scholarly journals Insights into Newer Antimicrobial Agents against Gram-negative Bacteria

2016 ◽  
Vol 9 ◽  
pp. MBI.S29459 ◽  
Author(s):  
Neelam Yaneja ◽  
Harsimran Kaur
Keyword(s):  
Infectious Disease ◽  
Antimicrobial Agents ◽  
Gram Negative Bacteria ◽  
Acinetobacter Species ◽  
Gram Negative ◽  
Limited Availability ◽  
The Past ◽  
Pseudomonas Species ◽  
Important Challenge ◽  
Novel Antibiotics

Currently, drug resistance, especially against cephalosporins and carbapenems, among gram-negative bacteria is an important challenge, which is further enhanced by the limited availability of drugs against these bugs. There are certain antibiotics (colistin, fosfomycin, temocillin, and rifampicin) that have been revived from the past to tackle the menace of superbugs, including members of Enterobacteriaceae, Acinetobacter species, and Pseudomonas species. Very few newer antibiotics have been added to the pool of existing drugs. There are still many antibiotics that are passing through various phases of clinical trials. The initiative of Infectious Disease Society of America to develop 10 novel antibiotics against gram-negative bacilli by 2020 is a step to fill the gap of limited availability of drugs. This review aims to provide insights into the current and newer drugs in pipeline for the treatment of gram-negative bacteria and also discusses the major challenging issues for their management.

Trends of Antimicrobial Resistance of Sepsis Pathogens at a University Hospital in New Delhi, India

Drug Research ◽  
2020 ◽  
Vol 70 (10) ◽  
pp. 463-471
Author(s):  
Md Shamshir Alam ◽  
Prem Kapur ◽  
ParuKutty Pillai ◽  
Krishna Kolappa Pillai
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Salmonella Typhi ◽  
University Hospital ◽  
Coagulase Negative Staphylococcus ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Acinetobacter Species ◽  
Gram Negative

AbstractKnowledge of the aetiological agents and its susceptibility to antimicrobial agents enables the clinician to initiate appropriate empirical antimicrobial therapy and guides diagnostic procedures. The aims of the study were to identify prevalence of bacterial pathogens causing sepsis and observe their antimicrobial resistance trends in hospitalized patients. A prospective cohort study was conducted on patients of sepsis admitted at a university hospital over a period of six months. Pathogens were identified by morphological, biochemical and serological tests as per the American Society for Microbiology. Antibacterial sensitivity of bacterial strains isolated from clinically diagnosed sepsis was carried out by Kirby-Bauer disk diffusion method and interpreted according Clinical and Laboratory Standards Institute guidelines. The data were analyzed by using Statistical Package for Social Sciences, version 16.0 (SPSS 16.0, Chicago, IL, USA). Coagulase negative Staphylococcus (63.5%) and Staphylococcus aureus (23.1%) were the most frequently isolated Gram positive bacteria. Acinetobacter species (31%) and Salmonella typhi (24.1%) were the most frequently isolated Gram negative bacteria. Coagulase negative Staphylococcus showed significant resistance to ciprofloxacin and tetracycline. Acinetobacter species showed significant resistance to ampicillin, amoxicillin and amoxiclav. Salmonella typhi showed significant resistance to ampicillin, amoxicillin, cefotaxime, netilmicin and, tetracycline. Escherichia coli showed significant resistance to ampicillin and netilmicin. All the stains of Staphylococcus aureus were resistant to amoxicillin. Coagulase negative Staphylococcus and Acinetobacter species were predominant Gram positive and Gram negative bacteria, respectively, causing sepsis. Increasing rates of bacterial resistance to commonly use antimicrobial agents were observed.

scholarly journals Prevalence of Gram Negative Infections by Acinetobacter and Pseudomonas Severely Resistant to Antibiotic Susceptibility Based on Minimum Growth Inhibitor Concentration

2019 ◽  
pp. 1-6
Author(s):  
Sahar Defaee ◽  
Maryam Farasatinasab ◽  
Mahin Jamshidi Makani ◽  
Hooman Rahimipour ◽  
Pouyan Alinia ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Treatment ◽  
Antimicrobial Agents ◽  
Growth Inhibitor ◽  
Multi Drug Resistance ◽  
Gram Negative Bacteria ◽  
Inhibitor Concentration ◽  
Gram Negative ◽  
The World ◽  
Pseudomonas Species

