Synergistic effect of two antimicrobial peptides, Nisin and P10 with conventional antibiotics against extensively drug-resistant Acinetobacter baumannii and colistin-resistant Pseudomonas aeruginosa isolates

2021 ◽  
Vol 150 ◽  
pp. 104700
Author(s):  
Abolfazl Jahangiri ◽  
Alireza Neshani ◽  
Seyed Ali Mirhosseini ◽  
Kiarash Ghazvini ◽  
Hosna Zare ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Synergistic Effect ◽  
Antimicrobial Peptides ◽  
Acinetobacter Baumannii ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Conventional Antibiotics

scholarly journals 1597. Ceftolozane-Tazobactam and Meropenem Synergy Testing Against Multi-Drug and Extensively-Drug Resistant Pseudomonas aeruginosa

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S794-S795
Author(s):  
Mary Francine P Chua ◽  
Syeda Sara Nida ◽  
Jerry Lawhorn ◽  
Janak Koirala
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Synergistic Effect ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Additive Effect ◽  
Teaching Hospitals ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Synergy Testing ◽  
Concentration Indices

Abstract Background Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) have limited therapeutic options for treatment. Ceftolozane/tazobactam is a newer anti-pseudomonal drug effective against resistant PA infections, however resistance against this drug has now also developed and is increasing. In this study, we explored the combination of ceftolozane/tazobactam (CT) and meropenem (MP) as a possible effective regimen against MDR and XDR PA. Methods We obtained 33 non-duplicate isolates of MDR and XDR PA grown from blood, urine and respiratory samples collected from patients admitted between 2015 and 2019 at our two affiliate teaching hospitals. MDR PA was defined as resistance to 3 or more classes of anti-pseudomonal antibiotics, and XDR PA as resistance to all but two or less classes of anti-pseudomonal antibiotics. Antimicrobial preparations of both MP and CT were made according to manufacturer instructions. Susceptibility testing was performed using the checkerboard method in accordance to CLSI guidelines (CLSI M100, 2017). The ATCC 27853 strain of PA used as control. Synergy, additive effect, indifference and antagonism were defined as FIC (fractional inhibitory concentration) indices of ≤0.5, >0.5 to <1, >1 to <4, and >4, respectively. Results Thirteen (39%) of 33 PA isolates were classified as XDR, while 20 (61%) PA isolates were MDR. All isolates were resistant to MP (MIC50 >32 ug/mL), while only 2 (6%) isolates were susceptible to CT (MIC50 64 ug/mL). A synergistic effect was seen in 9 (27.3%) of PA isolates (FIC index range 0.28 to 0.5)— 2 of which were XDR PA, and 7 were MDR PA. An additive effect was seen in 12 (36.4%), with indifference seen in 12 (36.4%) of isolates. In this study, no antagonism was seen when CT and MP were combined. Conclusion When used in combination, CT and MP can exert a synergistic effect against MDR and XDR PA. Additive effect and indifference can also be seen when both antibiotics were used. Moreover, there was no antagonism seen when both antibiotics were combined. This study shows that the use of CT and MP in combination may be an option against XDR and MDR PA infections. Disclosures All Authors: No reported disclosures

scholarly journals The Intestinal Biofilm of Pseudomonas aeruginosa and Staphylococcus aureus Is Inhibited by Antimicrobial Peptides HBD-2 and HBD-3

2021 ◽  
Vol 11 (14) ◽  
pp. 6595
Author(s):  
Alessandra Fusco ◽  
Vittoria Savio ◽  
Debora Stelitano ◽  
Adone Baroni ◽  
Giovanna Donnarumma
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Peptides ◽  
Opportunistic Infections ◽  
Epithelial Cell Line ◽  
Drug Resistant ◽  
Intestinal Epithelial ◽  
Genes Encoding ◽  
Conventional Antibiotics ◽  
And Staphylococcus Aureus

Background: The intestinal microbiota is a very active microbial community interacting with the host in maintaining homeostasis; it acts in cooperation with intestinal epithelial cells, which protect the host from the external environment by producing a diverse arsenal of antimicrobial peptides (AMPs), including β-defensins-2 and 3 (HBD-2 and HBD-3), considered among the most studied in this category. However, there are some circumstances in which an alteration of this eubiotic state occurs, with the triggering of dysbiosis. In this condition, the microbiota loses its protective power, leading to the onset of opportunistic infections. In this scenario, the emergence of multi-drug resistant biofilms from Pseudomonas aeruginosa and Staphylococcus aureus is very frequent. Methods: We created a Caco-2 intestinal epithelial cell line stably transfected with the genes, encoding HBD-2 and HBD-3, in order to evaluate their ability to inhibit the intestinal biofilm formation of P. aeruginosa and S. aureus. Results: Both HBD-2 and HBD-3 showed anti-biofilm activity against P. aeruginosa and S. aureus. Conclusions: The exploitation of endogenous antimicrobial peptides as a new anti-biofilm therapy, in isolation or in combination with conventional antibiotics, can be an interesting prospect in the treatment of chronic and multi-drug resistant infections.

scholarly journals Potentiation of antimicrobial activity of colistin with antibiotics of different groups against multidrug- and extensively drug-resistant strains of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa

