scholarly journals Interactions of polymyxin B with lipopolysaccharide-containing membranes

2021 ◽  
Author(s):  
Alice Goode ◽  
Vivien Yeh ◽  
Boyan B Bonev

Bacterial resistance to antibiotics constantly remodels the battlefront between infections and antibiotic therapy. Polymyxin B, a cationic peptide with anti-Gram-negative spectrum of activity is re-entering use as a last resort...

2020 ◽  
Vol 15 (17) ◽  
pp. 1631-1643
Author(s):  
Dorin Harpaz ◽  
Robert S Marks ◽  
Ariel Kushmaro ◽  
Evgeni Eltzov

Aim: The mechanisms behind antibiotic resistance by bacteria are important to create alternative molecules. Objective: This study focuses on the impact of environmental pollutants on bacterial resistance to antibiotics. Materials & methods: The effect of various environmental pollutants on noninherited bacterial resistance to antibiotics was examined. Results: The tolerance to the polymyxin-B antibiotic was shown to be conferred to Escherichia coli, by pretreatment with subinhibitory concentrations of environmental toxicants. The cell survival to a sublethal dosage of antibiotics was tested. Exposure to low concentrations of toxic compounds (500 ppb copper, 2% [v/v] ethanol or 0.5 μg/ml trimethoprim) stimulated the bacterial heat shock systems and led to increased tolerance to polymyxin B. Conclusion: Environmental pollutants induce a temporary bacterial noninheritable resistance to antibiotic.


2020 ◽  
Author(s):  
Nathan Peiffer-Smadja ◽  
Lila BOUADMA ◽  
Vincent MATHY ◽  
Kahina ALLOUCHE ◽  
Juliette PATRIER ◽  
...  

Abstract Background: Early appropriate antibiotic therapy reduces morbidity and mortality of severe pneumonia. However, the emergence of bacterial resistance requires the earliest use of antibiotics with the narrowest possible spectrum. The Unyvero Hospitalized Pneumonia (HPN, Curetis) test is a multiplex PCR (M-PCR) system detecting 21 bacteria and 19 resistance genes on respiratory samples within 5 hours. We assessed the performance and the potential impact of the M-PCR on the antibiotic therapy of ICU patients. Methods: In this prospective study we performed a M-PCR on bronchoalveolar lavage (BAL) or plugged telescoping catheters (PTC) samples of patients with ventilated HAP or VAP with Gram-negative bacilli or clustered Gram-positive cocci. This study was conducted in 3 ICUs in a French academic hospital; the medical and infectious diseases ICU, the surgical ICU and the cardio-surgical ICU. A multidisciplinary expert panel simulated the antibiotics changes they would have made if the M-PCR results had been available. Results We analyzed 95 clinical samples of ventilated HAP or VAP (72 BAL and 23 PTC) from 85 patients (62 males, median age 64 years). The median turnaround time of the M-PCR was 4.6 hours (IQR 4.4-5). A total of 90/112 bacteria were detected by the M-PCR system with a global sensitivity of 80% (95%CI, 73-88%) and specificity of 99% (95%CI 99-100). The sensitivity was better for Gram-negative bacteria (90%) than for Gram-positive cocci (62%) (p=0.005). Moreover, 5/8 extended-spectrum beta-lactamases (CTX-M gene) and 4/4 carbapenemases genes (3 NDM, one oxa-48) were detected. The M-PCR could have led to the earlier initiation of an effective antibiotic in 20/95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one (1%) inadequate antimicrobial therapy. Among 17 empiric antibiotic treatments with carbapenems, 10 could have been de-escalated in the following hours according to the M-PCR results. The M-PCR also led to 2 unexpected diagnosis of severe legionellosis confirmed by culture methods. Conclusions: Our results suggest that the use of a M-PCR system for respiratory samples of patients with VAP and ventilated HAP could improve empirical antimicrobial therapy and reduce the use of broad-spectrum antibiotics.


2020 ◽  
Author(s):  
Nathan Peiffer-Smadja ◽  
Lila BOUADMA ◽  
Vincent MATHY ◽  
Kahina ALLOUCHE ◽  
Juliette PATRIER ◽  
...  

