scholarly journals Aspirin, sodium benzoate and sodium salicylate reverse resistance to colistin in Enterobacteriaceae and Pseudomonas aeruginosa

2020 ◽  
Vol 75 (12) ◽  
pp. 3568-3575
Author(s):  
Cristina F Malla ◽  
Natalia A Mireles ◽  
Ana S Ramírez ◽  
José B Poveda ◽  
María M Tavío

Abstract Background MDR bacterial infections are currently a serious problem for clinicians worldwide. Klebsiella pneumoniae and Enterobacter spp., among Enterobacteriaceae, and Pseudomonas aeruginosa, are part of the group of ESCAPE pathogens or bacteria that ‘escape’ from common antibacterial treatments. The lack of effectiveness of the first common line of antibiotics has led to the search for new therapies based on older antibiotics, such as colistin. Objectives We searched for new enhancers of the action of colistin against MDR Gram-negative bacteria that can be easily applicable to clinical treatments. Methods Colistin MICs were determined alone and with the protonophores CCCP, sodium benzoate, sodium salicylate and aspirin using the broth microdilution method and FIC indexes were calculated to assess synergy between colistin and each chemical. Time–kill assays of colistin with and without protonophores were performed to determine the bactericidal action of combinations of colistin with protonophores. Likewise, the effect of sucrose, l-arginine and l-glutamic acid on the MICs of colistin alone and combined with each protonophore was assessed. Results It was found that sodium benzoate, sodium salicylate and aspirin, at concentrations allowed for human and animal use, partially or totally reversed resistance to colistin in P. aeruginosa and highly resistant enterobacterial strains. The mechanism of action could be related to their negative charge at a physiological pH along with their lipid-soluble character. Conclusions Sodium benzoate, sodium salicylate and aspirin are good enhancers to use in antibiotic therapies that include colistin.

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Shanmugapriya Perumal ◽  
Roziahanim Mahmud ◽  
Nornisah Mohamed

Pseudomonas aeruginosa is naturally resistant to many classes of antipseudomonal antibiotics due to the species ability to easily acquire resistance. Plant-based antibacterial agent in combination with the existing antibiotic proposes an alternative treatment regimen for the eradication of resistant bacterial infections. The antibacterial effects of the isolated epicatechin 3-gallate compound from Euphorbia hirta in combination with cefepime were investigated in vitro against resistant P. aeruginosa. The fractional inhibitory concentration index of the combination was determined using checkerboard broth microdilution method. Epicatechin 3-gallate combined with cefepime had produced synergistic effect against P. aeruginosa (with average FIC index of 0.24). The MIC of epicatechin 3-gallate was effectively reduced to MIC/4, MIC/8, MIC/16, and MIC/32 in the presence of cefepime. Time-kill study of epicatechin 3-gallate combined with cefepime exhibited remarkable bactericidal activity where the eradication of P. aeruginosa occurred within 4 h of treatment. Scanning electron micrographs revealed apparent cell membrane damage and leakage of cytoplasmic contents from P. aeruginosa cells which eventually led to the cell lysis after the combination treatment of epicatechin 3-gallate and cefepime. The potential of epicatechin 3-gallate to act synergistically with cefepime against clinically resistant P. aeruginosa strain possibly will maximize the successful outcomes when choosing empirical antibiotic treatment in hospitals or health care institutions.


2020 ◽  
pp. jim-2020-001573
Author(s):  
Sanjida Jahan ◽  
Heather Davis ◽  
Deborah S Ashcraft ◽  
George A Pankey

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.


2020 ◽  
Vol 19 (2) ◽  
pp. 258
Author(s):  
Maria Helena Pereira de Lira ◽  
Gustavo Fernandes Queiroga Moraes ◽  
Girlene Macena Santos ◽  
Francisco Patrício de Andrade Júnior ◽  
Fillipe De Oliveira Pereira ◽  
...  

<p><strong>Introduction</strong>: bacterial infections are a public health problem. Besides, the emergence of strains resistant to antimicrobials has<br />contributed to the search for new alternatives, such for the terpenes with antimicrobial potential. <strong>Objectives</strong>: the objective of this<br />study was to determine the possible interaction of isolated monoterpenes (-)-Carveol, Geraniol, Citronellol, α-terpineol, R-(-) Carvone,<br />(-)-Menthol, Linalool, D-Dihydrocarvone, and (-)-Terpine-4-ol with conventional antimicrobials (Chloramphenicol, Minocycline,<br />Amoxicillin and Ciprofloxacin) when they are evaluated on Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis,<br />Escherichia coli and Pseudomonas aeruginosa strains. <strong>Methodology</strong>: the minimum inhibitory concentrations of these test drugs<br />were determined using the microdilution method. The Checkerboard method was used to assess the interactions, by determining<br />the fractional inhibitory concentration index (FIC index). <strong>Results</strong>: aamong the monoterpenes, only Carveol, Citronellol, and Geraniol<br />presented antimicrobial activity (MIC &lt; 1024 μg/mL). They presented synergistic effects against Pseudomonas aeruginosa ATCC-9027<br />(FIC index ≤ 0.5) when in combination with Minocycline. <strong>Conclusion</strong>: this study contributes to the development of new approaches<br />to control bacterial resistance and to the possibility of discovering new drugs.</p>


