Mutations in the gyrA and parC genes and in vitro activities of fluoroquinolones in 114 clinical isolates of Pseudomonas aeruginosa derived from urinary tract infections and their rapid detection by denaturing high-performance liquid chromatography

2012 ◽  
Vol 40 (5) ◽  
pp. 440-444 ◽  
Author(s):  
Minori Matsumoto ◽  
Katsumi Shigemura ◽  
Toshiro Shirakawa ◽  
Yuzo Nakano ◽  
Hideaki Miyake ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Rapid Detection ◽  
High Performance ◽  
Clinical Isolates ◽  
Tract Infections

scholarly journals Quorum sensing and virulence of Pseudomonas aeruginosa during urinary tract infections

2012 ◽  
Vol 6 (06) ◽  
pp. 501-507 ◽  
Author(s):  
Sezgi Senturk ◽  
Seyhan Ulusoy ◽  
Gulgun Bosgelmez-Tinaz ◽  
Aysegul Yagci
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Urinary Tract Infections ◽  
Clinical Isolates ◽  
Pcr Analysis ◽  
Signal Molecules ◽  
Tract Infections

Introduction: In the opportunistic pathogen Pseudomonas aeruginosa, the production of several virulence factors depends on quorum sensing (QS) involving N-acylhomoserine lactone signal molecules. In vitro studies have suggested that the QS system is crucial in the pathogenesis of P. aeruginosa. However, it is unclear whether QS systems of P. aeruginosa play the same role during infections. Methodology:  In this study, to explore the contribution of QS systems to the pathogenesis of P. aeruginosa during urinary tract infections, we collected 82 clinical isolates. Detection of N-acyl-homoserine lactones (C12-HSL and C4-HSL) was performed on agar plates employing biosensor strains C. violaceum. Elastase and biofilm production were determined spectrophotometrically. QS genes were detected by PCR and subsequently underwent sequencing. Results and conclusion:  Six isolates were found to be negative in the production of both C12-HSL and C4-HSL and all virulence factors tested.  PCR analysis of these isolates revealed that four isolates contained all four QS genes while one isolate was negative for lasR gene, and one isolate negative for lasI, lasR and rhlR genes. Sequence analyses of these isolates showed that the lasR, lasI, rhlR and rhlI genes had point mutations. The combination of these mutations probably explains their C12-HSL, C4-HSL and virulence factor deficiencies. Results of this study suggest that QS deficient clinical isolates occur and are still capable of causing clinical infections in humans. 

scholarly journals Ceftazidime/Avibactam: Who Says You Can’t Teach an Old Drug New Tricks?

2016 ◽  
Vol 19 (4) ◽  
pp. 448 ◽  
Author(s):  
Katie E. Barber ◽  
Jessica K. Ortwine ◽  
Ronda L Akins
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
The United States ◽  
Phase Iii ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Tract Infections ◽  
Abdominal Infections

Purpose: Gram-negative resistance continues to rise with treatment options becoming more limited. Ceftazidime/avibactam was recently approved in the United States and Europe, which combines an established third-generation cephalosporin with a new, unique, non-β-lactam β-lactamase inhibitor. This review conducts a thorough examination of structure, pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, in vitro and clinical efficacy and safety/tolerability of ceftazidime/avibactam, as well as detailed future directions for the agent. Methods: Pubmed and clinicaltrials.gov searches, as well as abstracts from the 2015 Interscience Conference on Antimicrobial Agents and Chemotherapy/International Society of Chemotherapy (ICAAC/ICC) and ID Week meetings and the 2016 American Society of Microbiology Microbe meeting, were conducted from January 2004 – September 2016. Relevant search terms included ceftazidime, ceftazidime/avibactam, avibactam, NXL104 and AVE1330A. The US package insert for ceftazidime/avibactam (02/2015) and European public assessment report (06/2016) were also reviewed. Results: In vitro susceptibility for ceftazidime/avibactam displayed potent activity against many Enterobacteriaceae including extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing strains, as well as Pseudomonas aeruginosa. Phase II clinical trials utilized for approval demonstrated comparable safety and efficacy to imipenem/cilistatin for treatment of complicated urinary tract infections (70.4% vs. 71.4%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (91.2% vs 93.4%). Phase III data displayed non-inferior efficacy of ceftazidime/avibactam compared to doripenem for complicated urinary tract infections (70.2% vs 66.2%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (82.5% vs 84.9%), as well as comparable safety. Ceftazidime/avibactam was well-tolerated but does require renal adjustments. Additionally, 3 case series and a single case report have demonstrated the potential for ceftazidime/avibactam against multidrug resistant organisms for compassionate use or failure after previous therapy. Conclusion: By adding avibactam to ceftazidime, clinicians’ antimicrobial armamentarium is expanded, potentially increasing the ability to combat multi-drug resistant gram-negative pathogens, particularly ESBL and carbapenemase-producing organisms, as well as Pseudomonas aeruginosa. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Efficacy of single and multiple oral doses of fosfomycin against Pseudomonas aeruginosa urinary tract infections in a dynamic in vitro bladder infection model