Introduction: Currently, we are witnessing the formation of various species of gram-negative microorganisms, including Enterobacteriaceae, Pseudomonas aeruginosa and acinetobacter, resistant to antibiotics such as MDR, XDR and PDR. This study is important to confirm microbial resistance to an antimicrobial agent and also to monitor the activity of new antimicrobial agents. Regarding XDR gram-negative microorganisms isolated from samples, it was considered necessary to determine MIC. Methods: Patients suspected of various infections with septicemia diagnosed in different wards of the Firoozgar Hospital were enrolled. The quantitative value of minimum growth inhibitor concentration (MIC) was determined for infections caused by highly resistant gram-negative bacteria (acinetobacter and Pseudomonas species) (XDR) reported by antibiogram disk. Results: sample size was 117, of which 41.9% were female and 58.1% were male. Regarding Colistin, 80% of the cultures were resistant and 12% were intermittent; this value was 52% in the MIC test. Regarding tigecycline, 100% of the acinetobacter samples were susceptible to this antibiotic. Most of cultures which had antibiotic resistance were acinetobacter (61.4%) and pseudomonas (39.6%). Discussion: Acinetobacter baumannii is susceptible to tigecycline. Emergence of multi-drug resistance in Pseudomonas aeruginosa and A. baumannii is a major concern in the world, because several drugs, except polymyxins, are available to treat these infections. A significant resistance was found in MIC to Colistin (31.1%). Thus, there is resistance to Colistin, which is one of the last lines of antibiotic treatment. Conclusion: This study shows an increase in percentage resistance of these bacteria to antibiotics. This trend is a worrying process for antibiotic treatment of diseases.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

scholarly journals A novel chemical biology and computational approach to expedite the discovery of new-generation polymyxins against life-threatening Acinetobacter baumannii

2021 ◽  
Author(s):  
Xukai Jiang ◽  
Nitin A. Patil ◽  
Mohammad A. K. Azad ◽  
Hasini Wickremasinghe ◽  
Heidi Yu ◽  
...  
Keyword(s):  
Public Health ◽  
Chemical Biology ◽  
Multidrug Resistant ◽  
Computational Approach ◽  
Gram Negative Bacteria ◽  
Global Public Health ◽  
Gram Negative ◽  
Life Threatening ◽  
New Generation ◽  
Novel Antibiotics

Multidrug-resistant Gram-negative bacteria have been an urgent threat to global public health. Novel antibiotics are desperately needed to combat these 'superbugs'.

scholarly journals Super-Cationic Peptide Dendrimers—Synthesis and Evaluation as Antimicrobial Agents

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 695
Author(s):  
Estelle J. Ramchuran ◽  
Isabel Pérez-Guillén ◽  
Linda A. Bester ◽  
René Khan ◽  
Fernando Albericio ◽  
...  
Keyword(s):  
Antibacterial Agent ◽  
Antimicrobial Agents ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Cationic Peptide ◽  
Public Health Concern ◽  
Gram Negative ◽  
Peptide Dendrimers ◽  
Microbial Infections ◽  
Lead Candidate

Microbial infections are a major public health concern. Antimicrobial peptides (AMPs) have been demonstrated to be a plausible alternative to the current arsenal of drugs that has become inefficient due to multidrug resistance. Herein we describe a new AMP family, namely the super-cationic peptide dendrimers (SCPDs). Although all members of the series exert some antibacterial activity, we propose that special attention should be given to (KLK)2KLLKLL-NH2 (G1KLK-L2KL2), which shows selectivity for Gram-negative bacteria and virtually no cytotoxicity in HepG2 and HEK293. These results reinforce the validity of the SCPD family as a valuable class of AMP and support G1KLK-L2KL2 as a strong lead candidate for the future development of an antibacterial agent against Gram-negative bacteria.

Newer Quinolones in the Treatment of Continuous Ambulatory Peritoneal Dialysis (CAPD) Related Infections

1990 ◽  
Vol 10 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Paul Nikolaidis
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Adverse Reactions ◽  
Antimicrobial Agents ◽  
Hospital Staff ◽  
Gram Negative Bacteria ◽  
Promising Alternative ◽  
Gram Negative ◽  
Dosing Intervals ◽  
Good Oral Bioavailability

Newer fluoroquinolones such as ciprofloxacin, pefloxacin, ofloxacin, enoxacin, and fleroxacin are potent antimicrobial agents against many gram-negative bacteria, including Pseudomonas aeruginosa species and staphylococci-sensitive or resistant to methicillin. They are almost completely absorbed when given orally, reaching therapeutic plasma and dialysate concentrations, and their long half lives permit infrequent dosing intervals. Clinical studies on fluoroquinolones efficacy in continuous ambulatory peritoneal dialysis (CAPD) infections, although not extensive, demonstrate good results. They are well tolerated and the adverse reactions, consisting mainly of gastrointestinal disturbance, were uncommon, mild, and reversible. The fluoroquinolones offer a promising alternative to standard parenteral treatments in CAPD patients, while their good oral bioavailability makes them attractive and convenient for both patients and hospital staff. However, they must be used with caution until we have more information and gain further experience.

