scholarly journals Gram-Negative Bacterial Lysins

Antibiotics ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 74 ◽  
Author(s):  
Chandrabali Ghose ◽  
Chad W. Euler
Keyword(s):  
Cell Wall ◽  
Antibiotic Resistance ◽  
Standard Of Care ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Lytic Cycle ◽  
Human Society ◽  
Gram Negative ◽  
Critical Components ◽  
Conventional Antibiotics

Antibiotics have had a profound impact on human society by enabling the eradication of otherwise deadly infections. Unfortunately, antibiotic use and overuse has led to the rapid spread of acquired antibiotic resistance, creating a major threat to public health. Novel therapeutic agents called bacteriophage endolysins (lysins) provide a solution to the worldwide epidemic of antibiotic resistance. Lysins are a class of enzymes produced by bacteriophages during the lytic cycle, which are capable of cleaving bonds in the bacterial cell wall, resulting in the death of the bacteria within seconds after contact. Through evolutionary selection of the phage progeny to be released and spread, these lysins target different critical components in the cell wall, making resistance to these molecules orders of magnitude less likely than conventional antibiotics. Such properties make lysins uniquely suitable for the treatment of multidrug resistant bacterial pathogens. Lysins, either naturally occurring or engineered, have the potential of being developed into fast-acting, narrow-spectrum, biofilm-disrupting antimicrobials that act synergistically with standard of care antibiotics. This review focuses on newly discovered classes of Gram-negative lysins with emphasis on prototypical enzymes that have been evaluated for efficacy against the major antibiotic resistant organisms causing nosocomial infections.

scholarly journals Correlation between Antibiotic Resistance of Main Gram-Negative Pathogens and Antibiotic Consumption in a General Hospital of China

2019 ◽  
Author(s):  
Shaoqing Shen ◽  
Rui Wang ◽  
Jin Wang ◽  
Yun Cai
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Resistance ◽  
Mainland China ◽  
Antibiotic Use ◽  
Antibiotic Consumption ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Gram Negative ◽  
Positive Effects ◽  
Resistance Rates

Abstract Purpose Our hospital is a newly established hospital in China, which is located in the tropics. Better depicting antibiotic consumption and antibiotic resistance may help better develop and implement an antibiotic stewardship with regional characteristics.Methods Total antibiotic prescriptions, patient days and microbiological data from January 2014 to December 2017 were collected. Antibiotic use density (AUD) was expressed as daily defined dose (DDD) and normalized per 100 patient-days. The resistance rates of Gram-negative pathogens against commonly used antibiotics were calculated. The relationship between antibiotic consumption and bacterial resistance rate was described by Pearson’s correlation coefficient.Results Different from mainland China, A. baumannii was the leading Gram-negative pathogen, followed by K. pneumoniae , E. coli and P. aeruginosa . The AUD was gradually increased from 2014 to 2016, while it was slowly decreased in 2017. Ceftazidime/tazobactam, levofloxacin and meropenem were the top three consumed antibiotics. The proportion of multidrug resistant (MDR) Gram-negative bacteria was increased (>40%) before 2016, and it was decreased in 2017. The prevalence of MDR A. baumannii and MDR P. aeruginosa was correlated with the AUD of β-lactam/lactamase inhibitors, fluoroquinolones and carbapenems. The increased AUD of meropenem had positive effects on the incidence of carbapenem-resistant A. baumannii and P. aeruginosa .Conclusions Our study showed that there was an association between the resistance density of Gram-negative pathogens and the consumption of β-lactam/lactamase inhibitors, carbapenems and fluoroquinolones. Collectively, a multifaceted antimicrobial stewardship is necessary to decrease resistance density of available antibiotics.

scholarly journals Sorting out the Superbugs: Potential of Sortase A Inhibitors among Other Antimicrobial Strategies to Tackle the Problem of Antibiotic Resistance

