Establishment of epidemiological cut-off values for eravacycline, against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii and Staphylococcus aureus.

OBJECTIVES: To establish the epidemiology cut-off (ECOFF) values of eravacycline against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii and Staphylococcus aureus, from a multi-centre study in China. METHODS: We collected 2500 clinical isolates from five hospitals in China from 2017 to 2020. The MICs of eravacycline were determined using broth microdilution. The ECOFF values of eravacycline against the five species commonly causing cIAIs were calculated using visual estimation and ECOFFinder following the EUCAST guideline. RESULTS: The MICs of eravacycline against all the strains were in the range of 0.004-16 mg/L. The ECOFF values of eravacycline were 0.5 mg/L for E. coli, 2 mg/L for K. pneumonia and E. cloacae, and 0.25 mg/L for A. baumannii and S. aureus, consistent with the newest EUCAST publication of eravacycline ECOFF values for the populations. No discrepancy was found between the visually estimated and 99.00% ECOFF values calculated using ECOFFinder. CONCLUSIONS: The determined ECOFF values of eravacycline against the five species can assist in distinguishing wild-type from non-wild-type strains. Given its promising activity, eravacycline may represent a member of the tetracycline class in treating cIAIs caused by commonly encountered Gram-negative and Gram-positive pathogens.

Dissemination of blaOXA-23 in Acinetobacter spp. in China: main roles of conjugative plasmid pAZJ221 and transposon Tn2009.

Production of the OXA-23 carbapenemase is the most common reason for the increasing carbapenem resistance in Acinetobacter spp. This study was conducted to reveal the genetic basis of blaOXA-23 dissemination in Acinetobacter spp. in China. A total of 63 carbapenem-resistant OXA-23-producing Acinetobacter sp. isolates, representing different backgrounds, were selected from 28 hospitals in 18 provinces for this study. Generally, two patterns of plasmids carrying blaOXA-23 were detected according to S1-nuclease pulsed-field gel electrophoresis and Southern blot hybridization. A ca. 78-kb plasmid, designated pAZJ221, was found in 23 Acinetobacter baumannii and three Acinetobacter nosocomialis isolates, while a novel ca. 50-kb plasmid was carried by only two other A. baumannii isolates. Three of these isolates had an additional copy of blaOXA-23 on the chromosome. Transformation of the two plasmids succeeded, but only pAZJ221 was conjugative. Plasmid pAZJ221 was sequenced completely and found to carry no previously known resistance genes except blaOXA-23. The blaOXA-23 gene of the remaining 35 isolates was chromosome borne. The blaOXA-23 genetic environments were correlated with Tn2009 in 57 isolates, Tn2008 in 5 isolates, and Tn2006 in 1 isolate. The MIC values for the carbapenems with these isolates were not significantly associated with the genomic locations or the copy numbers of blaOXA-23. Overall, these observations suggest that the plasmid pAZJ221 and Tn2009 have effectively contributed to the wide dissemination of blaOXA-23 in Acinetobacter spp. in China and that horizontal gene transfer may play an important role in dissemination of the blaOXA-23 gene.

Clinical and microbiological characteristics of Klebsiella pneumoniae liver abscess in East China.

BACKGROUND: Klebsiella pneumoniae has been the dominant pathogen for liver abscesses in several Asian countries. Although the prevalence of K. pneumoniae liver abscess (KLA) in mainland China is increasing recently, the clinical and microbiological characteristics of KLA in China have not been elucidated. METHODS: Clinical and microbiology characteristics of 45 consecutive patients with KLA from a tertiary teaching hospital in China between June 2008 and June 2012 were retrospectively evaluated. RESULTS: Vast majority of the strains were susceptible to main antimicrobial agents. Most of K. pneumoniae strains from pyogenic liver abscess patients belonged to K1/K2 serotype (68.9% for K1 serotype and 20% for K2 serotype). All K. pneumoniae strains were rmpA positive, and 68.9% of these strains were magA positive. Overall, 57.8% (26/45) of K. pneumoniae strains belonged to ST23. Twenty-five of 26 ST23 K. pneumoniae isolates (96.2%) from KLA patients were magA-positive and K1 serotype. Only 28.9% (13/45) of KLA isolates exhibited hypermucoviscous phenotype, which is clinically used as the characteristic of hypervirulent K. pneumoniae (hvKP). Liver abscess sizes in patients infected with hvKP were tend to be larger than those in patients infected with cKP. There was no significant association between the microbiological and clinical characteristics including serotypes, magA and rmpA genotypes, and STs with the metastatic infection and prognosis of KLA. CONCLUSIONS: Neither the serotypes, magA and rmpA genotypes, nor the STs of K. pneumoniae were associated with the metastatic infection and prognosis of KLA. However, further studies with larger sample are needed in the future.

