scholarly journals Comparative In Vitro Activities of First and Second-Generation Ceragenins Alone and in Combination with Antibiotics Against Multidrug-Resistant Klebsiella pneumoniae Strains

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 130 ◽  
Author(s):  
Berna Ozbek-Celik ◽  
Damla Damar-Celik ◽  
Emel Mataraci-Kara ◽  
Cagla Bozkurt-Guzel ◽  
Paul B. Savage
Keyword(s):  
Klebsiella Pneumoniae ◽  
Second Generation ◽  
Synergistic Effects ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Resistant Bacteria ◽  
Microdilution Method ◽  
Kill Curve ◽  
Time Kill

Objectives: The ceragenins, or CSAs, were designed to mimic the activities of antimicrobial peptides and represent a new class of antimicrobial agent. The aim of this study was to comparatively investigate the antimicrobial activities of first/second generation ceragenins and various antibiotics against multidrug-resistant (MDR) Klebsiella pneumoniae, including colistin-resistant bacteria. Also, the synergistic effects of two ceragenins with colistin or meropenem were investigated with six K. pneumoniae strains presenting different resistant patterns. Methods: Minimal inhibition concentrations (MICs) were determined by the microdilution method according to the CLSI. Antibiotic combination studies were evaluated by the time–kill curve method. Results: MIC50 and MIC90 values of tested ceragenins ranged from 8 to 32 mg/L and 16 to 128 mg/L. Overall, among the ceragenins tested, CSA-131 showed the lowest MIC50 and MIC90 values against all microorganisms. The MICs of the ceragenins were similar or better than tested antibiotics, except for colistin. Synergistic activities of CSA-131 in combination with colistin was found for strains both at 1× MIC and 4× MIC. No antagonism was observed with any combination. Conclusions: First-generation ceragenins CSA-13 and CSA-44 and second-generation ceragenins CSA-131, CSA-138 and CSA-142 have significant antimicrobial effects on MDR K. pneumoniae. Mechanisms allowing resistance to clinical comparator antibiotics like colistin did not impact the activity of ceragenins. These results suggest that ceragenins may play a role in treating infections that are resistant to known antibiotics.

scholarly journals Antimicrobial Activities of Ceragenins against Clinical Isolates of Resistant Staphylococcus aureus

2007 ◽  
Vol 51 (4) ◽  
pp. 1268-1273 ◽  
Author(s):  
Judy N. Chin ◽  
Michael J. Rybak ◽  
Chrissy M. Cheung ◽  
Paul B. Savage
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Curve Analysis ◽  
Clinical Isolates ◽  
Resistant Bacteria ◽  
Inoculum Effect ◽  
Kill Curve ◽  
Time Required ◽  
Time Kill

ABSTRACT The rise in the rates of glycopeptide resistance among Staphylococcus aureus isolates is concerning and underscores the need for the development of novel potent compounds. Ceragenins CSA-8 and CSA-13, cationic steroid molecules that mimic endogenous antimicrobial peptides, have previously been demonstrated to possess broad-spectrum activities against multidrug-resistant bacteria. We examined the activities of CSA-8 and CSA-13 against clinical isolates of vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), as well as vancomycin-resistant S. aureus (VRSA) and compared them to those of daptomycin, linezolid, and vancomycin by susceptibility testing and killing curve analysis. We also examined CSA-13 for its concentration-dependent activity, inoculum effect, postantibiotic effect (PAE), and synergy in combination with various antimicrobials. Overall, the MICs and minimal bactericidal concentrations of CSA-13 were fourfold lower than those of CSA-8. Time-kill curve analysis of the VRSA, VISA, and hVISA clinical isolates demonstrated concentration-dependent bactericidal killing. An inoculum effect was also observed when a higher starting bacterial density was used, with the time required to achieve 99.9% killing reaching 1 h with a 6-log10-CFU/ml starting inoculum, whereas it was ≥24 h with a 8- to 9-log10-CFU/ml starting inoculum with 10× the MIC (P ≤ 0.001). A concentration-dependent PAE was demonstrated with CSA-13, nearly doubling from 2× to 4× the MIC (P = 0.03). With respect to the CSA-13 antimicrobial combinations, time-kill curve analysis showed no difference in the log10 CFU/ml at 24 h for the majority of the organisms tested. However, early synergy at 4 to 8 h was detected against the VRSA Pennsylvania strain (2002) when CSA-13 was tested in combination with gentamicin, while early additivity was demonstrated against all of the other organisms.

