scholarly journals Imipenem Resistance of Enterobacter aerogenes Mediated by Outer Membrane Permeability

2000 ◽  
Vol 38 (3) ◽  
pp. 1048-1052 ◽  
Author(s):  
Charléric Bornet ◽  
Anne Davin-Regli ◽  
Claude Bosi ◽  
Jean-Marie Pages ◽  
Claude Bollet

Multidrug-resistant Enterobacter aerogenes strains are increasingly isolated in Europe and especially in France. Treatment leads to imipenem resistance, because of a lack of porin. We studied the evolution of resistance in 29 strains isolated from four patients during their clinical course. These strains belonged to the prevalent epidemiological type observed in France in previous studies (C. Bosi, et al., J. Clin. Microbiol. 37:2165–2169, 1999; A. Davin-Regli et al., J. Clin. Microbiol. 34:1474–1480, 1996). They also harbored a TEM-24 extended-spectrum β-lactamase-coding gene. Thirteen strains were susceptible to gentamicin and resistant to imipenem and cefepime. All of the patients showed E. aerogenes strains with this resistance after an imipenem treatment. One patient showed resistance to imipenem after a treatment with cefpirome. Twelve of these 13 strains showed a lack of porin. Cessation of treatment with imipenem for three patients was followed by reversion of susceptibility to this antibiotic and the reappearance of porins, except in one case. For one patient, we observed three times in the same day the coexistence of resistant strains lacking porin and susceptible strains possessing porin. The emergence of multidrug-resistant E. aerogenes strains is very disquieting. In our study, infection by E. aerogenesincreased the severity of the patients' illnesses, causing a 100% fatality rate.

2004 ◽  
Vol 48 (6) ◽  
pp. 2153-2158 ◽  
Author(s):  
Charléric Bornet ◽  
Nathalie Saint ◽  
Lilia Fetnaci ◽  
Myrielle Dupont ◽  
Anne Davin-Régli ◽  
...  

ABSTRACT In Enterobacter aerogenes, β-lactam resistance often involves a decrease in outer membrane permeability induced by modifications of porin synthesis. In ATCC 15038 strain, we observed a different pattern of porin production associated with a variable antibiotic susceptibility. We purified Omp35, which is expressed under conditions of low osmolality and analyzed its pore-forming properties in artificial membranes. This porin was found to be an OmpF-like protein with high conductance values. It showed a noticeably higher conductance compared to Omp36 and a specific location of WNYT residues in the L3 loop. The importance of the constriction region in the porin function suggests that this organization is involved in the level of susceptibility to negative large cephalosporins such as ceftriaxone by bacteria producing the Omp35 porin subfamily.


2015 ◽  
Vol 60 (3) ◽  
pp. 1349-1359 ◽  
Author(s):  
Jean-Marie Pagès ◽  
Sabine Peslier ◽  
Thomas A. Keating ◽  
Jean-Philippe Lavigne ◽  
Wright W. Nichols

This study examined the activity of the novel antimicrobial combination ceftazidime-avibactam againstEnterobacteriaceaeexhibiting different outer membrane permeability profiles, specifically with or without porins and with or without expression of the main efflux pump (AcrAB-TolC). The addition of the outer membrane permeabilizer polymyxin B nonapeptide increased the antibacterial activities of avibactam alone, ceftazidime alone, and ceftazidime-avibactam against the characterized clinical isolates ofEscherichia coli,Enterobacter aerogenes, andKlebsiella pneumoniae. This enhancement of activities was mainly due to increased passive penetration of compounds since inhibition of efflux by the addition of phenylalanine-arginine β-naphthylamide affected the MICs minimally. OmpF (OmpK35) or OmpC (OmpK36) pores were not the major route by which avibactam crossed the outer membranes ofE. coliandK. pneumoniae. In contrast, Omp35 and Omp36 allowed diffusion of avibactam across the outer membrane ofE. aerogenes, although other diffusion channels for avibactam were also present in that species. It was clear that outer membrane permeability and outer membrane pore-forming proteins play a key role in the activity of ceftazidime-avibactam. Nevertheless, the MICs of ceftazidime-avibactam (with 4 mg/liter avibactam) against the ceftazidime-resistant clinical isolates of the three species ofEnterobacteriaceaestudied were ≤8 mg/liter, regardless of outer membrane permeability changes resulting from an absence of defined porin proteins or upregulation of efflux.


2009 ◽  
Vol 58 (4) ◽  
pp. 451-455 ◽  
Author(s):  
Javier Sánchez-Céspedes ◽  
Maria José Figueras ◽  
Carmen Aspiroz ◽  
Maria José Aldea ◽  
Miguel Toledo ◽  
...  

Several imipenem-susceptible and -resistant Aeromonas veronii biovar sobria isolates with different morphologies and antimicrobial susceptibilities recovered from bile samples of a patient with cholangitis were analysed. These isolates belonged to the same clone and the imipenem-resistant strains showed overexpression of the imiS gene, encoding a chromosomal carbapenemase. These results should make clinicians aware of the possible emergence of multidrug-resistant A. veronii biovar sobria, perhaps as a consequence of previous treatment of a urinary tract infection with amoxicillin plus clavulanic acid.