National surveillance of methicillin-resistant Staphylococcus aureus in China highlights a still-evolving epidemiology with 15 novel emerging multilocus sequence types.

The global spread of methicillin-resistant Staphylococcus aureus (MRSA) is a serious problem, particularly in mainland China. In order to better understand the national molecular epidemiology and resistance profiles of hospital-associated MRSA (HA-MRSA) in China, a laboratory-based multicenter surveillance study was conducted. Sixty-nine hospitals in 45 large cities in 27 provinces were involved, and a total of 1,141 HA-MRSA isolates were collected during the 6-month study period in 2011. All MRSA isolates were characterized by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, spa typing, detection of the Panton-Valentine leukocidin (PVL) locus (lukS-PV and lukF-PV), and antibiogram analysis. ST239-III-t030, ST239-III-t037, and ST5-II-t002 were the predominant HA-MRSA clones (overall prevalence rates, 57.1%, 12.9%, and 8.1%, respectively), although the prevalence rates of these major clones varied markedly in different administrative regions. Of note, 6.6% of the HA-MRSA isolates were found to belong to ST59, which had typical community-associated MRSA (CA-MRSA) features, including carriage of SCCmec type IV or V and PVL and less antimicrobial resistance than other major HA-MRSA clones. Moreover, among 36 MLST sequence types (STs) identified, 15 STs, accounting for 3.5% of total isolates, were novel. A novel ST designated ST2590, which is a single-locus variant of ST5-II-t002, was identified in three hospitals in two large cities, with a total of 17 isolates. To further monitor trends in HA-MRSA prevalence, epidemic clonal shifts, clone emergence, and transmission between community and health care settings, longitudinal national MRSA surveillance is required.

[Antimicrobial resistance of Gram-negative bacilli isolated from 13 teaching hospitals across China].

OBJECTIVE: To explore the antimicrobial resistance of nosocomial Gram-negative bacilli across China. METHODS: A total of 1247 consecutive and non-repetitive Gram-negative bacilli were isolated from 13 Chinese teaching hospitals from March to August 2012. All isolates were sent to a central laboratory for reidentification and susceptibility testing. The minimal inhibitory concentration (MICs) of meropenem and other antibacterial agents were determined by agar dilution method. And the data were analyzed with WHONET-5.6 software. RESULTS: The activity of antimicrobial agents against Enterobacteriaceae was in the following descending order of susceptibility rate: meropenem (97.5%, 849/871) , amikacin (94.5%, 823/871) , imipenem (93.6%, 815/871) , ertapenem (92.9%, 809/871) , piperacillin/tazobactam (89.9%, 783/871) , cefoperazone/sulbactam (83.5%, 727/871) , cefepime (78.1%, 680/871) , polymyxin B (77.0%, 670/871) , cefiazidime (69.6%, 606/871) , levofloxacin (69.2%, 603/871) , ciprofloxacin (63.6%, 554/871) , minocyline (63.1%, 550/871) , ceftriaxone (55.7%, 485/871) , cefotaxime (54.2%, 472/871) and cefoxitin (51.4%, 448/871) . The prevalence of extended-spectrum beta-lactamase (ESBL) was 64.3% (117/182) in Escherichia coli (E. coli) and 32.1% (60/187) in Klebsiella pneumonia (K. pneumoniae) . The sensitivities of E. coli to meropenem and imipenem were 100%. And over 90% of E. coli was sensitive to ertapenem, amikacin, piperacillin/tazobactam and polymyxin B. However, over 60% of E. coli was resistant to ciprofloxacin, levofloxacin, ceftriaxone and cefotaxime. The susceptibility of K. pneumoniae to meropenem, imipenem, amikacin and polymyxin B maintained at over 90%. The activities of antimicrobial agents against E. cloacae, E. aerogenes and Citrobacter freundii were in the following descending order of susceptibility rate: meropenem (96.0%-100%) , imipenem (96.0%-100%) , polymyxin B (95.8%-100%) , amikacin (92.2%-100%) , ertapenem (85.6%-93.3%) , cefepime (77.8%-93.3%) , cefoperazone/sulbactam (78.4%-90.0%) and piperacillin/tazobactam (65.0%-89.8%) . The most susceptible agent against Acinetobacter baumannii (A. baumannii) was polymyxin B (100%) . The susceptibilities of A.baumannii to imipenem, meropenem and minocyline were 37.8% (65/172) , 36.0% (62/172) and 62.8% (108/172) respectively. The most active agents against Pseudomonas aeruginosa (P. aeruginosa) were polymyxin B (97.2%, 173/178) , followed by amikacin (89.3%, 159/178) and cefiazidime (83.7%, 149/178) . Clinical and Laboratory Standards Institute revised P.aeruginosa susceptibility standard in 2012. The sensitivity of piperacillin/tazobactam changed from 83.7% (149/178) to 77.5% (138/178) . The sensitivity of meropenem decreased from 78.1% ( 139/178 ) to 71.3% ( 127/178 ) while that of imipenem declined from 69.7% (124/178) to 59.6% (106/178) . The prevalence of multi-drug resistant A. baumannii and P. aeruginosa were 65.7% (113/172) and 9.0% (16/178) respectively. CONCLUSIONS: Carbapenems remain highly active against Enterobacteriaceae. Increasing resistance of A. baumannii to all antimicrobial agents is noted. New breakpoint to P.aeruginosa has obvious effects on antimicrobial sensitivity.

