SENSITIVITY OF MULTI-RESISTANT PSEUDOMONAS AERUGINOSA STRAINS DEPENDING ON LOCALIZATION OF INFECTIOUS PROCESS

Objective of work was study of antibiotic resistance peculiarities and isolation localization of multi-resistant Pseudomonas aeruginosa strains. Materials and methods. The objects of investigation were multi-resistant P. aeruginosa strains isolated from pleural exudate, bronchial flushing fluid, blood, samples of wound surface and unaffected skin. Identification of the obtained cultures was carried out for morphological, tinctorial and cultural properties as well as using an automatic microbiological analyzer Vitek 32 (BioMerieux). The selected cultures were tested for sensitivity to a wide range of antibiotics using Vitek 32 (BioMerieux). Results. 18 cultures were selected among P. aeruginosa strains isolated from patients. Correspondingly to antibiotic resistance level, these strains were divided into three groups. The first group includes 7 strains (39%) with maximum resistance, representatives of the second group – 5 isolates (28%) were characterized by high resistance, and 6 cultures (33%) were referred to microorganisms with moderate resistance – the third group. Among 12 strains from the first and second groups, only two cultures were isolated in the intensive care unit. But, four cultures were isolated in the burn department, three – in orthopedics and traumatology, two – in surgery, and one – in proctology. It was found that in 50% of cases (9 strains) the cultures studied were isolated from the wound surface in patients with skin burns and after surgical intervention. At the same time, 3 strains (16% of all microorganisms) were localized in the composition of bronchial washings, as well as 2 strains (11% of all cultures) from pleural exudate and blood. From the abscess and skin of the ear, there was isolated one by one strain (6%). Conclusions. More often P. aeruginosa multi-resistant strains were isolated from the wound surface, however, the microorganisms isolated from pleural exudate were characterized the highest resistance to antibiotics, incl. to meropenem. All studied P. aeruginosa cultures retained sensitivity only to colistin and phosphomycin. The activity of other antibiotics was significantly limited, as only the netilmicin (43% of the sensitive strains), meropenem (41%), amikacin (33%), ciprofloxacin (28%) and norfloxacin (28%) influenced the isolated microorganisms.

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Evolution of Cost-Free Resistance under Fluctuating Drug Selection in Pseudomonas aeruginosa

mSphere ◽

10.1128/msphere.00158-17 ◽

2017 ◽

Vol 2 (4) ◽

Cited By ~ 18

Author(s):

Anita H. Melnyk ◽

Nicholas McCloskey ◽

Aaron J. Hinz ◽

Jeremy Dettman ◽

Rees Kassen

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Antibiotic Treatment ◽

Experimental Evolution ◽

Public Health Problem ◽

Content Type ◽

Compensatory Evolution ◽

High Fitness ◽

Treatment Conditions ◽

Resistant Strains

ABSTRACT Antibiotic resistance is a global problem that greatly impacts human health. How resistance persists, even in the absence of antibiotic treatment, is thus a public health problem of utmost importance. In this study, we explored the antibiotic treatment conditions under which cost-free resistance arises, using experimental evolution of the bacterium Pseudomonas aeruginosa and the quinolone antibiotic ciprofloxacin. We found that intermittent antibiotic treatment led to the evolution of cost-free resistance and demonstrate that compensatory evolution is the mechanism responsible for cost-free resistance. Our results suggest that discontinuous administration of antibiotic may be contributing to the high levels of antibiotic resistance currently found worldwide. Antibiotic resistance evolves rapidly in response to drug selection, but it can also persist at appreciable levels even after the removal of the antibiotic. This suggests that many resistant strains can both be resistant and have high fitness in the absence of antibiotics. To explore the conditions under which high-fitness, resistant strains evolve and the genetic changes responsible, we used a combination of experimental evolution and whole-genome sequencing to track the acquisition of ciprofloxacin resistance in the opportunistic pathogen Pseudomonas aeruginosa under conditions of constant and fluctuating antibiotic delivery patterns. We found that high-fitness, resistant strains evolved readily under fluctuating but not constant antibiotic conditions and that their evolution was underlain by a trade-off between resistance and fitness. Whole-genome sequencing of evolved isolates revealed that resistance was gained through mutations in known resistance genes and that second-site mutations generally compensated for costs associated with resistance in the fluctuating treatment, leading to the evolution of cost-free resistance. Our results suggest that current therapies involving intermittent administration of antibiotics are contributing to the maintenance of antibiotic resistance at high levels in clinical settings. IMPORTANCE Antibiotic resistance is a global problem that greatly impacts human health. How resistance persists, even in the absence of antibiotic treatment, is thus a public health problem of utmost importance. In this study, we explored the antibiotic treatment conditions under which cost-free resistance arises, using experimental evolution of the bacterium Pseudomonas aeruginosa and the quinolone antibiotic ciprofloxacin. We found that intermittent antibiotic treatment led to the evolution of cost-free resistance and demonstrate that compensatory evolution is the mechanism responsible for cost-free resistance. Our results suggest that discontinuous administration of antibiotic may be contributing to the high levels of antibiotic resistance currently found worldwide.

