scholarly journals Optimization of therapy against Pseudomonas aeruginosa with ceftazidime and meropenem using chemostats as model for infections

2017 ◽  
Vol 364 (14) ◽  
Author(s):  
Yanfang Feng ◽  
Roosmarijn T Bakker ◽  
Reinier M van Hest ◽  
Caspar J Hodiamont ◽  
Stanley Brul ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Opportunistic Pathogen ◽  
Similar Reduction ◽  
Therapeutic Goals ◽  
Cell Numbers ◽  
Development Of Resistance ◽  
Chemostat Cultures ◽  
Resistance Patterns ◽  
Life Threatening ◽  
High Concentrations

Abstract Pseudomonas aeruginosa is an opportunistic pathogen that can cause life-threatening infections in patients admitted to intensive care units. Resistance rapidly develops against two drugs of choice: ceftazidime and meropenem. Several therapeutic protocols were compared for reduction in viable cells and limiting development of resistance. Chemostat cultures were exposed to antibiotic concentrations measured in the blood of patients at low (5th percentile), medium (50th percentile) or high (95th percentile) levels in several therapy protocols to simulate therapy. Cultures exposed to ceftazidime recovered after 1 day at low, 2 days at medium and 3 days at high concentrations and developed corresponding levels of resistance. Patterns were very similar for meropenem except that recovery was delayed. Fluctuating levels and intermittent treatment achieved similar reduction of cell numbers at lower resistance costs. Treatment alternating ceftazidime and meropenem reduced cell numbers more than monotherapy, while strongly limiting resistance. Combination therapy was even more effective in both respects. Therapeutic goals are best reached with least risk of resistance when ceftazidime and meropenem are used in combination or alternating, at the highest concentrations the patient can endure. Monotherapy should also apply the highest concentration that is safe for the shortest time that achieves treatment objectives.

scholarly journals Dynamics of Mutations during Development of Resistance by Pseudomonas aeruginosa against Five Antibiotics

2016 ◽  
Vol 60 (7) ◽  
pp. 4229-4236 ◽  
Author(s):  
Yanfang Feng ◽  
Martijs J. Jonker ◽  
Ioannis Moustakas ◽  
Stanley Brul ◽  
Benno H. ter Kuile
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quantitative Relationship ◽  
Opportunistic Pathogen ◽  
Cellular Systems ◽  
Beta Lactam ◽  
Cellular Functions ◽  
Lower Growth ◽  
Content Type ◽  
Development Of Resistance ◽  
Considerable Morbidity

ABSTRACTPseudomonas aeruginosais an opportunistic pathogen that causes considerable morbidity and mortality, specifically during intensive care. Antibiotic-resistant variants of this organism are more difficult to treat and cause substantial extra costs compared to susceptible strains. In the laboratory,P. aeruginosarapidly developed resistance to five medically relevant antibiotics upon exposure to stepwise increasing concentrations. At several time points during the acquisition of resistance, samples were taken for whole-genome sequencing. The increase in the MIC of ciprofloxacin was linked to specific mutations ingyrA,parC, andgyrB, appearing sequentially. In the case of tobramycin, mutations infusA,HP02880,rplB, andcapDwere induced. The MICs of the beta-lactam compounds meropenem and ceftazidime and the combination of piperacillin and tazobactam correlated linearly with beta-lactamase activity but not always with individual mutations. The genes that were mutated during the development of beta-lactam resistance differed for each antibiotic. A quantitative relationship between the frequency of mutations and the increase in resistance could not be established for any of the antibiotics. When the adapted strains are grown in the absence of the antibiotic, some mutations remained and others were reversed, but this reversal did not necessarily lower the MIC. The increased MIC came at the cost of moderately reduced cellular functions or a somewhat lower growth rate. In all cases except ciprofloxacin, the increase in resistance seems to be the result of complex interactions among several cellular systems rather than individual mutations.

scholarly journals Pseudomonas aeruginosa a common opportunistic pathogen in Jordan: A review article.

