In vivo acquisition of extended-spectrum beta-lactamase inSalmonella enteritidis during antimicrobial therapy

1995 ◽  
Vol 14 (8) ◽  
pp. 703-706 ◽  
Author(s):  
F. Barguellil ◽  
C. Burucoa ◽  
A. Amor ◽  
J. L. Fauchère ◽  
C. Fendri
2019 ◽  
Author(s):  
Fabienne Benz ◽  
Jana S. Huisman ◽  
Erik Bakkeren ◽  
Joana A. Herter ◽  
Tanja Stadler ◽  
...  

AbstractHorizontal gene transfer, mediated by conjugative plasmids, is a major driver of the global spread of antibiotic resistance. However, the relative contributions of factors that underlie the spread of clinically relevant plasmids are unclear. Here, we quantified conjugative transfer dynamics of Extended Spectrum Beta-Lactamase (ESBL) producing plasmids in the absence of antibiotics. We showed that clinical Escherichia coli strains natively associated with ESBL-plasmids conjugate efficiently with three distinct E. coli strains and one Salmonella enterica serovar Typhimurium strain, reaching final transconjugant frequencies of up to 1% within 24 hours in vitro. The variation of final transconjugant frequencies varied among plasmids, donors and recipients and was better explained by variation in conjugative transfer efficiency than by variable clonal expansion. We identified plasmid-specific genetic factors, specifically the presence/absence of transfer genes, that influenced final transconjugant frequencies. Finally, we investigated plasmid spread within the mouse intestine, demonstrating qualitative agreement between plasmid spread in vitro and in vivo. This suggests a potential for the prediction of plasmid spread in the gut of animals and humans, based on in vitro testing. Altogether, this may allow the identification of resistance plasmids with high spreading potential and help to devise appropriate measures to restrict their spread.


2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Norihito Kaku ◽  
Kosuke Kosai ◽  
Kazuaki Takeda ◽  
Naoki Uno ◽  
Yoshitomo Morinaga ◽  
...  

ABSTRACT OP0595 (RG6080) is a novel diazabicyclooctane that inhibits class A and C serine beta-lactamases. Although the combination of OP0595 and cefepime (FEP) showed good in vitro activity against extended-spectrum-beta-lactamase (ESBL)-producing pathogens, the effect of the combination therapy against severe infections, such as pneumonia or bacteremia, remains unknown in vivo. In this study, we investigated the efficacy and pharmacokinetics of the combination therapy of OP0595 and FEP in a mouse model of pneumonia caused by Klebsiella pneumoniae harboring SHV- and CTX-M-9-type ESBLs. The infected BALB/c mice were intraperitoneally administered saline (control), 100 mg/kg of body weight of FEP, 20 mg/kg of OP0595, or both FEP and OP0595, twice a day. The MIC of FEP against the bacteria was 8 mg/liter and markedly improved to 0.06 mg/liter with the addition of 0.5 mg/ml of OP0595. In the survival study, the combination of FEP and OP0595 significantly improved the survival rate compared with that reported with either OP0595 or FEP alone (P < 0.001). The number of bacteria in the lungs and blood significantly decreased in the combination therapy group compared to that reported for the monotherapy groups (P < 0.001). In addition, the in vivo effect depended on the dose of FEP. However, pharmacokinetic analysis revealed that the percentage of time above MIC remained constant when increasing the dose of FEP in combination with 20 mg/kg of OP0595. The results of our study demonstrated the in vivo effectiveness of the combination of OP0595 and FEP.


1997 ◽  
Vol 41 (5) ◽  
pp. 1053-1057 ◽  
Author(s):  
C Thauvin-Eliopoulos ◽  
M F Tripodi ◽  
R C Moellering ◽  
G M Eliopoulos

The in vivo activities of piperacillin-tazobactam and cefepime were compared with those of ticarcillin-clavulanate, ceftazidime, cefotaxime, and imipenem in a rat model of intra-abdominal abscess with a strain of Klebsiella pneumoniae elaborating an extended-spectrum beta-lactamase (TEM-26). With the exception of ceftazidime, all of the antimicrobial agents significantly reduced bacterial counts within abscesses at the end of therapy compared with those in untreated controls. Residual viable cell counts (mean +/- standard deviation in log10 CFU/gram) were as follows: control, 8.76 +/- 0.97; ceftazidime, 8.00 +/- 0.76; piperacillin-tazobactam, 3.87 +/- 1.72; ticarcillin-clavulanate, 3.74 +/- 1.34; cefepime, 3.15 +/- 1.19; cefotaxime, 2.61 +/- 0.77; imipenem, 2.41 +/- 0.93. Imipenem was more effective than either of the inhibitor combinations (P < 0.05). Cefotaxime was unexpectedly effective given its poor in vivo activity against this organism in our earlier studies, which used a different dose and total duration of therapy (L. B. Rice, J. D. C. Yao, K. Klimm, G. M. Eliopoulos, and R. C. Moellering, Jr., Antimicrob. Agents Chemother. 35:1243-1244, 1991). These observations suggest that the effectiveness of cephalosporins in the treatment of experimental infections caused by extended-spectrum beta-lactamase-producing K. pneumoniae may be highly dependent on dosing regimens, even for a specific organism and site of infection.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S71-S72
Author(s):  
Ashlan Kunz Coyne ◽  
Anthony Casapao ◽  
Carmen Isache ◽  
James Morales ◽  
Yvette McCarter ◽  
...  

