P51 Efficacy and safety of polymyxin B in the treatment of infections caused by multidrug-resistant Gram-Negative infections: a retrospective review

2009 ◽  
Vol 34 ◽  
pp. S43
Author(s):  
H. Oh ◽  
L. Gan ◽  
I. Wee
Keyword(s):  
Retrospective Review ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Efficacy And Safety ◽  
Gram Negative

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.

scholarly journals Polymyxins Nebulization over Intravenous Injection: Pharmacokinetics and Pharmacodynamics-Based Therapeutic Evaluation

2019 ◽  
pp. 1-10
Author(s):  
Md. Jahidul Hasan
Keyword(s):  
Respiratory Tract ◽  
Adverse Drug Reactions ◽  
Intravenous Administration ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Drug Reactions ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Gram Negative ◽  
Tract Infections

Polymyxins are the last line potential antibiotics against multi-drug resistant gram-negative bacteria and consist of two sister antibiotics: Polymyxin B and colistin (polymyxin E). Intravenous use of polymyxins was started from a long ago in the treatment of serious gram-negative infections and once their uses were restricted due to potential adverse drug reactions, such as nephrotoxicity and neurotoxicity. Lack of in vivo clinical studies on polymyxins mostly, in human body makes the pharmacokinetics and pharmacodynamics of polymyxin B and colistin unclear in many aspects, such as the distribution of polymyxins in different compartments of lung. The nebulization of polymyxins is practicing very limitedly and lack of clinical evidence has not justified this administration technique yet properly to date. The main objective of this review study was to evaluate the pharmacokinetic and pharmacodynamic properties of intravenous and nebulized polymyxins and the related therapeutic potentialities. Aerosolized polymyxins directly administered to the respiratory tract was found with higher drug concentration in different subcompartments of lungs than the intravenous administration and sustainably meets the minimum inhibitory concentration locally with superior bactericidal properties in respiratory tract infections. In contrast, intravenous administration of polymyxins shows similar anti-infective superiority in other organs, such as blood, urinary tract etc. So, during this alarming situation of rapidly emerging multidrug-resistant organisms in human communities, therapeutic administration techniques of last resort polymyxins should be clinically evidence-based for achieving optimum therapeutic outcomes with minimum chance of adverse drug reactions.  

scholarly journals Outer Membrane Interaction Kinetics of New Polymyxin B Analogs in Gram-Negative Bacilli

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Noushin Akhoundsadegh ◽  
Corrie R. Belanger ◽  
Robert E. W. Hancock
Keyword(s):  
Outer Membrane ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Intact Cells ◽  
Membrane Interaction ◽  
Gram Negative ◽  
Content Type ◽  
Interaction Kinetics ◽  
Hill Numbers ◽  
Multiple Strains

ABSTRACT Infections caused by drug-resistant Gram-negative bacilli are a severe global health threat, limiting effective drug choices for treatment. In this study, polymyxin analogs designed to have reduced nephrotoxicity, direct activity, and potentiating activity were assessed for inhibition and outer membrane interaction kinetics against wild-type (WT) and polymyxin or multidrug-resistant (MDR) Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. In MIC assays, two polymyxin B (PMB) analogs (SPR1205 and SPR206) and a polymyxin E analog (SPR946), with shortened peptide side chains and branched aminobutyryl N termini, exhibited promising activity compared with PMB and previously tested control polymyxin analogs SPR741 and polymyxin B nonapeptide (PMBN). Using dansyl-polymyxin (DPX) binding to assess the affinity of interaction with lipopolysaccharide (LPS), purified or in the context of intact cells, SPR206 exhibited similar affinities to PMB but higher affinities than the other SPR analogs. Outer membrane permeabilization measured by the 1-N-phenyl-napthylamine (NPN) assay did not differ significantly between the polymyxin analogs. Moreover, Hill numbers were greater than 1 for most of the compounds tested on E. coli and P. aeruginosa strains which indicates that the disruption of the outer membrane by one molecule of compound cooperatively enhances the subsequent interactions of other molecules against WT and MDR strains. The high activity demonstrated by SPR206 as well as its ability to displace LPS and permeabilize the outer membrane of multiple strains of Gram-negative bacilli while showing cooperative potential with other membrane disrupting compounds supports further research with this polymyxin analog.

