scholarly journals Effect of Synergistic Action of Bovine Lactoferrin with Antibiotics on Drug Resistant Bacterial Pathogens

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 343
Author(s):  
Mohammed S. Al-Mogbel ◽  
Godfred A. Menezes ◽  
Mohamed T. Elabbasy ◽  
Manal M. Alkhulaifi ◽  
Ashfaque Hossain ◽  
...  
Keyword(s):  
Antibacterial Agents ◽  
Synergistic Effects ◽  
Bacterial Pathogens ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Bovine Lactoferrin ◽  
Drug Resistant ◽  
Therapeutic Choice ◽  
Life Saving ◽  
Mucosal Secretions

Background and Objectives: The multidrug resistant (MDR) bacterial pathogenic infection is one of the chief worldwide public health threat to humanity. The development of novel antibiotics against MDR Gram negative bacteria has reduced over the last half century. Research is in progress regarding the treatment strategies that could be engaged in combination with antibiotics to extend the duration of these life-saving antibacterial agents. The current study was therefore planned to assess the synergistic effects of bovine lactoferrin (bLF) in combination with different antibiotics that are conventionally used. This synergism would provide a newer therapeutic choice against MDR pathogens. LF is present in mucosal secretions, vastly in milk. LF is considered an important constituent in host defense. In previous reports, LF has been co-administered as a combination antibiotic therapy. Materials and Methods: This study included synergistic (LF + appropriate antibiotic) exposure against 147 locally encountered bacterial pathogens, which were completely characterized strains. The anti-biofilm effects and the outcome of bLF on minimum inhibitory concentrations (MICs) of antibacterials on clinical MDR bacterial pathogens were determined by standard techniques. Results: In our study, synergism of bLF with antibacterial agents were reproducible and found to be significant. LF on its own had an important effect of inhibiting the biofilm production of some significant bacterial pathogens. Conclusion: The results of this study provides useful data on the antibacterial potential of the combination of LF with antibiotics against drug resistant pathogens.

scholarly journals Resistance of uropathogens to antibacterial agents: Emerging threats, trends and treatments

2018 ◽  
Vol 90 (2) ◽  
pp. 85 ◽  
Author(s):  
Gianpaolo Perletti ◽  
Vittorio Magri ◽  
Tommaso Cai ◽  
Konstantinos Stamatiou ◽  
Alberto Trinchieri ◽  
...  
Keyword(s):  
Antibacterial Agents ◽  
Multidrug Resistant ◽  
Medical Emergency ◽  
Fluoroquinolone Resistance ◽  
Drug Resistant ◽  
Gram Negative ◽  
Resistance Determinants ◽  
Rapid Spread ◽  
The World ◽  
Tract Infections

Urinary tract infections are among the most common infectious diseases in humans. Today, resistance to nearly all antimicrobial classes is dramatically growing, and extremely drug-resistant or even pan-drug resistant pathogens are increasingly isolated around the world. It is foreseen that in the next decades the world will be facing a major medical emergency generated by the rapid spread of pathogens carrying resistance determinants of unprecedented power. Carbapenemase-producing Enterobacteriaceae, multidrug- resistant Enterococci and fluoroquinolone resistance determinants in both Gram-negative and Gram-positive uropathogens are among the greatest emergencies. In this article, the major emerging threats of particular interest to urologists are reviewed, worldwide resistance trends are illustrated, and novel and older – but still active – recommended drugs are summarized.

scholarly journals Broad Spectrum Antibacterial Ocotillol-Type Derivatives: Semi-Synthesis, Structure-Activity Relationship, and Membrane-Active Mode of Action

2021 ◽  
Author(s):  
Xianming Zeng ◽  
Ziyi Zhang ◽  
Yunyun Zhou ◽  
Shengyu Zhang ◽  
Zhiwen Zhou
Keyword(s):  
Antibacterial Activity ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Synergistic Effects ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Hek 293 ◽  
Low Cytotoxicity ◽  
New Compounds

