Antimicrobial Resistance in Escherichia coli

19/07/2018

Multidrug resistance in Escherichia coli has become a worrying issue that is increasingly observed in human but also in veterinary medicine worldwide. E. coli is intrinsically susceptible to almost all clinically relevant antimicrobial agents, but this bacterial species has a great capacity to accumulate resistance genes, mostly through horizontal gene transfer. The most problematic mechanisms in E. coli correspond to the acquisition of genes coding for extended-spectrum β-lactamases (conferring resistance to broad-spectrum cephalosporins), carbapenemases (conferring resistance to carbapenems), 16S rRNA methylases (conferring pan-resistance to aminoglycosides), plasmid-mediated quinolone resistance (PMQR) genes (conferring resistance to [fluoro]quinolones), and mcr genes (conferring resistance to polymyxins). Although the spread of carbapenemase genes has been mainly recognized in the human sector but poorly recognized in animals, colistin resistance in E. coli seems rather to be related to the use of colistin in veterinary medicine on a global scale. For the other resistance traits, their cross-transfer between the human and animal sectors still remains controversial even though genomic investigations indicate that extended-spectrum β-lactamase producers encountered in animals are distinct from those affecting humans. In addition, E. coli of animal origin often also show resistances to other—mostly older—antimicrobial agents, including tetracyclines, phenicols, sulfonamides, trimethoprim, and fosfomycin. Plasmids, especially multiresistance plasmids, but also other mobile genetic elements, such as transposons and gene cassettes in class 1 and class 2 integrons, seem to play a major role in the dissemination of resistance genes. Of note, coselection and persistence of resistances to critically important antimicrobial agents in human medicine also occurs through the massive use of antimicrobial agents in veterinary medicine, such as tetracyclines or sulfonamides, as long as all those determinants are located on the same genetic elements

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Genetic and Functional Characterization of an MCR-3-Like Enzyme-Producing Escherichia coli Isolate Recovered from Swine in Brazil

12/07/2018

A collection of 126 pigs was screened for carriage of colistin-resistant Enterobacteriaceae in a farm in Minas Gerais, Brazil. Out of this collection, eight colistin-resistant Escherichia coli isolates were recovered, including one from Minas Gerais State producing a new MCR-3 variant (MCR-3.12). Analysis of the lipopolysaccharide revealed that MCR-3.12 had a function similar to that of MCR-1 and MCR-2 as a result of the addition of a phosphoethanolamine group to the lipid A moiety. Genetic analysis showed that the mcr-3.12 gene was carried by an IncA/C2 plasmid and was embedded in an original genetic environment. This study reports the occurrence of the MCR-3-like determinant in South America and is the first to demonstrate the functionality of this group of enzymes as a phosphoethanolamine transferase nara ch

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Complete Genome Sequencing of Acinetobacter baumannii Strain K50 Discloses the Large Conjugative Plasmid pK50a Encoding Carbapenemase OXA-23 and Extended-Spectrum -Lactamase GES-11

29/05/2018

Multidrug-resistant (MDR) Acinetobacter baumannii strains appeared as serious emerging nosocomial pathogens in clinical environments and especially in intensive care units (ICUs). A. baumannii strain K50, recovered from a hospitalized patient in Kuwait, exhibited resistance to carbapenems and additionally to ciprofloxacin, chloramphenicol, sulfonamides, amikacin, and gentamicin. Genome sequencing revealed that the strain possesses two plasmids, pK50a (79.6 kb) and pK50b (9.5 kb), and a 3.75-Mb chromosome. A. baumannii K50 exhibits an average nucleotide identity (ANI) of 99.98% to the previously reported Iraqi clinical isolate AA-014, even though the latter strain lacked plasmid pK50a. Strain K50 belongs to sequence type 158 (ST158) (Pasteur scheme) and ST499 (Oxford scheme). Plasmid pK50a is a member of the Aci6 (replication group 6 [RG6]) group of Acinetobacter plasmids and carries a conjugative transfer module and two antibiotic resistance gene regions. The transposon Tn2008 carries the carbapenemase gene blaOXA-23, whereas a class 1 integron harbors the resistance genes blaGES-11, aacA4, dfrA7, qacEΔ1, and sul1, conferring resistance to all -lactams and reduced susceptibility to carbapenems and resistance to aminoglycosides, trimethoprim, quaternary ammonium compounds, and sulfamethoxazole, respectively. The class 1 integron is flanked by MITEs (miniature inverted-repeat transposable elements) delimiting the element at its insertion site. nara suisse

