Etiology and antibiotic susceptibility of bacterial pathogens responsible for community-acquired urinary tract infections in Poland

Urinary tract infections (UTIs) are some of the most common infections in both community and hospital settings infections. With their high rate of incidence, recurrence, complications, diverse etiologic agents, as well as growing antibiotic resistance, UTIs have proven to be a serious challenge for medical professionals. The aim of this study was to obtain data on the susceptibility patterns of pathogens responsible for UTIs in Poland to currently used antibiotics. A total of 396 bacterial isolates were collected between March and May 2013 from 41 centers in all regions of Poland. The majority of isolates were from adult patients (96.2 %); 144 (37.8 %) patients were diagnosed with uncomplicated UTI, while the remaining 237 (62.2 %) had a complicated infection. The most prevalent pathogen was Escherichia coli (71.4 %), followed by Klebsiella spp. (10.8 %) and the Proteae group (7.6 %). Escherichia coli was responsible for 80.6 % of cases of uncomplicated and 65.8 % of complicated infections. Only 65.8 % of E. coli isolates were susceptible to ciprofloxacin (uncomplicated 75.9 %, complicated 58.3 %), 64.0 % to nitrofurantoin (67.2 %, 62.8 %), 65.1 % to trimethoprim/sulfamethoxazole (68.1 %, 62.8 %), and 66.4 % to fosfomycin (77.6 %, 62.2 %). Among E. coli isolates from all UTIs, only 43.4 % were susceptible to ampicillin, with 47.4 % from uncomplicated compared with 40.4 % from complicated infections; 88.2 % to amoxicillin/clavulanic acid (91.4 % vs. 85.9 % complicated); 90.1 % to cefuroxime (93.1 %, 87.8 %); and 94.1 % to cefotaxime (98.2 %, 91.0 %). Thirty-five strains (10.4 %) were capable of producing extended-spectrum β-lactamases (ESBLs). This study demonstrates an increase in multidrug-resistant strains, especially among the leading pathogens associated with UTIs, including E. coli, Klebsiella spp., and Proteus spp.     

Association of diverse bacterial communities in human bile samples with biliary tract disorders: a survey using culture and polymerase chain reaction-denaturing gradient gel electrophoresis methods

Bacterial infection is considered a predisposing factor for disorders of the biliary tract. This study aimed to determine the diversity of bacterial communities in bile samples and their involvement in the occurrence of biliary tract diseases. A total of 102 bile samples were collected during endoscopic retrograde cholangiopancreatography (ERCP). Characterization of bacteria was done using culture and polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) methods. Antimicrobial susceptibility of the isolates was determined based on the Clinical and Laboratory Standards Institute (CLSI) guidelines and identity of the nucleotide sequences of differentiated bands from the DGGE gels was determined based on GenBank data. In total, 41.2 % (42/102) of the patients showed bacterial infection in their bile samples. This infection was detected in 21 % (4/19), 45.4 % (5/11), 53.5 % (15/28), and 54.5 % (24/44) of patients with common bile duct stone, microlithiasis, malignancy, and gallbladder stone, respectively. Escherichia coli showed a significant association with gallstones. Polymicrobial infection was detected in 48 % of the patients. While results of the culture method established coexistence of biofilm-forming bacteria (Pseudomonas aeruginosa, E. coli, Klebsiella pneumoniae, Enterococcus spp., and Acinetobacter spp.) in different combinations, the presence of Capnocytophaga spp., Lactococcus spp., Bacillus spp., Staphylococcus haemolyticus, Enterobacter or Citrobacter spp., Morganella spp., Salmonella spp., and Helicobacter pylori was also characterized in these samples by the PCR-DGGE method. Multidrug resistance phenotypes (87.5 %) and resistance to third- and fourth-generation cephalosporins and quinolones were common in these strains, which could evolve through their selection by bile components. Ability for biofilm formation seems to be a need for polymicrobial infection in this organ.     