2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Dee Shortridge ◽  
Mariana Castanheira ◽  
Michael A. Pfaller ◽  
Robert K. Flamm

ABSTRACT The activity of ceftolozane-tazobactam was compared to the activities of 7 antimicrobials against 3,851 Pseudomonas aeruginosa isolates collected from 32 U.S. hospitals in the Program to Assess Ceftolozane-Tazobactam Susceptibility from 2012 to 2015. Ceftolozane-tazobactam and comparator susceptibilities were determined using the CLSI broth microdilution method at a central monitoring laboratory. For ceftolozane-tazobactam, 97.0% of the isolates were susceptible. Susceptibilities of the other antibacterials tested were: amikacin, 96.9%; cefepime, 85.9%; ceftazidime, 85.1%; colistin, 99.2%; levofloxacin, 76.6%; meropenem, 81.8%; and piperacillin-tazobactam, 80.4%. Of the 699 (18.1%) meropenem-nonsusceptible P. aeruginosa isolates, 87.6% were susceptible to ceftolozane-tazobactam. Six hundred seven isolates (15.8%) were classified as multidrug resistant (MDR), and 363 (9.4%) were classified as extensively drug resistant (XDR). Only 1 isolate was considered pandrug resistant, which was resistant to all tested agents, including colistin. Of the 607 MDR isolates, 84.9% were ceftolozane-tazobactam susceptible, and 76.9% of XDR isolates were ceftolozane-tazobactam susceptible. In vitro activity against drug-resistant P. aeruginosa indicates ceftolozane-tazobactam may be an important agent in treating serious bacterial infections.


2015 ◽  
Vol 59 (6) ◽  
pp. 3059-3065 ◽  
Author(s):  
C. Pitart ◽  
F. Marco ◽  
T. A. Keating ◽  
W. W. Nichols ◽  
J. Vila

ABSTRACTCeftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200Enterobacteriaceaeand 25Pseudomonas aeruginosastrains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistantEnterobacteriaceaestrains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBLEscherichia coli(MIC90of 0.25 mg/liter), ESBLKlebsiella pneumoniae(MIC90of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC90of 1 mg/liter), non-ESBLE. coli(MIC90of ≤0.125 mg/liter), non-ESBLK. pneumoniae(MIC90of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistantP. aeruginosastrains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtainedin vitrofrom two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains ofEnterobacteriaceaeandP. aeruginosawere ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affectEnterobacteriaceaeandP. aeruginosasusceptibility to ceftazidime-avibactam; that is, there is no cross-resistance.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Nishanth Kumar Sasidharan ◽  
Sreerag Ravikumar Sreekala ◽  
Jubi Jacob ◽  
Bala Nambisan

Diarrhea is one of the leading causes of morbidity and mortality in humans in developed and developing countries. Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of this infectious disease worldwide. Therefore, there exists a need to develop alternative natural or combination drug therapies. The aim of the present study was to investigate the synergistic effect of curcumin-1 in combination with three antibiotics against five diarrhea causing bacteria. The antibacterial activity of curcumin-1 and antibiotics was assessed by the broth microdilution method, checkerboard dilution test, and time-kill assay. Antimicrobial activity of curcumin-1 was observed against all tested strains. The MICs of curcumin-1 against test bacteria ranged from 125 to 1000 μg/mL. In the checkerboard test, curcumin-1 markedly reduced the MICs of the antibiotics cefaclor, cefodizime, and cefotaxime. Significant synergistic effect was recorded by curcumin-1 in combination with cefotaxime. The toxicity of curcumin-1 with and without antibiotics was tested against foreskin (FS) normal fibroblast and no significant cytotoxicity was observed. From our result it is evident that curcumin-1 enhances the antibiotic potentials against diarrhea causing bacteria inin vitrocondition. This study suggested that curcumin-1 in combination with antibiotics could lead to the development of new combination of antibiotics against diarrhea causing bacteria.