scholarly journals OMN6 a novel bioengineered peptide for the treatment of multidrug resistant Gram negative bacteria

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shira Mandel ◽  
Janna Michaeli ◽  
Noa Nur ◽  
Isabelle Erbetti ◽  
Jonathan Zazoun ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Antimicrobial Agents ◽  
Cyclic Peptide ◽  
Safety Margin ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Development Of Resistance ◽  
Cecropin A

AbstractNew antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.

scholarly journals Current Pattern and Clinico-Bacteriological Profile of Healthcare Associated Infections (HAI) in an ICU Setting: An Observational Study

2021 ◽  
Author(s):  
Mradul Kumar Daga ◽  
Govind Mawari ◽  
Saman Wasi ◽  
Naresh Kumar ◽  
Udbhav Sharma ◽  
...  
Keyword(s):  
Age Groups ◽  
Healthcare Facility ◽  
Central Line ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Healthcare Associated Infections ◽  
Acinetobacter Species ◽  
Gram Negative ◽  
Causative Agents ◽  
Healthcare Associated

Abstract Objective To understand the pattern and types of healthcare associated infections (HAI) at our healthcare facility, and to determine the common causative agents and their antibiotic susceptibility profile. Methods One hundred consecutive patients diagnosed with HAI were enrolled and monitored; the causative organisms isolated on culture were recorded and their sensitivity profile was generated. Results Of the 100 patients diagnosed with HAI (mean age ± SD being 42 ± 17 years), there were a total of 110 hospital acquired infections with 10 patients having two infections each. Out of 100 patients with HAI, 69 patients had ventilator associated pneumonia (VAP), 21 patients had catheter associated urinary tract infection (CAUTI) patients, and 20 patients had central line associated bloodstream infection (CLABSI). There were 10 patients with both VAP and CAUTI. All of the HAIs were device associated. A total of 76 pathogens were isolated on culture. No organism was isolated in 40 HAI. Majority (94.7%) of the organisms isolated from HAIs were gram-negative bacteria and all were multidrug resistant. Seventy-seven of the enrolled patients expired while 23 were discharged from the hospital Conclusions Our study demonstrated that HAIs occur in patients of all age groups; younger patients are not spared. Majority of the HAIs were caused by multidrug resistant gram-negative bacteria and were associated with high patient mortality. Acinetobacter species was the most common organism associated with HAI.

scholarly journals Susceptibility trends of ceftolozane/tazobactam and comparators when tested against European Gram-negative bacterial surveillance isolates collected during 2012–18

2020 ◽  
Vol 75 (10) ◽  
pp. 2907-2913 ◽  
Author(s):  
Helio S Sader ◽  
Cecilia G Carvalhaes ◽  
Leonard R Duncan ◽  
Robert K Flamm ◽  
Dee Shortridge
Keyword(s):  
Eastern Europe ◽  
Active Compound ◽  
Western Europe ◽  
Antimicrobial Agents ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Systemic Infections

Abstract Background The Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) monitors the in vitro activity of ceftolozane/tazobactam and numerous antimicrobial agents against Gram-negative bacteria worldwide. Objectives To evaluate the activity of ceftolozane/tazobactam and resistance trends among Pseudomonas aeruginosa and Enterobacterales isolates in Europe between 2012 and 2018. Methods P. aeruginosa (7503) and Enterobacterales (30 582) isolates were collected from 53 medical centres in 26 countries in Europe and the Mediterranean region and tested for susceptibility by reference broth microdilution method in a central laboratory. MIC results were interpreted using EUCAST criteria. Results Ceftolozane/tazobactam was the most active compound tested against P. aeruginosa isolates after colistin, with overall susceptibility rates of 94.1% in Western Europe and 80.9% in Eastern Europe. Moreover, ceftolozane/tazobactam retained activity against 75.2% and 59.2% of meropenem-non-susceptible P. aeruginosa isolates in Western and Eastern Europe, respectively. Tobramycin was the third most active compound tested against P. aeruginosa, with susceptibility rates of 88.6% and 70.9% in Western and Eastern Europe, respectively. Ceftolozane/tazobactam was active against 94.5% of all Enterobacterales and 96.1% of meropenem-susceptible isolates from Western Europe. In Eastern Europe, ceftolozane/tazobactam was active against 79.4% of Enterobacterales overall and 86.2% of meropenem-susceptible isolates. Discussion Antimicrobial susceptibility rates for agents commonly used to treat serious systemic infections varied widely among nations and geographic regions and were generally lower in Eastern Europe compared with Western Europe. Ceftolozane/tazobactam demonstrated potent activity against P. aeruginosa, including MDR strains, and retained activity against most meropenem-susceptible Enterobacterales causing infection in European medical centres.

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