scholarly journals Antibiofilm and antipersister activity of acetic acid against extensively drug resistant Pseudomonas aeruginosa PAW1

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246020
Author(s):  
Madhumita S. Tawre ◽  
Ekta E. Kamble ◽  
Shital N. Kumkar ◽  
Mansura S. Mulani ◽  
Karishma R. Pardesi
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acetic Acid ◽  
Acid Treatment ◽  
Inhibitory Concentration ◽  
Treatment Time ◽  
Polymyxin B ◽  
Drug Resistant ◽  
Burn Wound ◽  
Extensively Drug Resistant ◽  
Acetic Acid Treatment

Pseudomonas aeruginosa is an ESKAPE pathogen associated with difficult-to-treat burn wound and surgical-site infections. This study aimed to characterise an extensively drug resistant (XDR) P. aeruginosa isolate (designated PAW1) and to investigate the antibiofilm and antipersister effect of acetic acid on PAW1. PAW1 was identified using biotypic (VITEK) and genotypic (16S rDNA) analysis. Minimum inhibitory concentration (MIC) and disc susceptibility testing showed high level resistance against all antibiotics from classes including beta lactams, cephems, carbapenems and fluoroquinolones. It was therefore identified as extensively drug resistant (XDR), showing resistance to all antibiotics except for, aminoglycoside (gentamicin and netilmicin) and lipopeptides (polymyxin B). Time kill assays showed antibiotic tolerant, persister cell formation in presence of 100X MICs of gentamicin and polymyxin B. Other virulence traits such as ability to produce lipase, protease, haemolysin, and siderophores and to form biofilms were additional factors which may contribute to its pathogenicity. PAW1 showed promising susceptibility against acetic acid with MIC and minimum biofilm inhibitory concentration of 0.156% (v/v). Percent viability of PAW1 was dependent on dose and treatment time of acetic acid. 0.625% acetic acid treatment of 5 minutes was effective in killing >90% planktonic cells showing lesser toxicity to L929 cells (IC50 = 0.625%). Biofilm disruption caused due to acetic acid was also dose dependent, showing 40.57% disruption after treatment with 0.625% acetic acid for 5 minutes. FESEM imaging and live dead staining of planktonic and biofilm forms of PAW1 confirmed that acetic acid treatment caused 19.04% of cell shrinkage and disruption of extracellular matrix resulting in killing of cells. Antipersister activity of acetic acid was demonstrated by showing complete killing of PAW1 at 4X MIC. Overall, this study characterised an XDR isolate P. aeruginosa showing resistance and tolerance to various antibiotics. Antipersister and antibiofilm effect of acetic acid demonstrates the importance of forgotten topical agents as an effective strategy to treat XDR pathogens.

scholarly journals 1597. Ceftolozane-Tazobactam and Meropenem Synergy Testing Against Multi-Drug and Extensively-Drug Resistant Pseudomonas aeruginosa

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S794-S795
Author(s):  
Mary Francine P Chua ◽  
Syeda Sara Nida ◽  
Jerry Lawhorn ◽  
Janak Koirala
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Synergistic Effect ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Additive Effect ◽  
Teaching Hospitals ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Synergy Testing ◽  
Concentration Indices

Abstract Background Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) have limited therapeutic options for treatment. Ceftolozane/tazobactam is a newer anti-pseudomonal drug effective against resistant PA infections, however resistance against this drug has now also developed and is increasing. In this study, we explored the combination of ceftolozane/tazobactam (CT) and meropenem (MP) as a possible effective regimen against MDR and XDR PA. Methods We obtained 33 non-duplicate isolates of MDR and XDR PA grown from blood, urine and respiratory samples collected from patients admitted between 2015 and 2019 at our two affiliate teaching hospitals. MDR PA was defined as resistance to 3 or more classes of anti-pseudomonal antibiotics, and XDR PA as resistance to all but two or less classes of anti-pseudomonal antibiotics. Antimicrobial preparations of both MP and CT were made according to manufacturer instructions. Susceptibility testing was performed using the checkerboard method in accordance to CLSI guidelines (CLSI M100, 2017). The ATCC 27853 strain of PA used as control. Synergy, additive effect, indifference and antagonism were defined as FIC (fractional inhibitory concentration) indices of ≤0.5, >0.5 to <1, >1 to <4, and >4, respectively. Results Thirteen (39%) of 33 PA isolates were classified as XDR, while 20 (61%) PA isolates were MDR. All isolates were resistant to MP (MIC50 >32 ug/mL), while only 2 (6%) isolates were susceptible to CT (MIC50 64 ug/mL). A synergistic effect was seen in 9 (27.3%) of PA isolates (FIC index range 0.28 to 0.5)— 2 of which were XDR PA, and 7 were MDR PA. An additive effect was seen in 12 (36.4%), with indifference seen in 12 (36.4%) of isolates. In this study, no antagonism was seen when CT and MP were combined. Conclusion When used in combination, CT and MP can exert a synergistic effect against MDR and XDR PA. Additive effect and indifference can also be seen when both antibiotics were used. Moreover, there was no antagonism seen when both antibiotics were combined. This study shows that the use of CT and MP in combination may be an option against XDR and MDR PA infections. Disclosures All Authors: No reported disclosures

scholarly journals Characterization of clinical extensively drug resistant Pseudomonas aeruginosa from a Chinese teaching hospital