Clinical and microbiological characteristics of peritoneal dialysis-related peritonitis caused by <Emphasis Type="Italic">Escherichia coli</Emphasis> in southern Taiwan

Peritonitis is a serious complication and major cause of treatment failure in patients undergoing peritoneal dialysis (PD). Escherichia coli is the major pathogen in extraintestinal Gram-negative infections, including PD-related peritonitis. The outcomes of E. coli peritonitis in PD varied from relatively favorable outcomes to a higher incidence of treatment failure. The aim of this study was to investigate the impact of bacterial virulence and host characteristics on the outcomes of PD-related peritonitis caused by E. coli. From January 2000 to June 2016, a total of 47 episodes of monomicrobial and 10 episodes of polymicrobial E. coli PD-related peritonitis, as well as 89 episodes of monomicrobial Gram-positive (56 Staphylococcus spp. and 33 Streptococcus spp.) PD-related peritonitis cases, were retrospectively enrolled. Clinical features, E. coli bacterial virulence, and outcomes were analyzed. Compared to Streptococcus spp. peritonitis, E. coli peritonitis had a higher peritoneal catheter removal rate (38 versus 12%; P =?0.0115). Compared to the monomicrobial group, patients in polymicrobial group were older and had higher peritoneal catheter removal rate (80 versus 38%; P =?0.0324). Treatment failure of E. coli peritonitis was associated with more polymicrobial peritonitis and immunocompromised comorbidity, longer duration of PD therapy, and more antimicrobial resistance. E. coli isolates with more iron-related genes had higher prevalence of phylogenetic group B2 and papG II, iha, ompT, and usp genes. This study demonstrates the important roles of clinical and bacterial characteristics in the outcomes of monomicrobial and polymicrobial E. coli PD-related peritonitis.     

Uropathogen distribution and antimicrobial susceptibility in uncomplicated cystitis in Belgium,a high antibiotics prescribing country: 20-year surveillance

Treatment of cystitis in primary care is usually empirical, guided by the prior probability of causal pathogens and their susceptibility. To re-evaluate empirical treatment guidelines, the actual distribution and susceptibility of uropathogens was examined and compared with two previous surveys in Belgium over the past 20 years. Because of the alarming increase in carriage of extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Escherichia coli, this specific resistance was explored. From May 2014 to December 2015, 120 general practitioners collected midstream urine specimens from adult pre- and postmenopausal female patients with suspected cystitis. A dipslide was inoculated and sent for microbiological analysis. Anal swabs were collected for ESBL and carbapenemase detection. Of 265 enrolled patients, 203 (79.3 %) had a positive culture. Escherichia coli (81.6 %) was the most frequently isolated uropathogen, followed by Staphylococcus saprophyticus (8 %), confirming the results of the 1995 and 2005 surveys. The susceptibility of E. coli remained nearly 100 % for nitrofurantoin and fosfomycin, decreased from nearly 100 % in 1995 to 94.2 % for quinolones, from 73.2 to 55.5 % for ampicillin, and from 83.3 to 76.3 % for trimethoprim–sulfamethoxazole (TMP-SMX). In E. coli present in positive urine cultures, ESBLs were found in 2.5 % and carbapenemases were absent. In fecal specimens, ESBL-producing E. coli were found in 7.9 % and carbapenemases were not detected. Over a 20-year period, the distribution of uropathogens in women with cystitis remained unchanged. Susceptibility remained excellent for nitrofurantoin and fosfomycin. For TMP-SMX, ampicillin, and quinolones, there was a decrease.     

Patterns and trends of pediatric bloodstream infections: a 7-year surveillance study

We characterize the epidemiology of pediatric bloodstream infections (BSIs) in Switzerland. We analyzed pathogen distribution and resistance patterns in monomicrobial and polymicrobial BSIs in children from 2008 to 2014 using data from the Swiss antibiotic resistance centre (ANRESIS). A confirmatory statistical analysis was performed comparing pathogens and resistance across 20 acute care hospitals. We identified 3,067 bacteremia episodes, of which 1,823 (59 %) were considered true BSI episodes. Overall, S. aureus (16.5 %, 300) was the most frequent pathogen, followed by E. coli (15.1 %, 276), coagulase-negative staphylococci (CoNS, 12.9 %, 235), S. pneumoniae (11.1 %, 202) and non-E. coli Enterobacteriaceae (8.7 %, 159). S. aureus and E. coli showed similar frequencies in all of the variables analyzed (e.g., hospital acquisition, hospital type, medical specialty). The proportion of these microorganisms did not change over time, resistance rates remained low (4.3 % methicillin resistance in S. aureus; 7.3 % third-/fourth-generation cephalosporin resistance in E. coli), and no significant resistance trends were observed. We observed a 50 % increase of CoNS BSIs from 2008 (9.8 %, 27) to 2014 (15.2 %, 46, p value for trend?=?0.03). S. pneumoniae decreased from 17.5 % (48) to 6.6 % (20) during that timeframe (p for trend?=?0.007). S. aureus and E. coli remained the most significant pathogens among pediatric BSIs in Switzerland, exhibiting low resistance rates. CoNS accounted for a greater proportion of BSIs over time. The decrease in bacteremic pneumococcal infections can likely be attributed to the introduction of the 13-valent conjugate vaccine in 2011.     