Abstract Background: Early appropriate antibiotic therapy reduces morbidity and mortality of severe pneumonia. However, the emergence of bacterial resistance requires the earliest use of antibiotics with the narrowest possible spectrum. The Unyvero Hospitalized Pneumonia (HPN, Curetis) test is a multiplex PCR (M-PCR) system detecting 21 bacteria and 19 resistance genes on respiratory samples within 5 hours. We assessed the performance and the potential impact of the M-PCR on the antibiotic therapy of ICU patients. Methods: In this prospective study we performed a M-PCR on bronchoalveolar lavage (BAL) or plugged telescoping catheters (PTC) samples of patients with ventilated HAP or VAP with Gram-negative bacilli or clustered Gram-positive cocci. This study was conducted in 3 ICUs in a French academic hospital; the medical and infectious diseases ICU, the surgical ICU and the cardio-surgical ICU. A multidisciplinary expert panel simulated the antibiotics changes they would have made if the M-PCR results had been available. Results We analyzed 95 clinical samples of ventilated HAP or VAP (72 BAL and 23 PTC) from 85 patients (62 males, median age 64 years). The median turnaround time of the M-PCR was 4.6 hours (IQR 4.4-5). A total of 90/112 bacteria were detected by the M-PCR system with a global sensitivity of 80% (95%CI, 73-88%) and specificity of 99% (95%CI 99-100). The sensitivity was better for Gram-negative bacteria (90%) than for Gram-positive cocci (62%) (p=0.005). Moreover, 5/8 extended-spectrum beta-lactamases (CTX-M gene) and 4/4 carbapenemases genes (3 NDM, one oxa-48) were detected. The M-PCR could have led to the earlier initiation of an effective antibiotic in 20/95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one (1%) inadequate antimicrobial therapy. Among 17 empiric antibiotic treatments with carbapenems, 10 could have been de-escalated in the following hours according to the M-PCR results. The M-PCR also led to 2 unexpected diagnosis of severe legionellosis confirmed by culture methods. Conclusions: Our results suggest that the use of a M-PCR system for respiratory samples of patients with VAP and ventilated HAP could improve empirical antimicrobial therapy and reduce the use of broad-spectrum antibiotics.


2015 ◽  
Vol 21 (28) ◽  
pp. 4095-4105 ◽  
Author(s):  
Roudayna Diab ◽  
Bahman Khameneh ◽  
Olivier Joubert ◽  
Raphael Duval

2007 ◽  
Vol 20 (11) ◽  
pp. 1421-1430 ◽  
Author(s):  
Christian Sohlenkamp ◽  
Kanaan A. Galindo-Lagunas ◽  
Ziqiang Guan ◽  
Pablo Vinuesa ◽  
Sally Robinson ◽  
...  

Lysyl-phosphatidylglycerol (LPG) is a well-known membrane lipid in several gram-positive bacteria but is almost unheard of in gram-negative bacteria. In Staphylococcus aureus, the gene product of mprF is responsible for LPG formation. Low pH-inducible genes, termed lpiA, have been identified in the gram-negative α-proteobacteria Rhizobium tropici and Sinorhizobium medicae in screens for acid-sensitive mutants and they encode homologs of MprF. An analysis of the sequenced bacterial genomes reveals that genes coding for homologs of MprF from S. aureus are present in several classes of organisms throughout the bacterial kingdom. In this study, we show that the expression of lpiA from R. tropici in the heterologous hosts Escherichia coli and Sinorhizobium meliloti causes formation of LPG. A wild-type strain of R. tropici forms LPG (about 1% of the total lipids) when the cells are grown in minimal medium at pH 4.5 but not when grown in minimal medium at neutral pH or in complex tryptone yeast (TY) medium at either pH. LPG biosynthesis does not occur when lpiA is deleted and is restored upon complementation of lpiA-deficient mutants with a functional copy of the lpiA gene. When grown in the low-pH medium, lpiA-deficient rhizobial mutants are over four times more susceptible to the cationic peptide polymyxin B than the wild type.


2021 ◽  
Vol 49 (1) ◽  
Author(s):  
Aryatara Shilpakar ◽  
Mehraj Ansari ◽  
Kul Raj Rai ◽  
Ganesh Rai ◽  
Shiba Kumar Rai

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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