scholarly journals Emergence of Antibiotic-Resistant Pseudomonas aeruginosa: Comparison of Risks Associated with Different Antipseudomonal Agents

1999 ◽  
Vol 43 (6) ◽  
pp. 1379-1382 ◽  
Author(s):  
Yehuda Carmeli ◽  
Nicolas Troillet ◽  
George M. Eliopoulos ◽  
Matthew H. Samore
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Cohort Study ◽  
Nosocomial Infections ◽  
Individual Agent ◽  
Antibiotic Resistant ◽  
Relative Risks ◽  
Hazard Ratios ◽  
Emergence Of Resistance

ABSTRACT Pseudomonas aeruginosa is a leading cause of nosocomial infections. The risk of emergence of antibiotic resistance may vary with different antibiotic treatments. To compare the risks of emergence of resistance associated with four antipseudomonal agents, ciprofloxacin, ceftazidime, imipenem, and piperacillin, we conducted a cohort study, assessing relative risks for emergence of resistantP. aeruginosa in patients treated with any of these drugs. A total of 271 patients (followed for 3,810 days) with infections due to P. aeruginosa were treated with the study agents. Resistance emerged in 28 patients (10.2%). Adjusted hazard ratios for the emergence of resistance were as follows: ceftazidime, 0.7 (P = 0.4); ciprofloxacin, 0.8 (P = 0.6); imipenem, 2.8 (P = 0.02); and piperacillin, 1.7 (P = 0.3). Hazard ratios for emergence of resistance to each individual agent associated with treatment with the same agent were as follows: ceftazidime, 0.8 (P = 0.7); ciprofloxacin, 9.2 (P = 0.04); imipenem, 44 (P = 0.001); and piperacillin, 5.2 (P= 0.01). We concluded that there were evident differences among antibiotics in the likelihood that their use would allow emergence of resistance in P. aeruginosa. Ceftazidime was associated with the lowest risk, and imipenem had the highest risk.

scholarly journals Annual relative increased in inpatient mortality from antimicrobial resistant nosocomial infections in Thailand

2019 ◽  
Vol 147 ◽  
Author(s):  
T. Phodha ◽  
A. Riewpaiboon ◽  
K. Malathum ◽  
P. C. Coyte
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Cohort Study ◽  
Nosocomial Infections ◽  
Retrospective Cohort ◽  
Clinical Characteristics ◽  
Inpatient Mortality ◽  
Major Health ◽  
Hazard Ratios

AbstractAntimicrobial resistance is a major health threat worldwide as it brings about poorer treatment outcome and places economic burden to the society. This study aims to estimate the annual relative increased in inpatient mortality from antimicrobial resistant (AMR) nosocomial infections (NI) in Thailand. A retrospective cohort study was conducted at Ramathibodi Hospital, Bangkok, Thailand, over 2008–2012. Survival model was used to estimate the hazard ratio of mortality of AMR relative to those patients without resistance (non-AMR) after controlling for nine potential confounders. The majority of NI (73.80%) were caused by AMR bacteria over the study period. Patients in the AMR and non-AMR groups had similar baseline clinical characteristics. Relative to patients in the non-AMR group, the expected hazard ratios of mortality for patients in the AMR group with Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were 1.92 (95% CI 0.10–35.52), 1.25 (95% CI 0.08–20.29), 1.60 (95% CI 0.13–19.10) and 1.84 (95% CI 0.04–95.58), respectively. In the complete absence of AMR bacteria, this study estimated that annually, in Thailand, there would be 111 295 fewer AMR cases and 48 258 fewer deaths.

scholarly journals Draft Genome Sequence of Antibiotic-Resistant Enterococcus faecalis Strain UMB0843, Isolated from the Female Urinary Tract

2020 ◽  
Vol 9 (20) ◽  
Author(s):  
Natalia Purta ◽  
Taylor Miller-Ensminger ◽  
Adelina Voukadinova ◽  
Alan J. Wolfe ◽  
Catherine Putonti
Keyword(s):  
Antibiotic Resistance ◽  
Urinary Tract ◽  
Enterococcus Faecalis ◽  
Genome Analysis ◽  
Nosocomial Infections ◽  
Draft Genome ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Female Urinary Tract ◽  
Multiple Antibiotics

Here, we introduce the 2.8-Mbp draft genome of Enterococcus faecalis strain UMB0843, isolated from the female urinary tract. E. faecalis is a leading cause of nosocomial infections, and many strains are often resistant to multiple antibiotics. We focus our genome analysis on the multiple genes involved in antibiotic resistance in this strain.