Distribution of common pathogens in patients with pyogenic liver abscess in China: a meta-analysis

Pyogenic liver abscess (PLA) is a potentially life-threatening disease in many parts of the world, especially in Asia. The aim of this study was to quantify the proportion of common pathogens in patients with PLA in China, using a meta-analysis method based on systematic review of published studies. Several electronic databases were searched to identify the studies reporting the pathogens of PLA. We performed a meta-analysis to calculate the pooled proportion of pathogens and subgroup analysis among the included studies using R 3.1.1 software. In total, 183 studies were included in our final analysis, Klebsiella spp (54 %), Escherichia spp (29 %), Enterobacter spp (9 %), Proteus spp (6 %) and Pseudomonas spp (5 %) comprised the major gram-negative bacteria. Gram-positive bacteria mainly included Staphylococcus spp (13 %), Streptococcus spp (8 %) and Enterococcus spp (7 %). The distribution of pathogens in PLA patients were different in different economic regions in China. The proportion of Klebsiella spp had an upward tendency in recent years compared to other pathogens. In addition, the proportion of common pathogens in PLA patients with diabetes mellitus (DM) were carried out indicating that the dominant pathogens were Klebsiella spp (66 %), Escherichia spp (21 %) and Enterobacter spp (11 %). This meta-analysis showed that the main pathogens of PLA were Klebsiella spp, Escherichia spp, Staphylococcus spp, and Enterobacter spp in China. To ensure a precise estimate of the epidemiology of the pathogens, further large-scale or even a population-based study is needed.     

Tetracycline use in the community may promote decreased susceptibility to quinolones in <Emphasis Type="Italic">Escherichia coli</Emphasis> isolates

We previously found that the hospital use of tetracyclines is associated with quinolone resistance in hospital isolates of Enterobacteriaceae. Tetracyclines are heavily used in the community. Our aim was to assess whether their use in the community favors quinolone resistance in community isolates of Escherichia coli. Monthly data of community antibiotics use and E. coli quinolone resistance in a 1.3 million inhabitant French area were obtained from 2009 to 2014, and were analyzed with autoregressive integrated moving average (ARIMA) models. Quinolone use decreased from 10.1% of the total antibiotic use in 2009 to 9.3% in 2014 (trend, ? 0.016; p-value < 0.0001), while tetracycline use increased from 16.5% in 2009 to 17.1% in 2014 (trend, 0.016; p < 0.0001). The mean (95% confidence interval) monthly proportions of isolates that were non-susceptible to nalidixic acid and ciprofloxacin were 14.8% (14.2%–15.5%) and 9.5% (8.8%–10.1%), respectively, with no significant temporal trend. After adjusting on quinolone use, tetracycline use in the preceding month was significantly associated with nalidixic acid non-susceptibility (estimate [SD], 0.01 [0.007]; p-value, 0.04), but not with ciprofloxacin non-susceptibility (estimate [SD], 0.01 [0.009]; p-value, 0.23). Tetracycline use in the community may promote quinolone non-susceptibility in E. coli. Decreasing both tetracycline and quinolone use may be necessary to fight against the worldwide growth of quinolone resistance.     