scholarly journals Pseudomonas aeruginosa PAO 1 In Vitro Time–Kill Kinetics Using Single Phages and Phage Formulations—Modulating Death, Adaptation, and Resistance

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 877
Author(s):  
Ana Mafalda Pinto ◽  
Alberta Faustino ◽  
Lorenzo M. Pastrana ◽  
Manuel Bañobre-López ◽  
Sanna Sillankorva
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Chronic Infections ◽  
Swarming Motility ◽  
Resistance Development ◽  
Healthcare Settings ◽  
Time Kill

Pseudomonas aeruginosa is responsible for nosocomial and chronic infections in healthcare settings. The major challenge in treating P. aeruginosa-related diseases is its remarkable capacity for antibiotic resistance development. Bacteriophage (phage) therapy is regarded as a possible alternative that has, for years, attracted attention for fighting multidrug-resistant infections. In this work, we characterized five phages showing different lytic spectrums towards clinical isolates. Two of these phages were isolated from the Russian Microgen Sextaphage formulation and belong to the Phikmvviruses, while three Pbunaviruses were isolated from sewage. Different phage formulations for the treatment of P. aeruginosa PAO1 resulted in diversified time–kill outcomes. The best result was obtained with a formulation with all phages, prompting a lower frequency of resistant variants and considerable alterations in cell motility, resulting in a loss of 73.7% in swimming motility and a 79% change in swarming motility. These alterations diminished the virulence of the phage-resisting phenotypes but promoted their growth since most became insensitive to a single or even all phages. However, not all combinations drove to enhanced cell killings due to the competition and loss of receptors. This study highlights that more caution is needed when developing cocktail formulations to maximize phage therapy efficacy. Selecting phages for formulations should consider the emergence of phage-resistant bacteria and whether the formulations are intended for short-term or extended antibacterial application.

scholarly journals Polymyxin Triple Combinations against Polymyxin-Resistant, Multidrug-Resistant, KPC-Producing Klebsiella pneumoniae

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Su Mon Aye ◽  
Irene Galani ◽  
Heidi Yu ◽  
Jiping Wang ◽  
Ke Chen ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Triple Therapy ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Infection Model ◽  
Bacterial Killing ◽  
Standard Dosage ◽  
Time Kill

ABSTRACT Resistance to polymyxin antibiotics is increasing. Without new antibiotic classes, combination therapy is often required. We systematically investigated bacterial killing with polymyxin-based combinations against multidrug-resistant (including polymyxin-resistant), carbapenemase-producing Klebsiella pneumoniae. Monotherapies and double- and triple-combination therapies were compared to identify the most efficacious treatment using static time-kill studies (24 h, six isolates), an in vitro pharmacokinetic/pharmacodynamic model (IVM; 48 h, two isolates), and the mouse thigh infection model (24 h, six isolates). In static time-kill studies, all monotherapies (polymyxin B, rifampin, amikacin, meropenem, or minocycline) were ineffective. Initial bacterial killing was enhanced with various polymyxin B-containing double combinations; however, substantial regrowth occurred in most cases by 24 h. Most polymyxin B-containing triple combinations provided greater and more sustained killing than double combinations. Standard dosage regimens of polymyxin B (2.5 mg/kg of body weight/day), rifampin (600 mg every 12 h), and amikacin (7.5 mg/kg every 12 h) were simulated in the IVM. Against isolate ATH 16, no viable bacteria were detected across 5 to 25 h with triple therapy, with regrowth to ∼2-log10 CFU/ml occurring at 48 h. Against isolate BD 32, rapid initial killing of ∼3.5-log10 CFU/ml at 5 h was followed by a slow decline to ∼2-log10 CFU/ml at 48 h. In infected mice, polymyxin B monotherapy (60 mg/kg/day) generally was ineffective. With triple therapy (polymyxin B at 60 mg/kg/day, rifampin at 120 mg/kg/day, and amikacin at 300 mg/kg/day), at 24 h there was an ∼1.7-log10 CFU/thigh reduction compared to the starting inoculum for all six isolates. Our results demonstrate that the polymyxin B-rifampin-amikacin combination significantly enhanced in vitro and in vivo bacterial killing, providing important information for the optimization of polymyxin-based combinations in patients.