2018 ◽  
Vol 12 (10) ◽  
pp. 835-841
Author(s):  
Mingxiang Zou ◽  
Haichen Wang ◽  
Jian Shui ◽  
Jun Li ◽  
Yongmei Hu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Opportunistic Pathogen ◽  
Polymyxin B ◽  
Microtiter Plate ◽  
Resistance Rate ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Drug Resistant Strains

Introduction: Pseudomonas aeruginosa, an important opportunistic pathogen, carries multiple virulence factors which contribute to its adaptation and pathogenicity. The goal of this study was to characterize the virulence factors among extensively drug-resistant P. aeruginosa. Methodology: In this study, 63 non-duplicated extensively drug-resistant P. aeruginosa clinical isolates were collected from December 2013 to July 2015. Polymerase chain reaction (PCR) was used to analyze the homogeneity and the type III secretion system. Microtiter plate method was performed to evaluate the ability to form biofilms associated to twitching and swimming motilities. Results: High percentage (96.8%) of isolates was sensitive to polymyxin B, while the resistance rate to other antibiotics (amikacin, aztreonam, ceftazidime, ciprofloxacin, gentamicin, imipenem, levofloxacin, meropenem, piperacillin-tazobactam) ranged from 80.9% to 100%. Enterobacterial repetitive intergenic consensus-PCR detected seven major groups with minimal genetic variation. All the isolates carried exoT gene, 96.8% carried exoY, 69.8% carried exoS, and 31.7% carried exoU gene. Biofilm formation was confirmed in all strains, out of which 41.3% formed strong biofilm. Motilities analysis showed heterogeneous diameters ranging from 6.02 to 26.09 mm for swimming and from 7.60 to 23.34 mm for twitching motilities. Conclusions: Our findings revealed that the clinical P. aeruginosa isolates tested are the major invasive types in nature and multiple virulence factors were commonly carried in the extensively drug-resistant strains.

scholarly journals Polymyxin B in Combination with Antimicrobials LackingIn VitroActivity versus Polymyxin B in Monotherapy in Critically Ill Patients with Acinetobacter baumannii or Pseudomonas aeruginosa Infections

2015 ◽  
Vol 59 (10) ◽  
pp. 6575-6580 ◽  
Author(s):  
Maria Helena Rigatto ◽  
Fabiane J. Vieira ◽  
Laura C. Antochevis ◽  
Tainá F. Behle ◽  
Natane T. Lopes ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Combination Therapy ◽  
Acinetobacter Baumannii ◽  
Protective Factor ◽  
Polymyxin B ◽  
Apache Ii Score ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Tract Infections

ABSTRACTThere is no clinical evidence supporting the use of polymyxin B in combination with another antimicrobial for infections caused by extensively drug-resistantAcinetobacter baumanniiorPseudomonas aeruginosaisolates. We developed a cohort study of patients in two intensive care units from teaching hospitals to evaluate treatment with intravenous polymyxin B for ≥48 h for severeA. baumanniiorP. aeruginosainfections. Covariates potentially associated with 30-day mortality were evaluated in a Cox proportional hazards model. A total of 101 patients were included; 33 (32.7%) were treated with polymyxin B in combination with an antimicrobial lackingin vitroactivity and 68 (67.3%) with polymyxin B in monotherapy. The overall 30-day mortality was 59.4% (60 patients), comprising 42.4% (14 of 33) and 67.6% (46 of 68) in combination and monotherapy groups, respectively (P= 0.03). The mortality rates were 18.5/1,000 patient days and 36.4/1,000 patient days in the combination and monotherapy groups, respectively (P= 0.02). Combination therapy was independently associated with lower 30-day mortality (hazard ratio, 0.33; 95% confidence interval, 0.17 to 0.64;P= 0.001). Creatinine clearance of ≥60 ml/min was also a protective factor, while a higher acute physiology and chronic health evaluation (APACHE II) score and polymicrobial infection were associated with increased mortality. The results did not change after adding a propensity score for prescribing combination therapy into the model. The protective effect remained when only combination with β-lactam or carbapenem was considered and in both subgroups of patients: those withA. baumanniiinfection and those with lower respiratory tract infections. To our knowledge, this is the first clinical study to show a benefit of combination over monotherapy with polymyxin B for severe extensively drug-resistantA. baumanniiorP. aeruginosainfections.

