scholarly journals Comparative study of in vitro activities of polymyxin B commercial products on Pseudomonas aeruginosa isolated from hospitalized patients

2021 ◽  
Vol 62 (3) ◽  
pp. 270-279
Author(s):  
Rezvan Goodarzi ◽  
Farhad Farahani ◽  
Mahdane Roshani ◽  
Mohammad Taheri ◽  
Babak Asghari
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Susceptibility Testing ◽  
Renal Toxicity ◽  
Polymyxin B ◽  
Microbiological Activity ◽  
Commercial Products ◽  
Gram Negative ◽  
In Vitro Antibacterial Activity

Introduction: Polymyxin B has been applied as one of the last-resort antibiotics for the treatment of multidrug resistance among Gram-negative bacterial infections. Due to side effects such as renal toxicity, the use of polymyxin is associated with limitations. The present study evaluates in vitro antibacterial activity of a number of polymyxin B commercial products against Pseudomonas aeruginosa. Methods: This study included 63 non-duplicated P. aeruginosa isolates examined for in vitro polymyxin B susceptibility testing using the following powder disks: polymyxin B sulfate, otosporin, Poly-Mxb, and Myxacort. MIC50 and MIC90 have also been identified for polymyxin B antibiotics. Results: Myxacort had functional activity against most P. aeruginosa isolates, and only seven isolates had a relatively high MIC. The activities of Poly-MXb and Myxacort were the same as otosporin. Conclusions: Our findings revealed that the national generic polymyxin B product (Myxacort), and two external products (Otosporin, Poly-MXb) are similar in terms of microbiological activity.

scholarly journals Antimicrobial Susceptibility Testing for Polymyxins: Challenges, Issues, and Recommendations

2018 ◽  
Vol 57 (4) ◽  
Author(s):  
Fereshteh Ezadi ◽  
Abdollah Ardebili ◽  
Reza Mirnejad
Keyword(s):  
Bacterial Infections ◽  
Susceptibility Testing ◽  
Agar Medium ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Professional Organizations ◽  
Gram Negative ◽  
Microtiter Plates ◽  
Critical Issues ◽  
Polymyxin E

ABSTRACTPolymyxins, including polymyxin B and polymyxin E (colistin), are now increasingly being used worldwide to treat patients with multidrug-resistant (MDR) Gram-negative bacterial infections. This necessitates that laboratories employ an accurate and reliable method for the routine performance of polymyxin susceptibility testing. A number of reasons have accounted for the difficulties with susceptibility testing for the polymyxins, including their multicomponent composition, poor diffusion in the agar medium, adsorption to microtiter plates, the lack of a reliable susceptibility test, the lack of a specific breakpoint from professional organizations, the synergistic effect of polysorbate 80, and the development of heteroresistance. This minireview discusses such problems that impact the results of currently available susceptibility testing methods. We also provide emerging concepts on mechanisms of polymyxin resistance, including chromosomally and plasmid-mediatedmcr-related resistance. Broad-range investigations on such critical issues in relation to polymyxins can be beneficial for the implementation of effective treatment against MDR Gram-negative bacterial infections.

scholarly journals In Vitro Antibacterial Activity of Cefiderocol against Multidrug-Resistant Acinetobacter baumannii

2021 ◽  
Author(s):  
Jacinda C. Abdul-Mutakabbir ◽  
Logan Nguyen ◽  
Philip T. Maassen ◽  
Kyle C. Stamper ◽  
Razieh Kebriaei ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Susceptibility Testing ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Strong Activity ◽  
Gram Negative ◽  
In Vitro Antibacterial Activity ◽  
Time Kill

Cefiderocol (CFDC), a novel siderophore cephalosporin, demonstrates strong activity against multidrug-resistant (MDR) Acinetobacter baumannii. Limited studies have evaluated CFDC alone and in combination with other Gram-negative antibiotics against MDR A. baumannii isolates. Susceptibility testing revealed lower CFDC minimum inhibitory concentration (MIC) values than the comparator Gram-negative agents (87% of MICs ≤ 4mg/L). Six isolates, with elevated CFDC MICs (16-32 mg/L), were selected for further experiments. Time-kill analyses presented with synergistic activity and beta-lactamase inhibitors increased CFDC susceptibility in each of the isolates.

scholarly journals In vitro Susceptibility Pattern of Major Gram Negative Isolates to Selected Antimicrobial Agents

2019 ◽  
pp. 1-8
Author(s):  
Shalini Gupta ◽  
Pankaj Mandale
Keyword(s):  
Antimicrobial Susceptibility ◽  
Bacterial Infections ◽  
Therapeutic Option ◽  
Polymyxin B ◽  
Susceptibility Pattern ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
E Coli ◽  
Susceptibility Data

