scholarly journals Resistance and Virulence of Pseudomonas aeruginosa Clinical Strains Overproducing the MexCD-OprJ Efflux Pump

2008 ◽  
Vol 52 (7) ◽  
pp. 2455-2462 ◽  
Author(s):  
Katy Jeannot ◽  
Sylvie Elsen ◽  
Thilo Köhler ◽  
Ina Attree ◽  
Christian van Delden ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Term Therapy ◽  
Clinical Strains ◽  
Initial Description ◽  
Moderate Resistance ◽  
Long Term Therapy ◽  
Variable Impact ◽  
Level Resistance

ABSTRACT Since their initial description 2 decades ago, MexCD-OprJ-overproducing efflux mutants of Pseudomonas aeruginosa (also called nfxB mutants) have rarely been described in the clinical setting. Screening of 110 nonreplicate clinical isolates showing moderate resistance to ciprofloxacin (MIC from 0.5 μg/ml to 4 μg/ml) yielded only four mutants (3.6%) of that type harboring various alterations in the repressor gene nfxB. MexCD-OprJ upregulation correlated with an increased resistance to ciprofloxacin, cefepime, and chloramphenicol in most of the clinical strains, concomitant with a higher susceptibility to ticarcillin, aztreonam, imipenem, and aminoglycosides. Evidence was obtained that this increased susceptibility to aminoglycosides results from the impaired activity of efflux pump MexXY-OprM. Furthermore, MexCD-OprJ upregulation was found to impair bacterial growth and to have a strain-specific, variable impact on rhamnolipid, elastase, phospholipase C, and pyocyanin production. Review of patient files indicated that the four nfxB mutants were responsible for confirmed cases of infection and emerged during long-term therapy with ciprofloxacin. Taken together, these data show that, while rather infrequent among P. aeruginosa strains with low-level resistance to ciprofloxacin, MexCD-OprJ-overproducing mutants may be isolated after single therapy with fluoroquinolones and may be pathogenic.

Buccal Adherence of Pseudomonas aeruginosa in Patients with Cystic Fibrosis under Long-Term Therapy with Azithromycin

Infection ◽  
2001 ◽  
Vol 29 (1) ◽  
pp. 7-11 ◽  
Author(s):  
U. Baumann ◽  
J.J. Fischer ◽  
P. Gudowius ◽  
M. Lingner ◽  
S. Herrmann ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Term Therapy ◽  
Long Term Therapy

scholarly journals Effect of Erythromycin on Chronic Respiratory Infection Caused by Pseudomonas aeruginosa with Biofilm Formation in an Experimental Murine Model

2004 ◽  
Vol 48 (6) ◽  
pp. 2251-2259 ◽  
Author(s):  
Towako Nagata ◽  
Hiroshi Mukae ◽  
Junichi Kadota ◽  
Tomayoshi Hayashi ◽  
Takeshi Fujii ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Murine Model ◽  
Biofilm Formation ◽  
Term Therapy ◽  
Diffuse Panbronchiolitis ◽  
Chronic Respiratory Infection ◽  
Model Treatment ◽  
Long Term Therapy

ABSTRACT Diffuse panbronchiolitis (DPB) is a chronic lower respiratory tract infection commonly associated with persistent late-stage Pseudomonas aeruginosa infection. However, low-dose long-term therapy with certain macrolides is effective in most patients with DPB. The present study was designed to examine the effects of long-term erythromycin (ERY) therapy by using our established murine model of chronic respiratory P. aeruginosa infection. ERY or saline was administered from day 80 after intubation with a P. aeruginosa-precoated tube for the subsequent 10, 20, 40, and 80 days. Bacteriologic and histologic analyses of the murine lungs and electron microscopy of the intubated tube were performed. In the murine model, treatment with ERY for 80 days significantly reduced the number of viable P. aeruginosa organisms in the lungs (P < 0.05). The biofilm formed in situ by P. aeruginosa on the inner wall of the inoculation tube placed into the murine bronchus became significantly thinner after 80 days of ERY treatment. We conclude that the clinical efficacy of macrolides in DPB may be due at least in part to the reduction in P. aeruginosa biofilm formation.

scholarly journals Role of the MexEF-OprN Efflux System in Low-Level Resistance of Pseudomonas aeruginosa to Ciprofloxacin

2011 ◽  
Vol 55 (12) ◽  
pp. 5676-5684 ◽  
Author(s):  
Catherine Llanes ◽  
Thilo Köhler ◽  
Isabelle Patry ◽  
Barbara Dehecq ◽  
Christian van Delden ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Reference Strain ◽  
Efflux Pump ◽  
Resistance Mechanisms ◽  
Efflux System ◽  
Content Type ◽  
Clinical Strains ◽  
Major Mechanism ◽  
Level Resistance