2021 ◽  
Vol 70 (7) ◽  
Author(s):  
Letícia Fernandes da Rocha ◽  
Bruna Pippi ◽  
Angélica Rocha Joaquim ◽  
Saulo Fernandes de Andrade ◽  
Alexandre Meneghello Fuentefria

Introduction. The presence of Candida biofilms in medical devices is a concerning and important clinical issue for haemodialysis patients who require constant use of prosthetic fistulae and catheters. Hypothesis/Gap Statement. This prolonged use increases the risk of candidaemia due to biofilm formation. PH151 and clioquinol are 8-hydroxyquinoline derivatives that have been studied by our group and showed interesting anti-Candida activity. Aim. This study evaluated the biofilm formation capacity of Candida species on polytetrafluoroethylene (PTFE) and polyurethane (PUR) and investigated the synergistic effects between the compounds PH151 and clioquinol and fluconazole, amphotericin B and caspofungin against biofilm cells removed from those materials. Further, the synergistic combination was evaluated in terms of preventing biofilm formation on PTFE and PUR discs. Methodology. Susceptibility testing was performed for planktonic and biofilm cells using the broth microdilution method. The checkerboard method and the time–kill assay were used to evaluate the interactions between antifungal agents. Antibiofilm activity on PTFE and PUR materials was assessed to quantify the prevention of biofilm formation. Results. Candida albicans, Candida glabrata and Candida tropicalis showed ability to form biofilms on both materials. By contrast, Candida parapsilosis did not demonstrate this ability. Synergistic interaction was observed when PH151 was combined with fluconazole in 77.8 % of isolates and this treatment was shown to be concentration- and time-dependent. On the other hand, indifferent interactions were predominantly observed with the other combinations. A reduction in biofilm formation on PUR material of more than 50 % was observed when using PH151 combined with fluconazole. Conclusion. PH151 demonstrated potential as a local treatment for use in a combination therapy approach against Candida biofilm formation on haemodialysis devices.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Johana Rondevaldova ◽  
Olga Leuner ◽  
Alemtshay Teka ◽  
Ermias Lulekal ◽  
Jaroslav Havlik ◽  
...  

Bacterial infections are in less-developed countries traditionally treated by remedies prepared from medicinal plants.Embelia schimperi(Vatke) is a plant used as a taenicide or disinfectant in Ethiopia, very often taken mixed with another plant species. In the present study, we examined two extracts prepared from seeds and twigs with leaves ofE. schimperiand its main present secondary metabolite embelin for their antibacterial combinatory effect with oxacillin and tetracycline against sensitive and resistantStaphylococcus aureusstrains. Minimum inhibitory concentrations were determined through the broth microdilution method, whereas the combinatory effect was evaluated through fractional inhibitory concentration sum (ΣFIC) indices. Results show many positive interactions and synergy occurring in embelin and oxacillin combinations against 4 out of 9 strains (ΣFIC 0.203–0.477) and for embelin and tetracycline combination against 3 out of 9 strains (ΣFIC 0.400–0.496). Moreover, the resistance to oxacillin has been overcome in 2 strains and to tetracycline in 3 strains. According to our knowledge, this is the first study showing antimicrobial combinatory effect ofE. schimperias well as of embelin. These findings can be used for the further research targeted on the development of new antistaphylococcal agents.


2020 ◽  
Vol 75 (10) ◽  
pp. 2907-2913 ◽  
Author(s):  
Helio S Sader ◽  
Cecilia G Carvalhaes ◽  
Leonard R Duncan ◽  
Robert K Flamm ◽  
Dee Shortridge

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.


2020 ◽  
Vol 13 (7) ◽  
pp. 153
Author(s):  
Artur Adamczak ◽  
Marcin Ożarowski ◽  
Tomasz M. Karpiński

Curcumin, a principal bioactive substance of turmeric (Curcuma longa L.), is reported as a strong antioxidant, anti-inflammatory, antibacterial, antifungal, and antiviral agent. However, its antimicrobial properties require further detailed investigations into clinical and multidrug-resistant (MDR) isolates. In this work, we tested curcumin’s efficacy against over 100 strains of pathogens belonging to 19 species. This activity was determined by the broth microdilution method and by calculating the minimum inhibitory concentration (MIC). Our findings confirmed a much greater sensitivity of Gram-positive than Gram-negative bacteria. This study exhibited a significantly larger variation in the curcumin activity than previous works and suggested that numerous clinical strains of widespread pathogens have a poor sensitivity to curcumin. Similarly, the MICs of the MDR types of Staphylococcus aureus, S. haemolyticus, Escherichia coli, and Proteus mirabilis were high (≥2000 µg/mL). However, curcumin was effective against some species and strains: Streptococcus pyogenes (median MIC = 31.25 µg/mL), methicillin-sensitive S. aureus (250 µg/mL), Acinetobacter lwoffii (250 µg/mL), and individual strains of Enterococcus faecalis and Pseudomonas aeruginosa (62.5 µg/mL). The sensitivity of species was not associated with its affiliation to the genus, and it could differ a lot (e.g., S. pyogenes, S. agalactiae and A. lwoffii, A. baumannii). Hence, curcumin can be considered as a promising antibacterial agent, but with a very selective activity.


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