scholarly journals The Pomegranate: Effects on Bacteria and Viruses That Influence Human Health

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Amy B. Howell ◽  
Doris H. D'Souza
Keyword(s):  
Antimicrobial Activity ◽  
Foodborne Pathogens ◽  
Clinical Results ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Oral Bacteria ◽  
Resistant Bacteria ◽  
Wide Range

Pomegranates have been known for hundreds of years for their multiple health benefits, including antimicrobial activity. The recent surge in multidrug-resistant bacteria and the possibility of widespread global virus pandemics necessitate the need for additional preventative and therapeutic options to conventional drugs. Research indicates that pomegranates and their extracts may serve as natural alternatives due to their potency against a wide range of bacterial and viral pathogens. Nearly every part of the pomegranate plant has been tested for antimicrobial activities, including the fruit juice, peel, arils, flowers, and bark. Many studies have utilized pomegranate peel with success. There are various phytochemical compounds in pomegranate that have demonstrated antimicrobial activity, but most of the studies have found that ellagic acid and larger hydrolyzable tannins, such as punicalagin, have the highest activities. In some cases the combination of the pomegranate constituents offers the most benefit. The positive clinical results on pomegranate and suppression of oral bacteria are intriguing and worthy of further study. Much of the evidence for pomegranates’ antibacterial and antiviral activities against foodborne pathogens and other infectious disease organisms comes fromin vitrocell-based assays, necessitating further confirmation ofin vivoefficacy through human clinical trials.

scholarly journals Molecular Composition and Antibacterial Effect of Five Essential Oils Extracted from Nigella sativa L. Seeds against Multidrug-Resistant Bacteria: A Comparative Study

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mohammed Dalli ◽  
Salah-eddine Azizi ◽  
Hind Benouda ◽  
Ali Azghar ◽  
Maroua Tahri ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Chemical Composition ◽  
Essential Oils ◽  
Nigella Sativa ◽  
Multidrug Resistant ◽  
Climatic Conditions ◽  
Diffusion Method ◽  
Resistant Bacteria ◽  
Microdilution Method

Nigella sativa L. (NS) and its volatile compounds are well known for their broad spectrum of effects. This study aimed to investigate the variability of the chemical composition and the in vitro antibacterial activity of five essential oils (Eos) originated from Morocco, Saudi Arabia, Syria, India, and France. These five samples were grown under different edaphic and climatic conditions. The agar diffusion method and microdilution method in 96-well plates were used to test the sensitivity of multidrug-resistant strains clinically isolated from patients (methicillin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii), for the determination of the minimum inhibitory concentration and bactericidal concentration. Among all the investigated Eos, the monoterpenes were highly present in the chemical composition. Moroccan, Saudi Arabian, and Syrian seeds were characterized by the presence α-phellandrene (20.03–30.54%), β-cymene (12.31–23.82 %), and 4−caranol (9.77–14.27%). The Indian seeds were rich with 4-caranol (18.81%), β-cymene (14.22%), α-phellandrene (10.58%), and β-chamigrene (9.54%), while France NS was rich with estragole (20.22%) and D-limonene (14.63%). The minimum inhibitory (MIC) and bactericidal concentration (MBC) obtained for the four Eos (with the exception of France because of the low yield) tested were ranging from 3 to 40 μl/ml. Gram-positive (+) bacteria were slightly sensitive to the Eos tested than the Gram-negative (−) bacteria. The results of this study showed that the Eos of NS seeds show interesting antibacterial activity which could be associated to the existence of different bioactive compounds. Indeed, these compounds can be used for preventive or curative purposes in the face of the noncontrolled emergence of resistance to antibiotics.

