An Efficient Combinatorial Approach for Beta-Lactam Antibiotics with Novel Adjuvants against Gram-Negative Organisms to Combat Multi-Drug Resistance

AbstractThe multi-drug resistance of Gram-negative rods is one of the most important issues of present medicine. In recent years, more and more strains resistant to the majority or to all possible therapeutic options have been isolated—especially Klebsiella spp. and Pseudomonas spp. representatives. It is very important to detect strains with these phenotypes as quickly and reliably as possible. The aim of the study was to evaluate the usefulness of eazyplex® SuperBug CRE test (Amplex Diagnostics) for the detection of the most important beta-lactam resistance genes. eazyplex® SuperBug CRE test is based on the loop-mediated isothermal amplification (LAMP) method, and detects genes for the following beta-lactamases: KPC, NDM-1, VIM, OXA-48, CTX-M1, CTX-M9 and OXA-181. The study involved 87 strains. For all of the positive strains in the LAMP method, additional PCR were performed to increase the spectrum of ESBLs detected by the genes encoding for enzymes belonging to TEM and SHV families. The results obtained by the tested method and standard PCR were consistent for all Klebsiella spp. strains. The discrepancy between the evaluated test and PCR results was observed for one P. aeruginosa strain. The eazyplex® SuperBug CRE test can be used for quick detection of the most important beta-lactam resistance mechanisms amongst Gram-negative rods.

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Combination antibiotic therapy versus monotherapy in the treatment of acute exacerbations of chronic obstructive pulmonary disease: an open-label randomized trial

BMC Infectious Diseases ◽

10.1186/s12879-021-06687-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Phuong Nguyen Thi Thu ◽

Minh Ngo Thị Huong ◽

Ngan Tran Thi ◽

Hoi Nguyen Thanh ◽

Khue Pham Minh

Keyword(s):

Clinical Success ◽

Chronic Obstructive ◽

Gram Negative Bacteria ◽

Beta Lactam ◽

Open Label ◽

Obstructive Pulmonary Disease ◽

Gram Negative ◽

Copd Exacerbations ◽

Beta Lactam Antibiotics ◽

Acute Exacerbations

Abstract Background The role of antibiotics in the treatment of chronic obstructive pulmonary disease (COPD) exacerbations and their effectiveness in combination have not been clearly established. To determine whether using a combination of fluoroquinolones and beta-lactams improves the clinical and microbiological efficacy of antibiotics on day 20 of treatment, we conducted an open-label randomized trial based on clinical outcomes, microbiological clearance, spirometry tests, and signs of systemic inflammation in patients hospitalized with acute exacerbations of COPD. Methods We enrolled 139 subjects with COPD exacerbations, defined as acute worsening of respiratory symptoms leading to additional treatment. Patients were divided randomly into two groups: 79 patients using beta-lactam antibiotics alone and 60 using beta-lactam antibiotics plus fluoroquinolones. Clinical and microbiological responses, spirometry tests, symptom scores, and serum C-reactive protein (CRP) levels were evaluated. Results Clinical success, lung function, and symptoms were similar in patients with or without fluoroquinolone administration on days 10 and 20. Combination therapy was superior in terms of microbiological outcomes and reduction in serum CRP value. Although equivalent to monotherapy in terms of clinical success, the combination showed superiority in terms of microbiological success and a decrease in CRP. The combination therapy group had a higher microbiological success rate with gram-negative bacteria than the monotherapy group with Pseudomonas aeruginosa (100% vs. 33.3%, respectively) and Acinetobacter baumanii (100% vs. 20%, respectively) (P < 0.05). Conclusions Concomitant use of fluoroquinolone and beta-lactam antibiotics for bacterial infections during COPD exacerbations caused by gram-negative bacteria appear to be effective and should be applied in clinical practice.