scholarly journals Phage steering of antibiotic-resistance evolution in the bacterial pathogen, Pseudomonas aeruginosa

2020 ◽  
Vol 2020 (1) ◽  
pp. 148-157 ◽  
Author(s):  
James Gurney ◽  
Léa Pradier ◽  
Joanne S Griffin ◽  
Claire Gougat-Barbera ◽  
Benjamin K Chan ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Bacterial Pathogen ◽  
Antibiotic Sensitivity ◽  
Resistant Bacteria ◽  
Phage Resistance ◽  
Antibiotic Resistant ◽  
Trade Off

Abstract Background and objectives Antimicrobial resistance is a growing global concern and has spurred increasing efforts to find alternative therapeutics. Bacteriophage therapy has seen near constant use in Eastern Europe since its discovery over a century ago. One promising approach is to use phages that not only reduce bacterial pathogen loads but also select for phage resistance mechanisms that trade-off with antibiotic resistance—so called ‘phage steering’. Methodology Recent work has shown that the phage OMKO1 can interact with efflux pumps and in so doing select for both phage resistance and antibiotic sensitivity of the pathogenic bacterium Pseudomonas aeruginosa. We tested the robustness of this approach to three different antibiotics in vitro (tetracycline, erythromycin and ciprofloxacin) and one in vivo (erythromycin). Results We show that in vitro OMKO1 can reduce antibiotic resistance of P. aeruginosa (Washington PAO1) even in the presence of antibiotics, an effect still detectable after ca.70 bacterial generations in continuous culture with phage. Our in vivo experiment showed that phage both increased the survival times of wax moth larvae (Galleria mellonella) and increased bacterial sensitivity to erythromycin. This increased antibiotic sensitivity occurred both in lines with and without the antibiotic. Conclusions and implications Our study supports a trade-off between antibiotic resistance and phage sensitivity. This trade-off was maintained over co-evolutionary time scales even under combined phage and antibiotic pressure. Similarly, OMKO1 maintained this trade-off in vivo, again under dual phage/antibiotic pressure. Our findings have implications for the future clinical use of steering in phage therapies. Lay Summary: Given the rise of antibiotic-resistant bacterial infection, new approaches to treatment are urgently needed. Bacteriophages (phages) are bacterial viruses. The use of such viruses to treat infections has been in near-continuous use in several countries since the early 1900s. Recent developments have shown that these viruses are not only effective against routine infections but can also target antibiotic resistant bacteria in a novel, unexpected way. Similar to other lytic phages, these so-called ‘steering phages’ kill the majority of bacteria directly. However, steering phages also leave behind bacterial variants that resist the phages, but are now sensitive to antibiotics. Treatment combinations of these phages and antibiotics can now be used to greater effect than either one independently. We evaluated the impact of steering using phage OMKO1 and a panel of three antibiotics on Pseudomonas aeruginosa, an important pathogen in hospital settings and in people with cystic fibrosis. Our findings indicate that OMKO1, either alone or in combination with antibiotics, maintains antibiotic sensitivity both in vitro and in vivo, giving hope that phage steering will be an effective treatment option against antibiotic-resistant bacteria.

scholarly journals Role of biofilm-specific antibiotic resistance genes PA0756-0757, PA5033 and PA2070 in Pseudomonas aeruginosa

2018 ◽  
Author(s):  
Prasanth Manohar ◽  
Thamaraiselvan Shanthini ◽  
Reethu Ann Philip ◽  
Subramani Ramkumar ◽  
Manali Kale ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Biofilm Formation ◽  
Tamil Nadu ◽  
Antibiotic Resistance Genes ◽  
Clinical Samples ◽  
Cross Sectional ◽  
Antibiotic Resistant ◽  
Resistant Genes