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 164 ◽  
Author(s):  
Nikita Zrelovs ◽  
Viktorija Kurbatska ◽  
Zhanna Rudevica ◽  
Ainars Leonchiks ◽  
Davids Fridmanis
Keyword(s):  
Cell Wall ◽  
Antibiotic Resistance ◽  
Pathogenic Bacteria ◽  
Resistance Mechanisms ◽  
Surface Proteins ◽  
Sortase A ◽  
Inhibitory Compounds ◽  
Alternative Means ◽  
Alternative Approaches ◽  
Conventional Antibiotics

Rapid spread of antibiotic resistance throughout the kingdom bacteria is inevitably bringing humanity towards the “post-antibiotic” era. The emergence of so-called “superbugs”—pathogen strains that develop resistance to multiple conventional antibiotics—is urging researchers around the globe to work on the development or perfecting of alternative means of tackling the pathogenic bacteria infections. Although various conceptually different approaches are being considered, each comes with its advantages and drawbacks. While drug-resistant pathogens are undoubtedly represented by both Gram(+) and Gram(−) bacteria, possible target spectrum across the proposed alternative approaches of tackling them is variable. Numerous anti-virulence strategies aimed at reducing the pathogenicity of target bacteria rather than eliminating them are being considered among such alternative approaches. Sortase A (SrtA) is a membrane-associated cysteine protease that catalyzes a cell wall sorting reaction by which surface proteins, including virulence factors, are anchored to the bacterial cell wall of Gram(+) bacteria. Although SrtA inhibition seems perspective among the Gram-positive pathogen-targeted antivirulence strategies, it still remains less popular than other alternatives. A decrease in virulence due to inactivation of SrtA activity has been extensively studied in Staphylococcus aureus, but it has also been demonstrated in other Gram(+) species. In this manuscript, results of past studies on the discovery of novel SrtA inhibitory compounds and evaluation of their potency were summarized and commented on. Here, we discussed the rationale behind the inhibition of SrtA, raised some concerns on the comparability of the results from different studies, and touched upon the possible resistance mechanisms as a response to implementation of such therapy in practice. The goal of this article is to encourage further studies of SrtA inhibitory compounds.

scholarly journals MULTIPLE ANTIBIOTIC RESISTANCE INDEXING OF NON- FERMENTING GRAM NEGATIVE BACILLI

2017 ◽  
Vol 10 (6) ◽  
pp. 78
Author(s):  
Bhuvaneshwari Gunasekar
Keyword(s):  
Antibiotic Resistance ◽  
Tertiary Care ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Care Hospital ◽  
Multiple Antibiotic Resistance ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Mar Index ◽  
Surgery Department

Objective: The multiple antibiotic resistance (MAR) indexing and finding Multidrug resistant (MDR) bacteria will help to indicate the origin from high risk of contamination where the antibiotics are often used. Hence this study was carried out to give the MAR index of non-fermenting Gram negative bacilli in a tertiary care hospital which would help our infection control team also.Methods: Drug resistance was tested by Kirby bauer’s disc diffusion method. MAR index was calculated using the formula, a/b (were a= number of antibiotics to which the organism was resistant and b= total number of antibiotics to which the organism was tested).Results: Out of 240 Gram negative non-fermenters isolated, 117 (49%) strains were greater than 0.2 of MAR index, 95(81%) was from in-patient department. 73(62%) were hospitalized for more than 3 days, 44 (38%) was from surgery department. 49(42%) was wound specimen. Out of 117 multiple antibiotic resistant isolates 99 (85%) were MDR isolates.Conclusion: 51% prevalence of isolates >0.2 MAR index shows that the source of contamination can still be brought up down by proper surveillance and management with proper usage of  surface and skin disinfectants especially in surgery ward where the MAR index has indicated more usage of antibiotics

scholarly journals Gram-Negative Taxa and Antimicrobial Susceptibility after Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Danielle Barrios Steed ◽  
Tiffany Wang ◽  
Divyanshu Raheja ◽  
Alex D. Waldman ◽  
Ahmed Babiker ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Susceptibility ◽  
Fecal Microbiota Transplantation ◽  
Antibiotic Prescription ◽  
Multidrug Resistant ◽  
Fecal Microbiota ◽  
Gram Negative ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Susceptibility Profiles