Background: The choice of choosing right anti-microbial therapy in hospitals depends on the knowledge of local anti-microbial susceptibility profile. This retrospective study was conducted to assess the in vitro susceptibility pattern of different pathogen isolates to various antibiotics including Cefepime-Amikacin-Antibiotic resistant breakers (ARBs)* in various hospitals across the Jaipur City. Methods: To characterize the antimicrobial susceptibility pattern of different isolates from various hospitals across the Jaipur City, a retrospective, observational analysis was done for antibiogram data. A total of 1201 Gram negative isolates collected during the period from January 2017 to December 2017 were included in the study. Antibiotic sensitivity testing was done in accordance with the recommendations of Clinical Laboratory Standard Institute (CLSI) guidelines. Results: Of the total 1201 Gram negative isolates included in this study, 51.6% were from wounds and pus specimens, 40.1% were from respiratory and 8.2% from blood. P. aeruginosa (49.7%) was the most frequently isolated pathogen distantly followed by A. baumannii (21.6%), K. pneumoniae (16.6%) and E. coli (12.1%). The highest susceptibility was reported to polymyxins (100%) including Colistin and Polymyxin B, among all the tested bacteria’s and system wise. Among all the antibiotic tested, (Cefepime-Amikacin-ARBs*) sensitivity ranged for 87.9% to 52% on pathogens (E. coli, K. pneumonia, P. aeruginosa) tested from samples of skin and soft tissue, respiratory tract, blood stream, followed by Meropenem ranged for 78.4% to 55% on pathogens (E. coli, K. pneumonia, P. aeruginosa), followed by ceftazidime-tazobactam ranged for 82.7% to 58% on pathogens (E. coli, K. pneumonia, P. aeruginosa) and 22.7% sensitive for A. baumannii to Cefoperazone sulbactam. Based on pathogen type, E. coli exhibited highest overall susceptibility and the lowest was reported by A. baumannii. The susceptibility of A. baumannii ranged from 1-26% to all the tested antibiotics except polymyxins with 100% susceptibility. Conclusions: This in vitro susceptibility data suggests that Cefepime-Amikacin-ARBs* can serve as important therapeutic option for the treatment of various resistant Gram-negative bacterial infections to relieve the excess pressure on last resort antibiotics, carbapenems and other drugs including Colistin and polymyxin B. Cefepime-Amikacin-ARBs*on the basis of antimicrobial susceptibility data can be considered as an effective therapeutic option for carbapenems in treating gram negative bacterial infections, and could be considered as a broad spectrum antibiotic sparer’s like carbapenem, colistin and Polymyxin B.

scholarly journals Bi-Functional Alginate Oligosaccharide–Polymyxin Conjugates for Improved Treatment of Multidrug-Resistant Gram-Negative Bacterial Infections

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1080
Author(s):  
Joana Stokniene ◽  
Lydia C. Powell ◽  
Olav A. Aarstad ◽  
Finn L. Aachmann ◽  
Philip D. Rye ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Bacterial Infections ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Laser Scanning Microscopy ◽  
Gram Negative ◽  
Therapeutic Benefits ◽  
Recent Emergence ◽  
Alginate Oligosaccharide

The recent emergence of resistance to colistin, an antibiotic of last resort with dose-limiting toxicity, has highlighted the need for alternative approaches to combat infection. This study aimed to generate and characterise alginate oligosaccharide (“OligoG”)–polymyxin (polymyxin B and E (colistin)) conjugates to improve the effectiveness of these antibiotics. OligoG–polymyxin conjugates (amide- or ester-linked), with molecular weights of 5200–12,800 g/mol and antibiotic loading of 6.1–12.9% w/w, were reproducibly synthesised. In vitro inflammatory cytokine production (tumour necrosis factor alpha (TNFα) ELISA) and cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) of colistin (2.2–9.3-fold) and polymyxin B (2.9–27.2-fold) were significantly decreased by OligoG conjugation. Antimicrobial susceptibility tests (minimum inhibitory concentration (MIC), growth curves) demonstrated similar antimicrobial efficacy of ester- and amide-linked conjugates to that of the parent antibiotic but with more sustained inhibition of bacterial growth. OligoG–polymyxin conjugates exhibited improved selectivity for Gram-negative bacteria in comparison to mammalian cells (approximately 2–4-fold). Both OligoG–colistin conjugates caused significant disruption of Pseudomonas aeruginosa biofilm formation and induced bacterial death (confocal laser scanning microscopy). When conjugates were tested in an in vitro “time-to-kill” (TTK) model using Acinetobacter baumannii, only ester-linked conjugates reduced viable bacterial counts (~2-fold) after 4 h. Bi-functional OligoG–polymyxin conjugates have potential therapeutic benefits in the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections, directly reducing toxicity whilst retaining antimicrobial and antibiofilm activities.

scholarly journals Resveratrol enhances the antimicrobial effect of polymyxin B on Klebsiella pneumoniae and Escherichia coli isolates with polymyxin B resistance

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Li Liu ◽  
Jingyi Yu ◽  
Xiaofei Shen ◽  
Xingwei Cao ◽  
Qing Zhan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Bacterial Infections ◽  
Antimicrobial Effect ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Gram Negative ◽  
Optimal Drug