scholarly journals Antimicrobial activities of widely consumed herbal tea’s alone or in combination with antibiotics: An in vitro study

2016 ◽  
Author(s):  
Mayram Tuysuz ◽  
Sibel Dosler ◽  
Ayse Seher Birteksoz Tan ◽  
Gulten Otuk
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
In Vitro Study ◽  
Antimicrobial Activities ◽  
Combination Studies ◽  
Kill Curve ◽  
Time Kill ◽  
Microbroth Dilution ◽  
Antagonistic Interactions

Background: Because of increasing antibiotic resistance, herbal teas are the most popular natural alternatives, which are gaining even more importance. We examined the antimicrobial activities of 31 herbal teas both alone and in combination with antibiotics or antifungals against the standard and clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, methicillin susceptible/resistant Staphylococcus aureus and Candida albicans. Methods: The antimicrobial activities of the teas were determined by using the disk diffusion and microbroth dilution methods, and the combination studies were examined by using the microbroth checkerboard and time killing curve methods. Results: Rosehip, rosehip bag, pomegranate blossom, thyme, wormwood, mint, echinacea bag, cinnamon, black, and green teas were active against most of the studied microorganisms. In the combination studies, we characterized all the expected effects (synergistic, additive, and antagonistic) between the teas and the antimicrobials. While synergy was observed more frequently between ampicillin, ampicillin-sulbactam, or nystatine, and the various tea combinations, most of the effects between the ciprofloxacin, erythromycin, cefuroxime, or amikacin and various tea combinations, particularly rosehip, rosehip bag, and pomegranate blossom teas, were antagonistic. The results of the time kill curve analyses showed that none of the herbal teas were bactericidal in their usage concentrations; however, in combination they were. Discussion: Some herbal teas, particularly rosehip and pomegranate blossom should be avoided because of antagonistic interactions during the course of antibiotic treatment or should be consumed alone.

Evaluation of the in vitro interaction of fosfomycin and meropenem against metallo-β-lactamase–producing Pseudomonas aeruginosa using Etest and time-kill assay

2020 ◽  
pp. jim-2020-001573
Author(s):  
Sanjida Jahan ◽  
Heather Davis ◽  
Deborah S Ashcraft ◽  
George A Pankey
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Time Kill ◽  
In Vitro Interaction ◽  
Antimicrobial Combinations

Pseudomonas aeruginosa is a nosocomial pathogen containing various resistance mechanisms. Among them, metallo-β-lactamase (MBL)–producing Pseudomonas are difficult to treat. Fosfomycin is an older antibiotic that has recently seen increased usage due to its activity against a broad spectrum of multidrug-resistant organisms. Our aim was to evaluate the combination of fosfomycin and meropenem against 20 MBL-producing P. aeruginosa (100% meropenem-resistant and 20% fosfomycin-resistant) using both an Etest minimal inhibitory concentration (MIC): MIC method and time-kill assay. MICs for fosfomycin and meropenem were determined by Etest and by broth microdilution method for the latter. The combination demonstrated synergy by Etest in 3/20 (15%) isolates and 5/20 (25%) isolates by time-kill assay. Results from the Etest method and time-kill assay were in agreement for 14/20 (70%) of isolates. No antagonism was found. Comparing both methods, Etest MIC: MIC method may be useful to rapidly evaluate other antimicrobial combinations.

