Clinical use of intravenous polymyxin B for the treatment of patients with multidrug-resistant Gram-negative bacterial infections: An evaluation of the current evidence

2021 ◽  
Vol 24 ◽  
pp. 342-359
Author(s):  
Matthew E. Falagas ◽  
Margarita Kyriakidou ◽  
Georgios L. Voulgaris ◽  
Filippos Vokos ◽  
Sevasti Politi ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Current Evidence ◽  
Clinical Use ◽  
Gram Negative

scholarly journals Resurgence of Polymyxin B for MDR/XDR Gram-Negative Infections: An Overview of Current Evidence

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Suneel Kumar Garg ◽  
Omender Singh ◽  
Deven Juneja ◽  
Niraj Tyagi ◽  
Amandeep Singh Khurana ◽  
...  
Keyword(s):  
Decision Making ◽  
Literature Review ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Current Evidence ◽  
Drug Resistant ◽  
Gram Negative

Polymyxin B has resurged in recent years as a last resort therapy for Gram-negative multidrug-resistant (MDR) and extremely drug resistant (XDR) infections. Understanding newer evidence on polymyxin B is necessary to guide clinical decision making. Here, we present a literature review of polymyxin B in Gram-negative infections with update on its pharmacology.

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 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 The Anthelmintic Drug Niclosamide Synergizes with Colistin and Reverses Colistin Resistance in Gram-Negative Bacilli

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Ronald Domalaon ◽  
P. Malaka De Silva ◽  
Ayush Kumar ◽  
George G. Zhanel ◽  
Frank Schweizer
Keyword(s):  
Bacterial Infections ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Colistin Resistance ◽  
Bacterial Killing ◽  
Gram Negative ◽  
Content Type ◽  
Anthelmintic Drug ◽  
Lipopeptide Antibiotic ◽  
Approved Drugs

ABSTRACTThere is an urgent need for new therapies to overcome antimicrobial resistance especially in Gram-negative bacilli (GNB). Repurposing old U.S. Food and Drug Administration-approved drugs as complementary agents to existing antibiotics in a synergistic combination presents an attractive strategy. Here, we demonstrate that the anthelmintic drug niclosamide selectively synergized with the lipopeptide antibiotic colistin against colistin-susceptible but more importantly against colistin-resistant GNB, including clinical isolates that harbor themcr-1gene. Breakpoints for colistin susceptibility in resistant Gram-negative bacilli were reached in the presence of 1 μg/ml (3 μM) niclosamide. Reversal of colistin resistance was also observed in combinations of niclosamide and polymyxin B. Enhanced bacterial killing was evident for the combination, in comparison to colistin monotherapy, against resistantPseudomonas aeruginosa,Acinetobacter baumannii,Klebsiella pneumoniae,Escherichia coli, andEnterobacter cloacae. Accumulating evidence in the literature, along with our results, strongly suggests the potential for the combination of niclosamide and colistin to treat colistin-resistant Gram-negative bacillary infections. Our finding is significant since colistin is an antibiotic of last resort for multidrug-resistant Gram-negative bacterial infections that are nonresponsive to conventional treatments. With the recent global dissemination of plasmid-encoded colistin resistance, the addition of niclosamide to colistin therapy may hold the key to overcome colistin resistance.

scholarly journals A New Surface Charge Neutralizing Nano-Adjuvant to Potentiate Polymyxins in Killing Mcr-1 Mediated Drug-Resistant Escherichia coli

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 250
Author(s):  
Hyejin Cho ◽  
Atanu Naskar ◽  
Sohee Lee ◽  
Semi Kim ◽  
Kwang-Sun Kim
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Underlying Mechanism ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Gene Products ◽  
Physical Status ◽  
Cellular Gene ◽  
Gram Negative ◽  
E Coli

Resistance to polymyxins when treating multidrug-resistant (MDR) Gram-negative bacterial infections limit therapeutic options. Here, we report the synthesis of a nickel (Ni) doped Zinc oxide (NZO) combined with black phosphorus (BP) (NZB) nanocomposite and its synergistic action with polymyxin B (PolB) against polymyxin-resistant Escherichia coli harboring mobilized colistin resistance (mcr-1) gene. NZB and PolB combination therapy expressed a specific and strong synergy against Mcr-1 expressing E. coli cells. The underlying mechanism of the synergy is the charge neutralization of the E. coli cell surface by NZB, resulting in a more feasible incorporation of PolB to E. coli. The synergistic concentration of NZB with PolB was proved biocompatible. Thus, the NZB is the first biocompatible nano-adjuvant to polymyxins against polymyxin-resistant E. coli cells, recognizing the physical status of bacteria instead of known adjuvants targeting cellular gene products. Therefore, NZB has the potential to revive polymyxins as leading last-resort antibiotics to combat polymyxin-resistant Gram-negative bacterial infections.

scholarly journals Prevalence of multidrug-resistant and extended-spectrum beta-lactamase producing Gram-negative isolates from clinical samples in a tertiary care hospital of Nepal

2021 ◽  
Vol 49 (1) ◽  
Author(s):  
Aryatara Shilpakar ◽  
Mehraj Ansari ◽  
Kul Raj Rai ◽  
Ganesh Rai ◽  
Shiba Kumar Rai
Keyword(s):  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Confirmatory Test ◽  
Clinical Samples ◽  
Care Hospital ◽  
Gram Negative ◽  
Extended Spectrum ◽  
Esbl Producers

Abstract Background The existence of multidrug-resistant organisms, including extended-spectrum beta-lactamases (ESBLs), is on rise across the globe and is becoming a severe problem. Knowledge of the prevalence and antibiogram profile of such isolates is essential to develop an appropriate treatment methodology. This study aimed to study the prevalence of Gram-negative isolates exhibiting ESBL at a tertiary care hospital and study their antibiogram profile. Methods A cross-sectional study was conducted at Shahid Gangalal National Heart Centre, Kathmandu, Nepal, from June 2018 to November 2018. A total of 770 clinical samples were collected and identified using the conventional biochemical tests following the Clinical and Laboratory Standard Institute (CLSI) guidelines. Antimicrobial susceptibility testing (AST) was performed using the standardized Kirby-Bauer disk diffusion method. The screening test for ESBL producers was performed as recommended by the CLSI and the confirmatory test was performed phenotypically using the E-test. Results Out of the 92 isolates, 84 (91.3%) were multidrug-resistant, and 47 (51.1%) were found to be potential ESBL producers. Of these, 16 isolates were confirmed ESBL producers by the E-test. Escherichia coli and Klebsiella pneumoniae were the predominant isolates and were also the major ESBL producers. Besides polymyxin B (100% sensitive), meropenem and imipenem showed high efficacy against the ESBL producers. Conclusion Multidrug resistance was very high; however, ESBL production was low. Polymyxin B and carbapenems are the choice of drugs against ESBL producers but should be used only as the last line drugs.

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