scholarly journals Analysis of Susceptibility Patterns of Pseudomonas aeruginosa and Isolation, Characterization of Lytic Bacteriophages Targeting Multi Drug Resistant Pseudomonas aeruginosa

2018 ◽  
Vol 11 (2) ◽  
pp. 1105-1117 ◽  
Author(s):  
Shri Natrajan Arumugam ◽  
Akarsh Chickamagalur Rudraradhya ◽  
Sathish Sadagopan ◽  
Sunilkumar Sukumaran ◽  
Ganesh Sambasivam ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Host Range ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Dilution Method ◽  
Drug Resistant ◽  
Susceptibility Pattern ◽  
Infectivity Rate

Pseudomonas aeruginosa is known to be a major cause of Hospital Acquired Infections leading to high mortality in immune-compromised patients. Due to precipitous rise in antibiotic resistance, bacteriophages are significant alternative therapeutic approach for treatment and to combat resistance development. Objective of the current study was to identify MDR Pseudomonas aeruginosa from clinical isolates and to isolate bacteriophages from sewage samples against these MDR Pseudomonas aeruginosa strains. One hundred and forty-four Pseudomonas isolates were tested for their susceptibility pattern with 13 different antibiotics by micro-broth dilution method. Frequency of multidrug resistant (MDR) and Extensive Drug resistant (XDR) of Pseudomonas aeruginosa were found to be 35.5% and 23.6%, respectively. 7.61% isolates were identified as Pan drug resistant (PDR). Rate of susceptibility pattern were Piperacillin/Tazobactam 75%, Polymyxin B 74.6%, Meropenem 73.6%, Colistin 69.2%, Cefepime 54.9%, Ciprofloxacin 54.2%, Gentamicin 54.2%, Aztreonam 53.5%, Tobramycin 47.9%, Ticarcillin/Clavulanic acid 46.9%, Ertapenem 45.8%, Ceftazidime 40.3% and Imipenem 39.2%. Ninety-four bacteriophages were isolated from sewage samples against Pseudomonas aeruginosa PAO1/ATCC9027/clinical strains and host range testing study was carried out with all MDR clinical isolates. Among 51 MDR strains 34 strains were infected by phages. Phage infectivity rate were calculated for individual phages based on their host range infectivity results. AP025 and AP006 phages exhibited good infectivity rate of 39% and 30% respectively against MDR strains. Combination of 5 phages (AP002, AP006, AP011, AP025 and AP067) lysed 62.7% of the strains. Based on the obtained results, phages could be employed for treatment of infections caused by MDR strains with substantiated in-vivo experiments.

scholarly journals In vivo emergence of resistance to cefiderocol in an XDR Pseudomonas aeruginosa and an MDR Citrobacter koseri after prolonged therapy: a case report.

2020 ◽  
Author(s):  
Carolina Grande Perez ◽  
Evelyne Maillart ◽  
Véronique Yvette Miendje Deyi ◽  
Te Din Daniel Huang ◽  
Prochore Kamgang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Class A ◽  
Stewardship Program ◽  
Class D ◽  
Emergence Of Resistance

Abstract The non-fermenters, e.g. Pseudomonas aeruginosa, and the extended spectrum β-lactamases or carbapenemases producing enterobacteriaceae represent a serious threat for patients admitted in Intensive Care Units (ICUs). News antibiotics have been developed to treat multidrug resistant bacteria. However, treatment emerging resistance has been shown for many of these newest antibiotics. Cefiderocol, a siderophore-antibiotic, has been developed to overcome most of the resistance mechanisms and shows great efficacy against most multi-drug resistant and extensively drug resistant Gram-negative bacteria, including the non-fermenters. We report the case of a patient abundantly treated with antibiotics. He received 158 days of antibiotherapy on 230 hospitalization days, including a six-week course of cefiderocol, in 14 different treatment lines. The patient developed a Pseudomonas aeruginosa (MIC: 8 µg/ml, GES type ESBL) and a Citrobacter koseri (MIC: 16 µg/ml, CTX-M group 9 type class A β-lactamase and a class D OXA-1 oxacillinase) resistant to cefiderocol. This antibiotic should be used with caution to preserve its efficacy, within a strict antimicrobial stewardship program.

scholarly journals Role of Aminoglycoside-Modifying Enzymes (AMEs) in Resistance to Aminoglycosides among Clinical Isolates of Pseudomonas aeruginosa in the North of Iran