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A large-scale comparison shows that genetic changes causing antibiotic resistance in experimentally evolved Pseudomonas aeruginosa predict those in naturally evolved bacteria

10.1101/674531 ◽

2019 ◽

Author(s):

Samuel J. T. Wardell ◽

Attika Rehman ◽

Lois W. Martin ◽

Craig Winstanley ◽

Wayne M. Patrick ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Experimental Evolution ◽

Large Scale ◽

Genetic Basis ◽

Clinical Isolates ◽

Resistant Bacteria ◽

Antibiotic Resistant ◽

Health Crisis ◽

Wide Range

AbstractPseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections. An increasing number of isolates have acquired mutations that make them antibiotic resistant, making treatment more difficult. To identify resistance-associated mutations we experimentally evolved the antibiotic sensitive strain P. aeruginosa PAO1 to become resistant to three widely used anti-pseudomonal antibiotics, ciprofloxacin, meropenem and tobramycin. Mutants were able to tolerate up to 2048-fold higher concentrations of antibiotic than strain PAO1. Genome sequences were determined for thirteen mutants for each antibiotic. Each mutant had between 2 and 8 mutations. There were at least 8 genes mutated in more than one mutant per antibiotic, demonstrating the complexity of the genetic basis of resistance. Additionally, large deletions of up to 479kb arose in multiple meropenem resistant mutants. For all three antibiotics mutations arose in genes known to be associated with resistance, but also in genes not previously associated with resistance. To determine the clinical relevance of mutations uncovered in experimentally-evolved mutants we analysed the corresponding genes in 457 isolates of P. aeruginosa from patients with cystic fibrosis or bronchiectasis as well as 172 isolates from the general environment. Many of the genes identified through experimental evolution had changes predicted to be function-altering in clinical isolates but not in isolates from the general environment, showing that mutated genes in experimentally evolved bacteria can predict those that undergo mutation during infection. These findings expand understanding of the genetic basis of antibiotic resistance in P. aeruginosa as well as demonstrating the validity of experimental evolution in identifying clinically-relevant resistance-associated mutations.ImportanceThe rise in antibiotic resistant bacteria represents an impending global health crisis. As such, understanding the genetic mechanisms underpinning this resistance can be a crucial piece of the puzzle to combatting it. The importance of this research is that by experimentally evolving P. aeruginosa to three clinically relevant antibiotics, we have generated a catalogue of genes that can contribute to resistance in vitro. We show that many (but not all) of these genes are clinically relevant, by identifying variants in clinical isolates of P. aeruginosa. This research furthers our understanding of the genetics leading to resistance in P. aeruginosa and provides tangible evidence that these genes can play a role clinically, potentially leading to new druggable targets or inform therapies.

