菌药物敏感性[株（％）]依次为：万古霉素671（100．0％），利奈唑胺671（100．0％），左氧氟沙星665（99．1％），青霉素595（88．7％），头孢曲松516（76．9％），头孢噻肟512（76．3％），磺胺甲基异噁唑－甲氧苄氨嘧啶（SMZ－TMP）103（15．4％），克林霉素28（4．2％），四环素26（3．9％），红霉素12（1．8％）。肺炎链球菌非侵袭性分离株对青霉素的敏感率2012—2014年分别为95．0％（96／101）、97．3％（110／113）、87．3％（343／393），3年间比较差异有统计学意义（χ2＝13．266， P＜0．05），且2012年青霉素的MIC50、MIC90、最大MIC值（ mg／L）分别为0．064、2．000、6．000，2014年上升至1．000、3．000、16．000；2012－2014年非侵袭性分离株对头孢曲松、头孢噻肟的敏感率3年间比较差异无统计学意义（χ2＝1．172、1．198，均P＞0．05），但头孢曲松、头孢噻肟MIC50、MIC90、最大MIC值（mg／L）均由2012年的0．500、2．000、8．000上升至2014年的0．750、4．000、32．000；非侵袭性分离株对其余抗菌药物3年间的耐药状况的比较差异无统计学意义（P＞0．05）。统一按肺炎链球菌脑膜炎静脉注射给药折点判断，607株非侵袭性分离株对头孢曲松、头孢噻肟、SMZ－TMP的敏感株数分别为281（46．3％）、278（45．8％）、78（12．9％），低于非脑脊液侵袭性分离株（40株）的敏感株数[28（70％）、28（70％）、14（35％），χ2＝8．453、8．817、15．094，均P＜0．0125]，亦低于脑脊液分离株（24株）的敏感株数[18（75％）、18（75％），χ2＝7．631、7．905，P＜0．0125；11（45．8％），P＝0．001]；不同标本来源肺炎链球菌分离株对其余抗菌药物的耐药状况比较差异无统计学意义（ P＞0．05）。结论2012—2014年山西省儿童医院住院患儿肺炎链球菌对万古霉素、利奈唑胺、左氧氟沙星等敏感率均超过95．0％，对青霉素、头孢曲松、头孢噻肟的敏感率分别为88．7％、76．9％、76．3％，对红霉素、克林霉素、SMZ－TMP、四环素等敏感率均低于20．0％；3年间非侵袭性分离株对青霉素的敏感率下降，对头孢曲松、头孢噻肟的敏感率无明显变化，但MIC50、MIC90、最大MIC水平上升；非侵袭性分离株对头孢曲松、头孢噻肟、SMZ－TMP的敏感率低于侵袭性分离株。

<strong>目的:</strong>对ICU肾衰竭接受连续性静脉-静脉血液滤过(continuous veno-venous haemofiltration,CVVH)治疗患者左氧氟沙星给药方案进行优化。<strong>方法:</strong>根据左氧氟沙星药效学及药动学参数等实验数据资料,应用蒙特卡洛模拟法计算累积反应分数(CFR),推荐最佳给药方案。<strong>结果:</strong>ICU肾衰竭接受CVVH治疗的患者,治疗肺炎克雷伯菌和肺炎链球菌感染时左氧氟沙星的最佳方案分别为500 mg qd iv和200 mg qd iv;ICU肾功能正常患者,对肺炎链球菌感染时左氧氟沙星的最佳方案为750 mg qd iv。对于肾衰竭或肾功能正常患者,当感染铜绿假单胞菌和金黄色葡萄球菌时,左氧氟沙星4种静注给药方案(200,300,500,750 mg qd)治疗效果均不佳,建议联合治疗或更换药物。<strong>结论:</strong>与ICU肾功能正常患者对比,ICU肾衰竭接受CVVH治疗患者使用左氧氟沙星时应根据不同病原菌感染考虑降低给药剂量。

BACKGROUND: Pneumococci are spread by persons with nasopharyngeal colonization a necessary precursor to invasive disease. Pneumococcal conjugate vaccines can prevent colonization with vaccine serotype strains. In 2011 Kenya became one of the first African countries to introduce the 10-valent pneumococcal conjugate vaccine (PCV10) into its national immunization program. Serial cross-sectional colonization surveys were conducted to assess baseline pneumococcal colonization antibiotic resistance patterns and factors associated with resistance. METHODS: Annual surveys were conducted in one urban and one rural site during 2009 and 2010 among children aged /=1 antibiotics (i.e. penicillin chloramphenicol levofloxacin erythromycin tetracycline cotrimoxazole and clindamycin); multidrug resistance (MDR) was defined as nonsusceptibility to >/=3 antibiotics. Weighted analysis was conducted when appropriate. Modified Poisson regression was used to calculate factors associated with antibiotic nonsusceptibility. RESULTS: Of 1087 enrolled (Kibera: 740 Lwak: 347) 90.0% of these were colonized with pneumococci and 37.3% were colonized with PCV10 serotypes. There were no differences by survey site or year. Of 657 (of 730; 90%) isolates tested for antibiotic susceptibility nonsusceptibility to cotrimoxazole and penicillin was found in 98.6 and 81.9% of isolates respectively. MDR was found in 15.9% of isolates and most often involved nonsusceptibility to cotrimoxazole and penicillin; 40.4% of MDR isolates were PCV10 serotypes. In the multivariable model PCV10 serotypes were independently associated with penicillin nonsusceptibility (Prevalence Ratio: 1.2 95% CI 1.1-1.3) but not with MDR. CONCLUSIONS: Before PCV10 introduction nearly all Kenyan children aged <5 years were colonized with pneumococci and PCV10 serotype colonization was common. PCV10 serotypes were associated with penicillin nonsusceptibility. Given that colonization with PCV10 serotypes is associated with greater risk for invasive disease than colonization with other serotypes successful PCV10 introduction in Kenya is likely to have a substantial impact in reducing vaccine-type pneumococcal disease and drug-resistant pneumococcal infection.