2020 ◽  
Vol 22 (2) ◽  
pp. 128-136
Author(s):  
Dmitry V. Tapalskiy ◽  
T.A. Petrovskaya ◽  
A.I. Kozlova ◽  
Mikhail V. Edelstein
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Bactericidal Activity ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Potentiation Effect ◽  
Resistant Strains ◽  
Drug Resistant Strains

Objective. To reveal antibiotics being capable of potentiating the antimicrobial activity of colistin against multidrug- and extensively drug-resistant strains of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. Materials and Methods. The minimum inhibitory concentrations (MIC) of colistin alone and in combination with fixed concentrations of antibiotics of different groups were determined for 272 multidrug- and extensively drug-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa. Bactericidal activity of colistin, carbapenems, clarithromycin and their combinations were also determined at fixed PK/PD breakpoint concentrations of antibiotics. Results. Potentiation of colistin antibacterial activity in the presence of fixed concentration of rifampicin (0.5 mg/L) was observed as a 4–16-fold MIC decrease for K. pneumoniae and A. baumannii. In the presence of fixed concentrations of azithromycin (2 mg/L) or clarithromycin (1 mg/L), the colistin MICs decreased 64–512 times for K. pneumoniae, 4–32 times for A. baumannii, 16–64 times for P. aeruginosa. Two- or more-fold reduction of MIC of colistin in the presence of 1 mg/L clarithromycin was observed for 85.2% of K. pneumoniae, 86.3% of A. baumannii and 60.2% of P. aeruginosa strains. In the presence of 1 mg/L clarithromycin and 8 mg/L meropenem, the potentiation effect was enhanced and was observed for an even larger percent of isolates: 96.1% K. pneumoniae, 98.0% A. baumannii and 61.3% P. aeruginosa. Colistin-based combinations with clarithromycin-meropenem and clarithromycin-doripenem were bactericidal against most isolates of A. baumannii and P. aeruginosa (91.4–100%), and against colistin-sensitive K. pneumoniae (95.3%) and colistin-resistant K. pneumoniae (79.1%). Conclusions. The ability of macrolides to significantly potentiate the colistin antimicrobial activity against both colistin-sensitive and colistin-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa was shown. This potentiation effect was enhanced in the presence of carbapenems. The most potent bactericidal activity was revealed with dual and triple combinations of colistin-clarithromycin and colistinclarithromycin-carbapenems.

Synergistic effect of Myrtus communis L. essential oils and conventional antibiotics against multi-drug resistant Acinetobacter baumannii wound isolates

Phytomedicine ◽  
2014 ◽  
Vol 21 (12) ◽  
pp. 1666-1674 ◽  
Author(s):  
Verica Aleksic ◽  
Neda Mimica-Dukic ◽  
Natasa Simin ◽  
Natasa Stankovic Nedeljkovic ◽  
Petar Knezevic
Keyword(s):  
Synergistic Effect ◽  
Essential Oils ◽  
Acinetobacter Baumannii ◽  
Drug Resistant ◽  
Myrtus Communis ◽  
Myrtus Communis L ◽  
Conventional Antibiotics

scholarly journals Polymyxin B in Combination with Antimicrobials LackingIn VitroActivity versus Polymyxin B in Monotherapy in Critically Ill Patients with Acinetobacter baumannii or Pseudomonas aeruginosa Infections

2015 ◽  
Vol 59 (10) ◽  
pp. 6575-6580 ◽  
Author(s):  
Maria Helena Rigatto ◽  
Fabiane J. Vieira ◽  
Laura C. Antochevis ◽  
Tainá F. Behle ◽  
Natane T. Lopes ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Combination Therapy ◽  
Acinetobacter Baumannii ◽  
Protective Factor ◽  
Polymyxin B ◽  
Apache Ii Score ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Tract Infections

ABSTRACTThere is no clinical evidence supporting the use of polymyxin B in combination with another antimicrobial for infections caused by extensively drug-resistantAcinetobacter baumanniiorPseudomonas aeruginosaisolates. We developed a cohort study of patients in two intensive care units from teaching hospitals to evaluate treatment with intravenous polymyxin B for ≥48 h for severeA. baumanniiorP. aeruginosainfections. Covariates potentially associated with 30-day mortality were evaluated in a Cox proportional hazards model. A total of 101 patients were included; 33 (32.7%) were treated with polymyxin B in combination with an antimicrobial lackingin vitroactivity and 68 (67.3%) with polymyxin B in monotherapy. The overall 30-day mortality was 59.4% (60 patients), comprising 42.4% (14 of 33) and 67.6% (46 of 68) in combination and monotherapy groups, respectively (P= 0.03). The mortality rates were 18.5/1,000 patient days and 36.4/1,000 patient days in the combination and monotherapy groups, respectively (P= 0.02). Combination therapy was independently associated with lower 30-day mortality (hazard ratio, 0.33; 95% confidence interval, 0.17 to 0.64;P= 0.001). Creatinine clearance of ≥60 ml/min was also a protective factor, while a higher acute physiology and chronic health evaluation (APACHE II) score and polymicrobial infection were associated with increased mortality. The results did not change after adding a propensity score for prescribing combination therapy into the model. The protective effect remained when only combination with β-lactam or carbapenem was considered and in both subgroups of patients: those withA. baumanniiinfection and those with lower respiratory tract infections. To our knowledge, this is the first clinical study to show a benefit of combination over monotherapy with polymyxin B for severe extensively drug-resistantA. baumanniiorP. aeruginosainfections.

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