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Leila Ahmadian ◽  
Zahra Norouzi Bazgir ◽  
Mohammad Ahanjan ◽  
Reza Valadan ◽  
Hamid Reza Goli
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Resistance Pattern ◽  
Dilution Method ◽  
The North ◽  
Agar Diffusion Test ◽  
North Of Iran ◽  
Encoding Genes

In recent years, the prevalence of resistance to aminoglycosides among clinical isolates of Pseudomonas aeruginosa is increasing. The aim of this study was to investigate the role of aminoglycoside-modifying enzymes (AMEs) in resistance to aminoglycosides in clinical isolates of P. aeruginosa. The clinical isolates were collected from different hospitals. Disk agar diffusion test was used to determine the antimicrobial resistance pattern of the clinical isolates, and the minimum inhibitory concentration of aminoglycosides was detected by microbroth dilution method. The PCR was performed for discovery of aminoglycoside-modifying enzyme-encoding genes. Among 100 screened isolates, 43 (43%) isolates were resistant to at least one tested aminoglycosides. However, 13 (13%) isolates were resistant to all tested aminoglycosides and 37 isolates were detected as multidrug resistant (MDR). The resistance rates of P. aeruginosa isolates against tested antibiotics were as follows: ciprofloxacin (41%), piperacillin-tazobactam (12%), cefepime (32%), piperacillin (26%), and imipenem (31%). However, according to the MIC method, 13%, 32%, 33%, and 37% of the isolates were resistant to amikacin, gentamicin, tobramycin, and netilmicin, respectively. The PCR results showed that AAC(6 ′ )-Ib was the most commonly (26/43, 60.4%) identified AME-encoding gene followed by AAC(6 ′ )-IIa (41.86%), APH(3 ′ )-IIb (34.8%), ANT(3 ″ )-Ia (18.6), ANT(2 ″ )-Ia (13.95%), and APH(3 ″ )-Ib (2.32%). However, APH(3 ′ )-Ib was not found in any of the studied isolates. The high prevalence of AME-encoding genes among aminoglycoside-resistant P. aeruginosa isolates in this area indicated the important role of AMEs in resistance to these antibiotics similar to most studies worldwide. Due to the transmission possibility of these genes between the Gram-negative bacteria, we need to control the prescription of aminoglycosides in hospitals.

scholarly journals A preliminary study of in vitro and in vivo synergistic effects of ciprofloxacin and D-tyrosine against Pseudomonas aeruginosa isolates

2020 ◽  
Vol 19 (8) ◽  
pp. 1731-1736
Author(s):  
Huirong Li ◽  
Wei Jiang ◽  
Xiaoshuang He ◽  
Mengting Chen
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Synergistic Effects ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Infection Model ◽  
Antimicrobial Effects ◽  
Kill Curve ◽  
Zebrafish Infection

Purpose: To investigate the synergistic antimicrobial effects of ciprofloxacin and D-tyrosine against drug-resistant bacteria.Method: The antimicrobial effects of ciprofloxacin and D-tyrosine on clinical isolates of multidrugresistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) no. 3556 were determined in vitro based on time-kill curve, and in vivo in P. aeruginosa-zebrafish infection model. Furthermore, 30 clinical isolates of multidrug-resistant P. aeruginosa were used in vitro to ascertain the synergistic effect of the two agents.Results: Combined use of ciprofloxacin and D-tyrosine produced synergistic effects against the clinical isolate of P. aeruginosa no. 3556 in vitro and in vivo. Synergism occurred in 96.67 % (95 % CI, range 83.33 - 99.41 %) of the clinical isolates, and ciprofloxacin dose was reduced in 90 % (95 % CI, range 74.38 - 96.54 %) of the clinical isolates in vitro.Conclusion: These preliminary results suggest that the combination of ciprofloxacin and D-tyrosine is a promising therapeutic strategy against MDR P. aeruginosa infections. Keywords: Ciprofloxacin, D-tyrosine, Synergistic, P. aeruginosa, Zebrafish infection model, Time-killing curve

scholarly journals Inhibition of Pseudomonas aeruginosa by Peptide-Conjugated Phosphorodiamidate Morpholino Oligomers