Intestinal microbiome as a risk factor for urinary tract infections in children

As urinary tract infection (UTI) pathogens originate from the gut, we hypothesized that the gut environment reflected by intestinal microbiome influences the risk of UTI. Our prospective case-control study compared the intestinal microbiomes of 37 children with a febrile UTI with those of 69 healthy children. We sequenced the regions of the bacterial 16S rRNA gene and used the LefSe algorithm to calculate the size of the linear discriminant analysis (LDA) effect. We measured fecal lactoferrin and iron concentrations and quantitative PCR for Escherichia coli. At the phylum level, there were no significant differences. At the genus level, Enterobacter was more abundant in UTI patients with an LDA score?>?3 (log 10), while Peptostreptococcaceae were more abundant in healthy subjects with an LDA score?>?3 (log 10). In total, 20 OTUs with significantly different abundances were observed. Previous use of antimicrobials did not associate with intestinal microbiome. The relative abundance of E. coli was 1.9% in UTI patients and 0.5% in controls (95% CI of the difference—0.8 to 3.6%). The mean concentration of E.coli in quantitative PCR was 0.14 ng/μl in the patients and 0.08 ng/μl in the controls (95% CI of the difference—0.04 to 0.16). Fecal iron and lactoferrin concentrations were similar between the groups. At the family and genus level, we noted several differences in the intestinal microbiome between children with UTI and healthy children, which may imply that the gut environment is linked with the risk of UTI in children.     

Activity of the novel siderophore cephalosporin cefiderocol against multidrug-resistant Gram-negative pathogens

The novel siderophore cephalosporin cefiderocol (S-649266) with potent activity against Gram-negative pathogens was recently developed (Shionogi & Co., Ltd.). Here, we evaluated the activity of this new molecule and comparators against a collection of previously characterized Gram-negative isolates using broth microdilution panels. A total of 753 clinical multidrug-resistant Gram-negative isolates collected from hospitals worldwide were tested against cefiderocol and antibiotic comparators (ceftolozane–tazobactam [CT], meropenem [MEM], ceftazidime [CAZ], ceftazidime–avibactam [CZA], colistin [CST], aztreonam [ATM], amikacin [AMK], ciprofloxacin [CIP], cefepime [FEP], and tigecycline [TGC]) for their susceptibility. The collection included Escherichia coli (n = 164), Klebsiella pneumoniae (n = 298), Enterobacter sp. (n = 159), Pseudomonas aeruginosa (n = 45), and Acinetobacter baumannii (n = 87). Resistance mechanisms included producers of carbapenemases and extended-spectrum β-lactamases (ESBLs). In addition, a series of colistin-resistant enterobacterial isolates (n = 74), including 15 MCR-1 producers, were tested. The MIC₉₀ of cefiderocol was 2 mg/L, while those of comparative drugs were >64 mg/L for CT, MEM, CAZ, CZA, and AMK, >32 mg/L for ATM, >16 mg/L for FEP, 8 mg/L for CST, and 2 mg/L for TGC. The MIC₅₀ of cefiderocol was 0.5 mg/L, while those of other drugs were >64 mg/L for CAZ, 64 mg/L for CT, >32 mg/L for ATM, >16 mg/L for FEP, 8 mg/L for MEM and AMK, >4 mg/L for CIP, 1 mg/L for CZA, 0.5 mg/L for TGC, and <0.5 mg/L for CST. Only 20 out of 753 strains showed MIC values of cefiderocol ≥8 μg/mL. Compared to the other drugs tested, cefiderocol was more active, with the exception of colistin and tigecycline showing equivalent activity against certain subgroups of bacteria.     

Clonal relationship between human and avian ciprofloxacin-resistant <Emphasis Type="Italic">Escherichia coli</Emphasis> isolates in North-Eastern Algeria