10.3823/827 ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Asem A. Shehabi ◽  
Aya M. Kamal
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Opportunistic Pathogen ◽  
Short Review ◽  
Hospital Length ◽  
Hospital Environment ◽  
Hospital Length Of Stay ◽  
Chronic Infections ◽  
Antimicrobial Susceptibility Pattern ◽  
Life Threatening ◽  
Water Plants

Pseudomonas aeruginosa is widely present in many diverse environments. It can be found in various living sources, including water, plants, intestinal tract of human and animals, and most importantly hospital environment. The organism is an important cause of nosocomial infections, such as septicemia and pneumonia, life-threatening infections in immunocompromised persons, and chronic infections in cystic fibrosis patients. Recent studies reported that hospitalized patients infected with multidrug resistance (MDR) P. aeruginosa have increased hospital length of stay and mortality. This short review focus on the current common occurrence and antimicrobial susceptibility pattern of P. aeruginosa in Jordan.

scholarly journals MECHANISMS OF ANTIMICROBIAL RESISTANCE SPECIFIC FOR PSEUDOMONAS AERUGINOSA AND ACINETOBACTER BAUMANNII

InterConf ◽  
2021 ◽  
pp. 266-274
Author(s):  
Greta Balan ◽  
Emilia Behta ◽  
Olga Brînza ◽  
Livia Ţapu ◽  
Olga Burduniuc
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Acinetobacter Baumannii ◽  
Single Agent ◽  
Mechanisms Of Resistance ◽  
Development Of Resistance ◽  
Resistance Patterns

The exposure of bacteria to antibiotics has led to the development of resistance againstevery single agent utilized. Through a understanding the mechanisms of resistance, the clinician can better comprehend and predict resistance patterns even to antibioticsnot reported on the antibiogram, and subsequently select the most appropriate antibiotic for the pathogen in question.

scholarly journals A Cationic Porphyrin, ZnPor, Disassembles Pseudomonas aeruginosa Biofilm Matrix, Kills Cells Directly, and Enhances Antibiotic Activity of Tobramycin

Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 875
Author(s):  
Neha Patel ◽  
Shawn Swavey ◽  
Jayne Robinson
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Opportunistic Pathogen ◽  
Uptake System ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Antibiotic Resistant ◽  
The Matrix ◽  
Life Threatening ◽  
Pre Treatment

One of the greatest threats to human health is the rise in antibiotic-resistant bacterial infections. Pseudomonas aeruginosa (PsA) is an “opportunistic” pathogen known to cause life-threatening infections in immunocompromised individuals and is the most common pathogen in adults with cystic fibrosis (CF). We report here a cationic zinc (II) porphyrin, ZnPor, that effectively kills planktonic and biofilm-associated cells of PsA. In standard tests against 16–18 h-old biofilms, concentrations as low as 16 µg/mL resulted in the extensive disruption and detachment of the matrix. The pre-treatment of biofilms for 30 min with ZnPor at minimum inhibitory concentration (MIC) levels (4 µg/mL) substantially enhanced the ability of tobramycin (Tobra) to kill biofilm-associated cells. We demonstrate the rapid uptake and accumulation of ZnPor in planktonic cells even in dedicated heme-uptake system mutants (ΔPhu, ΔHas, and the double mutant). Furthermore, uptake was unaffected by the ionophore carbonyl cyanide m-chlorophenyl hydrazine (CCCP). Cells pre-exposed to ZnPor took up the cell-impermeant dye SYTOXTM Green in a concentration-dependent manner. The accumulation of ZnPor did not result in cell lysis, nor did the cells develop resistance. Taken together, these properties make ZnPor a promising candidate for treating multi-drug-resistant infections, including persistent, antibiotic-resistant biofilms.

scholarly journals Suspended multiwalled, acid-functionalized carbon nanotubes promote aggregation of the opportunistic pathogen Pseudomonas aeruginosa

2020 ◽  
Author(s):  
Kristin Kovach ◽  
Indu Venu Sabaraya ◽  
Parth Patel ◽  
Mary Jo Kirisits ◽  
Navid B. Saleh ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Pseudomonas Aeruginosa ◽  
Functional Materials ◽  
Opportunistic Pathogen ◽  
Antibiotic Tolerance ◽  
Aqueous Systems ◽  
Low Concentrations ◽  
Animal Pathogens ◽  
High Concentrations ◽  
Bacterial Aggregates