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Screening and Potential of Multi-Drug Resistance in Gram-Negative Bacteria from Hospital Wastewater

Iranian Journal of Science and Technology Transactions A Science ◽

10.1007/s40995-018-0506-z ◽

2018 ◽

Author(s):

Manzar Alam ◽

Mohd Imran

Keyword(s):

Drug Resistance ◽

Multi Drug Resistance ◽

Gram Negative Bacteria ◽

Hospital Wastewater ◽

Gram Negative

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Molecular Detection of Carbapenem Resistant Gram Negative Bacterial Isolates from Dogs

Indian Journal of Animal Research ◽

10.18805/ijar.b-4297 ◽

2021 ◽

Author(s):

Surya Sankar ◽

Thresia . ◽

Anu Bosewell ◽

M. Mini

Keyword(s):

Companion Animals ◽

Multidrug Resistant ◽

Beta Lactam ◽

Gram Negative ◽

Extended Spectrum Beta Lactamase ◽

Beta Lactam Antibiotics ◽

Carbapenem Resistant ◽

Carbapenemase Gene ◽

Line Of Therapy ◽

Encoding Genes

Background: Carbapenems are beta-lactam antibiotics that are considered as the last line of therapy against multidrug resistant extended spectrum beta-lactamase. The resistance to carbapenems predominantly through carbapenemase is one of the most important emerging health problems worldwide in the therapy of clinical infections. The objective of the present study is to determine the presence of carbapenemase encoding genes among Gram- negative bacterial spp. associated with clinical infections in dogs. Methods: 30 Escherichia coli, 11 Klebsiella pneumoniae and three Pseudomonas aeruginosa isolated from urine, swabs from lesional skin and anterior vagina of dogs presented with different clinical ailments formed the samples for the study. Polymerase chain reaction was carried out to detect the presence of carbapenemase encoding genes viz., KPC, NDM, OXA, VIM and IMP among the isolates.Result: Out of the 44 Gram- negative isolates tested, 28 (76.3%) were positive for at least one tested carbapenemase gene. The highest frequency of carbapenemase recorded was for NDM followed by OXA-181, KPC, OXA-48 and VIM. Our study identified a high prevalence of carbapenemases among companion animals like dogs which could act as potential source of transmission of these resistance bacteria or their genomes to humans.

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Polymyxin B combinations with FDA-approved non-antibiotic phenothiazine drugs targeting multi-drug resistance of Gram-negative pathogens

Computational and Structural Biotechnology Journal ◽

10.1016/j.csbj.2020.08.008 ◽

2020 ◽

Vol 18 ◽

pp. 2247-2258

Author(s):

Maytham Hussein ◽

Xiaohan Hu ◽

Olivia K.A. Paulin ◽

Simon Crawford ◽

Qi Tony Zhou ◽

...

Keyword(s):

Drug Resistance ◽

Polymyxin B ◽

Multi Drug Resistance ◽

Gram Negative ◽

Phenothiazine Drugs

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Prevalence of Extended Spectrum Beta Lactamases (ESBL) and Metallo Beta Lactamases (MBL) Mediated Resistance in Gram Negative Bacterial Pathogens

Tribhuvan University Journal of Microbiology ◽

10.3126/tujm.v4i0.21677 ◽

2018 ◽

Vol 4 ◽

pp. 49-54 ◽

Cited By ~ 1

Author(s):

Pramila Pathak ◽

Nandalal Jaishi ◽

Binod Kumar Yadav ◽

Pradeep Kumar Shah

Keyword(s):

