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• Seasonality in antimicrobial resistance (AMR) rates of community-acquired E. coli bloodstream isolates was examined. • E. coli isolates showed seasonal variation in AMR rates to four agents from frequently used classes in ambulatory settings. • The proportion of multidrug-resistant E. coli increased during peak of antimicrobial prescription in winter months. Seasonal variation in community antimicrobial consumption has been demonstrated, with the lowest utilisation rates during summer months. This retrospective cohort study examined seasonality in antimicrobial resistance (AMR) rates of community-acquired Escherichia coli bloodstream isolates. Escherichia coli bloodstream isolates (2010–2015) were identified through the central Palmetto Health microbiology laboratory database. Multivariate logistic regression was used to examine seasonal variation in AMR. Poisson regression was used to evaluate the association between proportion of multidrug-resistant (MDR) isolates and bimonthly ambulatory antimicrobial prescription rates. Among 339 unique patients with community-acquired E. coli bloodstream infection [median age 65 years; 205 (60.5%) female], AMR rates were lower during summer (June–September) than the rest of the year for amoxicillin/clavulanic acid (17% vs. 29%; aOR = 0.53, 95% CI 0.30–0.92; P = 0.02), cefazolin (6% vs. 19%; aOR = 0.26, 95% CI 0.10–0.58; P < 0.001), ceftriaxone (2% vs. 6%; aOR = 0.25, 95% CI 0.04–0.93; P = 0.04) and trimethoprim/sulfamethoxazole (9% vs. 27%; aOR = 0.27, 95% CI 0.13–0.53; P < 0.001). The proportion of MDR E. coli declined from 31–36% during peak antimicrobial prescription to 11–14% in summer months; a 6.8% decline per interval decrease in antimicrobial prescription rates of 10/100 person-years (P = 0.01). There is significant seasonal variation in AMR rates of E. coli bloodstream isolates to four agents from frequently utilised antimicrobial classes in the community. Examination of seasonal variation in dominant serotypes of community-acquired E. coli bloodstream isolates in future will be valuable. [ABSTRACT FROM AUTHOR]