[Analysis of resistance tendency of bloodstream-infecting pathogens in China].

OBJECTIVE: To investigate the resistance profiles and the trend of bloodstream-infecting pathogens isolated from hospitalized patients during 2004-2010. METHODS: The bloodstream isolates were collected from 18 hospitals in 17 cities. Minimum inhibition concentrations (MIC) were determined using the agar dilution method recommended by CLSI (Clinical and Laboratory Standards Institute), and susceptibility results were analyzed according to the 2011 CLSI guideline. RESULTS: Among the 2004-2005, 2007-2008 and 2009-2010 periods, the proportions of clinical isolates were similar; 43.1% (149 isolates), 34.0% (151 isolates) and 47.5% (776 isolates) for Gram positive strains, 56.9% (197 isolates), 66.0% (293 isolates) and 52.5% (858 isolates) for Gram negative strains, respectively. The isolating rate of MRSA was 54.1% (20/37) in 2007-2008, which was the highest among the 3 periods during 2004 to 2010, while it decreased in 2009-2010 (36.5%, 62/170). The MRCNS proportions were similar across the 3 periods. One (1.8%) vancomycin-resistant Enterococcus faecium and 1 linezolid-resistant Enterococcus faecalis were found. Although the isolating rates of penicillin non-sensitive strains (oral) were similar between 2009-2010 and 2007-2008 [54.5% (6/11) and 53.9% (7/13), respectively], the resistant rates increased from 0% in 2007-2008 to 30.8% (4/13) in 2009-2010. The results were similar according to the non-meningitis criterion (IV), and the susceptibility rates decreased from 100.0% (11 isolates) in 2007-2008 to 84.6% (11/13) in 2009-2010. ESBL-harboring strains in E. coli were similar among the 3 periods during 2004 to 2010 [66.7% (30/45), 73.2% (71/97) and 67.9% (233/343), respectively]. ESBL-producing strains in Klebsilla pnuemoniae decreased year after year, 72.4% (21/29), 50.0% (18/36) and 41.1% (65/158) in 2004-2005, 2007-2008 and 2009-2010, respectively. Except that the sensitive rate of Enterobacter cloacae to ertapenem was 80% (32/40), the sensitive rates of other strains to carbapenems were still above 90% and the resistance rates were less than 5%. Acinetobacter baumannii had the highest multi-drug resistance rate (81.8%, 81/99). One strain (1.0%, 1/99) of Acinetobacter baumannii isolated in 2009-2010 was reported to be pan-resistant. CONCLUSIONS: We are facing a more serious situation of bacterial resistance. Acinetobacter baumannii resistance was most serious, usually with the characteristics of multiple drug resistance, and even pan-resistance. Carbapenems remain to be the most effective against enterobacteriaceae. Strains resistant to novel antibiotics (linezolid and tigecycline) have emerged.

[Antimicrobial susceptibility of community-acquired respiratory tract pathogens isolated from adults in China during 2009 and 2010].