A series of 3-amino substituted ocotillol-type derivatives were designed and synthesized for the first time. The in vitro antibacterial activity tests showed that some of the new compounds exhibited excellent antibacterial activity. Compound 13d, which was the most active one, displayed particularly strong antibacterial activity against S. aureus, B. subtilis, MRSA (methicillin-resistant S. aureus) and E. coli with minimum inhibitory concentration (MIC) values of 1-4 μg mL-1. Further research also suggested that 13d showed low cytotoxicity to human normal cells HEK-293 and L02, strong synergistic effects with kanamycin or chloramphenicol and a broad antibacterial spectrum including against multidrug-resistant strains. This active molecule 13d also induced bacterial resistance more slowly than norfloxacin and colistin. Furthermore, the research results demonstrated that this type of compounds could disperse the established bacterial biofilms, thus suppressing or delaying the development of drug resistance. Mechanism studies have shown that compound 13d could damage the integrity of cell membranes, which in turn facilitated the antibacterial agents binding to deoxyribonucleic acid (DNA), leading to cell death. Therefore, these results indicated that the membrane active ocotillol-type derivatives are a promising class of antibacterial agents to fight against super bacteria and deserve further attention.

scholarly journals Synergistic Effects and Antibiofilm Properties of Chimeric Peptides against Multidrug-Resistant Acinetobacter baumannii Strains

2013 ◽  
Vol 58 (3) ◽  
pp. 1622-1629 ◽  
Author(s):  
Ramamourthy Gopal ◽  
Young Gwon Kim ◽  
Jun Ho Lee ◽  
Seog Ki Lee ◽  
Jeong Don Chae ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Synergistic Effects ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Antibacterial Effects ◽  
Content Type ◽  
Chimeric Peptides ◽  
Novel Antibiotics

ABSTRACTThe increasing prevalence of drug-resistant pathogens highlights the need to identify novel antibiotics. Here we investigated the efficacies of four new antimicrobial peptides (AMPs) for potential drug development. The antibacterial activities, synergistic effects, and antibiofilm properties of the four chimeric AMPs were tested againstAcinetobacter baumannii, an emerging Gram-negative, nosocomial, drug-resistant pathogen. NineteenA. baumanniistrains resistant to ampicillin, cefotaxime, ciprofloxacin, tobramycin, and erythromycin were isolated at a hospital from patients with cholelithiasis. All four peptides exhibited significant antibacterial effects (MIC = 3.12 to 12.5 μM) against all 19 strains, whereas five commercial antibiotics showed little or no activity against the same pathogens. An exception was polymyxin, which was effective against all of the strains tested. Each of the peptides showed synergy against one or more strains when administered in combination with cefotaxime, ciprofloxacin, or erythromycin. The peptides also exhibited an ability to prevent biofilm formation, which was not seen with cefotaxime, ciprofloxacin, or erythromycin, though polymyxin also inhibited biofilm formation. Indeed, when administered in combination with ciprofloxacin, the AMP HPMA exerted a potent synergistic effect againstA. baumanniibiofilm formation. Collectively, our findings indicate that the AMPs tested have no cytotoxicity but possess potent antibacterial and antibiofilm activities and may act synergistically with commercial antibiotics.

scholarly journals Low cationicity is important for systemic in vivo efficacy of database-derived peptides against drug-resistant Gram-positive pathogens

2019 ◽  
Vol 116 (27) ◽  
pp. 13517-13522 ◽  
Author(s):  
Biswajit Mishra ◽  
Jayaram Lakshmaiah Narayana ◽  
Tamara Lushnikova ◽  
Xiuqing Wang ◽  
Guangshun Wang
Keyword(s):  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Host Factors ◽  
Cationic Peptides ◽  
Drug Resistant ◽  
Gram Positive ◽  
In Vivo Efficacy ◽  
The Common

