Antimicrobial activity of ceftaroline combined with avibactam tested against bacterial organisms isolated from acute bacterial skin and skin structure infections in United States medical centers (2010–2012)

Ceftaroline-avibactam and comparator agents were tested against clinical isolates collected at 174 medical centers from patients with acute bacterial skin and skin structure infection (ABSSSI) in the United States (USA) during 2010–2012. Isolates were processed at the medical centers and forwarded to a central laboratory for confirmatory identification and susceptibility testing using reference methods. Ceftaroline-avibactam was highly active against methicillin-susceptible (MIC_50/90, 0.25/0.25 μg/mL) and methicillin-resistant Staphylococcus aureus (MRSA; MIC_50/90, 0.5/1 μg/mL). Vancomycin, tigecycline, daptomycin, and linezolid were also active (>99.9% susceptible) against MRSA (51.4% of S. aureus), but activity against MRSA was decreased for erythromycin, levofloxacin, and clindamycin (10.8, 40.3, and 81.9% susceptible, respectively). β-Hemolytic streptococci were highly susceptible to β-lactam antimicrobials, including ceftaroline-avibactam (MIC_50/90, ≤0.03/≤0.03 μg/mL). Ceftaroline-avibactam was very active against Escherichia coli and Klebsiella pneumoniae (MIC_50/90, 0.03/0.06 and 0.06/0.25 μg/mL, respectively) including extended-spectrum β-lactamase (ESBL) screen–positive phenotypes (MIC_50/90, 0.06/0.12 and 0.12/1 μg/mL, respectively). Susceptibility of ESBL screen–positive E. coli and K. pneumoniae was 100.0/97.9% for tigecycline and 99.2/56.1% for meropenem, respectively. Susceptibility to other agents for ESBL screen–positive E. coli and K. pneumoniae was decreased. Ceftaroline-avibactam exhibited a broad-spectrum of in vitro activity against isolates from patients in the USA with ABSSSI including MRSA, β-hemolytic streptococci, E. coli, and K. pneumoniae as well as ESBL screen–positive phenotype isolates and merits further study in clinical indications where these resistant organisms may be a concern.     

Molecular characteristics of carbapenemase-producing Enterobacteriaceae in China from 2008 to 2011: Predominance of KPC-2 enzyme

Among 228 carbapenem-nonsusceptible Enterobacteriaceae isolated in China, 65 were carbapenemase-producing Enterobacteriaceae (CPE). Among them, 41, 22, 1, and 1 produced KPC-2, IMP-4, IMP-8, and IMP-1, respectively. KPC-2-producing CPE showed higher resistance than IMP-4-producing ones. Furthermore, the first outbreak of ST11 KPC-2-producing Klebsiella pneumoniae in a Beijing second-degree hospital was identified.     

Carbapenem-resistant Gram-negative bacteria: how to prioritize infection prevention and control interventions in resource-limited settings?

Emergences of carbapenem-resistant Gram-negative bacteria (CRGNB) have heightened global awareness of the prioritization of infection prevention and control (IPC) interventions to minimize infections attributed to these bacteria. Effective new antibiotic drugs for CRGNB are estimated to be at least 5 years off completion of trials and approval for use. Hence, effective IPC strategies remain at the core of clinical care and research for patients with CRGNB infection. The authors summarize current evidence and viewpoints for IPC strategies as related to the emergence, transmission and prevention of CRGNB.     

肠杆菌科细菌超广谱β-内酰胺酶的检测及药敏分析

目的 :了解超广谱 β 内酰胺酶 (ESBLS)在肠杆菌科细菌中的产生情况及其对部分药物的敏感性 ,以指导临床合理用药。方法 :用双纸片确证试验检测肠杆菌科细菌产ESBLS 的情况 ,用纸片扩散法对 8种抗生素的体外药敏试验结果进行初步分析。结果 :产ESBLS 的肠杆菌科细菌 4 7株 ,其中大肠埃希菌 2 5株、肺炎克雷伯菌 14株、阴沟肠杆菌 5株、催产克雷伯菌 1株、鼻硬结克雷伯菌 1株、液化沙雷菌 1株。在 8种抗生素的体外药敏试验中 ,亚胺培南和美洛培南的敏感率最高 (10 0 % ) ,其次为哌拉西林 /他唑巴坦 (89.4 % )、头孢西丁 (72 .4 % )和头孢替坦 (6 5 .9% )。结论 :产ESBLS 的肠杆菌科细菌主要以大肠埃希菌和肺炎克雷伯菌为主。对于由产ESBLS 株引起的感染 ,亚胺培南和美洛培南可作为首选治疗用药。哌拉西林 /他唑巴坦优于头霉菌素类药物和其他 β -内酰胺酶抑制剂的复合制剂     