In this study, the therapeutic efficacy of cefazolin was compared with that of extended-spectrum cephalosporins (ESCs) (cefotaxime, ceftriaxone and ceftazidime) as appropriate empirical therapy in adults with community-onset monomicrobial bacteraemia caused by Escherichia coli , Klebsiella spp. or Proteus mirabilis (EKP). Compared with cefazolin-treated patients ( n  = 135), significantly higher proportions of patients in the ESC treatment group ( n  = 456) had critical illness at bacteraemia onset (Pitt bacteraemia score ≥4) and fatal co-morbidities (McCabe classification). Of the 591 patients, 121 from each group were matched using propensity score matching (PSM) based on the following independent predictors of 28-day mortality: fatal co-morbidities (McCabe classification); Pitt bacteraemia score ≥4 at bacteraemia onset; initial syndrome of septic shock; and bacteraemia due to pneumonia. After appropriate PSM, no significant differences were observed in the early clinical failure rate (10.7% vs. 7.4%; P  = 0.37), the proportion of critical illness (Pitt bacteraemia score ≥4) (0% vs. 0%; P  = 1.00) and defervescence (52.6% vs. 42.6%; P  = 0.13) on Day 3 between the cefazolin and ESC treatment groups. Similarly, no significant differences were observed in the mean of time to defervescence (4.1 days vs. 4.9 days; P  = 0.15), late clinical failure rate (18.2% vs. 10.7%; P  = 0.10) and 28-day crude mortality rate (0.8% vs. 3.3%; P  = 0.37) between the two groups. These data suggest that the efficacy of cefazolin is similar to that of ESCs when used as appropriate empirical antimicrobial treatment for community-onset EKP bacteraemia. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the evolution with time of ceftiofur-resistant Escherichia coli clinical isolates from pigs in Québec, Canada, between 1997 and 2012 with respect to pathotypes, clones and antimicrobial resistance. Eighty-five ceftiofur-resistant E. coli isolates were obtained from the OIE (World Organisation for Animal Health) Reference Laboratory for Escherichia coli . The most prevalent pathovirotypes were enterotoxigenic E. coli (ETEC):F4 (40%), extraintestinal pathogenic E. coli (ExPEC) (16.5%) and Shiga toxin-producing E. coli (STEC):F18 (8.2%). Susceptibility testing to 15 antimicrobial agents revealed a high prevalence of resistance to 13 antimicrobials, with all isolates being multidrug-resistant. bla CMY-2 (96.5%) was the most frequently detected β-lactamase gene, followed by bla TEM (49.4%) and bla CTX-M (3.5%). Pulsed-field gel electrophoresis (PFGE) applied to 45 representative E. coli isolates revealed that resistance to ceftiofur is spread both horizontally and clonally. In addition, the emergence of extended-spectrum β-lactamase-producing E. coli isolates carrying bla CTX-M was observed in 2011 and 2012 in distinct clones. The most predominant plasmid incompatibility (Inc) groups were IncFIB, IncI1, IncA/C and IncFIC. Resistance to gentamicin, kanamycin and chloramphenicol as well as the frequency of bla TEM and IncA/C significantly decreased over the study period, whereas the frequency of IncI1 and multidrug resistance to seven antimicrobial categories significantly increased. These findings reveal that extended-spectrum cephalosporin-resistant porcine E. coli isolates in Québec belong to several different clones with diverse antimicrobial resistance patterns and plasmids. Furthermore, bla CMY-2 was the major β-lactamase gene in these isolates. From 2011, we report the emergence of bla CTX-M in distinct clones. [ABSTRACT FROM AUTHOR]

Escherichia coli recovered from three hospitals in Barcelona (Spain) were studied to determine the prevalence of isolates with acquired AmpC (ac-AmpC) and/or overproduced chromosomal AmpC (c-AmpC). Mechanisms involved in bla c-AmpC overexpression, bla ac-AmpC and the plasmids associated with their distribution as well as the prevalence of plasmid-mediated quinolone resistance (PMQR) in AmpC-producing isolates were also determined. Isolates were selected according to their resistance phenotype. bla ac-AmpC , alterations in the bla c-AmpC promoter/attenuator, and PMQR genes [ qnrA , qnrB , qnrS , aac(6′)-Ib -cr and qepA ] were characterised by PCR and sequencing. bla c-AmpC expression was determined by qRT-PCR. Population structure analysis was performed using PFGE, MLST and phylogenetic group PCR. Plasmids carrying bla ac-AmpC were characterised by PCR-based replicon typing and S1-PFGE. IncI1 and IncF plasmids were also analysed by plasmid MLST and replicon sequence typing, respectively. Among 21 563 E. coli isolates, 240 (1.1%) overproduced AmpC β-lactamases, including 180 (75.0%) harbouring ac-AmpC (132 CMY-2 variants and 48 DHA-1) and 60 (25.0%) c-AmpC enzymes. Three mutation profiles in the bla c-AmpC promoter/attenuator were associated with a 72.5-, 19.9- and 5.8-fold increased expression, respectively. Moreover, 63.3% of ac-AmpC and 43.3% of c-AmpC isolates belonged to B2, D, E or F phylogenetic groups. PMQR was found in 31% of ac-AmpC isolates [38 qnrB4 , 8 aac(6′)-Ib -cr, 6 qnrS1 and 3 qnrB19 ] and in 10% of c-AmpC isolates [5 aac(6′)-Ib -cr and 1 qnrS1 ]. IncI1-ST12 and IncF were associated with bla CMY-2 and bla DHA-1 , respectively. These results suggest that ac-AmpC β-lactamases were the main mechanism of AmpC production. Isolates and plasmids both showed high genetic diversity. [ABSTRACT FROM AUTHOR]