ABSTRACT Fecal microbiota transplantation (FMT) has promising applications in reducing multidrug-resistant organism (MDRO) colonization and antibiotic resistance (AR) gene abundance. However, data on clinical microbiology results after FMT are limited. We examined the changes in antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after treatment with FMT for recurrent Clostridioides difficile infection (RCDI). We also examined whether a history of FMT changed health care provider behavior with respect to culture ordering and antibiotic prescription. Medical records for RCDI patients who underwent FMT at Emory University between July 2012 and March 2017 were reviewed retrospectively. FMT-treated patients with Gram-negative culture data in the 1-year period preceding and the 1-year period following FMT were included. Demographic and clinical data were abstracted, including CDI history, frequency of Gram-negative cultures, microbiological results, and antibiotic prescription in response to positive cultures in the period following FMT. Twelve patients were included in this case series. We pooled data from infections at all body sites and found a decrease in the number of total and Gram-negative cultures post-FMT. We compared susceptibility profiles across taxa given the potential for horizontal transmission of AR elements and observed increased susceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, and the aminoglycosides. FMT did not drastically influence health care provider ordering of bacterial cultures or antibiotic prescribing practices. We observed a reduction in Gram-negative cultures and a trend toward increased antimicrobial susceptibility. This study supports further investigation of FMT as a means of improving antimicrobial susceptibility. IMPORTANCE Fecal microbiota transplantation (FMT), which is highly efficacious in treating recurrent C. difficile infection (RCDI), has a promising application in decolonization of multidrug-resistant organisms, reduction of antibiotic resistance gene abundance, and restoration of healthy intestinal microbiota. However, data representing clinical microbiology results after FMT are limited. We sought to characterize the differences in culture positivity and antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after FMT for RCDI. Drawing on prior studies that had demonstrated the success of FMT in eradicating extraintestinal infections and the occurrence of patient-level interspecies transfer of resistance elements, we employed an agnostic analytic approach of reviewing the data irrespective of body site or species. In a small RCDI population, we observed an improvement in the antimicrobial susceptibility profile of Gram-negative bacteria following FMT, which supports further study of FMT as a strategy to combat antibiotic resistance.

scholarly journals Risk factors and outcomes for multidrug-resistant Gram-negative bacilli bacteremia

2017 ◽  
Vol 5 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Swati Patolia ◽  
Getahun Abate ◽  
Nirav Patel ◽  
Setu Patolia ◽  
Sharon Frey
Keyword(s):  
Risk Factors ◽  
Urinary Catheter ◽  
Medical Center ◽  
Demographic Data ◽  
Significant Risk ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Solid Organ ◽  
Gram Negative ◽  
Source Of Infection

Background: The incidence of multidrug-resistant (MDR) organisms is increasing along with mortality. Identifying risk factors for the development of MDR Gram-negative bacilli (GNB) bacteremia could greatly impact patient care and management. Methods: Data from the electronic health record of patients with GNB over 13-month period were collected at a single university medical center. Baseline demographic data, risk factor, microbiological data, recurrence of bacteremia, and mortality were recorded. Results: A total of 177 patients were included in the analysis. MDR GNB occurred in 46 patients (26%). The mortality rate in the MDR group was 34.8% compared to 13.7% in non-MDR group ( p = 0.002). In multivariate analysis, diabetes mellitus [DM; odds ratio (OR): 2.8, 95% confidence interval (CI): 1–4.88], previous antibiotic use (OR: 2.93, 95% CI: 1.25–6.87), and urinary catheter as a source of infection (OR 5.96, 95% CI: 1.78–19.94) were significant risk factors for the development of MDR GNB. In addition, end-stage liver disease (OR: 3.64, 95% CI: 1.07–12.3), solid organ malignancy (OR: 3.64, 95% CI: 1.25–10.56), intra-abdominal source of infection (OR: 3.66, 95% CI: 1.14–11.73), inappropriate empiric antibiotics (OR 7.59, 95% CI: 1.68–34.34) and urinary catheter as a source of infection (OR 5.68, 95% CI: 1.37–23.5) were significant factors for mortality in patients with MDR GNB. Conclusion: Our study provides important information about the risk factors for the development of MDR GNB bacteremia and helps prognosticate patient with MDR GNB.