As bacterial resistance to traditional antibiotics continues to emerge, new alternatives are urgently needed. Antimicrobial peptides (AMPs) are important candidates. However, how AMPs are designed with in vivo efficacy is poorly understood. Our study was designed to understand structural moieties of cationic peptides that would lead to their successful use as antibacterial agents. In contrast to the common perception, serum binding and peptide stability were not the major reasons for in vivo failure in our studies. Rather, our systematic study of a series of peptides with varying lysines revealed the significance of low cationicity for systemic in vivo efficacy against Gram-positive pathogens. We propose that peptides with biased amino acid compositions are not favored to associate with multiple host factors and are more likely to show in vivo efficacy. Thus, our results uncover a useful design strategy for developing potent peptides against multidrug-resistant pathogens.

scholarly journals Advances in Phage Therapy: Targeting the Burkholderia cepacia Complex

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1331
Author(s):  
Philip Lauman ◽  
Jonathan J. Dennis
Keyword(s):  
Burkholderia Cepacia ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Modern Medicine ◽  
Burkholderia Cepacia Complex ◽  
Drug Resistant ◽  
The Past ◽  
Resistant Species

The increasing prevalence and worldwide distribution of multidrug-resistant bacterial pathogens is an imminent danger to public health and threatens virtually all aspects of modern medicine. Particularly concerning, yet insufficiently addressed, are the members of the Burkholderia cepacia complex (Bcc), a group of at least twenty opportunistic, hospital-transmitted, and notoriously drug-resistant species, which infect and cause morbidity in patients who are immunocompromised and those afflicted with chronic illnesses, including cystic fibrosis (CF) and chronic granulomatous disease (CGD). One potential solution to the antimicrobial resistance crisis is phage therapy—the use of phages for the treatment of bacterial infections. Although phage therapy has a long and somewhat checkered history, an impressive volume of modern research has been amassed in the past decades to show that when applied through specific, scientifically supported treatment strategies, phage therapy is highly efficacious and is a promising avenue against drug-resistant and difficult-to-treat pathogens, such as the Bcc. In this review, we discuss the clinical significance of the Bcc, the advantages of phage therapy, and the theoretical and clinical advancements made in phage therapy in general over the past decades, and apply these concepts specifically to the nascent, but growing and rapidly developing, field of Bcc phage therapy.

scholarly journals Antibiotic-induced black hairy tongue: two case reports and a review of the literature

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096127
Author(s):  
Jing Ren ◽  
Yao Zheng ◽  
Hui Du ◽  
Shan Wang ◽  
Linna Liu ◽  
...  
Keyword(s):  
Postoperative Infection ◽  
Antibacterial Agents ◽  
Case Reports ◽  
Treatment Strategies ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Central Neurocytoma ◽  
Review Of The Literature ◽  
Causative Agents ◽  
Black Hairy Tongue

Black hairy tongue (BHT) is characterized by a discolored, hairy tongue. We herein report two cases of BHT associated with antibacterial agents and review previous cases. In Case 1, a 17-year-old girl with a central neurocytoma was administered intravenous piperacillin–tazobactam for postoperative infection, and BHT developed 12 days later. Her symptoms resolved 8 days after she discontinued the piperacillin–tazobactam and brushed her tongue three times daily. In Case 2, a 65-year-old man was administered intravenous piperacillin–tazobactam and levofloxacin to treat multidrug-resistant Pseudomonas aeruginosa, and BHT developed 15 days later. The piperacillin–tazobactam was discontinued and the patient brushed his tongue, and the discoloration gradually subsided thereafter. However, the BHT reappeared after linezolid treatment. The patient had adverse drug reactions to both the piperacillin–tazobactam and linezolid treatments. The BHT might have been related to antibiotic use in both cases. We identified 19 cases of antibiotic-related BHT in a literature search, but none were related to piperacillin–tazobactam use. In all cases, symptoms resolved after discontinuation of the drug and brushing of the tongue. BHT may be a rare adverse effect of antibiotics. Treatment strategies include removal of the causative agents, mechanical debridement, and good oral hygiene.

scholarly journals Antibiotic Hybrids: the Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?