OBJECTIVE: To investigate the drug-resistance rates of community-acquired respiratory tract pathogens isolated from adults in China during 2009 and 2010. METHODS: A total of 1793 strains (S. aureus 421, S. pneumoniae 420, K. pneumoniae 404, H. influenzae 313, other Streptococcus. spp 149, and M. catarrhalis 86) of non-duplicated community-acquired respiratory tract pathogens were isolated from 11 hospitals in 6 cities. The MIC values were determined by the broth microdilution method, and the production of ß-lactamase was tested using a nitrocefin-based test. RESULTS: All of the S.aureus isolates were methicillin-sensitive (MSSA). Of the MSSA isolates, less than 1% (4/421) was resistant to ß-lactamase inhibitor combinations, about 13.1% (55/421) and 9% (38/421) resistant to levofloxacin and moxifloxacin, and 57% (240/421), 53.2% (224/421), and 88.7% (373/421) resistant to azithromycin, clarithromycin, and penicillin, respectively. No S. aureus isolates resistant to vancomycin were detected in this study. Based on different criteria, the percentages of penicillin-sensitive S. pneumoniae (PSSP), penicillin-intermediate S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP) were 24.4% (102/420), 27.3% (115/420), 48.3% (203/420) (Oral) and 1.9% (8/420), 9% (38/420), 89.1% (374/420) (parenteral), respectively. The resistance rates of S. pneumonia to azithromycin, clarithromycin, cefaclor, cefuroxime, ceftriaxone and amoxicillin with clavulanic acid were 88.2% (370/420), 87.4% (367/420), 45.3% (190/420), 41.9% (176/420), 10.2% (43/420), and 5.2% (22/420), respectively. About 2.6% (11/420) and 0.2% (1/420) of S. pneumonia isolates were resistant to levofloxacin and moxifloxacin. More than 70% (104/149) of ß-hemolytic streptococci isolates were resistant to azithromycin and clarithromycin, and about 10.1% (15/149) of isolates were resistant to levofloxacin. The resistance rates of K.pneumonia to most antibiotics were > 20% (81/404), and that of ceftazidime was lower than cefuroxime, cefaclor, and ceftriaxone. The mean prevalence value of ESBL producing K. pneumonia was 38.8% (157/404), with significantly regional variations. More than 90% of H. influenza and M. catarrhalis were susceptible to most antibiotics, with resistance rate of < 5% (16/313, H. influenza; 4/86, M. catarrhalis). The mean productions of ß-lactamase in H. influenza and M. catarrhalis were 13.1% (41/313) and 91.7% (79/86), respectively. CONCLUSIONS: The percentage of PRSP increased significantly, and the resistance rates of community-acquired respiratory tract pathogens to common antibiotics such as macrolide and cephalosporins increased gradually. New fluoroquinolones such as moxifloxacin showed a high antimicrobial activity against most of the respiratory pathogens.

Upregulation of lncRNA NONRATG019935.2 suppresses the p53-mediated apoptosis of renal tubular epithelial cells in septic acute kidney injury.

Although increasing evidence has confirmed that the apoptosis of renal tubular epithelial cells (RTECs) is a crucial contributor to the onset and development of septic acute kidney injury (AKI), the pathological mechanism by which RTEC apoptosis is upregulated during septic AKI is not entirely clear. In this study, a rat model of septic AKI was induced by a cecal ligation puncture procedure or lipopolysaccharide (LPS) injection. Four differentially expressed long noncoding RNAs (DE-Lncs) in the rat model of septic AKI were determined using RNA-sequencing and verified by qRT-PCR. Among the four DE-Lncs, the expression level of lncRNA NONRATG019935.2 (9935) exhibited the most significant reduction in both septic AKI rats and LPS-treated NRK-52E cells (a rat RTEC line). The overexpression of 9935 suppressed cell apoptosis and p53 protein level in LPS-treated NRK-52E cells, and retarded septic AKI development in the rat model of septic AKI. Mechanistically, 9935 decreased the human antigen R (HuR)-mediated Tp53 mRNA stability by limiting the combination of HuR and the 3'UTR region of Tp53 mRNA in RTECs. The overexpression of HuR abrogated the inhibitory effect of pcDNA-9935 on the LPS-induced apoptosis of NRK-52E and rat primary RTECs. In conclusion, 9935 exerts its role in septic AKI by suppressing the p53-mediated apoptosis of RTECs, and this essential role of 9935 relies on its destructive effect on HuR-mediated Tp53 mRNA stability.

[An antimicrobial resistance surveillance of gram-positive cocci isolated from 12 teaching hospitals in China in 2009].