The Bacteriological Profile of Burn Wound Infections at a Tertiary Burns Center in Nepal

2019 ◽  
Vol 40 (6) ◽  
pp. 838-845 ◽  
Author(s):  
Ojas Jyoti Singh Pujji ◽  
Kiran Kishor Nakarmi ◽  
Basudha Shrestha ◽  
Shankar Man Rai ◽  
Steven Leonard Alexander Jeffery
Keyword(s):  
Traffic Accidents ◽  
Burn Injury ◽  
Road Traffic ◽  
Average Distance ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Wound Infections ◽  
Burn Wound ◽  
Gram Negative

AbstractIn Nepal, burn is the third most common injury after falls and road traffic accidents. Infection is the leading cause of mortality in burn injury. A profile exploring predominant flora and antimicrobial sensitivity is important to facilitate treatment ahead of microbiology results and to aid prevention of multidrug-resistant organisms. The aim of this study was to document epidemiological and bacteriological data of burn wound infections at a tertiary level burns center in Nepal. Samples were collected from January 2017 to May 2017, over a period of 5 months. Patient notes were referred to and information regarding baseline characteristics and burn wound infection data was collected. A total of 76 patients were included in the study during the 5-month period, which resulted in 113 samples being included for review. Females were injured most with burns 70% (n = 53) compared with males 30% (n = 23). Only 6 (8%) of 77 patients lived locally in Kathmandu. The average distance traveled by patients was 233 km (median 208, range 0–765, SD 181). Average TBSA% of burn was 22% (median 20, range 3–50, SD 12). Gram-negative organisms predominated, with Acinetobacter spp. in 42 cases (55%), Pseudomonas aeruginosa in 26 cases (34%), and Enterobacter spp. in 16 cases (21%). Colistin, polymyxin B, and tigecycline were found to be most sensitive covering 108, 98, and 94 organisms. Gram-negative bacteria colonized the majority of burn wounds. Colistin, polymyxin B, and tigecycline were the most sensitive to gram-negative bacteria. Gram-positive Staphylococcus aureus was sensitive most to vancomycin and tigecycline.

scholarly journals Uptake of Polymyxin B into Renal Cells

2014 ◽  
Vol 58 (7) ◽  
pp. 4200-4202 ◽  
Author(s):  
Kamilia Abdelraouf ◽  
Kai-Tai Chang ◽  
Taijun Yin ◽  
Ming Hu ◽  
Vincent H. Tam
Keyword(s):  
Apical Membrane ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Tubular Epithelial Cells ◽  
Renal Cells ◽  
Kidney Cell Line ◽  
Gram Negative ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
B Uptake

ABSTRACTPolymyxin B is increasingly used as a treatment of last resort against multidrug-resistant Gram-negative infections. Using a mammalian kidney cell line, we demonstrated that polymyxin B uptake into proximal tubular epithelial cells was saturable and occurred primarily through the apical membrane, suggesting the involvement of transporters in the renal uptake of polymyxin B. Megalin might play a role in the uptake and accumulation of polymyxin B into renal cells.

scholarly journals Novel Engineered Peptides of a Phage Lysin as Effective Antimicrobials against Multidrug-Resistant Acinetobacter baumannii

2016 ◽  
Vol 60 (5) ◽  
pp. 2671-2679 ◽  
Author(s):  
Mya Thandar ◽  
Rolf Lood ◽  
Benjamin Y. Winer ◽  
Douglas R. Deutsch ◽  
Chad W. Euler ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bacterial Pathogen ◽  
Antibacterial Activities ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Gram Negative ◽  
Content Type ◽  
Human Red Blood Cells ◽  
Phage Lysin

ABSTRACTAcinetobacter baumanniiis a Gram-negative bacterial pathogen responsible for a range of nosocomial infections. The recent rise and spread of multidrug-resistantA. baumanniiclones has fueled a search for alternative therapies, including bacteriophage endolysins with potent antibacterial activities. A common feature of these lysins is the presence of a highly positively charged C-terminal domain with a likely role in promoting outer membrane penetration. In the present study, we show that the C-terminal amino acids 108 to 138 of phage lysin PlyF307, named P307, alone were sufficient to killA. baumannii(>3 logs). Furthermore, P307 could be engineered for improved activity, the most active derivative being P307SQ-8C(>5-log kill). Both P307 and P307SQ-8Cshowed highin vitroactivity againstA. baumanniiin biofilms. Moreover, P307SQ-8Cexhibited MICs comparable to those of levofloxacin and ceftazidime and acted synergistically with polymyxin B. Although the peptides were shown to kill by disrupting the bacterial cytoplasmic membrane, they did not lyse human red blood cells or B cells; however, serum was found to be inhibitory to lytic activity. In a murine model ofA. baumanniiskin infection, P307SQ-8Creduced the bacterial burden by ∼2 logs in 2 h. This study demonstrates the prospect of using peptide derivatives from bacteriophage lysins to treat topical infections and remove biofilms caused by Gram-negative pathogens.

Efficacy and safety of colistin for the treatment of infections caused by multidrug-resistant gram-negative bacilli

2020 ◽  
Author(s):  
Keisuke Kagami ◽  
Nobuhisa Ishiguro ◽  
Takehiro Yamada ◽  
Yusuke Niinuma ◽  
Sumio Iwasaki ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Efficacy And Safety ◽  
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.

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