scholarly journals Detection of Multidrug Resistant Gram Negative Bacteria in Healthy Cattle from Maiduguri Metropolitan, Nigeria

2020 ◽  
pp. 68-76
Author(s):  
Adam Mustapha ◽  
Mustafa Alhaji Isa ◽  
Ibrahim Yusuf Ngoshe ◽  
Hashidu Bala
Keyword(s):  
Antibiotic Resistance ◽  
Clinical Laboratory ◽  
Resistance Index ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Salmonella Spp ◽  
Gram Negative ◽  
Healthy Cattle

Aim: Prevalence of multidrug resistant bacteria on apparently health animals has turned antibiotic resistance to multifaceted process and threatens global food security and public health. The aim of the present study was to investigate the resistance profile of isolates from apparently healthy cattle in Maiduguri, Nigeria. Methodology: A total of 120 nasal swab samples were collected from cattle. Colony identification was according to the guidelines of Bergey’s Manual of Determinative Bacteriology. The susceptibility pattern of the isolates was conducted on the identified isolates according to the Modified Kirby-Baur disc diffusion method on Muller-Hilton agar and interpreted according to the procedures of Clinical Laboratory Standards Institute (CLSI, 2018) guidelines. Multiple Antibiotic Resistance Index (MARI) was calculated using the formula, MARI=a/b where “a” is the number of antibiotic resisted and “b” is the total number of antibiotic used in the study. Results: Of the total samples (120) from cattle 96 (80%) detected the following isolates; E. coli was the most commonly recovered isolates (33, 34.4%), followed by Klebsiella spp (28, 29.2%), Salmonella spp (21, 21.9%) and Pseudomonas aeruginosa (14, 14.5%). In this study, all the recovered isolates were found to be multidrug resistant gram negative bacteria, with highest resistance was shown by Salmonella spp. The high MARI observed in all the isolates in this study ranging from 0.7 to 0.9. MARI value of 0.2 > is suggests multiple antibiotic resistant bacteria and indicate presence of highly resistant bacteria. Conclusion: The study indicates highly resistant bacteria are carried by healthy food animals. Thus, there is need for continued monitoring of antibiotics use in animal husbandry to prevent further spread of resistance in Maiduguri, Nigeria.

Oral, nasopharyngeal, and gut decontamination in the ICU

2016 ◽  
Author(s):  
Evelien Oostdijk ◽  
Marc Bonten
Keyword(s):  
Digestive Tract ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Selective Decontamination ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Detailed Data ◽  
Multidrug Resistant Bacteria ◽  
Gram Negative ◽  
Selective Oropharyngeal Decontamination

Many infections are caused by enteric bacilli, presumably from endogenous origin. Selective decontamination of the digestive tract (SDD) was developed to selectively eliminate the aerobic Gram-negative bacilli from the digestive tract, leaving the anaerobic flora unaffected. As an alternative to SDD, investigators have evaluated the effects of selective oropharyngeal decontamination (SOpD) alone. Most detailed data on the effects of SDD and SOpD in ICU-patients come from two studies performed in Dutch ICUs. The Dutch studies provide strong evidence that SDD and SOpD reduce ICUmortality, ICU-acquired bacteraemia with Gram-negative bacteria, and systemic antibiotic use. Although successful application has been reported from several solitary ICUs across Europe, it is currently unknown to what extent these effects can be achieved in settings with different bacterial ecology. More studies are needed on the use of SDD or SOpD as a measure to control outbreaks with multidrug resistant bacteria.