AbstractThe increasing prevalence of carbon nanotubes (CNTs) as components of new functional materials has the unintended consequence of causing increases in CNT concentrations in aqueous environments. Aqueous systems are reservoirs for bacteria, including human and animal pathogens, that can form biofilms. At high concentrations, CNTs have been shown to display biocidal effects; however, at low concentrations, the interaction between CNTs and bacteria is more complicated, and antimicrobial action is highly dependent upon the properties of the CNTs in suspension. Here, impact of low concentrations of multiwalled CNTs (MWCNTs) on the biofilm-forming opportunistic human pathogen Pseudomonas aeruginosa is studied. Using phase contrast and confocal microscopy, flow cytometry, and antibiotic tolerance assays, it is found that sub-lethal concentrations (2 mg/L) of MWCNTs promote aggregation of P. aeruginosa into multicellular clusters. However, the antibiotic tolerance of these “young” bacterial-CNT aggregates is similar to that of CNT-free cultures. Overall, our results indicate that the co-occurrence of MWCNTs and P. aeruginosa in aqueous systems, which promotes the increased number and size of bacterial aggregates, could increase the dose to which humans or animals are exposed.

scholarly journals Evaluation of Sphingomonas paucimobilis as an emerging nosocomial pathogen in a teaching hospital in Uttarakhand

2021 ◽  
Author(s):  
Ranjana Rohilla ◽  
Dimple Raina ◽  
Malvika Singh ◽  
Ajay Kumar Pandita ◽  
Shiwang Patwal
Keyword(s):  
Opportunistic Pathogen ◽  
Tertiary Hospital ◽  
Fourth Generation ◽  
Sphingomonas Paucimobilis ◽  
Resistance Patterns ◽  
Life Threatening ◽  
Vitek 2 ◽  
One Year ◽  
Tract Infections ◽  
Susceptibility Patterns

Background and Objectives: Sphingomonas paucimobilis is an opportunistic pathogen and was rarely encountered in clin- ical specimens previously. This study aimed to investigate the clinical features, associated co-morbidities, and antimicrobial susceptibility patterns of S. paucimobilis infection in a tertiary hospital in Uttarakhand. Materials and Methods: S. paucimobilis isolates cultured from various sections of hospital and OPDs were identified and an- alyzed for their antibiograms in the microbiology laboratory for a duration of one year from January 2020 to December 2020. Results: S. paucimobilis was isolated from 49 samples (0.01%) out of 3792 samples processed in VITEK 2 Compact auto- mated ID/AST instrument. The maximum number of isolates were obtained from urine samples (31%), followed by blood (24%). Septicemia (41%), meningitis (17%), lower respiratory tract infections and ventilator associated pneumonia (14%) constituted a major portion of infections caused by this organism. Diabetes mellitus (22%) and steroid usage (16%) were major associated co-morbid conditions. Third and Fourth generation cephalosporins like ceftriaxone (81%) and cefepime (86%) were found to be the most susceptible drugs whereas 61% of isolates were resistant to colistin. Conclusion: This organism is an up-and-coming pathogen and should not be simply labeled as a contaminant. Although the organism is not grossly virulent and still might not be associated with serious life-threatening infections; however their evolving resistance patterns and increased spectrum of infections should be seriously taken into account.

scholarly journals Calcium regulated protein, CarP, responds to multiple host signals and mediates calcium regulation of Pseudomonas aeruginosa virulence

2021 ◽  
Author(s):  
Michelle King ◽  
Aya Kubo ◽  
Leah Kafer ◽  
Reygan Braga ◽  
Daniel McLeod ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Laboratory Strain ◽  
Opportunistic Pathogen ◽  
Host Factors ◽  
Intergenic Sequence ◽  
Triple Mutant ◽  
Regulatory Circuits ◽  
Life Threatening