The objectives of this study were to determine rates, patterns, and mechanisms of antibiotic resistance, and to assess connections between chicken commensal, human commensal, and pathogenic ciprofloxacin-resistant Escherichia coli isolates. All E. coli isolates collected from chickens, their farmers, and patients in the Constantine region (North-east Algeria) were analyzed for bla and plasmid-mediated quinolone resistance (PMQR) gene contents, phylogroups, Rep-PCR profiles, and multilocus sequence types. A high prevalence of resistance to fluoroquinolones (51.4 % to ciprofloxacin) was recorded in avian isolates. Of these, 22.2 % carried the aac(6’)-Ib-cr gene, whereas lower resistance levels to these antibiotics were recorded in chicken farmers’ isolates. None of the commensal isolates harbored the qnr, qepA, or oqxAB genes. One human pathogenic isolate was ertapenem-resistant and harbored the bla _OXA-48 gene, 84 showed an extended-spectrum β-lactamase phenotype, with bla _CTX-M-15 gene prevalent in 87.2 % of them. Seventy isolates were resistant to fluoroquinolones, with aac(6’)-Ib-cr present in 72.8 %, qnrB in 5.7 %, and qnrS in 10 %. Three Rep-PCR profiles were common to chicken commensal and human pathogenic isolates (phylogroups D and B1; ST21, ST48, and ST471 respectively); one was found in both chicken and chicken-farmer commensal strains (D; ST108), while another profile was identified in a chicken-farmer commensal strain and a human pathogenic one (B1; ST19). These findings suggest clonal and epidemiologic links between chicken and human ciprofloxacin-resistant E. coli isolates and the important role that poultry may play in the epidemiology of human E. coli infections in the Constantine region.     

Characterization of carbapenem-resistant <Emphasis Type="Italic">Escherichia coli</Emphasis> and <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> from a healthcare region in Hong Kong

Carbapenem-resistant Enterobacteriaceae represents a major public health issue. This study investigated the clonality and resistance mechanisms of 92 carbapenem-resistant E. coli (n?=?21) and K. pneumoniae (n?=?71) isolates collected consecutively from clinical specimens and patients at high risk of carriage between 2010 and 2012 in a healthcare region in Hong Kong. Combined disk tests (CDTs) and the Carba NP test were used for phenotypic detection of carbapenemases. PCR assays were used to detect carbapenemase genes. All isolates were intermediate or resistant to at least one carbapenem. Nine (9.8 %) isolates were genotypic carbapenemase producers and included six K. pneumoniae (one ST1306/bla _IMP-4, one ST889/bla _IMP-4, two ST11/bla _KPC-2, one ST258/bla _KPC-2, one ST483/bla _NDM-1) and three E. coli (one ST131/bla _IMP-4, two ST744/ bla _NDM-1) isolates. All nine isolates carrying carbapenemase genes could be detected by the CDTs and the Carba NP test. PCR identified bla _CTX-M and bla _AmpC alone or in combination in 77.8 % (7/9) and 96.4 % (80/83) of the carbapenemase-producers and non-producers, respectively. Porin loss was detected in 22.2 % (2/9) and 59.0 % (49/83) of the carbapenemase-producers and non-producers, respectively. Overall, the E. coli clones were diverse (14 different STs), but 36.6 % (26/71) of the K. pneumoniae isolates belonged to ST11. In conclusion, the prevalence of carbapenemases among carbapenem-nonsusceptible E. coli and K. pneumoniae remained low in Hong Kong. Porin loss combined with AmpC and/or CTX-M type ESBL was the major mechanism of carbapenem resistance in the study population.     

Bloodstream infections caused by <Emphasis Type="Italic">Escherichia coli</Emphasis> producing AmpC β-lactamases: epidemiology and clinical features

The aim of the study was to investigate the epidemiology and clinical features of bloodstream infections due to Escherichia coli producing AmpC β-lactamases (AmpC-Ec-BSI). In a multi-centre case–control study, all third-generation-cephalosporin-resistant Escherichia coli BSI (3GC-Ec-BSI) isolates were analysed. Acquired bla _AmpC (bla _ac-AmpC) detection was done by polymerase chain reaction (PCR) and sequencing. Chromosomal bla _AmpC (bla _c-AmpC) expression was quantified by real-time PCR. Cases were patients with AmpC-Ec-BSI. Controls were patients with cephalosporin-susceptible E. coli BSI, matched 1:1 by sex and age. Demographics, comorbidities, intrinsic and extrinsic risk factors for antimicrobial resistance, clinical presentation and outcomes were investigated. Among 841 E. coli BSI, 17 were caused by AmpC-Ec (2 %). Eleven isolates (58.8 %) had bla _ac-AmpC and six were bla _c-AmpC overproducers. The mean age of cases was 66.2 years and 71 % were men. Cases were more frequently healthcare-related (82 vs. 52 % controls, p?<?0.05) and presented more intrinsic and extrinsic risk factors. At least one risk factor was present in 94.1 % of cases vs. 41.7 % of controls (p?=?0.002). Severity and length of stay (LOS) were higher among cases (mean Pitt Score 2.6 vs. 0.38 in controls, p?=?0.03; LOS 17.5 days vs. 6 in controls, p?=?0.02). Inappropriate empirical therapy (IET) was administered to 70.6 % of cases and 23.5 % of controls (p?<?0.003). No differences were found in terms of cure rate at the 14th day and mortality. Bloodstream infections due to AmpC-Ec (mostly plasmid-mediated) are infrequent in our area. AmpC-Ec-BSI affects mainly patients with intrinsic risk factors and those with previous antibiotic exposure. A high proportion received IET.     