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Integrase-Mediated Recombination of the bel-1 Gene Cassette Encoding the Extended-Spectrum -Lactamase BEL-1

29/05/2018

Integrons are genetic elements that can acquire and rearrange gene cassettes. The blaBEL-1 gene encodes an extended-spectrum -lactamase, BEL-1, that is present at the second position of the variable region of class 1 integrons identified in Pseudomonas aeruginosa. The mobility of the bel-1 gene cassette was analyzed under physiological conditions and with the integrase gene being overexpressed. Cassette mobility in Escherichia coli was detected by excision/integration into the recipient integron In3 on the conjugative plasmid R388 with the overproduced integrase. Despite several antibiotic pressures, the bel-1 cassette remained at the second position in the integron, highlighting its stability in P. aeruginosa. Overexpression of the integrase gene in E. coli induced bel-1 cassette recombination. However, cassettes containing two genes (blaBEL-1 and smr2 or blaBEL-1 and aacA4) were excised, suggesting that the bel-1 cassette attC site was defective. We show that bel-1 is a stable gene cassette under physiological growth conditions, irrespective of the selective antibiotic pressure, that may be mobilized upon overexpression of the integrase gene. nara suisse

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Transposition of Tn1213 Encoding the PER-1 Extended- Spectrum -Lactamase

29/05/2018

PER-1 is an extended-spectrum -lactamase that is encoded by a gene located in composite transposon Tn1213 made by two distinct insertion sequences, namely, ISPa12 and ISPa13. In vitro mobilization performed in Escherichia coli shows that Tn1213 is functional and is able to mobilize the blaPER-1 gene, although at a very low frequency (ca. 1  109). nara - suisse

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High Rate of Association of 16S rRNA Methylases and Carbapenemases in Enterobacteriaceae Recovered from Hospitalized Children in Angola

29/05/2018

Acquired 16S rRNA methylases (RMTases) conferring pan-drug resistance to aminoglycosides were searched among enterobacterial isolates recovered in Angola. A total of 36 hospitalized children were screened for rectal colonization using the Superaminoglycoside selective medium. Twenty-two pan-aminoglycosideresistant enterobacterial isolates were recovered, all of which produced RMTases, i.e., RmtB, ArmA, and RmtC. Highly diverse genetic backgrounds were identified for Escherichia coli and Klebsiella pneumoniae isolates, most of which coproduced carbapenemases NDM-1 or NDM-5, respectively. nara suisse

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Evaluation of three broth microdilution systems to determine colistin susceptibility of Gram-negative bacilli

29/05/2018

Background: The broth microdilution (BMD) method is currently the recommended technique to determine susceptibility to colistin. Objectives: We evaluated the accuracy of three commercialized BMD panels [Sensititre (ThermoFisher Diagnostics), UMIC (Biocentric) and MicroScan (Beckman Coulter)] to determine colistin susceptibility. Methods: A collection of 185 isolates of Gram-negative bacilli (133 colistin resistant and 52 colistin susceptible) was tested. Manual BMD according to EUCAST guidelines was used as the reference method, and EUCAST 2017 breakpoints were used for susceptibility categorization. Results: The UMIC system gave the highest rate of very major errors (11.3%) compared with the Sensititre and MicroScan systems (3% and 0.8%, respectively). A high rate of major errors (26.9%) was found with the MicroScan system due to an overestimation of the MICs for the non-fermenting Gram-negative bacilli, whereas no major errors were found with the Sensititre and UMIC systems. Conclusions: The UMIC system was easy to use, but failed to detect .10% of colistin-resistant isolates. The MicroScan system showed excellent results for enterobacterial isolates, but non-susceptible results for nonfermenters should be confirmed by another method and the range of MICs tested was narrow. The Sensititre system was the most reliable marketed BMD panel with a categorical agreement of 97.8%. nara suisse

