scholarly journals Enzymatic Inactivation of a New Aminoglycoside Antibiotic, Sisomicin, by Resistant Strains of Pseudomonas aeruginosa

1974 ◽  
Vol 5 (6) ◽  
pp. 558-561 ◽  
Author(s):  
K. O'Hara ◽  
M. Kono ◽  
S. Mitsuhashi
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Aminoglycoside Antibiotic ◽  
Enzymatic Inactivation ◽  
Resistant Strains

Tobramycin-Induced Hypersensitivity Reaction

1995 ◽  
Vol 29 (7-8) ◽  
pp. 704-706 ◽  
Author(s):  
Janet S Schretlen-Doherty ◽  
William G Troutman
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Hypersensitivity Reaction ◽  
Aminoglycoside Antibiotic ◽  
Drug Regimen ◽  
Hypersensitivity Reactions ◽  
Left Chest ◽  
The Third ◽  
Access System ◽  
Case Summary

Objective: To report a case of a hypersensitivity reaction associated with the use of intravenous tobramycin in a patient with cystic fibrosis. Case Summary: An 18-year-old man was hospitalized for exacerbation of his cystic fibrosis. Tobramycin 125 mg iv q6h and ceftazidime 2 g iv q8h were administered through the patient's implantable access system in the left chest. Within seconds of receiving the third dose of tobramycin, the patient experienced shaking, his left arm turned white, and urticaria and pruritus were noted on the left side of the patient's chest. The patient had experienced a similar incident, accompanied by breathing difficulty, with intravenous tobramycin 4 years príor to this incident. The patient had been skin-tested for tobramycin allergy and had been desensitized and was receiving tobramycin since that time without incident. The patient's desensitization was maintained with tobramycin 160 mg/d hs by nebulization, but the drug had been discontinued by the patient 6 months prior to the latest event. Discussion: Hypersensitivity reactions to aminoglycosides are unusual. Hypersensitivity to 1 aminoglycoside antibiotic frequently is associated with hypersensitivity to at least 1 other aminoglycoside. In patients who develop hypersensitivity to an aminoglycoside antibiotic, desensitization may be an effective alternative to changing therapy. Conclusions: Tobramycin is very important in the drug regimen for Pseudomonas aeruginosa infections in patients with cystic fibrosis. Effective desensitization can be maintained by daily administration of nebulized tobramycin.

Enzymatic Inactivation of Aminoglycoside Antibiotics by Resistant Strains of Bacteria

1972 ◽  
pp. 337-341 ◽  
Author(s):  
S. Mitsuhashi ◽  
F. Kobayashi ◽  
M. Yamaguchi ◽  
K. O’Hara ◽  
M. Kono
Keyword(s):  
Aminoglycoside Antibiotics ◽  
Enzymatic Inactivation ◽  
Resistant Strains

scholarly journals A Novel Cecropin D-Derived Short Cationic Antimicrobial Peptide Exhibits Antibacterial Activity Against Wild-Type and Multidrug-Resistant Strains of Klebsiella pneumoniae and Pseudomonas aeruginosa

2020 ◽  
Vol 16 ◽  
pp. 117693432093626
Author(s):  
Iván Darío Ocampo-Ibáñez ◽  
Yamil Liscano ◽  
Sandra Patricia Rivera-Sánchez ◽  
José Oñate-Garzón ◽  
Ashley Dayan Lugo-Guevara ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Health Concern ◽  
Wild Type ◽  
Cationic Antimicrobial Peptide ◽  
Promising Alternative ◽  
Resistant Strains

Infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa and Klebsiella pneumoniae are a serious worldwide public health concern due to the ineffectiveness of empirical antibiotic therapy. Therefore, research and the development of new antibiotic alternatives are urgently needed to control these bacteria. The use of cationic antimicrobial peptides (CAMPs) is a promising candidate alternative therapeutic strategy to antibiotics because they exhibit antibacterial activity against both antibiotic susceptible and MDR strains. In this study, we aimed to investigate the in vitro antibacterial effect of a short synthetic CAMP derived from the ΔM2 analog of Cec D-like (CAMP-CecD) against clinical isolates of K pneumoniae (n = 30) and P aeruginosa (n = 30), as well as its hemolytic activity. Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of CAMP-CecD against wild-type and MDR strains were determined by the broth microdilution test. In addition, an in silico molecular dynamic simulation was performed to predict the interaction between CAMP-CecD and membrane models of K pneumoniae and P aeruginosa. The results revealed a bactericidal effect of CAMP-CecD against both wild-type and resistant strains, but MDR P aeruginosa showed higher susceptibility to this peptide with MIC values between 32 and >256 μg/mL. CAMP-CecD showed higher stability in the P aeruginosa membrane model compared with the K pneumoniae model due to the greater number of noncovalent interactions with phospholipid 1-Palmitoyl-2-oleyl-sn-glycero-3-(phospho-rac-(1-glycerol)) (POPG). This may be related to the boosted effectiveness of the peptide against P aeruginosa clinical isolates. Given the antibacterial activity of CAMP-CecD against wild-type and MDR clinical isolates of P aeruginosa and K pneumoniae and its nonhemolytic effects on human erythrocytes, CAMP-CecD may be a promising alternative to conventional antibiotics.