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Antibiotic resistance and bacteriophages commercial drugs susceptibility of Klebsiella pneumonia and Pseudomonas aeruginosa clinical strains

Sanitarnyj vrač (Sanitary Inspector) ◽

10.33920/med-08-2109-08 ◽

2021 ◽

pp. 73-80

Author(s):

D. A. Sedova ◽

A. S. Kaljuzhin ◽

Juliya Alexandrovna Romanovskaya

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Klebsiella Pneumoniae ◽

High Resistance ◽

Hemolytic Activity ◽

Clinical Isolates ◽

Klebsiella Pneumonia ◽

Clinical Strains ◽

Resistant Strains ◽

High Degree

The article provides information about hemolytic activity, susceptibility to different groups of antibiotics and bacteriophages commercial drugs of Klebsiella pneumoniae and Pseudomonas aeruginosa clinical strains. The analysis of the obtainedresults showed a high degree of hemolytic activity dissemination among Pseudomonas aeruginosa (78,60 % of strains), as well as their high resistance to cefotaxime, chloramphenicol, azithromycin and tetracycline (82,14–100 % of resistant strains). K. pneumoniae clinical isolates were resistant to cefazolin, azithromycin, and the nitrofuran group (66,67–81,48 %). In turn, specific phagolysates for treatment deseases of K. pneumoniae and P. aeruginosa etiology showed the greatest efficiency against both groups of microorganisms among the studied commercial preparations of bacteriophages.

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Genetic Variations in MexAB-OprM Efflux Pump Regulators and Their Association with Antibiotic Resistance and Sequence type in Clinical and Epidemiologically High-risk Clones of Pseudomonas Aeruginosa.

10.21203/rs.3.rs-56805/v1 ◽

2020 ◽

Author(s):

Pamela Aguilar-Rodea ◽

Gerardo Zúñiga ◽

René Cerritos ◽

Benjamín Antonio Rodríguez-Espino ◽

Gerardo E. Rodea ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

High Risk ◽

Efflux Pump ◽

Phylogenetic Network ◽

Principal Component ◽

Sequence Type ◽

Efflux Pump Inhibitor ◽

Wide Range ◽

The Relationship

Abstract Background: Pseudomonas aeruginosa is a major opportunistic pathogen involved in healthcare-associated infections with high mortality rates. This bacterium exhibits elevated resistance to a wide range of antibiotics, resulting in part from the overexpression of efflux pumps, among which MexAB-OprM stands out as constitutive. Antibiotic resistance in clinical isolates is associated with mutations in the mexR, nalC, and nalD repressors that modulate the expression of this efflux pump. This study identifies point mutations in the mexR, nalC, and nalD genes and investigates their associations with antibiotic resistance and sequence type in clinical and epidemiologically high-risk clones of P. aeruginosa. Results: A total of 91 P. aeruginosa strains isolated at a pediatric hospital in Mexico (2007–2015) were classified according to their resistance to antibiotics. The strains were typed by multilocus sequencing of 7 genes. The MexAB-OprM efflux pump phenotype was determined using the minimal inhibitory concentration for the reporter antibiotic carbenicillin in the presence/absence of the efflux pump inhibitor Phe-Arg-β-naphthylamine. Sequencing of the mexR, nalC, and nalD genes to identify mutations was performed. Genetic relationship among the strains was evaluated by a phylogenetic inference analysis using maximum likelihood to construct a phylogenetic network. The relationship between variables was determined by a principal component analysis. STs revealed six main complexes. Mutations in the mexR, nalC, and nalD genes revealed 27 different haplotypes. Pan-drug and extensive drug resistant profiles were associated with specific STs with haplotypes 1 (ST1725, endemic clone), 8, 12 (ST233, epidemiologically high-risk clone), and 5 [related to dead when compared to ST1725 and ST233 (RRR 23.34; p=0.009 and RRR 32.01; p=0.025)], however the resistance in these strains was not mainly attributed to the MexAB-OprM phenotype. Strains with the same haplotype and resistant profile showed different pump behavior.Conclusions: A significant relationship between ST and resistant profiles was observed; on one hand, the mexR-nalC-nalD haplotypes were not related to the MexAB-OprM efflux pump phenotypic behavior. On the other hand, the relationship between mexR-nalC-nalD haplotypes and phylogenetically related ST, suggest mutations in these repressors are highly maintained within these STs.