scholarly journals A Study of Ethno-Veterinary Medicinal Plants and In Vitro Antimicrobial Activities Against Bovine Mastitis Isolated Bacterial Pathogens in Algeria

2019 ◽  
Vol 76 (2) ◽  
pp. 154
Author(s):  
Radhwane SAIDI ◽  
Nora MIMOUNE ◽  
Ratiba BAAZIZI ◽  
Mohamed Hocine BENAISSA ◽  
Djamel KHELEF ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Bovine Mastitis ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Economic Losses ◽  
Resistant Bacteria ◽  
Mentha Pulegium ◽  
Antibiotic Resistant ◽  
Marrubium Vulgare

Bovine mastitis is the most serious dairy problem in terms of economic losses to the dairy industry. In Algeria, dominates as one of the most prevalent diseases in dairy cattle among the dairy farms. Mastitis treatment with antibiotics leads to the development of antibiotic resistant strains and consumer health problem. Multidrug-resistant bacteria have become a major health issue. With new generations of virulence and resistant bacteria, we need to improve our understanding and produce novel techniques to control these pathogenic strains. In our study, the activity of several extracts from seven medicinal plants, namely Mentha pulegium, Lavandula dentate, Origanium sp, Marrubium vulgare, Salvia bicolor, Blackstonia perfoliata, and Phlomis crinita, traditionally used in Algeria was investigated against 26 methicillin resistant staphylococci and multi-resistant Escherichia coli. (E.coli) isolated from animals with mastitis manifestation by the disc diffusion method.Results revealed the potential of extracts of Salvia bicolor, Marrubium vulgare and Phlomis crinita as antibacterial agents against strains isolated from bovine mastitis and support the possible use of these phytotherapic agents in the clinical management of the disease. Further studies into their toxicity and phytochemistry are advocated.

In vitro and in vivo synergistic effects of tigecycline combined with aminoglycosides on carbapenem-resistant Klebsiella pneumoniae

2021 ◽  
Author(s):  
Wentao Ni ◽  
Deqing Yang ◽  
Jie Guan ◽  
Wen Xi ◽  
Dexun Zhou ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Synergistic Effects ◽  
Molecular Characteristics ◽  
Synergistic Activity ◽  
Significant Activity ◽  
Clinical Pharmacokinetics ◽  
Carbapenem Resistant ◽  
Time Kill

Abstract Objectives Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections represent severe threats to public health worldwide. The aim of this study was to assess potential synergistic interaction between tigecycline and aminoglycosides via in vitro and in vivo studies. Methods Antibiotic resistance profiles and molecular characteristics of 168 CR-KP clinical isolates were investigated by susceptibility testing, PCR and MLST. Chequerboard tests and time–kill assays were performed for 20 CR-KP isolates to evaluate in vitro synergistic effects of tigecycline combined with aminoglycosides. A tissue-cage infection model of rats was established to evaluate in vivo synergistic effects. Different doses of tigecycline and aminoglycosides alone or in combination were administered for 7 days via tail vein injection. Antibiotic efficacy was evaluated in tissue-cage fluid and emergence of resistance was screened. Results The chequerboard tests showed that this combination displayed synergistic or partial synergistic activity against CR-KP. The time–kill assays further demonstrated that strong synergistic effects of such a combination existed against isolates that were susceptible to both drugs but for resistant isolates no synergy was observed if clinical pharmacokinetics were taken into consideration. The in vivo study showed that the therapeutic effectiveness of combination therapies was better than that of monotherapy for susceptible isolates, suggesting in vivo synergistic effects. Furthermore, combinations of tigecycline with an aminoglycoside showed significant activity in reducing the occurrence of tigecycline-resistant mutants. Conclusions Compared with single drugs, tigecycline combined with aminoglycosides could exert synergistic effects and reduce the emergence of tigecycline resistance. Such a combination might be an effective alternative when treating CR-KP infections in clinical practice.

Sign in / Sign up

Export Citation Format

Share Document