Successful High-Dosage Monotherapy of Tigecycline in a Multidrug-Resistant Klebsiella pneumoniae Pneumonia–Septicemia Model in Rats

Weide, Hessel van der; Kate, Marian T. ten; Jongh, Denise M C Vermeulen-de; Meijden, Aart van der; Wijma, Rixt A.; Boers, Stefan A.; Westreenen, Mireille van; Hays, John P.; Goessens, W. H. F.; Bakker-Woudenberg, Irma A. J. M.

doi:10.3390/antibiotics9030109

Cited by 7 publications

(9 citation statements)

References 54 publications

(64 reference statements)

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“…53 Some studies have suggested that monotherapy with a high dose of tigecycline is safe and optimally effective and can improve the outcome. [53][54][55][56][57] Nevertheless, other opinions have…”

Section: Discussionmentioning

confidence: 99%

Machine perfusion combined with antibiotics prevents donor-derived infections caused by multidrug-resistant bacteria

Liu

Peng

et al. 2022

American Journal of Transplantation

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Section: Discussionmentioning

confidence: 99%

Machine perfusion combined with antibiotics prevents donor-derived infections caused by multidrug-resistant bacteria

Liu

Peng

et al. 2022

American Journal of Transplantation

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“…The present study shows that although both nanomedicines resulted in significantly improved therapeutic efficacy in terms of increased rat survival time compared with free AA139, survival of all infected rats was not achieved. In relation to this, it should be noted that the pneumonia-septicemia rat model used in this study is representative of multidrug-resistant bacterial infections that are associated with very high mortality rates in patients and are particularly challenging to treat successfully (38). Furthermore, there is published evidence that rats may be more sensitive to the innate immune activation known to be caused by AMPs, including histamine release (39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

“…Bacterial strains. The ESBL-positive strain K. pneumoniae ESBL EMC2003 (referred to in this publication as K. pneumoniae ESBL) used in this study has previously been characterized in terms of its genotype and antimicrobial susceptibility profile and was used to establish pneumonia-septicemia in rats (38). The stability of the plasmid-containing K. pneumoniae ESBL strain was confirmed through five consecutive passages in Mueller-Hinton II (MH-II) broth (Becton, Dickinson BV, Vianen, The Netherlands).…”

Section: Methodsmentioning

confidence: 99%

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Therapeutic Efficacy of Novel Antimicrobial Peptide AA139-Nanomedicines in a Multidrug-Resistant Klebsiella pneumoniae Pneumonia-Septicemia Model in Rats

Weide

Cossío

Gracia

et al. 2020

Antimicrob Agents Chemother

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Antimicrobial peptides (AMPs) have seen limited clinical use as antimicrobial agents, largely due to issues relating to toxicity, short biological half-life, and lack of efficacy against Gram-negative bacteria. However, the development of novel AMP-nanomedicines, i.e. AMPs entrapped in nanoparticles, has the potential to ameliorate these clinical problems. The authors investigated two novel nanomedicines based on AA139, an AMP currently in development for the treatment of multidrug-resistant Gram-negative infections. AA139 was entrapped in polymeric nanoparticles (PNP) or lipid-core micelles (MCL). The antimicrobial activity of AA139-PNP and AA139-MCL was determined in vitro. The biodistribution and limiting doses of AA139-nanomedicines were determined in uninfected rats via endotracheal aerosolization. The early bacterial killing activity of the AA139-nanomedicines in infected lungs was assessed in a rat model of pneumonia-septicemia caused by an extended-spectrum β-lactamase-producing Klebsiella pneumoniae. In this model, the therapeutic efficacy was determined by once-daily (q24h) administration over 10 days. Both AA139-nanomedicines showed equivalent in vitro antimicrobial activities (similar to free AA139) and in uninfected rats they exhibited longer residence times in the lungs compared to free AA139 (∼20% longer for AA139-PNP and ∼80% longer for AA139-MCL), as well as reduced toxicity enabling a higher limiting dose. In rats with pneumonia-septicemia, both AA139-nanomedicines showed significantly improved therapeutic efficacy in terms of an extended rat survival time, although survival of all rats was not achieved. These results demonstrate potential advantages that can be achieved using AMP-nanoformulations. AA139-PNP and AA139-MCL may be promising novel therapeutic agents for the treatment of patients suffering from multidrug-resistant Gram-negative pneumonia-septicemia.

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“…In each group, the dosage of substances used was the same: hBD-3 and Epi-1, 10 mg/kg; and meropenem, 25 mg/kg. Meropenem dosage was chosen in accordance with previous study of H. Van der Weide et al [ 41 ].…”

Section: Methodsmentioning

confidence: 99%

Antimicrobial Peptides Epinecidin-1 and Beta-Defesin-3 Are Effective against a Broad Spectrum of Antibiotic-Resistant Bacterial Isolates and Increase Survival Rate in Experimental Sepsis

Bolatchiev

2022

Antibiotics

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The antimicrobial peptides human Beta-defensin-3 (hBD-3) and Epinecidin-1 (Epi-1; by Epinephelus coioides) could be a promising tool to develop novel antibacterials to combat antibiotic resistance. The antibacterial activity of Epi-1 + vancomycin against methicillin-resistant Staphylococcus aureus (22 isolates) and Epi-1 + hBD-3 against carbapenem-resistant isolates of Klebsiella pneumoniae (n = 23), Klebsiella aerogenes (n = 17), Acinetobacter baumannii (n = 9), and Pseudomonas aeruginosa (n = 13) was studied in vitro. To evaluate the in vivo efficacy of hBD-3 and Epi-1, ICR (CD-1) mice were injected intraperitoneally with a lethal dose of K. pneumoniae or P. aeruginosa. The animals received a single injection of either sterile saline, hBD-3 monotherapy, meropenem monotherapy, hBD-3 + meropenem, or hBD-3 + Epi-1. Studied peptides showed antibacterial activity in vitro against all studied clinical isolates in a concentration of 2 to 32 mg/L. In both experimental models of murine sepsis, an increase in survival rate was seen with hBD-3 monotherapy, hBD-3 + meropenem, and hBD-3 + Epi-1. For K. pneumoniae-sepsis, hBD-3 was shown to be a promising option in overcoming the resistance of Klebsiella spp. to carbapenems, though more research is needed. In the P. aeruginosa-sepsis model, the addition of Epi-1 to hBD-3 was found to have a slightly reduced mortality rate compared to hBD-3 monotherapy.

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Successful High-Dosage Monotherapy of Tigecycline in a Multidrug-Resistant Klebsiella pneumoniae Pneumonia–Septicemia Model in Rats

Cited by 7 publications

References 54 publications

Machine perfusion combined with antibiotics prevents donor-derived infections caused by multidrug-resistant bacteria

Machine perfusion combined with antibiotics prevents donor-derived infections caused by multidrug-resistant bacteria

Therapeutic Efficacy of Novel Antimicrobial Peptide AA139-Nanomedicines in a Multidrug-Resistant Klebsiella pneumoniae Pneumonia-Septicemia Model in Rats

Antimicrobial Peptides Epinecidin-1 and Beta-Defesin-3 Are Effective against a Broad Spectrum of Antibiotic-Resistant Bacterial Isolates and Increase Survival Rate in Experimental Sepsis

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