In vitro and in vivo assessment of the antibacterial activity of colistin alone and in combination with other antibiotics against Acinetobacter baumannii and Escherichia coli

Wang, Yale; Li, He; Xie, Xiaoqian; Wu, Xiaohan; Li, Xinxin; Zhao, Zeyue; Luo, Shasha; Wan, Zhijie; Liu, Jingjing; Fu, Lei; Li, Xiaotian

doi:10.1016/j.jgar.2019.09.013

Cited by 14 publications

(10 citation statements)

References 51 publications

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“…To shed light upon the matter, we can compare the hemolysis activity of melittin with colistin as a clinically approved AMP. A recently published study showed that colistin had no hemolytic activity at concentrations up to 256 µg/mL [36]. Also the colistin IC 50 value was reported about 113 µg/mL in RAW 264.7 cell line (macrophage) [37].…”

Section: Discussionmentioning

confidence: 98%

In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria

Askari

Namaei

Ghazvini

et al. 2021

BMC Pharmacol Toxicol

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Background Melittin is one of the most studied antimicrobial peptides, and several in vitro experiments have demonstrated its antibacterial efficacy. However, there is evidence showing melittin has non-promising effects such as cytotoxicity and hemolysis. Therefore, concerns about unwanted collateral toxicity of melittin lie ahead in the path toward its clinical development. With these considerations, the present study aimed to fill the gap between in vitro and in vivo studies. Methods In the first step, in vitro toxicity profile of melittin was assessed using cytotoxicity and hemolysis tests. Next, a maximum intraperitoneal (i.p.) sub-lethal dose was determined using BALB/c mice. Besides toxicity, antimicrobial efficacy of melittin against extensively drug-resistant (XDR) Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and KPC-producing Klebsiella pneumonia (KPC-KP) pathogens were tested using both in vitro and in vivo methods. Results Melittin showed extensive hemolysis (HD50 = 0.44 µg/mL), and cytotoxicity (IC50 = 6.45 µg/mL) activities with i.p. LD50 value of 4.98 mg/kg in BALB/c mice. In vitro antimicrobial evaluation showed melittin MIC range from 8 to 32 µg/mL for the studied pathogens. Treatment of infected mice with repeated sub-lethal doses of melittin (2.4 mg/kg) displayed no beneficial effect on their survival and peritoneal bacterial loads. Conclusions These results indicate that melittin at its safe dose could not exhibit antimicrobial activity, which hinders its application in clinical practice.

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Section: Discussionmentioning

confidence: 98%

In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria

Askari

Namaei

Ghazvini

et al. 2021

BMC Pharmacol Toxicol

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“…Among several proposed therapies for the further treatment of GNB infections [ 42 , 43 ], a combination of colistin with other antibiotics is considered a potential approach associated with overcoming the outer membrane permeability barrier, a broader antibacterial spectrum, synergistic effects and reduced risk for emerging resistance during therapy [ 20 , 44 , 45 ]. In addition, many studies have demonstrated that, in contrast to monotherapy, combination therapy may enhance antimicrobial effects and provide synergism [ 46 , 47 , 48 , 49 , 50 ]. In this study, the NCL179 + colistin combination showed synergistic activity against all tested GNB pathogens, including colistin-resistant A. baumannii and E. coli isolates, comparable to other synergy reports of combining colistin with other antibiotics [ 44 , 46 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, many studies have demonstrated that, in contrast to monotherapy, combination therapy may enhance antimicrobial effects and provide synergism [ 46 , 47 , 48 , 49 , 50 ]. In this study, the NCL179 + colistin combination showed synergistic activity against all tested GNB pathogens, including colistin-resistant A. baumannii and E. coli isolates, comparable to other synergy reports of combining colistin with other antibiotics [ 44 , 46 , 51 ]. In addition, it has been suggested that IV colistimethate sodium monotherapy may not be an optimal option if the MIC against GNB pathogens is higher than 1 µg/mL [ 46 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of a Novel Anticoccidial Analogue on Systemic Staphylococcus aureus Infection in a Bioluminescent Mouse Model

et al. 2022

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In this study, we investigated the potential of an analogue of robenidine (NCL179) to expand its chemical diversity for the treatment of multidrug-resistant (MDR) bacterial infections. We show that NCL179 exhibits potent bactericidal activity, returning minimum inhibitory concentration/minimum bactericidal concentrations (MICs/MBCs) of 1–2 µg/mL against methicillin-resistant Staphylococcus aureus, MICs/MBCs of 1–2 µg/mL against methicillin-resistant S. pseudintermedius and MICs/MBCs of 2–4 µg/mL against vancomycin-resistant enterococci. NCL179 showed synergistic activity against clinical isolates and reference strains of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa in the presence of sub-inhibitory concentrations of colistin, whereas NCL179 alone had no activity. Mice given oral NCL179 at 10 mg/kg and 50 mg/kg (4 × doses, 4 h apart) showed no adverse clinical effects and no observable histological effects in any of the organs examined. In a bioluminescent S. aureus sepsis challenge model, mice that received four oral doses of NCL179 at 50 mg/kg at 4 h intervals exhibited significantly reduced bacterial loads, longer survival times and higher overall survival rates than the vehicle-only treated mice. These results support NCL179 as a valid candidate for further development to treat MDR bacterial infections as a stand-alone antibiotic or in combination with existing antibiotic classes.

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“…Combined therapy is recommended when all conventional drugs become ineffective against the A. baumannii [ 127 ]. Synergy and combinations of drugs through in vitro andin vivoexperiments have shown extremely bactericidal activity against the hospital strains of MDR A. baumannii [ 128 , 129 ]. Two or three classes of the following antibiotics are included in such synergic combinations: rifampin, polymixins, sulbactam, tigecycline, aminoglycosides, or β-lactams, such as broad-spectrum cephalosporins or carbapenems [ 130 , 131 , 132 ].…”

Section: Antimicrobial Therapymentioning

confidence: 99%

Virulence Potential and Treatment Options of Multidrug-Resistant (MDR) Acinetobacter baumannii

2021

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Acinetobacter baumannii is an opportunistic pathogen which is undoubtedly known for a high rate of morbidity and mortality in hospital-acquired infections. A. baumannii causes life-threatening infections, including; ventilator-associated pneumonia (VAP), meningitis, bacteremia, and wound and urinary tract infections (UTI). In 2017, the World Health Organization listed A. baumannii as a priority-1 pathogen. The prevalence of A. baumannii infections and outbreaks emphasizes the direct need for the use of effective therapeutic agents for treating such infections. Available antimicrobials, such as; carbapenems, tigecycline, and colistins have insufficient effectiveness due to the appearance of multidrug-resistant strains, accentuating the need for alternative and novel therapeutic remedies. To understand and overcome this menace, the knowledge of recent discoveries on the virulence factors of A. baumannii is needed. Herein, we summarized the role of various virulence factors, including; outer membrane proteins, efflux pumps, biofilm, penicillin-binding proteins, and siderophores/iron acquisition systems. We reviewed the recent scientific literature on different A. baumannii virulence factors and the effective antimicrobial agents for the treatment and management of bacterial infections.

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In vitro and in vivo assessment of the antibacterial activity of colistin alone and in combination with other antibiotics against Acinetobacter baumannii and Escherichia coli

Cited by 14 publications

References 51 publications

In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria

In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria

Impact of a Novel Anticoccidial Analogue on Systemic Staphylococcus aureus Infection in a Bioluminescent Mouse Model

Virulence Potential and Treatment Options of Multidrug-Resistant (MDR) Acinetobacter baumannii

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