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
James J. Howard ◽  
Carolyn R. Sturge ◽  
Dina A. Moustafa ◽  
Seth M. Daly ◽  
Kimberly R. Marshall-Batty ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Essential Genes ◽  
Content Type ◽  
Novel Approach ◽  
Phosphorodiamidate Morpholino Oligomers

ABSTRACT Pseudomonas aeruginosa is a highly virulent, multidrug-resistant pathogen that causes significant morbidity and mortality in hospitalized patients and is particularly devastating in patients with cystic fibrosis. Increasing antibiotic resistance coupled with decreasing numbers of antibiotics in the developmental pipeline demands novel antibacterial approaches. Here, we tested peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs), which inhibit translation of complementary mRNA from specific, essential genes in P. aeruginosa. PPMOs targeted to acpP, lpxC, and rpsJ, inhibited P. aeruginosa growth in many clinical strains and activity of PPMOs could be enhanced 2- to 8-fold by the addition of polymyxin B nonapeptide at subinhibitory concentrations. The PPMO targeting acpP was also effective at preventing P. aeruginosa PAO1 biofilm formation and at reducing existing biofilms. Importantly, treatment with various combinations of a PPMO and a traditional antibiotic demonstrated synergistic growth inhibition, the most effective of which was the PPMO targeting rpsJ with tobramycin. Furthermore, treatment of P. aeruginosa PA103-infected mice with PPMOs targeting acpP, lpxC, or rpsJ significantly reduced the bacterial burden in the lungs at 24 h by almost 3 logs. Altogether, this study demonstrates that PPMOs targeting the essential genes acpP, lpxC, or rpsJ in P. aeruginosa are highly effective at inhibiting growth in vitro and in vivo. These data suggest that PPMOs alone or in combination with antibiotics represent a novel approach to addressing the problems associated with rapidly increasing antibiotic resistance in P. aeruginosa.

scholarly journals Antibiotic Susceptibility Pattern ofMycobacterium marinum

2000 ◽  
Vol 44 (11) ◽  
pp. 3133-3136 ◽  
Author(s):  
Alexandra Aubry ◽  
Vincent Jarlier ◽  
Sylvie Escolano ◽  
Chantal Truffot-Pernot ◽  
Emmanuelle Cambau
Keyword(s):  
Antibiotic Susceptibility ◽  
Geometric Mean ◽  
Multidrug Resistant ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Susceptibility Pattern ◽  
Cutaneous Infections ◽  
Agar Dilution

ABSTRACT In vitro activities of 17 antibiotics against 53 clinical strains of Mycobacterium marinum, an atypical mycobacterium responsible for cutaneous infections, were determined using the reference agar dilution method. Rifampin and rifabutin were the most active drugs (MICs at which 90% of the isolates tested were inhibited [MIC90s], 0.5 and 0.6 μg/ml, respectively). MICs of minocycline (MIC90, 4 μg/ml), doxycycline (MIC90, 16 μg/ml), clarithromycin (MIC90, 4 μg/ml), sparfloxacin (MIC90, 2 μg/ml), moxifloxacin (MIC90, 1 μg/ml), imipenem (MIC90, 8 μg/ml), sulfamethoxazole (MIC90, 8 μg/ml) and amikacin (MIC90, 4 μg/ml) were close to the susceptibility breakpoints. MICs of isoniazid, ethambutol, trimethoprim, azithromycin, ciprofloxacin, ofloxacin, and levofloxacin were above the concentrations usually obtained in vivo. For each drug, the MIC50, geometric mean MIC, and modal MIC were very close, showing that all the strains had a similar susceptibility pattern. Percent agreement (within ±1 log2 dilution) between MICs yielded by the Etest method and by the agar dilution method used as reference were 83, 59, 43, and 24% for minocycline, rifampin, clarithromycin, and sparfloxacin, respectively. Reproducibility with the Etest was low, in contrast to that with the agar dilution method. In conclusion, M. marinum is a naturally multidrug-resistant species for which the agar dilution method is more accurate than the Etest for antibiotic susceptibility testing.

scholarly journals Involvement of pmrAB and phoPQ in Polymyxin B Adaptation and Inducible Resistance in Non-Cystic Fibrosis Clinical Isolates of Pseudomonas aeruginosa

2009 ◽  
Vol 53 (10) ◽  
pp. 4345-4351 ◽  
Author(s):  
Kristen N. Schurek ◽  
Jorge L. M. Sampaio ◽  
Carlos R. V. Kiffer ◽  
Sumiko Sinto ◽  
Caio M. F. Mendes ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Membrane Permeability ◽  
Outer Membrane ◽  
Resistance Genes ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Resistant Isolate ◽  
Dependent Manner ◽  
Concentration Dependent Manner