AbstractTo evaluate the presence of biofilm-specific antibiotic-resistant genes, PA0756-0757, PA5033 and PA2070 in Pseudomonas aeruginosa isolated from clinical samples in Tamil Nadu. For this cross-sectional study, 24 clinical isolates (included pus, urine, wound, and blood) were collected from two diagnostic centers in Chennai from May 2015 to February 2016. Biofilm formation was assessed using microtiter dish biofilm formation assay and minimal inhibitory concentration (MIC) and minimal bactericidal concentrations (MBC) were determined for planktonic and biofilm cells (MBC assay). Further, PCR amplification of biofilm-specific antibiotic resistance genes PA0756-0757, PA5033 and PA2070 were performed. Biofilm formation was found to be moderate/strong in 16 strains. MBC for planktonic cells showed that 4, 7, 10 and 14 strains were susceptible to gentamicin, ciprofloxacin, meropenem and colistin respectively. In MBC assay for biofilm cells (MBC-B), all the 16 biofilm producing strains were resistant to ciprofloxacin and gentamicin whereas nine and four were resistant to meropenem, and colistin respectively. The biofilm-specific antibiotic-resistant genes PA0756-0757 was found in 10 strains, 6 strains with PA5033 and 9 strains with PA2070 that were found to be resistant phenotypically. This study highlighted the importance of biofilm-specific antibiotic resistance genes PA0756-0757, PA5033, and PA2070 in biofilm-forming P. aeruginosa.

scholarly journals Detection of antibiotic resistance genes among multiple drug resistant Pseudomonas aeruginosa strains isolated from clinical sources in selected health institutions in Kwara State.

2021 ◽  
Vol 10 (1) ◽  
pp. 40-48
Author(s):  
O.C. Adekunle ◽  
A. Mustapha ◽  
G. Odewale ◽  
R.O. Ojedele
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Multiple Drug Resistance ◽  
Antibiotic Resistance Genes ◽  
Clinical Samples ◽  
Multiple Drug ◽  
Antibiotic Resistant ◽  
Clinical Specimens ◽  
Health Institutions

Introduction: Pseudomonas aeruginosa (P. aeruginosa) is a frequent nosocomial pathogen that causes severe diseases in many clinical and community settings. The objectives were to investigate the occurrence of multiple antibiotic resistant P. aeruginosa strains among clinical samples and to detect the presence of antibiotic resistance genes in the DNA molecules of the strains.Methods: Clinical specimens were collected aseptically from various human anatomical sites in five selected health institutions within Kwara State, Nigeria. Multiple drug resistance patterns of isolated micro-organisms to different antibiotics were determined using the Bauer Kirby disc diffusion technique. The DNA samples of the multiple resistant P. aeruginosa strains were extracted and subjected to Polymerase Chain Reaction (PCR) for resistance gene determination.Results: A total of 145 isolates were identified as P. aeruginosa from the clinical samples. Absolute resistance to ceftazidime, gentamicin and ceftriaxone was observed while low resistance to ciprofloxacin, piperacillin and imipenem was documented. The prevalence of bla VIM , ,bla CTX-M and blaTEM were 34.4 %, 46.7 % and 16.7 % respectively.Conclusion: This study has shown that there is a high occurrence of metallo â-lactamase- producing and antibiotic-resistant strains of P. aeruginosa in clinical specimens from the studied area. Keywords: Metallo â-lactamase enzyme, P. aeruginosa, clinical samples, antibiotic-resistance genes

scholarly journals Pseudomonas aeruginosa infection of avian origin: Zoonosis and one health implications

2021 ◽  
pp. 2155-2159
Author(s):  
Wafaa A. Abd El-Ghany
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Public Health Problem ◽  
Lung Damage ◽  
Antibiotic Resistant ◽  
Poultry Products ◽  
Chicken Carcass ◽  
Enteric Infections ◽  
Commercial Poultry ◽  
Avian Origin

Zoonotic diseases are diseases that are transmitted from animals to humans and vice versa. Pseudomonas aeruginosa (P. aeruginosa) is a pathogen with zoonotic nature. Commercial poultry could be infected with P. aeruginosa, especially at young ages with great losses. Infection of embryos with P. aeruginosa induced death in the shell, while infection of chicks led to septicemia, respiratory and enteric infections, and high mortality. Humans are also highly susceptible to P. aeruginosa infection, and the disease is associated with severe lung damage, especially in immunocompromised patients. Chicken carcass and related poultry retail products play an important role in the transmission of P. aeruginosa to humans, especially after processing in abattoirs. Treatment of P. aeruginosa infection is extremely difficult due to continuous development of antibiotic resistance. The transfer of antibiotic-resistant genes from poultry products to humans creates an additional public health problem. Accordingly, this study focused on avian pseudomonad, especially P. aeruginosa, with respect to infection of poultry, transmission to humans, and treatment and antibiotic resistance.

scholarly journals Antibiotic Resistance of Pseudomonas aeruginosa Strains in the Patients Admitted to Imam Reza Hospital in Kermanshah, Iran (2016-2018)