Pseudomonas aeruginosa is an opportunistic pathogen causing life-threatening infections. Previously, we showed that elevated calcium (Ca2+) levels increase the production of virulence factors in P. aeruginosa. In the effort to characterize the Ca2+ regulatory network, we identified a Ca2+–regulated β-propeller protein, CarP, and showed that expression of the encoding gene is controlled by the Ca2+-regulated two-component system CarSR. Here, by using a Galleria melonella model, we showed that CarP plays a role in regulating P. aeruginosa virulence. By using RNA-Seq, RT-PCR, RT-qPCR, and promoter fusions, we determined that carP is transcribed into at least two transcripts and regulated by several bacterial and host factors. The transcription of carP is elevated in response to Ca2+ in P. aeruginosa cystic fibrosis isolates and PAO1 laboratory strain. Elevated Fe2+ also induces carP. Simultaneous addition of Ca2+ and Fe2+ increased the carP promoter activity synergistically, which requires the presence of CarR. In silico analysis of the intergenic sequence upstream of carP predicted recognition sites of RhlR/LasR, OxyR, and LexA, suggesting regulation by quorum sensing (QS) and oxidative stress. In agreement, the carP promoter was activated in response to stationary-phase PAO1 supernatant and required the presence of elevated Ca2+ and CarR, but remained silent in the triple mutant lacking rhlI, lasI, and pqsA synthases. We also showed that carP transcription is regulated by oxidative stress and that CarP contributes to P. aeruginosa Ca2+-dependent H2O2 tolerance. The multifactorial regulation of carP suggests that CarP plays an important role in P. aeruginosa adaptations to host environments. IMPORTANCE P. aeruginosa is a human pathogen causing life-threatening infections. It is particularly notorious for its ability to adapt to diverse environments within the host. Understanding the signals and the signaling pathways enabling P. aeruginosa adaptation is imperative for developing effective therapies to treat infections caused by this organism. One host signal of particular importance is calcium. Previously, we identified a component of P. aeruginosa calcium-signaling network, CarP, whose expression is induced by elevated levels of calcium. Here we show that carP plays an important role in P. aeruginosa virulence and is up-regulated in P. aeruginosa strains isolated from sputa of patients with cystic fibrosis. We also identified several bacterial and host factors that regulate the transcription of carP. Such multifactorial regulation highlights the interconnectedness between regulatory circuits and together with the pleotropic effect of CarP on virulence suggests the importance of this protein in P. aeruginosa adaptations to the host.

scholarly journals Traditional Chinese Medicine is an Alternative Therapeutic Option for Treatment of Pseudomonas aeruginosa Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Zheng Pang ◽  
Qingjun Zhu
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Therapeutic Option ◽  
Clinical History ◽  
Opportunistic Pathogen ◽  
Antibiotic Resistant ◽  
Life Threatening ◽  
Conventional Antibiotics

Pseudomonas aeruginosa is an opportunistic pathogen causing life-threatening infections in cystic fibrosis patients and immunocompromised individuals, and it is a leading cause of nosocomial infections associated with significant morbidity and mortality. Treatment of P. aeruginosa infections is challenging due to the antibiotic resistance to most of the conventional antibiotics. Development of alternative therapeutic options is urgently demanded for the patients who have antibiotic-resistant infections. Traditional Chinese medicine (TCM) has a clinical history of thousands of years for prevention and treatment of infectious diseases in China, taking advantages of improving clinical outcomes, producing less side effects, inhibiting pathogen, and modulating host immunity. Recent research has revealed a variety of natural products derived from TCM showing significant antimicrobial effects on antibiotic-resistant strains of P. aeruginosa alone or combined with antibiotics in vitro or in animal models, suggesting that TCM is a promising complementary and alternative therapeutic approach for treatment of chronic P. aeruginosa infections. This review summarizes the recent findings attempting to dissect the mechanisms of TCM combating P. aeruginosa infections and highlights the molecular targets of TCM on P. aeruginosa and host.