2020 ◽  
Vol 75 (7) ◽  
pp. 1879-1888 ◽  
Author(s):  
Iain J Abbott ◽  
Elke van Gorp ◽  
Rixt A Wijma ◽  
Jordy Dekker ◽  
Peter D Croughs ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Single Dose ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Infection Model ◽  
Post Exposure ◽  
High Level ◽  
Tract Infections ◽  
Emergence Of Resistance

Abstract Objectives We used a dynamic bladder infection in vitro model with synthetic human urine (SHU) to examine fosfomycin exposures to effectively kill, or prevent emergence of resistance, among Pseudomonas aeruginosa isolates. Methods Dynamic urinary fosfomycin concentrations after 3 g oral fosfomycin were simulated, comparing single and multiple (daily for 7 days) doses. Pharmacodynamic response of 16 P. aeruginosa (MIC range 1 to >1024 mg/L) were examined. Baseline disc diffusion susceptibility, broth microdilution MIC and detection of heteroresistance were assessed. Pathogen kill and emergence of resistance over 72 h following a single dose, and over 216 h following daily dosing for 7 days, were investigated. The fAUC0–24/MIC associated with stasis and 1, 2 and 3 log10 kill were determined. Results Pre-exposure high-level resistant (HLR) subpopulations were detected in 11/16 isolates after drug-free incubation in the bladder infection model. Five of 16 isolates had >2 log10 kill after single dose, reducing to 2/16 after seven doses. Post-exposure HLR amplification occurred in 8/16 isolates following a single dose and in 11/16 isolates after seven doses. Baseline MIC ≥8 mg/L with an HLR subpopulation predicted post-exposure emergence of resistance following the multiple doses. A PK/PD target of fAUC0–24/MIC >5000 was associated with 3 log10 kill at 72 h and 7 day-stasis. Conclusions Simulated treatment of P. aeruginosa urinary tract infections with oral fosfomycin was ineffective, despite exposure to high urinary concentrations and repeated daily doses for 7 days. Emergence of resistance was observed in the majority of isolates and worsened following prolonged therapy. Detection of a baseline resistant subpopulation predicted treatment failure.

scholarly journals Relationship between the Presence of the nalC Mutation and Multidrug Resistance inPseudomonas aeruginosa

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Nourkhoda Sadeghifard ◽  
Azar Valizadeh ◽  
Mohammad Reza Zolfaghary ◽  
Mohammad Hossien Maleki ◽  
Abbas Maleki ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Clinical Isolates ◽  
Efflux System ◽  
Tract Infections ◽  
The Relationship

Objectives. The current study was conducted to determine the relationship between the presences of significant multidrug resistance inPseudomonas aeruginosa(P. aeruginosa) having intactmexRgenes (nalC) to different antibiotics.Methods. In order to identify nalC, fifty strains ofP. aeruginosawere obtained. All isolates were found in urinary tract infections. They were evaluated against different antibiotics. The nalC mutant was identified by PCR.Results. The 50 clinical isolates ofP. aeruginosaoriginated from two hospitals in Iran, in which 32 isolates were found in Milad hospital, and 18 isolates were collected in the Ilam Hospital. The results in Milad hospital of nalC revealed that allP. aeruginosaresistant to oxacillin showed the presence of nalC. In Ilam hospital only three (16.6%) isolates were resistant to oxacilin and aztreonam, and among these three isolates only one isolate revealed resistance to ceftazidime and amikacin. The resistant isolates showed the presence of both OXA-10 and nalC.Conclusion. Our results showed that the presence of nalC was observed amongP. aeruginosaresistance to oxacilin. Thus, the finding suggested relationship between oxacilin resistance and presence of nalC and consequently overproduction of the MexABOprM efflux system.