Abstract Background Molecular rapid diagnostic tests (mRDT) may help expedite the time to optimal antimicrobial therapy (TTOT) for extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing bacteria in bloodstream infections (BSI). The greatest impact of mRDT appears to occur when combined with antimicrobial stewardship program (ASP) intervention. The purpose of this study was to evaluate if mRDT + ASP influences the TTOT for patients with ESBL- and carbapenemase-producing E. coli and K. pneumoniae in BSI compared to conventional microbiological methods with ASP (CONV + ASP). Methods Multicenter, retrospective, cohort study evaluating five years of patients that had a positive E. coli or K. pneumoniae blood culture determined to be ESBL- or carbapenemase-producing by mRDT and/or CONV. Patients were excluded if they had polymicrobial BSI, transferred–in with previously identified positive blood cultures, were immunosuppressed, or died before culture results. Primary outcome was TTOT defined as time from blood culture draw to start of carbapenem therapy for ESBL-producing BSI and ceftazidime-avibactam, meropenem-vaborbactam, or at least one drug active in-vitro with the most-narrow spectrum for carbapenemase-producing BSI. Secondary outcomes were time to microbial clearance (TTMC) defined as the time from index blood culture draw to the time of first negative blood culture or hospital discharge, all-cause hospital mortality, 30-, 60- and 90-day readmission rates, and Clostridioides difficile rates. Results A total of 378 patients were included for analysis. Baseline characteristics were balanced between mRDT + ASP (n=164) and CONV + ASP (n=214). Infectious diseases consults were significantly greater for CONV + ASP compared to mRDT + ASP (82.2% vs 34.8%; p&lt; 0.001). The mRDT + ASP demonstrated a statistically significant decrease in TTOT (20.5 hrs [(IQR 17.0–42.2 hrs)] vs 50.1 hrs [(IQR 27.6–77.9 hrs)]; p&lt; 0.001) and TTMC (71.9 hrs [(IQR 54.1–108.5 hrs)] vs 91.2 hrs [(IQR 64.6–134.3 hrs)]; p=0.007). Other secondary endpoints were similar between groups. Table 1. Comparison of baseline characteristics for the mRDT+ASP and CONV+ASP groups Graph 1. Kaplan Meier time to optimal antimicrobial therapy Graph 2. Kaplan Meier time to microbial clearance Conclusion Our study supports the additional benefit of mRDT to ASP on shortening the TTOT and TTMC in patients with ESBL- or carbapenemase-producing E. coli and K. pneumoniae in BSI compared to CONV + ASP. Disclosures All Authors: No reported disclosures


2010 ◽  
Vol 4 (12) ◽  
pp. 779-803 ◽  
Author(s):  
Mohammed Bouchakour ◽  
Khalid Zerouali ◽  
Jean David Perrier Gros Claude ◽  
Hamid Amarouch ◽  
Naima El Mdaghri ◽  
...  

Introduction: Although independently acquired, plasmid-mediated quinolone resistance appears to be linked with extended-spectrum or AmpC-type beta-lactamases. Since no data are available in African countries, the prevalence of qnr genes at the University Hospital Ibn Rochd, Casablanca, Morocco, was investigated. Methodology: Between October 2006 and March 2007, the following 39 randomly selected non-duplicate Enterobacteriaceae producing an extended-spectrum beta-lactamase (ESBL), representing 20% of ESBL strains with respect to species and ward origin, were collected: Escherichia coli (n = 16); Klebsiella spp (n = 14); Enterobacter cloacae (n = 8); Proteus mirabilis (n = 1). Antibiotic susceptibility testing was performed according to CLSI guidelines. ESBL detection was performed by the double disc diffusion test. A multiplex PCR was conducted to detect qnrA, qnrB and qnrS genes that were confirmed by sequencing of the PCR product. Results: The estimated overall prevalence of qnr reached 36% (n = 14; qnrA, 10.25%; qnrB, 23.07%; qnrS, 2.56%). Genes were identified in E. coli, Klebsiella and Enterobacter with a respective prevalence of 18.7%, 50% and 62.5%.  The qnr genes were detected in nine wards and qnrA1, qnrB1-B2-B4 and qnrS1 variants were identified. Three genes were identified among nalidixic acid susceptible strains (n = 6); three of those were also susceptible to ciprofloxacin. Among nalidixic acid and ciprofloxacin resistant strains, all strains had qnrB. Conclusions: This study highlights the high prevalence of qnr genes among ESBL strains in the Ibn Rochd CHU, Casablanca. Moreover, qnr were present in quinolone-susceptible strains which could lead to in vivo selection of ciprofloxacin-resistant strains.


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