Abstract: This study aimed to detect and characterise clinical Escherichia coli isolates suspected of carrying chromosomally encoded CTX-M enzymes. Escherichia coli (n =356) obtained in Germany, The Netherlands and the UK (2005–2009) and resistant to third-generation cephalosporins were analysed for the presence of ESBL-/AmpC-encoding genes within the European SAFEFOODERA-ESBL project. β-Lactamases and their association with IS26 and ISEcp1 were investigated by PCR. Isolates were typed by phylogenetic grouping, MLST and PFGE. Plasmids were visualised by S1 nuclease PFGE, and the location of bla CTX-M genes was determined by Southern hybridisation of XbaI-, S1- and I-CeuI-digested DNA. ESBL enzymes could not be located on plasmids in 17/356 isolates (4.8%). These 17 isolates, from different countries and years, were ascribed to phylogenetic groups D (9), B2 (6) and B1 (2), and to seven sequence types, with ST38 being the most frequent (7 phylogroup D isolates). Eleven isolates produced CTX-M-15. bla CTX-M-15 genes were associated with ISEcp1. The remaining isolates expressed the CTX-M group 9 β-lactamases CTX-M-14 (4), CTX-M-9 (1) and CTX-M-51 (1). bla CTX-M probes hybridised with I-CeuI- and/or XbaI-digested DNA, but not with S1-digested DNA, corroborating their chromosomal location. To summarise, only 4.8% of a large collection of ESBL-producing E. coli isolates harboured chromosomal bla CTX-M genes. These isolates were of human origin and belonged predominantly to ST38 and ST131, which possibly indicates the role of these sequence types in this phenomenon. However, heterogeneity among isolates was found, suggesting that their spread is not only due to the dispersion of successful E. coli clones. [Copyright &y& Elsevier]

Abstract: Based on the new recommendations of the Clinical and Laboratory Standards Institute (CLSI), the revised cephalosporin breakpoints may result in many CTX-M-producing Escherichia coli being reported as susceptible to ceftazidime. We determined the activity of ceftazidime and other parenteral β-lactam agents in standard- and high-inoculum minimum inhibitory concentration (MIC) tests against CTX-M-producing E. coli isolates. Antimicrobial susceptibility was determined using a broth microdilution MIC method with inocula that differed 100-fold in density. An inoculum effect was defined as an eight-fold or greater increase in MIC on testing with the higher inoculum. When the revised CLSI ceftazidime breakpoint of 4μg/mL was applied, 34 (34.3%) of the 99 CTX-M-producers tested were susceptible. More specifically, for 42 CTX-M-14-producing E. coli isolates, 32 (76.2%) were susceptible at 4μg/mL. Cefotaxime, ceftazidime, cefepime and piperacillin/tazobactam were found to be associated with inoculum effects in 100% of the evaluable tests for extended-spectrum β-lactamase-producing E. coli isolates. The MIC50 (MIC required to inhibit 50% of isolates) of ceftazidime was 16μg/mL in the standard-inoculum tests and >512μg/mL in the high-inoculum tests. In the high-inoculum tests including isolates encoding CTX-M-14, ceftazidime was dramatically affected, with susceptibility decreasing from 82.1% of isolates inhibited at 4μg/mL in the standard-inoculum tests to 0% at high inoculum. Although further studies may demonstrate that ceftazidime has a role in the treatment of infections caused by these organisms, we suggest that until more data become available, clinicians should be cautious about treating serious CTX-M-producing E. coli infections with ceftazidime or cefepime. [Copyright &y& Elsevier]