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Prediction of antibiotic resistant strains of bacteria from their beta-lactamases protein

10.1101/2021.06.26.450028 ◽

2021 ◽

Author(s):

Lubna Maryam ◽

Anjali Dhall ◽

Sumeet Patiyal ◽

Salman Sadullah Usmani ◽

Neelam Sharma ◽

...

Keyword(s):

Amino Acids ◽

Antibiotic Resistance ◽

Prediction Models ◽

Training Dataset ◽

Validation Dataset ◽

Side Chains ◽

Beta Lactamase ◽

Beta Lactamases ◽

Wide Range ◽

Resistant Strains

Number of beta-lactamase variants have ability to deactivate ceftazidime antibiotic, which is the most commonly used antibiotic for treating infection by Gram-negative bacteria. In this study an attempt has been made to develop a method that can predict ceftazidime resistant strains of bacteria from amino acid sequence of beta-lactamases. We obtained beta-lactamases proteins from the β-lactamase database, corresponding to 87 ceftazidime-sensitive and 112 ceftazidime-resistant bacterial strains. All models developed in this study were trained, tested, and evaluated on a dataset of 199 beta-lactamases proteins. We generate 9149 features for beta-lactamases using Pfeature and select relevant features using different algorithms in scikit-learn package. A wide range of machine learning techniques (like KNN, DT, RF, GNB, LR, SVC, XGB) has been used to develop prediction models. Our random forest-based model achieved maximum performance with AUROC of 0.80 on training dataset and 0.79 on the validation dataset. The study also revealed that ceftazidime-resistant beta-lactamases have amino acids with non-polar side chains in abundance. In contrast, ceftazidime-sensitive beta-lactamases have amino acids with polar side chains and charged entities in abundance. Finally, we developed a webserver- ABCRpred, for the scientific community working in the era of antibiotic resistance to predict the antibiotic resistance/susceptibility of beta-lactamase protein sequences. The server is freely available at (http://webs.iiitd.edu.in/raghava/abcrpred/ ).

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Detection of qnrS and tetA resistance coding genes in Pseudomonas aeruginosaof egg-laying hens farmin Cianjur Regency, West Java

Jurnal Natural ◽

10.24815/jn.v21i2.20584 ◽

2021 ◽

Vol 21 (2) ◽

pp. 64-71

Author(s):

FAUZAN ARISANDI ◽

SAFIKA . SAFIKA ◽

FACHRIYAN HASMI PASARIBU

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Laying Hens ◽

Disease Incidence ◽

Antibiotic Sensitivity ◽

Cloacal Swab ◽

Egg Laying ◽

West Java ◽

Resistance Level ◽

Antibiotic Sensitivity Test

The use of antibiotics is an alternative to reduce disease incidence and is used to increase egg-laying hens. This study aims to detect the presence of antibiotic resistance to resistance coding genes in Pseudomonas aeruginosa bacteria. The cloacal swab samples were collected randomly as many 66 samples from several egg-laying hens farms in Cianjur Regency, West Java. The collected isolates were examined bacteriologically. The results of the antibiotic sensitivity test of 8 samples (12.1%) of the Pseudomonas aeruginosa showed the resistance level of antibiotics class tetracycline (tetracycline50%, oxytetracycline75%, and doxycycline50%), fluoroquinolone (enrofloxacin 12.5%), and phenicol (chloramphenicol 12.5%). Pseudomonas aeruginosa was resistant to tetracyclines, oxytetracyclines, doxycycline, enrofloxacin and is sensitive to chloramphenicol. The detection of resistance coding genes showed the genes amount of tetA (62.5%) and qnrS (75%). Efforts to determine the level of resistance and use of antibiotics in farms need regular surveillance and monitoring to ensure the wise use of antibiotics.