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Rapid Polymyxin NP test for the detection of polymyxin resistance mediated by the mcr-1/mcr-2 genes

29/05/2018

The Rapid Polymyxin NP test has been recently developed to rapidly detect polymyxin resistance in Enterobacteriaceae. Here we evaluated this test for detecting MCR-1/MCR-2-producing Enterobacteriaceae using a collection of 70 non-redundant strains either recovered from the environment, animals, or humans. Sensitivity and specificity were found to be 100%. nara suisse

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CHROMagar mSuperCARBA and RAPIDEC® Carba NP test for detection of carbapenemase-producing EnterobacteriaceaeCHROMagar mSuperCARBA and RAPIDEC® Carba NP test for detection of carbapenemase-producing Enterobacteriaceae

29/05/2018

A novel chromogenic mediumCHROMagar mSuperCARBA was evaluated to detect carbapenem-resistant Gramnegatives. This medium is as sensitive and as specific as the SUPERCARBA medium for detecting KPC, MBL and OXA-48-type producers (100% and 100%, respectively) and is compatible with subsequent testing of carbapenemase activity using the RAPIDEC® CARBA NP. nara suisse

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Klebsiella pneumoniae co-producing KPC and RmtG, finally targeting Switzerland

29/05/2018

A carbapenem- and pan-aminoglycoside-resistant Klebsiella pneumoniae strain was isolated from a Brazilian patient hospitalized in a Swiss hospital. The clinical isolate carried genes encoding the KPC-2 carbapenemase and the RmtG 16S rRNA methyltransferase. This is the first report of a carbapenem-resistant K. pneumoniae producing RmtG in Europe. nara suisse

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A culture medium for screening 16S rRNA methylase-producing pan-aminoglycoside resistant Gram-negative bacteria

29/05/2018

The amikacin plus gentamicin-containing SuperAminoglycoside mediumwas developed for screening multipleaminoglycoside resistance in Gram-negative bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii). It was evaluated using aminoglycoside-susceptible (n=12) and aminoglycosideresistant (n=59) Gram-negative isolates, including 16S rRNA methylase producers (n=20). Its sensitivity and specificity of detectionwere, respectively, of 95% and 96% for detecting multiple aminoglycoside-resistant methylase producers. NARA SUISSE

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Comparison of methods for detection of plasmid-mediated and chromosomally encoded colistin resistance in Interobacteriaceae

29/05/2018

Objectives: Because of the emergence of plasmid-mediated (mcr-1 and mcr-2 genes) and chromosomally encoded colistin resistance, reliable methods for detecting colistin resistance/susceptibility in routine laboratories are required. We evaluated the respective performances of the BD Phoenix automated system, the newly developed Rapid Polymyxin NP test and the broth microdilution (BMD) reference method to detect colistin resistance in Enterobacteriaceae, and particularly those producing mcr-1 and mcr-2. Methods: Colistin susceptibility of 123 enterobacterial clinical isolates ( 40 colistin-susceptible and 83 colistin-resistant isolates) was tested with the BD Phoenix automated system, the Rapid Polymyxin NP test and the BMD method. Molecular mechanisms responsible for plasmid-mediated and chromosomally encoded colistin resistance mechanisms were investigated by PCR and sequencing. Results: Considering BMD as a reference method. the BD Phoenix system failed to detect ten colistin­resistant isolates (one Escherichia coli, one Klebsiella pneumoniae, seven Enterobacter species and one Salmonella enterica). The Rapid Polymyxin NP test failed to detect the same single E. coli isolate. Those two latter methods detected the 16 E. coli, K. pneumoniae and S. enterica isolates producing the plasmid­encoded mcr-1 and mcr-2. Conclusions: The BD Phoenix system and the Rapid Polymyxin NP test are reliable techniques for detecting plasmid-mediated mcr-1 and mcr-2-related colistin resistance. However, a high rate of false susceptibility was observed with the BD Phoenix system, indicating that susceptibility results obtained with that system should be confirmed by BMD method. By contrast. the Rapid Polymyxin NP test showed a good agreement with the BMD method, and results were obtained rapidly (within 2 hours). The BMD method should be performed if minimum inhibitory concentration values are needed. A. Jayol, ain Microbiol lnfect 2018;24:175 . NARA-CH