scholarly journals Efficacy of Ethanolic Extract of Syzygium aromaticum in the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Clinical Isolates Associated with Urinary Tract Infections

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Osama Ahmed ◽  
Hassan Mohamed ◽  
Wesam Salem ◽  
Magdy Afifi ◽  
Yuanda Song
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Ethanolic Extract ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gas Chromatography Mass Spectrometry ◽  
Syzygium Aromaticum ◽  
Medicinal Plant Extracts ◽  
Tract Infections

Pseudomonas aeruginosa is an organism commonly found in the environment and one of the most common causes of human urinary tract infections in developed and developing countries. The present study aimed to investigate the effect of five medicinal plant extracts on the isolated drug-resistant P. aeruginosa clinical isolates. A total of 100 urine samples were collected from Nagaa Hammadi and Qena General Hospitals and private medical analysis laboratories in Qena governorate, Upper Egypt. Samples were screened for the prevalence of UTI pathogens by biochemical tests, antibiotics sensitivity, detection of virulence, and antibiotic-resistant genes by using multiplex PCR. P. aeruginosa is by far the subdominant causative agent with a percentage of 14%. Clinical isolates were multidrug-resistant, containing blaTEM, blaSHV, toxA, lasB, pslA, and fliC resistant and virulence genes. Based on bioactivity, the ethanolic extract of clove (Syzygium aromaticum) was the most active extract among tested medicinal plants and had the maximum zone of inhibition sized 23 mm against tested bacteria. The results of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) showed a high decrease of inhibition within a concentration range of (10 to 121.25 mg/mL and 20 to 30 mg/mL, respectively). Further, major compounds of oleic acid (27.22%), guanosine (8.91%), indole (6.83%), 1-eicosene (6.30%), and cis-10-nonadecenoic acid (5.37%) were determined among 12 bioactive compounds in the ethanolic extract of S. aromaticum using gas chromatography-mass spectrometry (GC-MS). These results indicated that the ethanolic extract of S. aromaticum is a promising antibacterial agent for further studies aiming to control bacterial infections including MDR bacteria and develop novel therapeutic alternatives for the treatment of UTI.

scholarly journals Inhibition of quorum sensing in Pseudomonas aeruginosa by azithromycin and its effectiveness in urinary tract infections

2011 ◽  
Vol 60 (3) ◽  
pp. 300-306 ◽  
Author(s):  
Anju Bala ◽  
Ravi Kumar ◽  
Kusum Harjai
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Quorum Sensing ◽  
Urinary Tract Infections ◽  
Opportunistic Pathogen ◽  
Signal Molecules ◽  
Chronic Infections ◽  
Beneficial Effects ◽  
Tract Infections

Pseudomonas aeruginosa, an opportunistic pathogen, is the third most common pathogen associated with nosocomial urinary tract infections (UTIs). The virulence of this organism is due to its ability to produce quorum-sensing (QS) signal molecules and form biofilms. These biofilms are usually resistant to conventional antibiotics and host immune responses. Recently, beneficial effects of macrolides, especially azithromycin (AZM), have been shown in patients suffering from chronic infections caused by P. aeruginosa. These were due to anti-inflammatory and modulatory effects of AZM on the expression of virulence factors of this pathogen. The present study was designed to evaluate the potential of AZM to inhibit QS signal molecules and its ability to attenuate the virulence of P. aeruginosa in an experimental UTI model. Sub-MIC concentrations of AZM significantly inhibited the production of QS signals, swimming, swarming and twitching motilities, and biofilm formation in vitro. The therapeutic evaluation of AZM in this experimental UTI model showed complete clearance of the organisms from the mouse kidneys. The results of this study highlight the potential effectiveness of AZM in attenuating the virulence of P. aeruginosa in a UTI model.

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