Currently, the data on pneumococcal invasive disease in the Indonesian population are limited. In this study, we investigated the serotype distribution and antimicrobial susceptibility ofStreptococcus pneumoniae.These samples were isolated from the sputum of adult patients with non-specific clinical symptoms aged 18鈥87 years in Jakarta, Indonesia, from August to October 2014. Of the 349 sputum specimens, thirteen isolates were identified asS. pneumoniaestrains (4%), with two strains each for serotype 19F, 3, and 15A, and one strain each for serotype/serogroup 13, 23A, 6, 34, 17F, 16F, and untypeable. Resistance to tetracycline was most common with only 5 of 13 strains being susceptible. In conclusion, these data provide an initial in the surveillance of invasive pneumococcus in the Indonesia population.

To mitigate the burden of pneumococcal infections in Niger, a 13-valent pneumococcal vaccine, PCV13, was introduced for routine child vaccination in July 2014. In order to provide pre-vaccine baseline data and allow appreciation of changes on carriage due to vaccination, we analyzed retrospectively pneumococcal isolates obtained from healthy, 0 to 2 year old children prior to the vaccine introduction. From June 5, 2007, to May 26, 2008, 1200 nasopharyngeal swabs were collected from healthy 0 to 2 year old children and analyzed by standard microbiological methods. Serotyping was done by SM-PCR and the data were analyzed with R version 2.15.0 (2012-03-30). Streptococcus pneumoniaewas detected in 654/1200 children (54.5%) among whom 339 (51.8%) were males. The ages of the study subjects varied from few days to 26 months (mean = 7.1, median = 6, 95% CI [6.8鈥7.4]). Out of 654 frozen isolates, 377 (54.8%) were able to be re-grown and analyzed. In total, 32 different serogroups/serotypes were detected of which, the most prevalent were 6/(6A/6B/6C/6D) (15.6%), 23F (10.6%), 19F (9.3%), 14 (9%), 19A (5.6%), 23B (4.0%), 25F/38 (3.7%), 18/(18A/18B/18C/18F) (2.9%) and PCR non-typeable (16.4%). Eleven serogroups/serotypes accounting for 57.3% (216/377) were of PCV13 types. Of the 211/377 (56%) isolates tested for drug sensitivity, 23/211 (10.9%), 24/211 (11.4%), 9/211(4.3%) and 148/210 (70.5%) were respectively resistance to oxacillin, chloramphenicol, erythromycin and tetracycline. Thirteen of the oxacillin resistant isolates were additionally multidrug-resistant. No resistance was however detected to gentamycin500渭gand to fluoroquinolones (酶 Norfloxacin5渭g<7mm). Age > 3 months and presence in family of more than one sibling aged < 6 years were significant risk factors for carriage. A global rate of 54.5% pneumococcal carriage was detected in this study. The introduced PCV13 vaccine should cover 57.3% (216/377) of circulating serogroups/serotypes, among which were those resistant to antibiotics. Age > 3 months and presence in family of children aged < 6 years were significant factors for pneumococcal carriage. The present data should help understanding post vaccine introduction changes in pneumococcal carriage and infections for better action.

Invasive pneumococcal disease continues to be a major cause of morbidity and mortality among children younger than 5 years of age in India. We aimed to provide nationally representative data for the pattern of disease due toStreptococcus pneumoniae, trends in the serotype of invasive pneumococci, and invasive pneumococci antimicrobial resistance patterns, in India. In this prospective hospital-based and retrospective laboratory-based surveillance study, we prospectively enrolled children aged younger than 5 years with suspected or proven invasive pneumococcal disease from 18 hospitals or institutional centres and retrospectively included laboratory-confirmed pneumococcal isolates from ten sentinel laboratories, together representing 11 states in India. Eligibility criteria were fever higher than 38掳C without localising symptoms, clinical presentation of suspected meningitis or pneumonia, and evidence of radiographic pneumonia. We cultured blood and other normally sterile body fluids, reconfirmed and serotyped pneumococcal isolates, and established antimicrobial susceptibility using standard study protocols. Between Jan 1, 2011, and June 30, 2015, we enrolled 4377 patients. Among 361 (8%) patients with culture-proven pneumococcal disease, all clinical data were known for 226 (63%); among these patients, 132 (58%) presented with pneumonia, 78 (35%) presented with meningitis, and 16 (7%) had other clinical conditions. 131 (3%) died overall and 29 (8%) patients with invasive pneumococcal disease died. Serotypes 14 (52 [14%] of 361), 1 (49 [14%]), 5 (37 [10%]), and 19F (33 [9%]) were the most common. Penicillin non-susceptibility occurred in isolates from 29 (8%) patients, co-trimoxazole resistance occurred in 239 (66%), erythromycin resistance occurred in 132 (37%), and chloramphenicol resistance occurred in 33 (9%). We found multidrug resistance in 33 (9%) of 361 patients. The proportion of positive blood cultures, number of isolates, geographical representation, and data generated over the 4路5 years of the study are representative of data for most of India. Continued surveillance is warranted as the decision to introduce protein conjugated vaccine in India is made. GlaxoSmithKline India.