OBJECTIVE: To investigate antimicrobial resistance among gram-positive cocci in China in 2009. METHODS: From June to December 2009, 1169 consecutive and non-repetitive gram-positive cocci were collected from 12 teaching hospitals at 9 cities. The minimal inhibitory concentration (MIC) of antibacterial agents was determined by agar dilution method. RESULTS: The prevalences of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococci (MRCoNS) were 45.3% (211/466) and 89.5% (214/239), respectively. The isolation rate of MRSA was 33.3% - 68.1% from different samples. All Staphylococci isolates were susceptible to vancomycin, teicoplanin and linezolid. Five point five percent (7/128) E.faecium strains were resistant to vancomycin. All E. faecalis strains were susceptible to vancomycin. About 99.1% (108/109) of E.faecalis and E.faecium were susceptible to linezolid. The prevalence of penicillin-intermediate Streptococcus pneumoniae (PISP) was 21.6% (48/222). Only 1 (0.5%, 1/222) Streptococcus pneumoniae strain was resistant to penicillin. Teicoplanin, vancomycin, linezolid and tigecycline were the most active agents against Streptococcus pneumoniae (susceptible rate 100%). CONCLUSIONS: The high prevalence of methicillin-resistance is among Staphylococcus strains. Different samples show a different MRSA prevalence. Teicoplanin, vancomycin and linezolid show very high activity to Staphylococci, E. faecalis, E. faecium and Streptococcus pneumoniae.

Polymyxin for the treatment of intracranial infections of extensively drug-resistant bacteria in children after neurosurgical operation.

BACKGROUND: Increased meningitis caused by extensively drug-resistant bacillary presents a significant challenge in antibiotic selection. The aim of our study was to evaluate the efficacy and safety of polymyxin in the treatment of post-neurosurgical meningitis due to the extensively drug-resistant bacillary in children. METHODS: We performed a retrospective study on post-neurosurgical meningitis caused by the extensively drug-resistant bacillary in children, who were treated with polymyxin for ≥ 3 days. RESULTS: Among five post-neurosurgical meningitis cases that were included, the children were infected by Acinetobacter baumannii (n = 3), Klebsiella pneumonia (n = 1), and Pseudomonas aeruginosa (n = 1). The drug susceptibility test showed that they were extensively drug-resistant bacillary. Two patients received intravenous polymyxin E. Three children received intravenous combined with intraventricular injection of polymyxin B. One patient infected by Klebsiella pneumonia eventually died of septic shock. No serious adverse effects of polymyxin were observed. CONCLUSIONS: Polymyxin is a safe and effective therapy for post-neurosurgical, multidrug-resistant bacillary meningitis in children.

Evaluation of phenotypic tests for detection of metallo-beta-lactamase-producing Pseudomonas aeruginosa strains in China.

A total of 264 nonduplicate strains of imipenem (IPM)-nonsusceptible Pseudomonas aeruginosa were isolated from hospitals in 16 different regions throughout China. These 264 IPM-nonsusceptible clinical isolates of P. aeruginosa were examined by PCR, a metallo-beta-lactamase (MBL) Etest, a double-disk synergy test (DDST), and a test using combined IPM disks supplemented with various amounts of EDTA. A total of 24 strains positive for MBLs were confirmed by PCR and DNA sequence analysis: 10 strains positive for the bla(VIM-2) gene, 13 strains positive for the bla(IMP-9) gene, and 1 strain positive for the bla(IMP-1) gene. Real-time reverse transcriptase PCR (RT-PCR) was used to verify whether the isolates harboring MBL genes produced the enzyme and was considered the standard for evaluation of the methodology in this study. Of these 24 MBL-positive stains, 21 were confirmed as MBL-producing strains by real time RT-PCR for MBL expression and the other 3 had no expression of MBLs. The sensitivities, specificities, and positive and negative predictive values for the MBL Etest, the DDST, and the combined disk (CD) assay were evaluated. The best method for screening for MBL production in P. aeruginosa strains from China was the CD assay (IMP-EDTA) using 750 microg of EDTA/disk with a breakpoint of >or=6 mm. In the CD assay (IPM-EDTA) with 290 microg and 750 microg EDTA, the zone diameter increases for VIM-2-producing P. aeruginosa isolates were greater than those for IMP-9-producing P. aeruginosa isolates (P = 0.00).

Clinical evaluation of oral levofloxacin 500 mg once-daily dosage for treatment of lower respiratory tract infections and urinary tract infections: a prospective multicenter study in China.