Incidence and antimicrobial resistance trends in bloodstream infections caused by ESKAPE and <Emphasis Type="Italic">Escherichia coli</Emphasis> at a large teaching hospital in Rome,a 9-year analysis (2007–2015)

The proportion of antimicrobial resistance (AMR) among the ESKAPE and Escherichia coli (ESKAPEEc) pathogens causing bloodstream infection (BSI) increased worldwide. We described longitudinal trends in ESKAPEEc BSI and AMR over 9 years (2007–2015) at a large teaching hospital in Italy. Of 9720 unique BSI episodes, 6002 (61.7%) were caused by ESKAPEEc pathogens. The majority of these episodes (4374; 72.9%) were hospital-onset infections. The most frequent pathogen was E. coli (32.8%), followed by Staphylococcus aureus (20.6%), Klebsiella pneumoniae (16.1%), and Pseudomonas aeruginosa (11.6%). There was a significant increase of hospital-onset K. pneumoniae (from 2.3 to 5.0 per 10,000 patient-days; P =?0.001) and community-onset E. coli (from 3.3 to 9. 1 per 10,000 emergency admissions; P =?0.04) BSIs. Among hospital-onset BSIs, increases of extended-spectrum β-lactamase (ESBL)-producing E. coli (from 25.4 to 35.2%, P?= 0.006), carbapenemase-producing K. pneumoniae (from 4.2 to 51.6%, P <?0.001), and methicillin-resistant S. aureus (from 33.9 to 44.4%, P <?0.001) BSIs were observed between the 2007–2009 and 2010–2012 study periods. In contrast, a decrease of BSIs caused by P. aeruginosa resistant to ceftazidime (from 45.5 to 28.2%, P <?0.001), ciprofloxacin (from 46 to 36.3%, P =?0.05), and meropenem (from 55 to 39.9%, P =?0.03) was observed through all 9 years of the study period. Among community-onset BSIs, increases of BSIs caused by ESBL-producing E. coli (from 28.6 to 42.2%, P =?0.002) and carbapenemase-producing K. pneumoniae (from 0 to 17.6%) were observed between the 2007–2009 and 2010–2012 study periods. Our findings show increased rates of BSI and relative AMR for specific pathogen-health care setting combinations, and call for continued active surveillance and infection control policies.     

A Retrospective Study on the Efficacy of Trastuzumab in HER2-Positive and Tamoxifen-Refractory Breast Cancer with Brain Metastasis

Background and Objective

The role of trastuzumab in breast cancer with brain metastasis is still in discussion. This study was conducted to investigate the efficacy of trastuzumab in the management of human epidermal growth factor receptor 2 (HER2)–positive, tamoxifen-refractory breast cancer with brain metastasis.

Methods

This retrospective study was conducted between January 2008 and December 2012. A total of 33 patients receiving trastuzumab treatment for HER2-positive, tamoxifen-refractory breast cancer with brain metastasis were assigned to the experimental group, while a matched group of 35 patients who received systemic therapy without trastuzumab were assigned to the control group. Data on the patient characteristics and clinical outcomes were collected and evaluated.

Results

Patients in the trastuzumab group showed a significantly better response to treatment than those in the control group (p = 0.025). Univariate and multivariate Cox proportional regression analyses indicated that progression-free survival was significantly longer in patients receiving trastuzumab therapy than in the control group (hazard ratio [HR] 2.213 [p = 0.003] and HR 3.056 [p < 0.001], respectively) and significantly shorter in patients with two or more extracranial metastases (HR 0.417 [p = 0.002] and HR 0.317 [p < 0.001], respectively). Furthermore, patients on trastuzumab treatment experienced longer overall survival than patients in the control group (HR 2.844 [p < 0.001] and HR 4.017 [p < 0.001], respectively), while shorter overall survival was seen in patients with two or more extracranial metastases (HR 0.524 [p = 0.021] and HR 0.430 [p = 0.005], respectively) and in those receiving capecitabine-based therapy as compared with anthracycline-based therapy (HR 0.558 [p = 0.030] and HR 0.449 [p = 0.011], respectively).