2020 ◽  
Vol 24 (4) ◽  
Author(s):  
Ronak Miladi ◽  
Mohammad Hossein Zamanian ◽  
Alireza Janbakhsh ◽  
Feizollah Mansouri ◽  
Babak Sayad ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Nosocomial Infections ◽  
Epidemiological Studies ◽  
Cross Sectional Study ◽  
Diffusion Method ◽  
Emergency Ward ◽  
Cross Sectional ◽  
National Programs ◽  
Standard Disc

Background: Nosocomial infections are important medical concerns in developed and developing countries. Pseudomonas aeruginosa is considered the third leading cause of nosocomial infections following Staphylococcus aureus and Escherichia coli. Objectives: The present study aimed to determine the antibiotic resistance of isolated P. aeruginosa strains in the patients admitted to Imam Reza Hospital in Kermanshah, Iran. Methods: This descriptive, cross-sectional study was conducted on 900 patients with positive P. aeruginosa cultures who were admitted to Imam Reza Hospital in Kermanshah, Iran during 2016-2018. Bacterial isolates were separated using laboratory tests, and the standard disc-diffusion method was used to assess antibiotic susceptibility based on the CLSI protocol. Data analysis was performed in SPSS version 24. Results: The majority of the P. aeruginosa-positive cases were isolated from the emergency ward (44.3%), intensive care unit (21.9%), blood samples (40.4%), and urine samples (18.7%). The highest antibiotic resistance was observed against cotrimoxazole, ceftriaxone, ampicillin, ampicillin-sulbactam, nitrofurantoin, nalidixic acid, cefazolin, and cefixime. In addition, ciprofloxacin and imipenem were the most effective antibiotics against P. aeruginosa with the sensitivity of 68.1% and 57.2%, respectively. Conclusions: According to the results, P. aeruginosa had high resistance against antibiotics such as cotrimoxazole and ceftriaxone. Therefore, these antibiotics should be used correctly and reasonably, and epidemiological studies in this regard should be focused on proposing national programs to prevent the further spread of antibiotic resistance.

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

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.

scholarly journals Dynamics of Mutator and Antibiotic-Resistant Populations in a Pharmacokinetic/Pharmacodynamic Model of Pseudomonas aeruginosa Biofilm Treatment

2011 ◽  
Vol 55 (11) ◽  
pp. 5230-5237 ◽  
Author(s):  
María D. Macià ◽  
José L. Pérez ◽  
Soeren Molin ◽  
Antonio Oliver
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Resistance Development ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Mutant Prevention Concentration ◽  
Resistant Mutants

ABSTRACTBiofilm growth, antibiotic resistance, and mutator phenotypes are key components of chronic respiratory infections byPseudomonas aeruginosain cystic fibrosis patients. We examined the dynamics of mutator and antibiotic-resistant populations inP. aeruginosaflow-cell biofilms, using fluorescently tagged PAO1 and PAOMS (mutator [mutS] derivative) strains. Two-day-old biofilms were treated with ciprofloxacin (CIP) for 4 days (t4) at 2 μg/ml, which correlated with the mutant prevention concentration (MPC) and provided an AUC/MIC ratio of 384 that should predict therapeutic success. Biofilms were monitored by confocal laser scanning microscopy (CLSM), and the numbers of viable cells and resistant mutants (4- and 16-fold MICs) were determined. Despite optimized pharmacokinetic/pharmacodynamic (PK/PD) parameters, CIP treatment did not suppress resistance development inP. aeruginosabiofilms. One-step resistant mutants (MexCD-OprJ or MexEF-OprN overexpression) were selected for both strains, while two-step resistant mutants (additional GyrA or GyrB mutation) were readily selected only from the mutator strain. CLSM analysis of competition experiments revealed that PAOMS, even when inoculated at a 0.01 proportion, took over the whole biofilm after only 2 days of CIP treatment outnumbering PAO1 by 3 log at t4. Our results show that mutational mechanisms play a major role in biofilm antibiotic resistance and that theoretically optimized PK/PD parameters fail to suppress resistance development, suggesting that the increased antibiotic tolerance driven by the special biofilm physiology and architecture may raise the effective MPC, favoring gradual mutational resistance development, especially in mutator strains. Moreover, the amplification of mutator populations under antibiotic treatment by coselection with resistance mutations is for the first time demonstratedin situforP. aeruginosabiofilms.

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