Levofloxacin (LVFX), a fluoroquinolone agent, has a broad spectrum that covers Gram-positive and -negative bacteria and atypical pathogens. It demonstrates good clinical efficacy in the treatment of various infections, including lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs). To evaluate the efficacy and safety of oral LVFX 500 mg once daily, a large open-label clinical trial was conducted in 1266 patients (899 with LRTIs and 367 with UTIs) at 32 centers in China. In the per-protocol population, the clinical efficacy rate (cure or improvement) at 7 to 14 days after the end of treatment was 96.4% (666/691) for LRTIs and 95.7% (267/279) for UTIs. In 53 patients diagnosed with atypical pneumonia the treatment was effective. The bacteriological efficacy rate was 96.6% (256/265) for LRTIs and 93.3% (126/135) for UTIs. The eradication rate of the causative pathogens was 100% (33/33) for Haemophilus influenzae and 96.0% (24/25) for Streptococcus pneumoniae in LRTIs, and 94.1% (80/85) for Escherichia coli in UTIs. The overall efficacy rates were 89.3% (617/691) for LRTIs and 87.8% (245/279) for UTIs. The incidence of drug-related adverse events (ADRs) was 17.3% (215/1245), and the incidence of drug-related laboratory abnormalities was 15.7% (191/1213). Common ADRs were dizziness, nausea, and insomnia. Common laboratory abnormalities included "WBC decreased", "alanine aminotransferase (ALT) increased", "aspartate aminotransferase (AST) increased", and "lactate dehydrogenase (LDH) increased". All of these events were mentioned in the package inserts of fluoroquinolones including LVFX, and most events were mild and transient. Thirty-four patients (2.7%) were withdrawn from the study because of the ADRs. No new ADRs were found. This study concluded that the dosage regimen of LVFX 500 mg once daily was effective and tolerable for the treatment of LRTIs and UTIs.

Sepsis resulting from Enterobacter aerogenes resistant to carbapenems after liver transplantation.

BACKGROUND: Sepsis due to Enterobacter aerogenes (E. aerogenes) is rare after liver transplantation but is also a serious infection that may cause liver abscess. The purpose of this case report is to relate an unusual presentation of liver transplantation to show how successive treatment can be an appropriate option in septic patients after liver transplantation. METHOD: We report on a patient with liver transplantation who developed sepsis due to extended spectrum beta-lactamases and AmpC-producing E. aerogenes. RESULTS: A 39-year-old man had a biliary fistula and then was found to have multiple liver abscesses through abdominal ultrasound and an abdominal computed tomography scan, and carbapenem-sensitive E. aerogenes infection was confirmed. The patient was not successfully treated with conservative treatment consisting of intravenous carbapenems, percutaneous transhepatic cholangial drainage, and biliary stent placement by endoscopic retrograde cholangiopancreatography, so a second liver transplantation followed. Carbapenem-resistant E. aerogenes was detected in bile and blood after a five-week course of carbapenem therapy. The patient developed septic shock and multiple organ dysfunction syndrome. CONCLUSIONS: We first report an unusual case of sepsis caused by E. aerogenes after liver transplantation in China. Carbapenem-resistant E. aerogenes finally leads to uncontrolled sepsis with current antibiotics. We hypothesize that the infection developed as a result of biliary fistula and predisposing immunosuppressive agent therapy. Further research is progressing on the aspect of immunomodulation therapy.

[Resistance study of community respiratory pathogens isolated in China from 2005 to 2007].

OBJECTIVE: To investigate the antimicrobial resistance of community respiratory pathogens isolated in China. METHODS: The strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, S. pyogenes were isolated from patients with community-acquired respiratory tract infections at 14 Chinese hospitals from 2005 to 2007. Etest and disk diffusion methods were used to survey the susceptibility of 14 antibiotics against these strains. These antibiotics included penicillin G, ampicillin, amoxicillin/clavulanic acid, cefaclor, cefprozil, ceftriaxone, cefepime, levofloxacin, gatifloxacin, ciprofloxacin, tetracycline, clindamycin, erythromycin and trimethoprim/sulfamethoxazole (SXT). RESULTS: A total of 1870 strains were collected including S. pneumoniae (n = 997), S. pyogenes (n = 176), H. influenzae (n = 499) and M. catarrhalis (n = 198). The 2005 - 2007 prevalence of penicillin-susceptible S. pneumoniae (PSSP) were 92.6%, 73.9%, 74.1% and penicillin-intermediate S. pneumoniae (PISP) 4.5%, 9.5%, 14.3% and penicillin-resistant S. pneumoniae (PRSP) 2.9%, 16.6%, 11.6% respectively. 36.9% of S. pneumoniae strains isolated from or= 92.9%. CONCLUSIONS: Antimicrobial resistance in S. pneumoniae is rising. The prevalence of PNSSP isolated from children < or = 6 years old is higher than other age groups. Amoxicillin-clavulanic acid, ceftriaxone, cefepime, gatifloxacin and levofloxacin remain highly active against common community respiratory pathogens.

Utilization of echocardiography during septic shock was associated with a decreased 28-day mortality: a propensity score-matched analysis of the MIMIC-III database.