scholarly journals Long-Term Compassionate Use of Cefiderocol To Treat Chronic Osteomyelitis Caused by Extensively Drug-Resistant Pseudomonas aeruginosa and Extended-Spectrum-β-Lactamase-Producing Klebsiella pneumoniae in a Pediatric Patient

2019 ◽  
Vol 64 (4) ◽  
Author(s):  
Zain I. Alamarat ◽  
Jessica Babic ◽  
Truc T. Tran ◽  
Susan H. Wootton ◽  
An Q. Dinh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Chronic Osteomyelitis ◽  
Polymyxin B ◽  
Adolescent Male ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Extended Spectrum

ABSTRACT We report a 15 year-old Nigerian adolescent male with chronic osteomyelitis caused by an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain of sequence type 773 (ST773) carrying blaNDM-1 and an extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae strain. The patient developed neurological side effects in the form of circumoral paresthesia with polymyxin B and asymptomatic elevation of transaminases with aztreonam (used in combination with ceftazidime-avibactam). Cefiderocol treatment for 14 weeks plus bone implantation resulted in apparent cure and avoided amputation.

scholarly journals Polymyxin B in Combination with Enrofloxacin Exerts Synergistic Killing against Extensively Drug-Resistant Pseudomonas aeruginosa

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Yu-Wei Lin ◽  
Heidi H. Yu ◽  
Jinxin Zhao ◽  
Mei-Ling Han ◽  
Yan Zhu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Population Analysis ◽  
Polymyxin B ◽  
Infection Model ◽  
Limiting Factor ◽  
Drug Resistant ◽  
Limit Of Quantification ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Time Kill

ABSTRACT Polymyxins are increasingly used as a last-resort class of antibiotics against extensively drug-resistant (XDR) Gram-negative bacteria. However, resistance to polymyxins can emerge with monotherapy. As nephrotoxicity is the major dose-limiting factor for polymyxin monotherapy, dose escalation to suppress the emergence of polymyxin resistance is not a viable option. Therefore, novel approaches are needed to preserve this last-line class of antibiotics. This study aimed to investigate the antimicrobial synergy of polymyxin B combined with enrofloxacin against Pseudomonas aeruginosa . Static time-kill studies were conducted over 24 h with polymyxin B (1 to 4 mg/liter) and enrofloxacin (1 to 4 mg/liter) alone or in combination. Additionally, in vitro one-compartment model (IVM) and hollow-fiber infection model (HFIM) experiments were performed against P. aeruginosa 12196. Polymyxin B and enrofloxacin in monotherapy were ineffective against all of the P. aeruginosa isolates examined, whereas polymyxin B-enrofloxacin in combination was synergistic against P. aeruginosa , with ≥2 to 4 log 10 kill at 24 h in the static time-kill studies. In both IVM and HFIM, the combination was synergistic, and the bacterial counting values were below the limit of quantification on day 5 in the HFIM. A population analysis profile indicated that the combination inhibited the emergence of polymyxin resistance in P. aeruginosa 12196. The mechanism-based modeling suggests that the synergistic killing is a result of the combination of mechanistic and subpopulation synergy. Overall, this is the first preclinical study to demonstrate that the polymyxin-enrofloxacin combination is of considerable utility for the treatment of XDR P. aeruginosa infections and warrants future clinical evaluations.

scholarly journals Genomic analysis of an extensively drug-resistant Pseudomonas aeruginosa ST312 harbouring IncU plasmid-mediated blaKPC-2 isolated from ascitic fluid

2021 ◽  
Vol 25 ◽  
pp. 151-153
Author(s):  
Daniela Cristina Tartari ◽  
Caetana Paes Zamparette ◽  
Graciele Martini ◽  
Sandra Christakis ◽  
Luiz Henrique Costa ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Ascitic Fluid ◽  
Genomic Analysis ◽  
Drug Resistant ◽  
Extensively Drug Resistant

scholarly journals Draft Genome Sequence of a Clinically Isolated Extensively Drug-Resistant Pseudomonas aeruginosa Strain

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Bhavani Manivannan ◽  
Niranjana Mahalingam ◽  
Sudhir Jadhao ◽  
Amrita Mishra ◽  
Pravin Nilawe ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Genome Assembly ◽  
Biofilm Formation ◽  
Draft Genome ◽  
Drug Resistant ◽  
Draft Genome Assembly ◽  
Extensively Drug Resistant ◽  
History Of ◽  
Urinary Tuberculosis

We present the draft genome assembly of an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain isolated from a patient with a history of genito urinary tuberculosis. The draft genome is 7,022,546 bp with a G+C content of 65.48%. It carries 7 phage genomes, genes for quorum sensing, biofilm formation, virulence, and antibiotic resistance.

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