Abstract: The aim of this study was to uncover the mechanisms underlying Shigella flexneri resistance to cefalothin. In this study, a resistance-related S. flexneri isolate, S. flexneri YDC, was obtained from S. flexneri mel-1998023/zz pre-incubated with cefalothin at a dose of 0.5× the minimum inhibitory concentration. The ISEcp1 coding element was identified upstream of bla CTX-M-55 in S. flexneri YDC. To further determine the role of ISEcp1 in S. flexneri resistance, plasmids containing bla CTX-M-55 recombinant with or without the ISEcp1 sequence were constructed and named as pCTX and pISECTX, respectively. It was shown that Escherichia coli DH5α(pISECTX) was resistant to all β-lactams tested. In contrast, E. coli DH5α(pCTX) was sensitive to all except β-lactams cefazolin and cefalothin. In addition, reverse transcription PCR showed that expression levels of bla CTX-M-55 were higher in E. coli DH5α(pISECTX). The Clinical and Laboratory Standards Institute (CLSI) assay demonstrated that extended-spectrum β-lactamase was only positively detected in E. coli DH5α(pISECTX) but not in E. coli DH5α(pCTX). Taken together, these results suggest that the translocated ISEcp1 element upstream of bla CTX-M-55 is required for overexpression of bla CTX-M-55, leading to cephalosporin resistance. [Copyright &y& Elsevier]

Abstract: Early appropriate antibiotic treatment reduces mortality in severe sepsis, but current methods to identify antibiotic resistance still generally rely on bacterial culture. Modern diagnostics promise rapid gene detection, but the apparent diversity of relevant resistance genes in Enterobacteriaceae is a problem. Local surveys and analysis of publicly available data sets suggested that the resistance gene pool is dominated by a relatively small subset of genes, with a very high positive predictive value for phenotype. In this study, 152 Escherichia coli and 115 Klebsiella pneumoniae consecutive isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum inhibitory concentration (MIC) of ≥2μg/mL were collected from seven major hospitals in Sydney (Australia) in 2008–2009. Nearly all of those with a MIC in excess of European Committee on Antimicrobial Susceptibility Testing (EUCAST) resistance breakpoints contained one or more representatives of only seven gene types capable of explaining this phenotype, and this included 96% of those with a MIC≥2μg/mL to any one of these drugs. Similarly, 97% of associated gentamicin-non-susceptibility (MIC≥8μg/mL) could be explained by three gene types. In a country like Australia, with a background prevalence of resistance to third-generation cephalosporins of 5–10%, this equates to a negative predictive value of >99.5% for non-susceptibility and is therefore suitable for diagnostic application. This is an important proof-of-principle that should be tested in other geographic locations. [Copyright &y& Elsevier]

Abstract: We examined the effect of applying the updated 2010 Clinical and Laboratory Standards Institute (CLSI) susceptibility breakpoints for extended-spectrum cephalosporins (ESCs) to detect extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. In total, 202 ESBL-producing, plasmidic AmpC- and carbapenemase-negative isolates derived from separate patients were collected from three Greek hospitals during 2007–2011, including 150 Escherichia coli, 43 Klebsiella pneumoniae and 9 Enterobacter cloacae clinical isolates. ESBLs were detected using the ESBL CLSI confirmatory test and PCR assays. Sequencing analysis showed that 91 (45.0%) of the ESBL-producers carried the bla CTX-M-3 gene, 66 (32.7%) carried the bla CTX-M-15 gene and the remaining 45 (22.3%) carried the bla SHV-5 gene. Minimum inhibitory concentrations for cefotaxime, ceftazidime and cefepime were determined by the agar dilution method. Based on the new CLSI breakpoints, 13 (6.4%) of the ESBL-producers were susceptible to cefotaxime, 90 (44.6%) to ceftazidime and 112 (55.4%) to cefepime; as many as 145 (71.8%) were susceptible to at least one ESC. Among the 150 E. coli, 12 (8.0%), 87 (58.0%) and 79 (52.7%) were susceptible to cefotaxime, ceftazidime and cefepime, respectively, whilst among the 43 K. pneumoniae, 1 (2.3%), 3 (7.0%) and 25 (58.1%) were susceptible to the above ESCs, respectively. None of the nine E. cloacae were susceptible to cefotaxime and ceftazidime, but all except one were susceptible to cefepime. By implementation of the new 2010 CLSI breakpoints, a considerable proportion of ESBL-possessing Enterobacteriaceae would be reported as susceptible, mostly to ceftazidime and cefepime, leading to possible infection control and therapeutic implications. [Copyright &y& Elsevier]