scholarly journals Pseudomonas aeruginosa isolates from patients with cystic fibrosis have different beta-lactamase expression phenotypes but are homogeneous in the ampC-ampR genetic region.

1997 ◽  
Vol 41 (6) ◽  
pp. 1380-1384 ◽  
Author(s):  
J I Campbell ◽  
O Ciofu ◽  
N Høiby
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Intergenic Region ◽  
Regulatory Proteins ◽  
Base Substitution ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Genetic Region ◽  
Resistant Strains

Pseudomonas aeruginosa isolates from 1 of 17 cystic fibrosis patients produced secondary beta-lactamase in addition to the ampC beta-lactamase. Isolates were grouped into three beta-lactamase expression phenotypes: (i) beta-lactam sensitive, low basal levels and inducible beta-lactamase production; (ii) beta-lactam resistant, moderate basal levels and hyperinducible beta-lactamase production; (iii) beta-lactam resistant, high basal levels and constitutive beta-lactamase production. Apart from a base substitution in the ampR-ampC intergenic region of an isolate with moderate-basal-level and hyperinducible beta-lactamase production, sensitive and resistant strains were identical in their ampC-ampR genetic regions. Thus, enhanced beta-lactamase expression is due to mutations in regulatory proteins other than AmpR.

scholarly journals Evaluation of different phenotypic tests for detection of metallo-β-lactamases in imipenem-resistant Pseudomonas aeruginosa

2017 ◽  
Vol 9 (04) ◽  
pp. 249-253 ◽  
Author(s):  
Rohit Sachdeva ◽  
Babita Sharma ◽  
Rajni Sharma
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Large Scale ◽  
Wide Spectrum ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Clinical Samples ◽  
Resistant Strains ◽  
Synergy Test ◽  
Phenotypic Tests ◽  
Simple Screening

Abstract PURPOSE: Pseudomonas aeruginosa causes a wide spectrum of infections including bacteremia, pneumonia, urinary tract infection, etc., Metallo-beta-lactamase (MBL) producing P. aeruginosa is an emerging threat and cause of concern as they have emerged as one of the most feared resistance mechanisms. This study was designed to know the prevalence of MBL production in P. aeruginosa and to evaluate the four phenotypic tests for detection of MBL production in imipenem-resistant clinical isolates of P. aeruginosa. METHODS: Totally, 800 isolates of P. aeruginosa isolated from various clinical samples were evaluated for carbapenem resistance and MBL production. All imipenem-resistant strains were tested for carabapenemase production by modified Hodge test. Screening for MBL production was done by double-disc synergy test and combined disc test (CDT). Confirmation of MBL production was done by the E-test (Ab BioDisk, Solna, Sweden). RESULTS: Out of the 800 isolates of P. aeruginosa, 250 isolates were found resistant to imipenem. Based on the results of E-test, 147 (18.37%) isolates of P. aeruginosa were positive for MBL production. The CDT has the highest sensitivity and specificity for the detection of MBL production as compared to other tests. CONCLUSION: The results of this study are indicative that MBL production is an important mechanism of carbapenem resistance among P. aeruginosa. Use of simple screening test like CDT will be crucial step toward large-scale monitoring of these emerging resistant determinants. Phenotypic test for MBL production has to be standardized, and all the isolates should be routinely screened for MBL production.