ABSTRACT During investigation of susceptibility testing methods for polymyxins, 24 multidrug-resistant clinical isolates of Pseudomonas aeruginosa were observed to have a distinct, reproducible phenotype in which skipped wells were observed during broth microdilution testing for polymyxin B. Possible mechanisms underlying this phenotype were investigated. The effects of various concentrations of polymyxin B on growth, the expression of resistance genes, and outer-membrane permeability were observed. Real-time PCR was performed to compare the expression, in response to selected concentrations of polymyxin B, of genes related to the PhoP-PhoQ and PmrA-PmrB two-component regulatory systems in polymyxin B-susceptible isolate PAO1, polymyxin B-resistant isolate 9BR, and two isolates (19BR and 213BR) exhibiting the skipped-well phenotype. 19BR and 213BR appeared to have similar basal levels of expression compared to that of PAO1 for phoQ, arnB, and PA4773 (from the pmrAB operon), and in contrast, 9BR had 52- and 280-fold higher expression of arnB and PA4773, respectively. The expression of arnB and PA4773 increased in response to polymyxin B in a concentration-dependent manner for 9BR but not for 19BR and 213BR. For these isolates, expression was significantly increased for arnB and PA4773, as well as phoQ, only upon exposure to 2 μg/ml polymyxin B but not at a lower concentration of 0.125 μg/ml. The sequencing of the pmrAB and phoPQ operons for all three isolates revealed a number of unique mutations compared to that for PAO1. 1-N-phenylnaphthylamine (NPN) was used to study the effect of preincubation with polymyxin B on the self-promoted uptake of polymyxin B across the outer membrane. The preincubation of cells with 2 μg/ml polymyxin B affected baseline membrane permeability in 19BR and 213BR and also resulted in a reduced rate of NPN uptake in these isolates and in PAO1 but not in 9BR. The results presented here suggest that the skipped-well isolates have the ability to adapt to specific concentrations of polymyxin B, inducing known polymyxin B resistance genes involved in generating alterations in the outer membrane.

scholarly journals Battacin (Octapeptin B5), a New Cyclic Lipopeptide Antibiotic from Paenibacillus tianmuensis Active against Multidrug-Resistant Gram-Negative Bacteria

2011 ◽  
Vol 56 (3) ◽  
pp. 1458-1465 ◽  
Author(s):  
Chao-Dong Qian ◽  
Xue-Chang Wu ◽  
Yi Teng ◽  
Wen-Peng Zhao ◽  
Ou Li ◽  
...  
Keyword(s):  
Polymyxin B ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Content Type ◽  
Lipopeptide Antibiotic

ABSTRACTHospital-acquired infections caused by drug-resistant bacteria are a significant challenge to patient safety. Numerous clinical isolates resistant to almost all commercially available antibiotics have emerged. Thus, novel antimicrobial agents, specifically those for multidrug-resistant Gram-negative bacteria, are urgently needed. In the current study, we report the isolation, structure elucidation, and preliminary biological characterization of a new cationic lipopeptide antibiotic, battacin or octapeptin B5, produced from aPaenibacillus tianmuensissoil isolate. Battacin kills bacteriain vitroand has potent activity against Gram-negative bacteria, including multidrug-resistant and extremely drug-resistant clinical isolates. Hospital strains ofEscherichia coliandPseudomonas aeruginosaare the pathogens most sensitive to battacin, with MICs of 2 to 4 μg/ml. The ability of battacin to disrupt the outer membrane of Gram-negative bacteria is comparable to that of polymyxin B, the last-line therapy for infections caused by antibiotic-resistant Gram-negative bacteria. However, the capacity of battacin to permeate bacterial plasma membranes is less extensive than that of polymyxin B. The bactericidal kinetics of battacin correlate with the depolarization of the cell membrane, suggesting that battacin kills bacteria by disrupting the cytoplasmic membrane. Other studies indicate that battacin is less acutely toxic than polymyxin B and has potentin vivobiological activity againstE. coli. Based on the findings of the current study, battacin may be considered a potential therapeutic agent for the treatment of infections caused by antibiotic-resistant Gram-negative bacteria.

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