Abstract: In 2010, a total of 1327 clinical Escherichia coli isolates from five hospitals in the Kyoto and Shiga regions of Japan were analysed by PCR. The prevalences of plasmid-mediated AmpC β-lactamase (pAmpC)-producers, extended-spectrum β-lactamase (ESBL)-producers and co-producers of pAmpC and ESBL were 1.7%, 9.7% and 0.3%, respectively. Less than one-half of the pAmpC-producers were reported to be resistant to third-generation cephalosporins, cephamycins and β-lactam/β-lactam inhibitors using the old 2009 Clinical and Laboratory Standards Institute (CLSI) breakpoints. CMY-2 was the most prevalent pAmpC type (95%), and CTX-M-14 (38%), CTX-M-15 (26%) and CTX-M-27 (19%) were the most prevalent ESBL types. The worldwide O25b-ST131-B2 clone accounted for 11% of pAmpC-producers and 41% of ESBL-producers. The O25b-ST131-B2 clone was characterised by a CTX-M-27- or CTX-M-15-type ESBL and ciprofloxacin-non-susceptibility with quadruple mutations in the quinolone resistance-determining regions (S83L and D87N in GyrA and S80I and E84V in ParC). A significant proportion of pAmpC-producers and the O25b-ST131-B2 clone were found in Japan by a recent regional surveillance programme. [Copyright &y& Elsevier]

Abstract: This study determined the antimicrobial susceptibility of Escherichia coli causing community-acquired, acute, uncomplicated, non-recurrent urinary tract infection in unselected women aged 18–65 years and compared the results with those obtained 8 years earlier in the first ECO·SENS study (1999–2000). During 2007–2008, urine samples were taken from 1697 women in Austria, Greece, Portugal, Sweden and the UK. The countries were chosen to represent areas of Europe indicated to have more (Greece and Portugal) or less (UK, Austria and Sweden) problems with resistance. Antimicrobial susceptibility testing of 903 E. coli isolates (150–200 isolates per country) to 14 antimicrobials was performed by disk diffusion using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. In E. coli, resistance to mecillinam, cefadroxil (representing oral cephalosporins), nitrofurantoin, fosfomycin trometamol, gentamicin and the third-generation cephalosporins cefotaxime and ceftazidime was <2%, with the following exceptions: gentamicin in Portugal (2.8%); fosfomycin in Greece (2.9%); and cephalosporins in Austria (2.7–4.1%). Resistance levels were higher for amoxicillin/clavulanic acid (2.0–8.9%) and ciprofloxacin (0.5–7.6%) and much higher to ampicillin (21.2–34.0%), sulfamethoxazole (21.2–31.3%), trimethoprim (14.9–19.1%) and trimethoprim/sulfamethoxazole (14.4–18.2%). Resistance to quinolones and trimethoprim increased between the ECO·SENS I (1999–2000) and ECO·SENS II (2007–2008): nalidixic acid 4.3% to 10.2%; ciprofloxacin 1.1% to 3.9%; and trimethoprim 13.3% to 16.7%. In the previous study, no isolates with extended-spectrum β-lactamase were found; however, in the present study 11 isolates were identified as having either CTX-M or AmpC. [Copyright &y& Elsevier]