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

mSphere ◽  
2017 ◽  
Vol 2 (4) ◽  
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.

scholarly journals Mechanisms of Resistance to Ceftolozane/Tazobactam in Pseudomonas aeruginosa: Results of the GERPA Multicenter Study

2020 ◽  
Author(s):  
Damien Fournier ◽  
Romain Carrière ◽  
Maxime Bour ◽  
Emilie Grisot ◽  
Pauline Triponney ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Hydrolytic Activity ◽  
Resistance Mechanisms ◽  
Group 3 ◽  
High Production ◽  
Resistant Strains ◽  
Recycling Pathway ◽  
French Hospital ◽  
Almost All ◽  
Moderately Resistant

Resistance mechanisms of Pseudomonas aeruginosa to ceftolozane/tazobactam (C/T) were assessed on a collection of 420 nonredundant strains non-susceptible to ceftazidime (MIC > 8 μg/ml) and/or imipenem (> 4 μg/ml), collected by 36 French hospital laboratories over a one month period (GERPA study). Rates of C/T resistance (MIC > 4/4 μg/ml) were equal to 10% in this population (42/420 strains), and 23.2% among the isolates resistant to both ceftazidime and imipenem (26/112). A first group of 21 strains (50%) was found to harbor various extended-spectrum β-lactamases (1 OXA-14; 2 OXA-19; 1 OXA-35; 1 GES-9; 3 PER-1), carbapenemases (2 GES-5; 1 IMP-8; 8 VIM-2), or both (1 VIM-2/OXA-35; 1 VIM-4/SHV-2a). All the strains of this group belonged to widely distributed epidemic clones (ST111, ST175, CC235, ST244, ST348, ST654), and were highly resistant to almost all the antibiotics tested except colistin. A second group was composed of 16 (38%) isolates moderately resistant to C/T (MIC from 8/4 to 16/4 μg/ml), of which 7 were related to international clones (ST111, ST253, CC274, ST352, ST386). As demonstrated by targeted mass spectrometry, cloxacillin-based inhibition tests and gene blaPDC deletion experiments, this resistance phenotype was correlated to an extremely high production of cephalosporinase PDC. In part accounting for this strong PDC upregulation, genomic analyses revealed the presence of mutations in regulator AmpR (D135N/G in 6 strains) and enzymes of the peptidoglycan recycling pathway such as AmpD, PBP4, and Mpl (9 strains). Finally, all the 5 (12%) remaining C/T resistant strains (group 3) appeared to encode PDC variants with mutations known to improve the hydrolytic activity of the β-lactamase to ceftazidime and C/T (F147L, ΔL223-Y226, E247K, N373I). Collectively, our results highlight the importance of both intrinsic and transferable mechanisms in C/T resistant P. aeruginosa. Which mutational events lead some clinical strains to massively produce the natural cephalosporinase PDC remains incompletely understood.

scholarly journals Clinically Relevant Plasma Concentrations of Colistin in Combination with Imipenem Enhance Pharmacodynamic Activity against Multidrug-Resistant Pseudomonas aeruginosa at Multiple Inocula

2011 ◽  
Vol 55 (11) ◽  
pp. 5134-5142 ◽  
Author(s):  
Phillip J. Bergen ◽  
Alan Forrest ◽  
Jürgen B. Bulitta ◽  
Brian T. Tsuji ◽  
Hanna E. Sidjabat ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Therapy ◽  
Systematic Study ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Bacterial Killing ◽  
Content Type ◽  
Resistant Strains ◽  
Time Kill

ABSTRACTThe use of combination antibiotic therapy may be beneficial against rapidly emerging resistance inPseudomonas aeruginosa. The aim of this study was to systematically investigatein vitrobacterial killing and resistance emergence with colistin alone and in combination with imipenem against multidrug-resistant (MDR)P. aeruginosa. Time-kill studies were conducted over 48 h using 5 clinical isolates and ATCC 27853 at two inocula (∼106and ∼108CFU/ml); MDR, non-MDR, and colistin-heteroresistant and -resistant strains were included. Nine colistin-imipenem combinations were investigated. Microbiological response was examined by log changes at 6, 24, and 48 h. Colistin combined with imipenem at clinically relevant concentrations increased the levels of killing of MDR and colistin-heteroresistant isolates at both inocula. Substantial improvements in activity with combinations were observed across 48 h with all colistin concentrations at the low inoculum and with colistin at 4× and 16× MIC (or 4 and 32 mg/liter) at the high inoculum. Combinations were additive or synergistic against imipenem-resistant isolates (MICs, 16 and 32 mg/liter) at the 106-CFU inoculum in 9, 11, and 12 of 18 cases (i.e., 9 combinations across 2 isolates) at 6, 24, and 48 h, respectively, and against the same isolates at the 108-CFU inoculum in 11, 7, and 8 cases, respectively. Against a colistin-resistant strain (MIC, 128 mg/liter), combinations were additive or synergistic in 9 and 8 of 9 cases at 24 h at the 106- and 108-CFU inocula, respectively, and in 5 and 7 cases at 48 h. This systematic study provides important information for optimization of colistin-imipenem combinations targeting both colistin-susceptible and colistin-resistant subpopulations.

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