2018 ◽  
Vol 31 (2) ◽  
Author(s):  
Ronald Domalaon ◽  
Temilolu Idowu ◽  
George G. Zhanel ◽  
Frank Schweizer
Keyword(s):  
Antibacterial Agents ◽  
Therapeutic Strategy ◽  
Antimicrobial Effect ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Intrinsic Resistance ◽  
Gram Negative ◽  
The Past ◽  
Antibiotic Drug

SUMMARYThe global incidence of drug-resistant Gram-negative bacillary infections has been increasing, and there is a dire need to develop novel strategies to overcome this problem. Intrinsic resistance in Gram-negative bacteria, such as their protective outer membrane and constitutively overexpressed efflux pumps, is a major survival weapon that renders them refractory to current antibiotics. Several potential avenues to overcome this problem have been at the heart of antibiotic drug discovery in the past few decades. We review some of these strategies, with emphasis on antibiotic hybrids either as stand-alone antibacterial agents or as adjuvants that potentiate a primary antibiotic in Gram-negative bacteria. Antibiotic hybrid is defined in this review as a synthetic construct of two or more pharmacophores belonging to an established agent known to elicit a desired antimicrobial effect. The concepts, advances, and challenges of antibiotic hybrids are elaborated in this article. Moreover, we discuss several antibiotic hybrids that were or are in clinical evaluation. Mechanistic insights into how tobramycin-based antibiotic hybrids are able to potentiate legacy antibiotics in multidrug-resistant Gram-negative bacilli are also highlighted. Antibiotic hybrids indeed have a promising future as a therapeutic strategy to overcome drug resistance in Gram-negative pathogens and/or expand the usefulness of our current antibiotic arsenal.

scholarly journals Multi-drug resistant tuberculosis burden and risk factors: An update

1970 ◽  
Vol 8 (1) ◽  
pp. 116-125 ◽  
Author(s):  
SB Marahatta
Keyword(s):  
Risk Factors ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Inverse Association ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Resource Poor ◽  
Mdr Tb

Multi-drug resistant (MDR) tuberculosis is defined as disease caused by Mycobacterium tuberculosis with resistance to at least two anti-tubercular drugs Isoniazid and Rifampicin. Recent surveillance data have revealed that prevalence of the drug resistant tuberculosis has risen to the highest rate ever recorded in the history. Drug resistant tuberculosis generally arises through the selection of mutated strains by inadequate therapy. The most powerful predictor of the presence of MDR-TB is a history of treatment of TB. Shortage of drugs has been one of the most common reasons for the inadequacy of the initial anti-TB regimen, especially in resource poor settings. Other major issues significantly contributing to the higher complexity of the treatment of MDR-TB is the increased cost of treatment. Other factors also play important role in the development of MDR-TB such as poor administrative control on purchase and distribution of the drugs with no proper mechanism on quality control and bioavailability tests. Tuberculosis control program implemented in past has also partially contributed to the development of drug resistance due to poor follow up and infrastructure. The association known for centuries between TB and poverty also applies to MDR-TB, a rather significant inverse association with MDR-TB. Various treatment strategies have been employed, including the use of standardised treatment regimens based upon representative local susceptibility patterns, empirical treatment based upon previous treatment history and local Drug Susceptibility Test (DST) patterns, and individualised treatment designed on the basis of individual DST results. Treatment outcomes among MDR-TB cases have varied widely; a recent survey of five Green Line Committee (GLC) approved sites in resource-limited countries found treatment success rates of 70%. Treatment continues to be limited in the resource poor countries where the demand is high. The ultimate strategy to control multidrug resistant tuberculosis is one that implements comprehensive approach incorporating treatment of multidrug-resistant tuberculosis based upon principles closely related to those of its general DOTS strategy for TB control: sustained political commitment; a rational case-finding strategy including accurate, timely diagnosis through quality assured culture and DST; appropriate treatment strategies that use second-line drugs under proper case management conditions; uninterrupted supply of quality-assured antituberculosis drugs; standardised recording and reporting system. Key words: DOTS Plus; Multi drug resistant (MDR) tuberculosis burden; risk factors. DOI: 10.3126/kumj.v8i1.3234 Kathmandu University Medical Journal (2010), Vol. 8, No. 1, Issue 29, 116-125

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