Chloroquinolines block antibiotic efflux pumps in antibiotic-resistant Enterobacter aerogenes isolates

Efflux mechanisms protect bacterial cells by pumping out toxic compounds and actively contribute to bacterial multidrug resistance. Agents inhibiting efflux pumps are of interest for the control of multidrug-resistant bacterial infections. Herein we report the effects of new chloroquinoline derivatives that render resistant Enterobacter aerogenes isolates noticeably more susceptible to structurally unrelated antibiotics. In addition, some of these chloroquinolines increase the intracellular concentration of chloramphenicol. Some of the molecules tested in this work are able to inhibit the main efflux pump (AcrAB-TolC), which is involved in E. aerogenes antibiotic resistance.     

Proactive infection control measures to prevent nosocomial transmission of carbapenem-resistant Enterobacteriaceae in a non-endemic area

Background Identification of hospitalized carbapenem-resistant Enterobacteriaceae （CRE）-positive patient is important in preventing nosocomial transmission.The objective of this study was to illustrate the implementation of proactive infection control measures in preventing nosocomial transmission of CRE in a healthcare region of over 3200 beds in Hong Kong between October 1,2010 and December 31,2011.Methods The program included active surveillance culture in patients with history of medical tourism with hospitalization and surgical operation outside Hong Kong within 12 months before admission,and ＂added test＂ as an opportunistic CRE screening in all fecal specimens submitted to the laboratory.Outbreak investigation and contact tracing were conducted for CRE-positive patients.Serial quantitative culture was performed on CRE-positive patients and the duration of fecal carriage of CRE was analyzed.Results During the study period,a total of 6533 patients were screened for CRE,of which 76 patients were positive （10 from active surveillance culture,65 from ＂added test＂,and 1 secondary case from contact tracing of 223 patients with no nosocomial outbreak）,resulting in an overall rate of CRE fecal carriage of 1.2％.The median time of fecal carriage of CRE was 43 days （range,13-119 days）.Beta-lactam-beta-lactamase-inhibitors,cephalosporins,and fluoroquinolones were associated significantly with high fecal bacterial load when used 90 days before CRE detection,while use of cephalosporins,carbapenems,and fiuoroquinolones after CRE detection are significantly associated with longer duration of carriage.The duration of fecal carriage of CRE also correlates significantly with the initial fecal bacterial load （Pearson correlation：0.53; P=0.02）.Conclusion Proactive infection control measures by enhanced surveillance program identify CRE-positive patients and data obtained are useful for the planning of and resource allocation for CRE control.     

Evolution of antimicrobial resistance among Enterobacteriaceae (focus on extended spectrum β-lactamases and carbapenemases)

Introduction: Bacteria within the family Enterobacteriaceae are important pathogens in nosocomial and community settings. Over the past two decades, antimicrobial resistance among Enterobacteriaceae dramatically escalated worldwide. The authors review the mechanisms of antimicrobial resistance among Enterobacteriaceae, epidemiology and global spread of resistance elements and discuss therapeutic options.

Areas covered: An exhaustive search for literature relating to Enterobacteriaceae was performed using PubMed, using the following key words: Enterobacteriaceae; Klebsiella pneumoniae; Escherichia coli; antimicrobial resistance; plasmids; global epidemiology; carbapenemases (CPEs); extended spectrum β-lactamases (ESBLs) and multidrug resistance (MDR).

Expert opinion: Enterobacteriaceae are inhabitants of intestinal flora and spread easily among humans (via hand carriage, contaminated food or water or environmental sources). Antimicrobial resistance may develop via plasmids, transposons or other mobile resistance elements. Mutations conferring resistance typically increase over time; the rate of increase is amplified by selection pressure from antibiotic use. Factors that enhance spread of antimicrobial resistance include: crowding; lack of hygiene; overuse and over-the-counter use of antibiotics; tourism; refugees and international travel. Clonal spread of resistant organisms among hospitals, geographic regions and continents has globally fueled the explosive rise in resistance. The emergence and widespread dissemination of MDR clones containing novel resistance elements (particularly ESBLs and CPEs) has greatly limited therapeutic options. In some cases, infections due to MDR Enterobacteriaceae are untreatable with existing antimicrobial agents. The authors discuss current and future therapeutic options for difficult-to-treat infections due to these organisms.