Drug Resistance ◽

Hospital Setting ◽

Multi Drug Resistance ◽

Microbiological Analysis ◽

Bacterial Isolates ◽

Biochemical Tests ◽

Gram Negative ◽

Beta Lactamases ◽

Clinical Specimens ◽

Extended Spectrum

Objectives: This study was conducted to determine the prevalence of multi-drug resistance (MDR) along with Extended Spectrum β-lactamase (ESBL) and Metallo β-lactamase (MBL) producing gram negative bacterial isolates among the patients attending Shahid Gangalal National Heart Centre, Kathmandu, Nepal.Methods: This cross-sectional study was carried out from June to December; 2016. Altogether 977 clinical specimens were processed for analysis of bacteriological profile and the isolates were identified by culture, morphological and biochemical tests. Antibiotic susceptibility testing of the isolates was performed by Kirby Bauer disc diffusion methods following Clinical and Laboratories Standard Institute guideline and the isolates were tested for ESBL and MBL by combined disk method.Results: out of 977 clinical specimens, 254 (25.99%) were found to be gram negative bacterial isolates, among them Klebsiella pneumoniae 83 (32.67%) was the most predominant organism followed by E. coli 51 (20.07%), Pseudomonas aeruginosa 36 (14.17%), K. oxytoca 32 (12.59%), Proteus mirabilis 13 (5.11%) and P. vulgaris 13 (5.11%), Acinetobacter spp. 11 (4.33%), Citrobacter spp. 10 (3.93%) and Enterobacter spp. 5 (1.96%) respectively. 83 (32.67%) isolates were found to be MDR, 38(14.96%) were positive for ESBL while 19 (7.48%) were MBL producer.Conclusion: The determent drug resistance among ESBL and MBL producers, reflect the extensive use of antibiotics possessing difficulties in therapeutic potions in hospital setting which might be overcome by proper microbiological analysis of pathogenic isolates and judicious use of antibiotics for emergence of resistance strains.

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A high prevalence of multi-drug resistant Gram-negative bacilli in a Nepali tertiary care hospital and associated widespread distribution of Extended-Spectrum Beta-Lactamase (ESBL) and carbapenemase-encoding genes

Annals of Clinical Microbiology and Antimicrobials ◽

10.1186/s12941-020-00390-y ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Sulochana Manandhar ◽

Raphael M. Zellweger ◽

Nhukesh Maharjan ◽

Sabina Dongol ◽

Krishna G. Prajapati ◽

...

Keyword(s):

Drug Resistance ◽

Tertiary Care ◽

Multi Drug Resistance ◽

Gram Negative Bacteria ◽

Care Hospital ◽

Global Public Health ◽

Gram Negative ◽

E Coli ◽

Extended Spectrum ◽

High Prevalence

Abstract Background Multi-drug resistance (MDR) and extensive-drug resistance (XDR) associated with extended-spectrum beta-lactamases (ESBLs) and carbapenemases in Gram-negative bacteria are global public health concerns. Data on circulating antimicrobial resistance (AMR) genes in Gram-negative bacteria and their correlation with MDR and ESBL phenotypes from Nepal is scarce. Methods A retrospective study was performed investigating the distribution of ESBL and carbapenemase genes and their potential association with ESBL and MDR phenotypes in E. coli, Klebsiella spp., Enterobacter spp. and Acinetobacter spp. isolated in a major tertiary hospital in Kathmandu, Nepal, between 2012 and 2018. Results During this period, the hospital isolated 719 E. coli, 532 Klebsiella spp., 520 Enterobacter spp. and 382 Acinetobacter spp.; 1955/2153 (90.1%) of isolates were MDR and half (1080/2153) were ESBL producers. Upon PCR amplification, blaTEM (1281/1771; 72%), blaCTXM-1 (930/1771; 53%) and blaCTXM-8 (419/1771; 24%) were the most prevalent ESBL genes in the enteric bacilli. BlaOXA and blaOXA-51 were the most common blaOXA family genes in the enteric bacilli (918/1771; 25%) and Acinetobacter spp. (218/382; 57%) respectively. Sixteen percent (342/2153) of all isolates and 20% (357/1771) of enteric bacilli harboured blaNDM-1 and blaKPC carbapenemase genes respectively. Of enteric bacilli, Enterobacter spp. was the most frequently positive for blaKPC gene (201/337; 60%). The presence of each blaCTX-M and blaOXA were significantly associated with non-susceptibility to third generation cephalosporins (OR 14.7, p < 0.001 and OR 2.3, p < 0.05, respectively).The presence of each blaTEM, blaCTXM and blaOXA family genes were significantly associated with ESBL positivity (OR 2.96, p < 0.001; OR 14.2, p < 0.001 and OR 1.3, p < 0.05 respectively) and being MDR (OR 1.96, p < 0.001; OR 5.9, p < 0.001 and OR 2.3, p < 0.001 respectively). Conclusions This study documents an alarming level of AMR with high prevalence of MDR ESBL- and carbapenemase-positive ESKAPE microorganisms in our clinical setting. These data suggest a scenario where the clinical management of infected patients is increasingly difficult and requires the use of last-resort antimicrobials, which in turn is likely to intensify the magnitude of global AMR crisis.

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