scholarly journals Fucoidan-Stabilized Gold Nanoparticle-Mediated Biofilm Inhibition, Attenuation of Virulence and Motility Properties in Pseudomonas aeruginosa PAO1

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 208 ◽  
Author(s):  
Fazlurrahman Khan ◽  
Panchanathan Manivasagan ◽  
Jang-Won Lee ◽  
Dung Pham ◽  
Junghwan Oh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Growth ◽  
Biofilm Formation ◽  
Inhibitory Concentration ◽  
Brown Seaweed ◽  
Opportunistic Pathogen ◽  
Biofilm Inhibition ◽  
Transmission Electron ◽  
Inhibition Concentration ◽  
Life Threatening

The emergence of antibiotic resistance in Pseudomonas aeruginosa due to biofilm formation has transformed this opportunistic pathogen into a life-threatening one. Biosynthesized nanoparticles are increasingly being recognized as an effective anti-biofilm strategy to counter P. aeruginosa biofilms. In the present study, gold nanoparticles (AuNPs) were biologically synthesized and stabilized using fucoidan, which is an active compound sourced from brown seaweed. Biosynthesized fucoidan-stabilized AuNPs (F-AuNPs) were subjected to characterization using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), field emission transmission electron microscopy (FE-TEM), dynamic light scattering (DLS), and energy dispersive X-ray diffraction (EDX). The biosynthesized F-AuNPs were then evaluated for their inhibitory effects on P. aeruginosa bacterial growth, biofilm formation, virulence factor production, and bacterial motility. Overall, the activities of F-AuNPs towards P. aeruginosa were varied depending on their concentration. At minimum inhibitory concentration (MIC) (512 µg/mL) and at concentrations above MIC, F-AuNPs exerted antibacterial activity. In contrast, the sub-inhibitory concentration (sub-MIC) levels of F-AuNPs inhibited biofilm formation without affecting bacterial growth, and eradicated matured biofilm. The minimum biofilm inhibition concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were identified as 128 µg/mL. Furthermore, sub-MICs of F-AuNPs also attenuated the production of several important virulence factors and impaired bacterial swarming, swimming, and twitching motilities. Findings from the present study provide important insights into the potential of F-AuNPs as an effective new drug for controlling P. aeruginosa-biofilm-related infections.

Antibiotic treatment of Pseudomonas aeruginosa biofilms stimulates expression of the magnesium transporter gene mgtE

Microbiology ◽  
2014 ◽  
Vol 160 (1) ◽  
pp. 165-178 ◽  
Author(s):  
Carly V. Redelman ◽  
Shubham Chakravarty ◽  
Gregory G. Anderson
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Treatment ◽  
Type Iii Secretion ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Transporter Protein ◽  
Magnesium Transporter ◽  
High Concentrations ◽  
Serious Disease

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen with the capacity to cause serious disease, including chronic biofilm infections in the lungs of cystic fibrosis (CF) patients. These infections are treated with high concentrations of antibiotics. Virulence modulation is an important tool utilized by P. aeruginosa to propagate infection and biofilm formation in the CF airway. Many different virulence modulatory pathways and proteins have been identified, including the magnesium transporter protein MgtE. We have recently found that isogenic deletion of mgtE leads to increased cytotoxicity through effects on the type III secretion system. To explore the role of the CF lung environment in MgtE activity, we investigated mgtE transcriptional regulation following antibiotic treatment. Utilizing quantitative real-time-PCR, we have demonstrated an increase in mgtE transcript levels following antibiotic treatment with most of the 12 antibiotics tested. To begin to determine the regulatory network governing mgtE expression, we screened a transposon-mutant library of P. aeruginosa to look for mutants with potentially altered mgtE activity, using cytotoxicity as a readout. In this screen, we observed that AlgR, which regulates production of the biofilm polysaccharide alginate, alters MgtE-mediated cytotoxicity. This cross-talk between MgtE and AlgR suggests that AlgR is involved in linking external inducing signals (e.g. antibiotics) to mgtE transcription and downstream virulence and biofilm activities. Analysing such interactions may lead to a better understanding of how the CF lung environment shapes P. aeruginosa biofilm infections.

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