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Characterizing non-linear effects of hospitalisation duration on antimicrobial resistance in respiratory isolates: an analysis of a prospective nationwide surveillance system

27/05/2018

Objectives: Our objective was to systematically study the influence of length of hospital stay on bacterial resistance in relevant respiratory tract isolates. Methods: Using prospective epidemiological data from the National Swiss Antibiotic Resistance Surveillance System, susceptibility testing results for respiratory isolates retrospectively retrieved from patients hospitalised between 2008 and 2014 were compiled. Generalized additive models were used to illustrate resistance rates relative to hospitalisation duration and to adjust for co-variables. Results: In all, 19 622 isolates of six relevant and predominant species were included. Resistance patterns for the predominant species showed a species-specific and antibiotic-resistance-specific profile in function of hospitalisation duration. The oxacillin resistance profile in Staphylococcus aureus isolates was constantly increasing (monophasic). The pattern of resistance to cefepime in Pseudomonas aeruginosa was biphasic with a decreasing resistance rate for the first 5 days of hospitalisation and an increase for days 6e30. A different biphasic pattern occurred in Escherichia coli regarding amoxicillin-clavulanic acid resistance: odds/day increased for the first 7 days of hospitalisation and then remained stable for days 8 e30. In the adjusted models epidemiological characteristics such as age, ward type, hospital type and linguistic region were identified as relevant co-variables for the resistance rates. The contribution of these confounders was specific to the individual species/antibiotic resistance models. Conclusions: Resistance rates do not follow a dichotomic pattern (early versus late nosocomial) as suggested by current hospital-acquired pneumonia treatment guidelines. Duration of hospitalisation rather appears to have a more complex and non-linear relationship with bacterial resistance in hospitalacquired pneumonia, also depending on host and environmental factors. R. Sommerstein, Clin Microbiol Infect 2018;24:45 © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. nara-ch

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Incidence of bloodstream infections: a nationwide surveillance of acute care hospitals in Switzerland 2008–2014

25/05/2018

Background: Bloodstream infections are often associated with significant mortality and morbidity. We aimed to investigate changes in the epidemiology of bloodstream infections in Switzerland between 2008 and 2014. Methods: Data on bloodstream infections were obtained from the Swiss antibiotic resistance surveillance system (ANRESIS). Results: The incidence of bloodstream infections increased throughout the study period, especially among elderly patients and those receiving care in emergency departments and university hospitals. Escherichia coli was the predominant pathogen, with Enterococci exhibiting the most prominent increase over the study period. Conclusions: The described trends may impact morbidity, mortality and healthcare costs associated with bloodstream infections. nara.suisse

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

25/05/2018

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-/fourthgeneration 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 val ue for trend = 0. 0 3 ) . 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.