2019 ◽  
Vol 49 ◽  
pp. 135-157
Author(s):  
Chikviladze D. ჩიკვილაძე დ. ◽  
Gachechiladze Kh. გაჩეჩილაძე ხ. ◽  
Mikeladze M. მიქელაძე მ. ◽  
მეტრეველი დ. Metreveli D.

  The spectrum of sensitivity of 112 E. coli strains isolated from patients with acute intestinal infection to 23 antibiotics was investigated  by the agar dilution method, which revealed an increase in drug resistance and the emergence of multidrug-resistant strains  (33.04%). It was found that the drug resistance of the pathogen to nalidixic acid and carbopenems increased and its high sensitivity to some ftuoroquinolones, III and IV generation aminoglycosides, penicillins and cephalosporins preserved. The drug resistance in future may lead to the formation of hospital strains among E. coli and alter an epidemiological process and the clinical course of the disease.


2016 ◽  
Author(s):  
Bianca Regenbogen ◽  
Matthias Willmann ◽  
Matthias Steglich ◽  
Boyke Bunk ◽  
Ulrich Nübel ◽  
...  

AbstractColistin is a last resort antibiotic commonly used against multidrug-resistant strains of Pseudomonas aeruginosa. To investigate the potential for in-situ evolution of resistance against colistin and map the molecular targets of colistin resistance, we exposed two P. aeruginosa isolates to colistin using a continuous culture device known as morbidostat. Colistin resistance emerged within two weeks along with highly stereotypic yet strain specific mutation patterns. The majority of mutations hit the prmAB two component signaling system and genes involved in lipopolysaccharide synthesis, including lpxC, pmrE, and migA. In seven out of 18 cultures, we observed mutations in mutS along with a mutator phenotype that seemed to facilitate resistance evolution.


2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Bianca Dößelmann ◽  
Matthias Willmann ◽  
Matthias Steglich ◽  
Boyke Bunk ◽  
Ulrich Nübel ◽  
...  

ABSTRACT Colistin is a last-resort antibiotic commonly used against multidrug-resistant strains of Pseudomonas aeruginosa. To investigate the potential for in situ evolution of resistance against colistin and to map the molecular targets of colistin resistance, we exposed two P. aeruginosa isolates to colistin using a continuous-culture device known as a morbidostat. As a result, colistin resistance reproducibly increased 10-fold within 10 days and 100-fold within 20 days, along with highly stereotypic yet strain-specific mutation patterns. The majority of mutations hit the pmrAB two-component signaling system and genes involved in lipopolysaccharide (LPS) synthesis, including lpxC, pmrE, and migA. We tracked the frequencies of all arising mutations by whole-genome deep sequencing every 3 to 4 days to obtain a detailed picture of the dynamics of resistance evolution, including competition and displacement among multiple resistant subpopulations. In 7 out of 18 cultures, we observed mutations in mutS along with a mutator phenotype that seemed to facilitate resistance evolution.


2002 ◽  
Vol 46 (9) ◽  
pp. 2901-2907 ◽  
Author(s):  
Bernard Lakaye ◽  
Alain Dubus ◽  
Bernard Joris ◽  
Jean-Marie Frère

ABSTRACT The outer membrane of gram-negative bacteria plays a major role in β-lactam resistance as it slows down antibiotic entry into the periplasm and therefore acts in synergy with β-lactamases and efflux systems. Up to now, the quantitative estimation of low outer membrane permeability by the method of Zimmermann and Rosselet was difficult because of the secreted and cell surface-associated β-lactamases. The method presented here uses the acylation of a highly sensitive periplasmic penicillin-binding protein (PBP) (BlaR-CTD) to assess the rate of β-lactam penetration into the periplasm. The method is dedicated to measurement of low permeability and is only valid when the diffusion rate through the outer membrane is rate limiting. Cytoplasmic membrane associated PBPs do not interfere since they are acylated after the very sensitive BlaR-CTD. This method was used to measure the permeability of β-lactamase-deficient strains of Enterobacter cloacae and Enterobacter aerogenes to benzylpenicillin, ampicillin, carbenicillin, cefotaxime, aztreonam, and cephacetrile. Except for that of cephacetrile, the permeability coefficients were equal to or below 10−7 cm/s. For cephacetrile, carbenicillin, and benzylpenicillin, the outer membrane of E. cloacae was 20 to 60 times less permeable than that of Escherichia coli, whereas for cefotaxime, aztreonam, and ampicillin it was, respectively, 400, 1,000, and 700 times less permeable. The permeability coefficient for aztreonam is the lowest ever measured (P = 3.2 × 10−9 cm/s). Using these values, the MICs for a β-lactamase-overproducing strain of E. cloacae were successfully predicted, demonstrating the validity of the method.


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