ABSTRACTIn this study, we investigated the resistance mechanisms to fluoroquinolones of 85 non-cystic fibrosis strains ofPseudomonas aeruginosaexhibiting a reduced susceptibility to ciprofloxacin (MICs from 0.25 to 2 μg/ml). In addition to MexAB-OprM (31 of 85 isolates) and MexXY/OprM (39 of 85), the MexEF-OprN efflux pump (10 of 85) was found to be commonly upregulated in this population that is considered susceptible or of intermediate susceptibility to ciprofloxacin, according to current breakpoints. Analysis of the 10 MexEF-OprN overproducers (nfxCmutants) revealed the presence of various mutations in themexT(2 isolates),mexS(5 isolates), and/ormvaT(2 isolates) genes, the inactivation of which is known to increase the expression of themexEF-oprNoperon in reference strain PAO1-UW. However, these genes were intact in 3 of 10 of the clinical strains. Interestingly, ciprofloxacin at 2 μg/ml or 4 μg/ml preferentially selectednfxCmutants from wild-type clinical strains (n= 10 isolates) and from first-step mutants (n= 10) overexpressing Mex pumps, thus indicating that MexEF-OprN represents a major mechanism by whichP. aeruginosamay acquire higher resistance levels to fluoroquinolones. These data support the notion that thenfxCmutants may be more prevalent in the clinical setting than anticipated and strongly suggest the involvement of still unknown genes in the regulation of this efflux system.

Antithrombotic Therapy for DVT/PE

1997 ◽  
Vol 17 (03) ◽  
pp. 161-162
Author(s):  
Thomas Hyers
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Cost Effective ◽  
Therapeutic Agents ◽  
Great Promise ◽  
Term Therapy ◽  
Low Molecular Weight ◽  
Long Term Therapy

SummaryProblems with unfractionated heparin as an antithrombotic have led to the development of new therapeutic agents. Of these, low molecular weight heparin shows great promise and has led to out-patient therapy of DVT/PE in selected patients. Oral anticoagulants remain the choice for long-term therapy. More cost-effective ways to give oral anticoagulants are needed.

Office-based post-marketing surveillance study on the influence of long term therapy with aripiprazole in patients with schizophrenia

2007 ◽  
Vol 40 (05) ◽  
Author(s):  
M Kungel ◽  
A Engelhardt ◽  
T Spevakné-Göröcs ◽  
M Ebrecht ◽  
C Werner ◽  
...  
Keyword(s):  
Surveillance Study ◽  
Term Therapy ◽  
Post Marketing Surveillance ◽  
Post Marketing ◽  
Long Term Therapy

scholarly journals Amiodarone-induced thyroid dysfunction in children: insights from the THYRAMIO study

2021 ◽  
Vol 12 ◽  
pp. 204201882110011
Author(s):  
Sarah Montenez ◽  
Stéphane Moniotte ◽  
Annie Robert ◽  
Lieven Desmet ◽  
Philippe A. Lysy
Keyword(s):  
Predictive Value ◽  
Thyroid Dysfunction ◽  
Term Therapy ◽  
Older Children ◽  
Thyroid Status ◽  
Clinical Series ◽  
Amiodarone Treatment ◽  
Long Term Therapy ◽  
Treatment Dosage

Background: Amiodarone treatment is effective against various types of arrhythmias but is associated with adverse effects affecting, among other organs, thyroid function. Amiodarone-induced thyroid dysfunction was not thoroughly evaluated in children as it was in adults, yet this affection may lead to irreversible neurodevelopmental complications. Our study aimed to define the incidence and risk factors of amiodarone-induced thyroid dysfunction in children. Methods: The study was designed as an observational study with a retrospective clinical series of 152 children treated by amiodarone in the Pediatric Cardiology Unit of our center from 1990 to 2019. All patients were divided into three groups according to their thyroid status: euthyroid, AIH (amiodarone-induced hypothyroidism) or AIT (amiodarone-induced thyrotoxicosis). Patients from these three groups were compared in terms of key clinical and therapeutic features. Results: Amiodarone-induced thyroid dysfunction was present in 23% of patients. AIT (5.3%) was three times less common than AIH (17.7%), and its occurrence increased with older age ( p < 0.05), treatment dosage ( p < 0.05), treatment duration ( p < 0.05) and the number of loading doses administered ( p < 0.05). There were no distinctive clinical features between euthyroid and AIH groups. A multivariable prediction model of AIT was built, with a yield of 66.7% as positive predictive value and 96.7% as negative predictive value. Conclusion: We observed that one in five children developed amiodarone-induced thyroid dysfunction. Special attention is required for older children with a high dosage and long-term therapy and who received a large number of loading doses, since these children are at risk to develop AIT, which is more delicate to manage than AIH.

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