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Prevalence of faecal carriage of colistin-resistant Gramnegative rods in a university hospital in western France, 2016

25/05/2018

Plasmid-mediated and chromosomally-encoded colistin resistance is increasingly being reported worldwide. We aimed to determine the prevalence of faecal carriage of colistin-resistant Gram-negative rod isolates in a university hospital in western France. From February to May 2016, rectal swabs from 653 patients hospitalized in various clinical settings were recovered and subsequently screened for colistin resistance using the SuperPolymyxin medium. Antimicrobial susceptibilities were determined according to EUCAST guidelines. Genetic detection of plasmid-mediated colistin resistance was performed by PCR. The faecal carriage with intrinsic colistin-resistant isolates was high (23 %), while the faecal carriage with Gram-negative rods showing acquired resistance was low (1.4 %). No isolate carried the plasmid-mediated mcr-1/mcr-2 genes. It was noteworthy that none of the patients carrying isolates with acquired colistin resistance had previously received a colistin-based treatment, while these isolates were not multidrug resistant. nara.suisse

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In-Vitro-Study-of-ISApl1-Mediated-Mobilization-of-the-Colistin-Resistance-Gene-mcr-1

25/05/2018

The plasmid-mediated mcr-1 gene encodes a phosphoethanolamine transferase that confers resistance to polymyxins. The mcr-1 gene is associated with insertion sequence ISApl1 (IS30 family). In vitro mobilization assays demonstrated the functionality of the composite transposon structure ISApl1-mcr-1-ISApl1. Transposition generated a 2-bp duplication and occurred in AT-rich DNA regions. This is the first report demonstrating the mobility of the mcr-1 gene by transposition.

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Recent advances in biochemical and molecular diagnostics for the rapid detection of antibiotic-resistant Enterobacteriaceae: a focus on ß-lactam resistance

25/05/2018

The rapid detection of resistance is a challenge for clinical microbiologists who wish to prevent deleterious individual and collective consequences such as (i) delaying efficient antibiotic therapy, which worsens the survival rate of the most severely ill patients, or (ii) delaying the isolation of the carriers of multidrug-resistant bacteria and promoting outbreaks; this last consequence is of special concern, and there are an increasing number of approaches and market-based solutions in response. nara-suisse

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Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study

25/05/2018

Gaps in the diagnostic capacity and heterogeneity of national surveillance and reporting standards in Europe make it diffi cult to contain carbapenemase-producing Enterobacteriaceae. We report the development of a consistent sampling framework and the results of the fi rst structured survey on the occurrence of carbapenemaseproducing Klebsiella pneumoniae and Escherichia coli in European hospitals. nara-ch

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Diagnosing antimicrobial resistance

11/05/2018

Antimicrobial resistance constitutes a global burden and is one of the major threats to public health. Although the emergence of resistant microorganisms is a natural phenomenon, the overuse or inappropriate use of antimicrobials has had a great effect on resistance evolution. Rapid diagnostic tests that identify drug-resistant bacteria, determine antimicrobial susceptibility and distinguish viral from bacterial infections can guide effective treatment strategies. Moreover, rapid diagnostic tests could facilitate epidemiological surveillance, as emerging resistant infectious agents and transmission can be monitored. In this Viewpoint article, several experts in the field discuss the drawbacks of current diagnostic methods that are used to identify antimicrobial resistance, novel diagnostic strategies and how such rapid tests can inform drug development and the surveillance of resistance evolution. nara-suisse

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Moraxella Species as Potential Sources of MCR-Like Polymyxin Resistance Determinants

11/05/2018

Plasmid-mediated resistance to polymyxins mediated by the MCR-1/2 determinants has been reported in Enterobacteriaceae worldwide. Using PCR-based and cloning strategies, a series of Moraxella spp. were screened for mcr-like genes. Moraxella spp. that are mainly animal pathogens but may also be human pathogens were identified as potential reservoirs of mcr-like genes. nara.ch

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High-Level Resistance to Colistin Mediated by Various Mutations in the crrB Gene among Carbapenemase- Producing Klebsiella pneumoniae

11/05/2018

Mutations in crrAB genes encoding a two-component regulator involved in modifications of lipopolysaccharide were searched for among a collection of colistinresistant Klebsiella pneumoniae isolates. Four isolates, respectively, producing carbapenemases NDM-1, OXA-181, or KPC-2 showed mutated CrrB proteins compared with those in wild-type strains. Complementation assays with a wild-type CrrB protein restored the susceptibility to colistin in all cases, confirming the involvement of the identified substitutions in the resistance phenotype.