Conclusion

Trastuzumab was found to benefit patients with HER2-positive, tamoxifen-refractory breast cancer with brain metastasis by improving progression-free and overall survival.

     

Time to positivity of blood culture and its prognostic value in bloodstream infection

The purpose of this study was to investigate the relationship between the time to positivity (TTP) of blood cultures and outcome in patients with bloodstream infections (BSIs). Between January 1st, 2011 and December 31st, 2013, the blood cultures of inpatients with BSI or catheter-related BSI were collected at Peking University Third Hospital. The TTP of different isolates was analyzed, and the relationship between the TTP of isolates and outcome of patients with Enterobacter BSI was retrospectively analyzed. We analyzed the TTP of 886 isolates. Escherichia coli has the shortest (11.97?±?10.06 h) and Candida has the longest first TTP (61.62?±?42.77 h). 68.01 % of isolates reached positivity within 24 h and 88.33 % within 48 h. Over 90 % of E. coli isolates reached positivity within 24 h. Over 50 % of Candida isolates reached positivity within 48 h. The TTP differed significantly between cultures that were single or double positive for coagulase-negative staphylococci isolates, Enterobacteriaceae, and Pseudomonas aeruginosa, and between aerobic and anaerobic cultures of E. coli (p?<?0.05). However, the TTP did not differ significantly between coagulase-negative staphylococci (double positivity) and Staphylococcus aureus. The best TTP threshold for prediction of mortality from Enterobacter species BSI was 16.3 h [area under the curve (AUC) 0.730, 95 % confidence interval (CI) 0.557, 0.864, sensitivity 100 %, specificity 44.4 %]. The TTP of clinical isolates may represent a valuable marker of the clinical significance of BSIs. Laboratories and clinics should consider using the TTP to predict the prognosis of patients with BSI by bacteria, including Enterobacter and other species.     

Role of topoisomerase mutations,plasmid mediated resistance (<Emphasis Type="Italic">qnr</Emphasis>) and acrAB efflux pump in fluoroquinolone resistant clinical isolates of avian <Emphasis Type="Italic">Escherichia coli</Emphasis>

Introduction

We investigated the role of topoisomerase mutations, increased level of the multidrug efflux pump AcrAB, and the plasmid-borne genes (qnr) in the fluoroquinolone (FQ) resistant avian Escherichia coli simultaneously.

Material and method

Here, we used four FQs (ciprofloxacin, enrofloxacin, ofloxacin and pefloxacin) and eight clinical isolates of E. coli containing six fluoroquinolone-resistant and two fluoroquinolone- susceptible. PCR and direct sequencing methods were used to detect the role of regulator/ repressor gene (acrR).

Objective

The objective of this study was to determine the relationship of these resistance mechanisms for fluoroquinolone resistance.

Result

The results showed that (i) all four fluoroquinolone- resistant isolates have topoisomerase mutation and plasmid borne genes qnrS and aac(6')-Ib; (ii) three FQ (enrofloxacin, ofloxacin and pefloxacin) resistant isolates harboring qnrS genes; (iii) two FQ (ciprofloxacin and pefloxacin) resistant isolates had topoisomerase mutation and plasmid borne gene qnrS; (iv) all fluoroquinolone susceptible were not harboring qnrS gene and topoisomerase mutation (v) All isolates were negative for qnrA and qnrB.

Conclusion

We found that FQs resistance combination was correlated with synergistically contribution of these resistance mechanisms. Plasmid mediated resistance by qnrS was correlated to pefloxacin resistance but did not correlate to ofloxacin, enrofloxacin and ciprofloxacin. This mechanism might be account for the pefloxacin resistance in avian E. coli.