BACKGROUND: Hemodynamic management is of paramount importance in patients with septic shock. Echocardiography has been increasingly used in assessing volume status and cardiac function. However, whether the utilization of echocardiography has an impact on prognosis is unknown. Thus, we intended to explore its effect on the outcomes of patients with septic shock. METHODS: The study was based on the Medical Information Mart for Intensive Care (MIMIC) III database. Septic shock patients were divided into two groups according to the usage of echocardiography during the onset of septic shock. The primary outcome was 28-day mortality. Secondary outcomes included the usage of inotropes, ventilation-free and norepinephrine-free time, and fluids input. Propensity-score matching was used to reduce the imbalance. RESULTS: Among 3,291 eligible patients, 1,289 patients who underwent echocardiography (Echo), and 1,289 who did not receive the Echo, had similar propensity scores and were included in the analyses. After matching, the Echo group had a significantly lower 28-day mortality (33.2% vs. 37.7%, P=0.019). More patients in the Echo group received pulmonary artery catheter (PAC) (4.2% vs. 0.2%, P<0.001) and inotropes (17.8% vs. 7.1%, P<0.001). In the survival analysis, Echo utilization was associated with improved 28-day mortality [hazard ratio (HR): 0.83; 95% confidence interval (CI), 0.73-0.95, P=0.005]. A reduced likelihood of 28-day mortality in patients with Echo vs. those without Echo was maintained either when excluding patients receiving multiple echocardiography scans (HR, 0.82; 95% CI, 0.72-0.94; P=0.004) or when excluding patients undergoing PAC or pulse index continuous cardiac output (PiCCO) (HR, 0.87; 95% CI, 0.76-0.99; P=0.034). CONCLUSIONS: Utilization of echocardiography was associated with improved 28-day outcomes in patients with septic shock.

Plasmid-borne armA methylase gene, together with blaCTX-M-15 and blaTEM-1, in a Klebsiella oxytoca isolate from China.

An armA-producing Klebsiella oxytoca isolate, strain 157, was detected after screening of 447 extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates in China. K. oxytoca 157 was resistant to aminoglycosides, ciprofloxacin and most beta-lactams. Resistance to aminoglycosides and beta-lactams could be transferred to recipient Escherichia coli by conjugation. armA, blaCTX-M-15 and blaTEM-1 genes were detected in K. oxytoca 157 and transconjugant E. coli strain 600(pEC157). Mutation of aa 87 in GyrA was found in K. oxytoca 157. A plasmid of approximately 55 kb was extracted from K. oxytoca 157(pKO157) and E. coli 600(pEC157). Southern blot hybridization confirmed that the armA, blaCTX-M-15 and blaTEM-1 genes were all located on this conjugative plasmid (pEC157). PCR mapping was also performed to investigate the genetic environment of armA. The armA gene was found to be flanked by the same putative transposable elements as reported previously in E. coli, Klebsiella pneumoniae and Citrobacter freundii isolates from different countries.

In vivo development of carbapenem resistance in clinical isolates of Enterobacter aerogenes producing multiple beta-lactamases.

Four clinical strains of extended-spectrum beta-lactamase- and AmpC-producing Enterobacter aerogenes were isolated successively from a liver transplantation patient. Isolates C(1) and C(2) were isolated prior to carbapenem therapy, whilst isolates C(3) and C(4) were recovered after 40 days of carbapenem therapy. The homology of these strains was analysed by pulsed-field gel electrophoresis (PFGE). beta-Lactamases were analysed by isoelectric focusing, polymerase chain reaction (PCR) and sequencing. Outer membrane proteins were analysed by PCR, sequencing, sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blot. Disruption of OmpE36 in C(1) in vitro was also performed by homologous gene recombination. The isolates demonstrated an indistinguishable PFGE pattern. Molecular characterisation revealed that, in addition to the pre-existing multiple beta-lactamases (DHA-1, TEM-1, SHV-5, CTX-M-3 and CTX-M-14) found in C(1) and C(2), isolates C(3) and C(4) failed to express OmpE36 owing to insertional inactivation by an IS903-like insertion sequence. Other resistance mechanisms, such as production of carbapenem-hydrolysing enzymes or expression of chromosomal efflux, were apparently not involved. Completely replacing OmpE36 by the kanamycin resistance gene (kan) resulted in a significant increase in carbapenem minimum inhibitory concentrations of an ompE36 mutant. Thus, C(3) and C(4) were apparently derived from the previously imipenem-susceptible isolates C(1) and C(2). Following carbapenem exposure, depletion of OmpE36 expression resulted in the collateral effect of carbapenem resistance.

High Serum Iron level is Associated with Increased Mortality in Patients with Sepsis.