Abstract: Oral cephalosporins and mecillinam are used to treat Shigella infections, but are compromised by extended-spectrum β-lactamases (ESBLs) and plasmid AmpC β-lactamases. Potential solutions include combining an oral or intravenous cephalosporin with a β-lactamase inhibitor (BLI) or using an oral penem. These strategies were examined using Escherichia coli transconjugants and clinical isolates with ESBLs or AmpC, as a proxy for shigellae. The Clinical and Laboratory Standards Institute agar dilution method was used with inocula of 104 and 106 colony-forming units/spot. ESBLs conferred resistance to the cephalosporins and mecillinam, at least at high inoculum, although: (i) ceftibuten was significantly compromised only by SHV and CTX-M-15 ESBLs, but not by TEM or CTX-M-9 and -14; (ii) cefdinir was little affected by TEM-type ESBLs, and mecillinam was little affected by CTX-M-9 group enzymes. The BLI clavulanic acid reduced the minimum inhibitory concentrations (MICs) of cephalosporins and mecillinam to ≤2mg/L for ESBL-producers, even at high inocula; sulbactam in particular and tazobactam were less effective, especially against SHV types. Strains with AmpC were resistant to all cephalosporins±inhibitors, but mecillinam remained active (MIC=1mg/L) against a strain with AmpC alone, whereas strains with TEM-1+AmpC were susceptible to mecillinam+clavulanic acid at ≤2mg/L. Faropenem was active against all ESBL- and AmpC-producers at 4mg/L, with little inoculum effect or inhibitor potentiation. In conclusion, cephalosporin+clavulanic acid combinations overcame ESBLs, with ceftibuten+clavulanic acid being particularly promising. Mecillinam+clavulanic acid and faropenem overcame both ESBLs and AmpC enzymes. Clinical utility will depend also on a drug''s ability to reach intracellular shigellae in the intestinal epithelium and this deserves exploration for clavulanic acid and faropenem. [Copyright &y& Elsevier]

Abstract: The aim of the present study was to investigate whether replacement of broad-spectrum cephalosporins (CEPs) by piperacillin/tazobactam (TZP) as first-line empirical therapy may have an effect on β-lactam resistance among Klebsiella pneumoniae and Escherichia coli in a tertiary care hospital. Data regarding CEP and TZP consumption and resistance were collected on a bimonthly basis during an open-label 2-year (1 year observational and 1 year interventional) study. Consumption of ceftazidime was reduced by 64.5%. In contrast, consumption of the other third-generation CEPs (cefotaxime and ceftriaxone) remained almost stable, whereas an increase in consumption of TZP by 2.8-fold was observed. A significant decrease in resistance to third-generation cephalosporins among K. pneumoniae isolates was observed, and the incidence of extended-spectrum β-lactamase-producing isolates was notably reduced. These findings were less evident among E. coli isolates. Despite the significant increase in TZP consumption, the respective resistance rates of both bacterial species examined have remained almost unchanged. [Copyright &y& Elsevier]

Abstract: Three Escherichia coli isolates resistant to third-generation cephalosporins but negative for extended-spectrum β-lactamase production were isolated from hospitalised patients in Zagreb, Croatia, during June 2003 to February 2004. Resistance was due to the inducible production of a DHA-1 cephalosporinase. Each isolate contained an integron-associated bla DHA-1–ampR sequence carried by similar-sized plasmids, of which one was self-transferable. Serotyping and polymerase chain reaction typing using ERIC2 primer indicated that the isolates were distinct. This is the first description of DHA β-lactamase production in E. coli. [Copyright &y& Elsevier]