     

Association between dementia and reduced walking ability and 30-day mortality in patients with extended-spectrum beta-lactamase-producing <Emphasis Type="Italic">Escherichia coli</Emphasis> bacteremia

Previous studies have shown controversial results of factors associated with short-term mortality in patients with extended-spectrum beta-lactamase (ESBL)-producing E. coli bacteremia and no research has investigated the impact of the geriatric assessment criteria on short-term mortality. Our objective was to determine whether dementia and walking ability are associated with 30-day mortality in patients with ESBL-producing E. coli bacteremia. All blood bottle cultures, analyzed from January 2008 to April 2015, in the Bacteriology Department of a 2,600-bed, university-affiliated center, Nantes, France, were retrospectively extracted. Factors associated with short-term mortality in patients with ESBL-producing E. coli bacteremia: 140 patients with an ESBL-producing E. coli bloodstream infection were included; 22 (15.7%) patients died within 30 days following the first positive blood bottle culture of ESBL-producing E.coli. In multivariate analysis, a reduced ability to walk (OR = 0.30; p = 0.021), presence of dementia (OR = 54.51; p = 0.040), a high Sepsis-related Organ Failure Assessment (SOFA) score (OR = 1.69; p < 0.001), presence of neutropenia (OR = 12.94; p = 0.049), and presence of a urinary tract infection (OR = 0.07; p = 0.036), were associated with 30-day mortality. Our findings provide new data showing an independent association between 30-day mortality with dementia and reduced walking ability, in patients with ESBL-producing E. coli bacteremia. These criteria should be considered in the therapeutic management of patients with ESBL-producing E. coli bacteremia.     

Innate immune evasion of <Emphasis Type="Italic">Escherichia coli</Emphasis> clinical strains from orthopedic implant infections

Escherichia coli is one of the first causes of Gram-negative orthopedic implant infections (OII). Those infections, usually hematogenous, mostly originate from the urinary tract. We investigated the strategies developed by E. coli in this context to evade host innate immune responses, i.e. complement and polymorphonuclear neutrophils (PMN). Twenty strains from OII were compared with 20 strains from bacteremia in patients with non-infected orthopedic implant. In both groups, 6/20 (30 %) strains lysed PMNs, due to the production of the pore-forming toxin α-hemolysin (HlyA). For the others, resistance to phagocytic killing by PMN was not significantly different between both groups. In contrast, resistance to complement-mediated serum killing was significantly higher in OII strains than in the others (65 % vs 10 %; P <0.001). In E. coli, different mechanisms have been involved in complement resistance. Here, serum resistance was not linked to a group 2 capsule, or a loss of outer membrane permeability, or the recruitment of the complement inhibitor C4bp, but was significantly associated with the synthesis of long-chain LPS, regardless of the O-antigen. Thus, serum resistance could promote seeding of peri-implant tissues by helping E. coli to either persist in blood and reach the site of infection or overcome localized complement activation.     

Using MALDI-TOF MS typing method to decipher outbreak: the case of <Emphasis Type="Italic">Staphylococcus saprophyticus</Emphasis> causing urinary tract infections (UTIs) in Marseille,France

Staphylococcus saprophyticus is one of the leading causes of urinary tract infections (UTI). In December 2014, our surveillance system identified an abnormal increase in S. saprophyticus causing UTIs in four university hospitals in Marseille, indicating a suspected community S. saprophyticus UTI outbreak. This was detected by our surveillance system BALYSES (Bacterial real-time Laboratory-based Surveillance System). S. saprophyticus/ Escherichia coli UTI ratio increased three-fold from 0.0084 in 2002 to 0.025 in December 2015 in Marseille with an abnormal peak in December 2014, and with an annual estimated ratio trend of 5.10^?6 (p-value < 10^?3). Matrix-Assisted Laser Desorption Ionisation-Time of Flight Mass Spectrometry (MALDI-TOF MS) spectral analysis of strains was used to analyse strains cluster expansion, comparing strains from Marseille to those from Nice during the same period. MALDI-TOF MS spectral analysis revealed a geographical restricted clonal expansion of the strains clusters in Marseille as compared to Nice. Our finding suggests (i) a geographically restricted expansion of a specific S. saprophyticus strain clusters circulating in Marseille, and (ii) MALDI-TOF MS can be used as a cost-effective tool to investigate an outbreak.