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Key features of mcr-1-bearing plasmids from Escherichia coli isolated from humans and food

11/05/2018

Mcr-1-harboring Enterobacteriaceae are reported worldwide since their first discovery in 2015. However, a limited number of studies are available that compared full-length plasmid sequences of human and animal origins. nara-suisse

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Analysis-of-OXA-204-carbapenemase-producing-Enterobacteriaceae-reveals-possible-endoscopyassociated-transmission-France-2012-to-2014

11/05/2018

OXA-48-like beta-lactamase producing bacteria are now endemic in several European and Mediterranean countries. Among this carbapenemase family, the OXA- 48 and OXA-181 variants predominate, whereas other variants such as OXA-204 are rarely reported. Here, we report the molecular epidemiology of a collection of OXA-204-positive enterobacterial isolates (n = 29) recovered in France between October 2012 and May 2014. This study describes the first outbreak of OXA- 204-producing Enterobacteriaceae in Europe, involving 12 isolates of an ST90 Escherichia coliclone and nine isolates of an ST147 Klebsiella pneumoniae clone. All isolates co-produced the cephalosporinase CMY-4, and 60% of them co-produced the extended-spectrum beta-lactamase CTX-M-15. The blaOXA-204 gene was located on a 150-kb IncA/C plasmid, isolated from various enterobacterial species in the same patient, indicating a high conjugative ability of this genetic vehicle. nara-suisse

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Plazomicin activity against polymyxin-resistant Enterobacteriaceae, including MCR-1-producing isolates

11/05/2018

Objectives: Plazomicin, a novel aminoglycoside with in vitro activity against MDR Gram-negative organisms, is under development to treat patients with serious enterobacterial infections. We evaluated the activity of plazomicin and comparators against colistin-resistant enterobacterial isolates.

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Antimicrobial activity of octenidine against multidrug-resistant Gram-negative pathogens

11/05/2018

Multidrug-resistant (MR) Gram-negative (GN) pathogens pose a major and growing threat for healthcare systems, as therapy of infections is often limited due to the lack of available systemic antibiotics. Well-tolerated antiseptics, such as octenidine dihydrochloride (OCT), may be a very useful tool in infection control to reduce the dissemination of MRGN. This study aimed to investigate the bactericidal activity of OCTagainst international epidemic clones ofMRGN. A set of five different species (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii, and Pseudomonas aeruginosa) was studied to prove OCT efficacy without organic load, under Bclean conditions^ (0.3 g/L albumin) and under Bdirty conditions^ (3 g/L albumin + 3 mL/L defibrinated sheep blood), according to an official test norm (EN13727). We used five clonally unrelated isolates per species, including a susceptible wildtype strain, and four MRGN isolates, corresponding to either the 3MRGN or 4MRGN definition of multidrug resistance. A contact time of 1 min was fully effective for all isolates by using different OCT concentrations (0.01% and 0.05%), with a bacterial reduction factor of >5 log10 systematically observed. Growth kinetics were determined with two different wild-type strains (A. baumannii and K. pneumoniae), proving a time-dependent efficacy of OCT. These results highlight that OCT may be extremely useful to eradicate emerging highly resistant Gram-negative pathogens associated with nosocomial infections. nara-suisse

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

11/05/2018

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 colistinresistant 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.