Abstract: Bacteria harbouring extended-spectrum β-lactamases (ESBLs), derived by mutation from TEM-1, TEM-2 or SHV-1 β-lactamases, have been described world-wide. The in vitro activities of these enzymes against β-lactam antibiotics, including oral cephalosporins, are well recognised. The aim of this investigation was to assess the bactericidal activity of oral β-lactam antibiotics available in Croatia (amoxicillin/clavulanate, cephalexin, cefuroxime, cefadroxil and ceftibuten), in biological fluids against isogenic Escherichia coli strains producing broad-spectrum (TEM-1, TEM-2 and SHV-1) and extended-spectrum β-lactamases (SHV-2, SHV-3, SHV-4, SHV-5, SHV-12). Bactericidal activity of oral β-lactams in plasma and urine was tested in time-kill experiments and by determining bactericidal titres at different time intervals post-dose. The killing rate of antibiotics in urine was slower than in plasma, but faster than in Mueller–Hinton broth. High bactericidal titres in urine were only maintained throughout the whole dosing interval by ceftibuten against strains producing broad-, SHV-2 and SHV-3 β-lactamases. The older generation cephalosporins can be considered for the therapy of urinary tract infections caused by E. coli harbouring TEM-1, TEM-2 and SHV-1 β-lactamases but a shorter dosing interval is needed. Ceftibuten can be recommended with caution in ESBL producing E. coli except those producing SHV-4, SHV-5 and SHV-12 that confer resistance to it. If these enzymes are produced, fluoroquinolones or carbapenems could be considered. [Copyright &y& Elsevier]

Abstract: Cefdinir is an oral cephalosporin approved by the US Food and Drug Administration in 1997 for the treatment of community-acquired (CA) respiratory tract and uncomplicated skin and soft tissue infections. The objective of the present study was to evaluate the in vitro activity of cefdinir against recent clinical isolates collected from CA-urinary tract infections (UTIs), a possible expanded indication. A total of 456 isolates from CA-UTI were collected from medical centres in North America (NA; United States and Canada) in 2003 and susceptibility tested by NCCLS reference broth microdilution methods. Cefdinir and cefpodoxime were the most active compounds tested against Escherichia coli (98.7% susceptibility), followed by nitrofurantoin (97.0%) and ciprofloxacin (95.0%). Cefdinir was 8- to 16-fold more potent than cefuroxime axetil and cefprozil against E. coli, Klebsiella spp. and Staphylococcus saprophyticus. The activity of cefdinir was most similar to that of cefpodoxime against E. coli and Klebsiella spp., but cefpodoxime showed inferior activity against S. saprophyticus. The cefdinir spectrum was significant superior (+3.8 to 16.5%) to that of trimethoprim/sulphamethoxazole against all pathogens evaluated. The cefdinir spectrum and potency were comparable or superior to other orally administered β-lactams tested against recent (2003) clinical isolates from CA-UTI. [Copyright &y& Elsevier]

• Third-generation cephalosporin (3GC) resistance of community E. coli significantly decreased in France from 2015 to 2017. • 3GC and quinolone consumption significantly decreased in the French community. • Reducing antibiotic consumption is not instantly followed by a decrease in antimicrobial resistance. Since the early 2000s, Escherichia coli resistance to third-generation cephalosporins (3GCs) has been increasing in all European countries, mainly due to the spread of extended spectrum β-lactamases (ESBLs). Here we present a retrospective study that combines resistance of E. coli to 3GCs and quinolones with data on antibiotic use in the community in a region of Northeastern France. Since 2012, an observational surveillance of antimicrobial resistance and antibiotic use in the community was conducted: data on antimicrobial resistance in E. coli isolates were collected from 11 private laboratories, and consumption data were collected from the three main healthcare insurances. A significant decrease in the prevalence of resistance to 3GCs (from 5.6% to 4.2%; P < 0.001), nalidixic acid (from 16.7% to 14.8%; P = 0.004) and ciprofloxacin (from 10.9% to 8.1%; P < 0.001) was reported between 2015 and 2017. Although total antibiotic consumption did not vary significantly between 2012 and 2017, a decrease in the consumption of 3GCs (–32.%; P < 0.001) and quinolones (–25.5%; P < 0.001) was observed. Here we report a decrease in the prevalence of E. coli isolates resistant to 3GCs and quinolones in outpatients in the context of significant decreasing consumption of these two antibiotic classes. [ABSTRACT FROM AUTHOR]