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Microbiological and Molecular Genetic Aspects of Antibiotic Resistance of Pseudomonas aeruginosa and Acinetobacter baumannii

Epidemiology and Vaccinal Prevention ◽

10.31631/2073-3046-2019-18-6-34-38 ◽

2020 ◽

Vol 18 (6) ◽

pp. 34-38

Author(s):

Yu. E. Skurikhina ◽

V. B. Turkutyukov

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Acinetobacter Baumannii ◽

Molecular Genetic ◽

Resistance Mechanisms ◽

Steady Increase ◽

Molecular Genetic Study ◽

Antibiotic Resistant ◽

Resistant Strains ◽

High Level

Relevance. The increase in the frequency of infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii, which have a high level of resistance to many groups of antibiotics, requires a comprehensive study, including modern research methods.Aims. The study of regional features of the dynamics of the formation and circulation of antibiotic-resistant strains A. baumannii and P. aeruginosa.Materials and methods. During 2009-2018 we analyzed the data of microbiological laboratories of multidisciplinary hospitals and carried out a molecular genetic study of the determinants of antibiotic resistance by PCR of A. baumannii and P. aeruginosa strains isolated from clinical material in order to determine the level of variability of resistance.Results. The study revealed a tendency to increase in the proportion of strains A. baumannii and P. aeruginosa in the etiological structure of healh-care associated infections and purulent-septic infections; high incidence of strains resistant to cephalosporins, carbapenems, beta-lactams and multi-resistant strains. The appearance and distribution of the determinants of antibiotic resistance NDM-1 and MCR-1 in these bacteria were also detected.Conclusions. Over the past decade, a steady increase in the proportion of A. baumannii and P. Aeruginosa resistant to many antibiotics in patients in intensive care unit and surgery departments in hospitals of Vladivostok (Primorsky reg., Russia), and the emergence of new antimicrobial resistance mechanisms in these microorganisms.

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Pseudomonas aeruginosa bacteremia: Associations with a source of infection and antibiotic resistance

Medicina ◽

10.3390/medicina45010001 ◽

2008 ◽

Vol 45 (1) ◽

pp. 1

Author(s):

Asta Dambrauskienė ◽

Dalia Adukauskienė ◽

Jolanta Jeroch ◽

Astra Vitkauskienė

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Respiratory Tract ◽

Lower Respiratory Tract ◽

Multidrug Resistant ◽

Diffusion Method ◽

Disc Diffusion ◽

Disc Diffusion Method ◽

Source Of Infection ◽

Resistant Strains

Aim of the study. To determine the associations between the source of infection and antibiotic resistance in patients with Pseudomonas aeruginosa bacteremia. Material and methods. A retrospective analysis of 50 patients with Pseudomonas aeruginosa bacteremia was carried out. If sepsis was suspected, blood culture was incubated in an automatic system BACTEC 9240. Then bacteria were identified, and their antibiotic resistance was estimated by disc diffusion method. If Pseudomonas aeruginosa strains were resistant to three or more antibiotics, they were considered as multidrug-resistant.Results. The origin of bacteremia was confirmed in 33 (66%) patients. Lower respiratory tract was the predominant source of Pseudomonas aeruginosa bacteremia (81.8%, n=27) as compared with infection of wound (39.4%, n=13), urinary tract (15.2%, n=5), and drain or cerebrospinal fluid (9.1%, n=3) (P<0.05). Eighteen percent (n=9) of strains, which caused bacteremia, were resistant to ceftazidime; 38% (n=19), to piperacillin; 22% (n=11), to imipenem; 26% (n=13), to meropenem; 24% (n=12), to ciprofloxacin; 40% (n=20), to gentamicin; and only 8% (n=4), to amikacin. Multidrug-resistant Pseudomonas aeruginosa strains were more frequently isolated if a source of infection was wound comparing to a source of other localization (61.5%, n=8 and 20.0%, n=4, respectively; P<0.05). Resistance of Pseudomonas aeruginosa strains to imipenem was associated with resistance to ciprofloxacin (13.2%, n=5 and 50.0%, n=6, retrospectively; P<0.05), but resistance to meropenem – both to ciprofloxacin and amikacin. Conclusions. The predominant source of Pseudomonas aeruginosa bacteremia was lower respiratory tract, and multidrug-resistant strains caused bacteremia more frequently if a source infection was wound. Pseudomonas aeruginosa resistance to carbapenems was associated with resistance to ciprofloxacin and resistance to meropenem – also to amikacin. Resistance of strains to ceftazidime and piperacillin was associated with resistance to gentamicin.