scholarly journals High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro–Gly Pairs

2020 ◽  
Vol 21 (3) ◽  
pp. 1140
Author(s):  
Boyan Jia ◽  
Yiming Wang ◽  
Ying Zhang ◽  
Zi Wang ◽  
Xue Wang ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Geometric Mean ◽  
Therapeutic Index ◽  
Helical Structure ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Membrane Mimetic ◽  
High Therapeutic Index ◽  
Low Toxicity ◽  
Conventional Antibiotics

Antimicrobial peptides (AMPs) have a unique action mechanism that can help to solve global problems in antibiotic resistance. However, their low therapeutic index and poor stability seriously hamper their development as therapeutic agents. In order to overcome these problems, we designed peptides based on the sequence template XXRXXRRzzRRXXRXX-NH2, where X represents a hydrophobic amino acid like Phe (F), Ile (I), and Leu (L), while zz represents Gly–Gly (GG) or d-Pro–Gly (pG). Showing effective antimicrobial activity against Gram-negative bacteria and low toxicity, designed peptides had a tendency to form an α-helical structure in membrane-mimetic environments. Among them, peptide LRpG (X: L, zz: pG) showed the highest geometric mean average treatment index (GMTI = 73.1), better salt, temperature and pH stability, and an additive effect with conventional antibiotics. Peptide LRpG played the role of anti-Gram-negative bacteria through destroying the cell membrane. In addition, peptide LRpG also exhibited an anti-inflammatory activity by effectively neutralizing endotoxin. Briefly, peptide LRpG has the potential to serve as a therapeutic agent to reduce antibiotic resistance owing to its high therapeutic index and great stability.

scholarly journals The Mortality Burden of Multidrug-resistant Pathogens in India: A Retrospective, Observational Study

2018 ◽  
Vol 69 (4) ◽  
pp. 563-570 ◽  
Author(s):  
Sumanth Gandra ◽  
Katie K Tseng ◽  
Anita Arora ◽  
Bhaskar Bhowmik ◽  
Matthew L Robinson ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Significant Risk ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Future Research ◽  
Middle Income ◽  
Health Crisis ◽  
Transmission Mechanisms ◽  
Hospital Study

Abstract Background The threat posed by antibiotic resistance is of increasing concern in low- and middle-income countries (LMICs) as their rates of antibiotic use increase. However, an understanding of the burden of resistance is lacking in LMICs, particularly for multidrug-resistant (MDR) pathogens. Methods We conducted a retrospective, 10-hospital study of the relationship between MDR pathogens and mortality in India. Patient-level antimicrobial susceptibility test (AST) results for Enterococcus spp., Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. were analyzed for their association with patient mortality outcomes. Results We analyzed data on 5103 AST results from 10 hospitals. The overall mortality rate of patients was 13.1% (n = 581), and there was a significant relationship between MDR and mortality. Infections with MDR and extensively drug resistant (XDR) E. coli, XDR K. pneumoniae, and MDR A. baumannii were associated with 2–3 times higher mortality. Mortality due to methicillin-resistant S. aureus (MRSA) was significantly higher than susceptible strains when the MRSA isolate was resistant to aminoglycosides. Conclusions This is one of the largest studies undertaken in an LMIC to measure the burden of antibiotic resistance. We found that MDR bacterial infections pose a significant risk to patients. While consistent with prior studies, the variations in drug resistance and associated mortality outcomes by pathogen are different from those observed in high-income countries and provide a baseline for studies in other LMICs. Future research should aim to elucidate the burden of resistance and the differential transmission mechanisms that drive this public health crisis.

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