• Bacteria can be resistant to piperacillin-tazobactam (TZP) but susceptible to cephalosporins (TZP-R/Ceph3-S) • TEM-1 hyperproduction causes in vitro TZP-R among Escherichia coli • Increasing tazobactam restores TZP susceptibility of TEM-1 hyperproducers • TZP humanized regimen showed efficacy against TZP-R/Ceph3-S in a septicemia model We previously reported the detection of Escherichia coli and Klebsiella pneumoniae that displayed in vitro piperacillin-tazobactam (TZP) resistance but were susceptible to third-generation cephalosporins (TZP-R/Ceph3-S). In this study, we assessed the phenotypic and genotypic profiles of 12 clinical non-clonal TZP-R/Ceph3-S E. coli and K. pneumoniae isolates derived from bloodstream infections. Whole-genome sequencing revealed that most of the TZP-R/Ceph3-S E. coli and K. pneumoniae isolates examined harbored bla TEM-1 and bla SHV-1 genes, respectively, but none harbored extended-spectrum β-lactamase, AmpC β-lactamase or carbapenemase genes. Increasing the tazobactam concentration from 4 mg/L to 16 mg/L restored TZP in vitro susceptibility among E. coli isolates expressing TEM-1, but had minimal impact on the susceptibility of K. pneumoniae to TZP. Real-time qPCR analysis showed that bla TEM-1 expression was amplified in TZP-R E. coli upon incubation with sub-inhibitory TZP concentrations. Using an immunocompetent murine septicemia model, the efficacy of TZP against TZP-R/Ceph3-S isolates was assessed using TZP doses that mimicked human plasma exposures following intravenous (IV) administration of TZP 4.5 g q6h over 0.5 h for 24 h. Efficacy was assessed by survival through 96 h. There was high mortality in untreated control mice for all tested isolates. Compared with controls, TZP human-simulated exposure significantly improved survival for all TZP-R/Ceph3-S E. coli and K. pneumoniae isolates examined (P < 0.05). Thus, TZP was associated with remarkable in vivo activity against TZP-R/Ceph3-S E. coli and K. pneumoniae despite the observed resistance in vitro. [ABSTRACT FROM AUTHOR]

Summary: This study examined the rates of susceptibility to third-generation cephalosporins and carbapenems among Enterobacteriaceae isolates that had been obtained from patients with intraabdominal infections in the Asia-Pacific region as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). Susceptibility profiles obtained using 2009 Clinical and Laboratory Standards Institute (CLSI) breakpoints were compared with those obtained using the 2011 CLSI breakpoints. From 2002 to 2010, Escherichia coli and Klebsiella pneumoniae together accounted for more than 60% of the 13714 Enterobacteriaceae isolates analyzed during the study period. Extended-spectrum β-lactamase (ESBL) producers comprised 28.2% of E. coli isolates and 22.1% of K. pneumoniae isolates in the Asia-Pacific region, with China (55.6% and 33.7%, respectively) and Thailand (43.1% and 40.7%, respectively) having the highest proportions of ESBL producers. Based on the 2011 CLSI criteria, 77.2% of the Enterobacteriaceae isolates, 40.4% of ESBL-producing E. coli, and 25.2% of ESBL-producing K. pneumoniae isolates were susceptible to ceftazidime. Carbapenems showed in vitro activity against >90% of Enterobacteriaceae isolates in all participating countries, except for ertapenem in South Korea (susceptibility rate 82.2%). Marked differences (>5%) in susceptibility of ESBL-producing E. coli and K. pneumoniae isolates to carbapenems were noted between the profiles obtained using the 2009 CLSI criteria and those using the 2011 CLSI criteria. Continuous monitoring of antimicrobial resistance is necessary in the Asia-Pacific region. [ABSTRACT FROM AUTHOR]