Abstract Background Multidrug resistant (MDR) Gram-negative bacterial infections are a serious threat to human health due to the lack of effective treatments. In this study, we selected 50 Gram-negative bacterial strains, including 26 strains of Klebsiella pneumoniae and 24 strains of Escherichia coli, to explore whether resveratrol and polymyxin B have a synergistic killing effect. Results MIC values against polymyxin B were ≥ 4 μg/mL for 44 of the strains and were 2 μg/mL for the other 6 strains. MICs against polymyxin B in the isolates tested were significantly reduced by the addition of resveratrol. The degree of decline depended on the bacteria, ranging from 1/2 MIC to 1/512 MIC, and the higher the concentration of resveratrol, the greater the decrease. Checkerboard analysis indicated a synergistic effect between resveratrol and polymyxin B; the optimal drug concentration for different bacteria was different, that of resveratrol ranging from 32 μg/mL to 128 μg/mL. Subsequent time-kill experiments showed that a combination of polymyxin B and resveratrol was more effective in killing bacteria. Conclusions Our in vitro studies have shown that resveratrol can increase the sensitivity of MDR bacterial strains to polymyxin B, suggesting a potential new approach to the treatment of MDR infections.

scholarly journals Comparing Quantitative and Qualitative Methods for Detecting the In Vitro Activity of Colistin against Different Gram-Negative Bacilli

2021 ◽  
Vol 8 (5) ◽  
Author(s):  
Shams N ◽  
◽  
AlHiraky H ◽  
Moulana N ◽  
Riahi M ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Susceptibility Testing ◽  
High Sensitivity ◽  
Multidrug Resistant ◽  
Disk Diffusion ◽  
Broth Microdilution ◽  
Testing Methods ◽  
Gram Negative ◽  
Phenotypic Profile

The surge in the prevalence of Multidrug-Resistant (MDR) Gram-negative bacterial infections with limited treatment led to colistin reusing to treat MDR infections. This study aimed to determine economical, simple, and reliable colistin susceptibility testing methods as an alternative to the microdilution technique. We compared seven colistin susceptibility testing methods, including quantitative and qualitative, namely: Disk diffusion, E-test, ComASPTM SensiTest Colistin, Colistin broth disk elution, and colistin agar test CHROMagarTM COL-APSE, and BD Phoenix ID/AST automated identification and susceptibility testing system to the gold standard Broth Microdilution (BMD). Whole-genome sequencing was performed on all isolates to determine if the genetic resistant factors affect the phenotypic profile of the colistin resistance. Our results revealed that disk diffusion is still an ineffective method for measuring colistin susceptibility in Gram-negative Bacilli with the highest major error (31.75%), the lowest Kappa 0 (0%), and categorical agreement (68.25%) values. Phoenix, and CompASPTM SensiTest colistin methods have remained superior in reproducibility, sturdiness, and simplicity of use, similar to the currently recommended broth microdilution procedure; with high sensitivity of 95.56%, and 97.73%, specificity of 95.24, and 100%, and Kappa values of 0.89 and 0.95, respectively. This study revealed that Phoenix, and ComASPTM SensiTest colistin methods are recommended for routine microbiology laboratories with a large workload.

scholarly journals Pharmacodynamics of Polymyxin B against Pseudomonas aeruginosa

2005 ◽  
Vol 49 (9) ◽  
pp. 3624-3630 ◽  
Author(s):  
Vincent H. Tam ◽  
Amy N. Schilling ◽  
Giao Vo ◽  
Samer Kabbara ◽  
Andrea L. Kwa ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bactericidal Activity ◽  
Bacterial Infections ◽  
Bacterial Load ◽  
Polymyxin B ◽  
Dose Fractionation ◽  
Infection Model ◽  
Wild Type ◽  
Clinical Dose

ABSTRACT Despite limited data, polymyxin B (PB) is increasingly used clinically as the last therapeutic option for multidrug-resistant (MDR) gram-negative bacterial infections. We examined the in vitro pharmacodynamics of PB against four strains of Pseudomonas aeruginosa. Clonal relatedness of the strains was assessed by random amplification of polymorphic DNA. Time-kill studies over 24 h were performed with approximately 105 and 107 CFU/ml of bacteria, using PB at 0, 0.25, 0.5, 1, 2, 4, 8, and 16× MIC. Dose fractionation studies were performed using an in vitro hollow-fiber infection model (HFIM) against a wild-type and a MDR strain. Approximately 105 CFU/ml of bacteria were exposed to placebo and three regimens (every 8 h [q8h], q12h, and q24h) simulating the steady-state unbound PB pharmacokinetics resulting from a daily dose of 2.5 mg/kg of body weight and 20 mg/kg (8 times the clinical dose). Samples were obtained over 4 days to quantify PB concentrations, total bacterial population, and subpopulation with reduced PB susceptibility (>3× MIC). The bactericidal activity of PB was concentration dependent, but killing was significantly reduced with a high inoculum. In HFIM studies, a significant reduction in bacterial load was seen at 4 h in all active regimens, but selective amplification of the resistant subpopulation(s) was apparent at 24 h with the clinical dose (both strains). Regrowth was eventually observed in all dosing regimens with the MDR strain, but its occurrence was prevented in the wild-type strain by using 8 times the clinical dose (regardless of dosing intervals). Our results suggested that the bactericidal activity of PB was concentration dependent and appeared to be related to the ratio of the area under the concentration-time curve to the MIC.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

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