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ANTIBIOTIC RESISTANCE AND ACID PRODUCTION AMONG STARTER CULTURES BELONGING TO THE GENUS STREPTOCOCCUS1

Journal of Milk and Food Technology ◽

10.4315/0022-2747-24.10.317 ◽

1961 ◽

Vol 24 (10) ◽

pp. 317-320 ◽

Cited By ~ 3

Author(s):

R. J. Richards ◽

H. E. Kennedy ◽

I. A. Gould

Keyword(s):

Antibiotic Resistance ◽

Acid Production ◽

Starter Cultures ◽

Single Strain ◽

Wide Range ◽

Resistance To Penicillin ◽

Resistant Strains ◽

Produce Acid

The susceptibility to penicillin of a wide range of single strain cultures of lactic streptococci was determined. Approximately 50% of the strains studied exhibited resistance to penicillin at the 0.1 unit/ml level. Eight of these cultures were adapted to grow in the presence of 0.5 unit penicillin/ml, but they were unable to produce acid at a rate or quantity equal to that of their sensitive parent strains. Cultures obtained from naturally resistant isolates produced more acid in the presence of low penicillin concentrations than their sensitive parent counterparts, but less than that produced by “trained” resistant strains from the same parent origin.

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Risk Factors and Outcomes of Antibiotic-resistant Pseudomonas aeruginosa Bloodstream Infection in Adult Patients With Acute Leukemia

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1522 ◽

2020 ◽

Vol 71 (Supplement_4) ◽

pp. S386-S393

Author(s):

Yuanqi Zhao ◽

Qingsong Lin ◽

Li Liu ◽

Runzhi Ma ◽

Juan Chen ◽

...

Keyword(s):

Risk Factors ◽

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Acute Leukemia ◽

Bloodstream Infection ◽

Clinical Characteristics ◽

Antibiotic Use ◽

Limited Information ◽

Antibiotic Resistant ◽

Resistant Strains

Abstract Background Pseudomonas aeruginosa (PA) bloodstream infection (BSI) is a common complication in patients with acute leukemia (AL), and the prevalence of antibiotic-resistant strains poses a serious problem. However, there is limited information regarding antibiotic resistance, clinical characteristics, and outcomes of PA BSI in AL patients. This study explored characteristics associated with the clinical outcomes of AL patients with PA BSI and analyzed factors associated with BSI caused by multidrug-resistant (MDR) or carbapenem-resistant strains. Methods This single-center retrospective study enrolled hospitalized AL patients who developed PA BSI during January 2014–December 2019. The Kaplan-Meier method was used to plot survival curves. Multivariate logistic regression analyses were also performed. Results Of 293 eligible patients with PA BSI, 55 (18.8%) received inappropriate empirical antibiotic therapy within 48 hours of BSI onset, whereas up to 65.8% MDR-PA BSI patients received inappropriate empirical treatment. The 30-day mortality rate was 8.5% for all patients. However, the 30-day mortality rates were 28.9% and 5.5% in MDR-PA BSI and non–MDR-PA BSI patients, respectively (P < .001). On multivariate analysis, previous use of quinolones (odds ratio [OR], 5.851 [95% confidence interval {CI}, 2.638–12.975]) and piperacillin/tazobactam (OR, 2.837 [95% CI, 1.151–6.994]) were independently associated with MDR-PA BSI; and MDR-PA BSI (OR, 7.196 [95% CI, 2.773–18.668]), perianal infection (OR, 4.079 [95% CI, 1.401–11.879]), pulmonary infection (OR, 3.028 [95% CI, 1.231–7.446]), and age ≥55 years (OR, 2.871 [95% CI, 1.057–7.799]) were independent risk factors for 30-day mortality. Conclusions MDR increases mortality risk in PA BSI patients, and previous antibiotic exposure is important in MDR-PA BSI development. Rational antibiotic use based on local antimicrobial susceptibility and clinical characteristics can help reduce antibiotic resistance and mortality.

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