Iron is an essential nutrient for bacterial survival and thus higher iron levels may precipitate bacterial infections. We investigated the association between the serum iron level and prognosis in patients with sepsis by using the single-centre Medical Information Mart for Intensive Care III (MIMIC-III) database. Sepsis patients with iron parameters measured on ICU admission were included and stratified according to quartiles of serum iron levels. A total of 1,891 patients diagnosed with sepsis according to the Sepsis-3 criteria were included in this study, 324 of whom were septic shock. After adjusting for confounding variables, higher iron quartile was associated with an increase in 90-day mortality in the Cox regression analysis. Moreover, a stepwise increase in the risk of 90-day mortality was observed as the quartiles of serum iron levels increased in the patients with sepsis. In conclusion, higher serum iron levels were independently associated with increased 90-day mortality in this large cohort of patients with sepsis.

Comparison of the predictive value of scoring systems on the prognosis of cirrhotic patients with suspected infection.

Cirrhotic patients with infection are prone to develop sepsis or even septic shock rendering poorer prognosis. However, few methods are available to predict the prognosis of cirrhotic patients with infection although there are some scoring systems can be used to predict general patients with cirrhosis. Therefore, we aimed to explore the predictive value of scoring systems in determining the outcome of critically ill cirrhotic patients with suspected infection.This was a retrospective cohort study based on a single-center database. The prognostic accuracy of the systemic inflammatory response syndrome (SIRS) criteria, quick Sequential Organ Failure Assessment (qSOFA), chronic liver failure (CLIF)-SOFA, quick CLIF-SOFA (qCLIF-SOFA), CLIF-consortium organ failure (CLIF-C OF), Model for End-Stage Liver Disease (MELD), and Simplified Acute Physiology Score (SAPS) II were compared by using area under the receiver operating characteristic (AUROC) curve and net benefit with decision curve analysis. The primary endpoint was in-hospital mortality while the secondary endpoints were duration of hospital and intensive care unit (ICU) stay and ICU mortality.A total of 1438 cirrhotic patients with suspected infection were included in the study. Nearly half the patients (50.2%) were admitted to the ICU due to hepatic encephalopathy and the overall in-hospital mortality was 32.0%. Hospital and ICU mortality increased as the score of each scoring system increased (P < .05 for all trends). The AUROC of CLIF-SOFA (AUROC, 0.742; 95% confidence interval, CI, 0.714-0.770), CLIF-C OF (AUROC, 0.741; 95% CI, 0.713-0.769), and SAPS II (AUROC, 0.759; 95% CI, 0.733-0.786) were significantly higher than SIRS criteria (AUROC, 0.618; 95% CI, 0.590-0.647), qSOFA (AUROC, 0.612; 95% CI, 0.584-0.640), MELD (AUROC, 0.632; 95% CI, 0.601-0.662), or qCLIF-SOFA (AUROC, 0.680; 95% CI, 0.650-0.710) (P < .05 for all). In the decision curve analysis, the net benefit of implementing CLIF-SOFA and CLIF-C OF to predict the prognosis of cirrhotic patients with suspected infection were higher compared with SIRS, qSOFA, MELD, or qCLIF-SOFA.CLIF-SOFA and CLIF-C OF scores, as well as SAPS II were better tools than SIRS, qSOFA, MELD, or qCLIF-SOFA to evaluate the prognosis of critically ill cirrhotic patients with suspected infection.

Simultaneous emergence and rapid spread of three OXA-23 producing Acinetobacter baumannii ST208 strains in intensive care units confirmed by whole genome sequencing.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a common nosocomial bacterial pathogen with limited treatment options. CRAB outbreaks are disastrous for critically ill patients. This study investigated carbapenemase-produced A. baumannii outbreaks in a tertiary hospital. Although multiple outbreaks were suggested by pulse-field gel electrophoresis, the genetic lineages and evolution between these isolates were not clear. To investigate the genomic epidemiology of these outbreaks and to reveal possible transmission routes, whole genome sequences (WGS) were compared and analyzed. From the WGS data, thirty isolates had the same sequence type (ST208); acquired resistance genes and chromosome resistant genes were detected and were responsible for multidrug resistance. A phylogenetic tree of single-nucleotide polymorphisms (SNPs) compared to the earliest index isolate found that three outbreaks had emerged and disseminated simultaneously. Of these, <10 SNPs were detected within the cluster, whereas at least 600 SNPs were found between the clusters. The probable transmission routes of outbreaks were generated combined with the genetic distance of isolates and patient epidemiological data. In conclusion, WGS was a convenient and accurate monitoring method for genomic epidemiologic investigation of outbreaks, and the genomic surveillance of multidrug-resistant bacterial pathogens would be a powerful warning system for the surveillance and prevention of outbreaks.