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Cross-resistance to human cationic antimicrobial peptides and to polymysins mediated by the plasmid-encoded MCR-1

11/05/2018

Objectives: To evaluate whether acquired resistance to cationic antimicrobial peptide (CAMP) group molecules, being normal components of the human immune system, may select co-resistance to antibiotic peptides such as polymyxins, considering they share the same mechanism of action. We aimed to evaluate strains producing the recently identified plasmid-encoded polymyxin resistance determinant MCR-1, which is a phosphoethanolamine transferase that modifies the lipopolysaccharide structure of Gram-negative bacteria. Methods: In vitro susceptibility studies were performed using human CAMPs, namely cathelicidin LL-37, a-defensin 5 (HD5), and b-defensin 3 (HDB3), towards MCR-1-producing and colistin-resistant Escherichia coli or Klebsiella pneumoniae. Results: Cross-resistance to CAMPs and colistin mediated by MCR-1 or chromosomal mechanisms was neither observed in E. coli nor in K. pneumoniae. Conclusion: Future therapeutic development of human CAMPs is not likely to be impeded by the spread of MCR-1 plasmid-mediated resistance to polymyxins, at least in E. coli. J. Dobias, Clin Microbiol Infect 2017;23:676.e1e676.e5 © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved nara-suisse

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Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

11/05/2018

Polymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria. Susceptibility testing is challenging with polymyxins, and currently available techniques are presented here. Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented. This review also presents recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyxin resistance determinant MCR-1. Epidemiological features summarizing the current knowledge in that field are presented. nara-ch

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Extended-spectrum-b-lactamaseAmpC-and-carbapenemaseproducing Enterobacteriaceae in animals: a threat for humans?

11/05/2018

There has been a great and long-term concern that extended-spectrum b-lactamase (ESBL)/AmpC- and carbapenemase-producing Enterobacteriaceae occurring in animals may constitute a public-health issue. A large number of factors with complex interrelations contribute to the spread of those bacteria among animals and humans. ESBL/AmpC- or carbapenemase-encoding genes are most often located on mobile genetic elements favouring their dissemination. Some shared reservoirs of ESBL/AmpC or carbapenemase genes, plasmids or clones have been identified and suggest cross-transmissions. Even though exposure to animals is regarded as a risk factor, evidence for a direct transfer of ESBL/AmpC-producing bacteria from animals to humans through close contacts is limited. Nonetheless, the size of the commensal ESBL/AmpC reservoir in non-human sources is dramatically rising. This may constitute an indirect risk to public health by increasing the gene pool from which pathogenic bacteria can pick up ESBL/AmpC/carbapenemase genes. The extent to which food contributes to potential transmission of ESBL/AmpC producers to humans is also not well established. Overall, events leading to the occurrence of ESBL/AmpC- and carbapenemase-encoding genes in animals seem very much multifactorial. The impact of animal reservoirs on human health still remains debatable and unclear; nonetheless, there are some examples of direct links that have been identified. J.-Y. Madec, Clin Microbiol Infect 2017;23:826 © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. nara.ch

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Rapid diagnostic tests for detecting emerging antibiotic resistance are mostly available and should be used now.

11/05/2018

Clinically-significant multidrug-resistant bacteria are increasingly reported within enterobacterial species (e.g., Escherichia coli, Klebsiella pneumoniae, Enterobacter spp) and also within the two nosocomial Gramnegative pathogens, namely Pseudomonas aeruginosa and Acinetobacter baumannii. nara-ch

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Rapid Aminoglycoside NP test for rapid detection of multiple aminoglycoside resistance in Enterobacteriaceae

11/05/2018

The rapid aminoglycoside NP (Nordmann/Poirel) test was developed to rapidly identify multiple aminoglycoside (AG) resistance in Enterobacteriaceae. It is based on the detection of the glucose metabolism related to enterobacterial growth in the presence of a defined concentration of amikacin plus gentamicin. Formation of acid metabolites was evidenced by a color change (orange to yellow) of the red phenol pH indicator. The rapid aminoglycoside NP test was evaluated by using bacterial colonies of 18 AG-resistant isolates producing 16S rRNA methylases, 20 AGresistant isolates expressing AG-modifying enzymes (acetyl-, adenyl-, and phosphotransferases), and 10 isolates susceptible to AG. Its sensitivity and specificity were 100% and 97%, respectively, compared to the broth dilution method, which was taken as the gold standard for determining aminoglycoside resistance. The test is inexpensive, rapid (2 h), and implementable worldwide. nara-ch

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