Postantibiotic effects and postantibiotic sub-MIC effects of tilmicosin, erythromycin and tiamulin on erythromycin-resistant Streptococcus suis

Wang, Liping; Zhang, Yuanshu

doi:10.1590/s1517-83822009000400033

Cited by 4 publications

(3 citation statements)

References 12 publications

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“…Probably, the so called "post-antibiotic sub-MIC effect" (PA-SME) is the phenomenon most closely related to PAEP. In contrast to PAEP, which involves two different agents, PA-SME results in sensitization to an antibiotic at subinhibitory concentrations after exposure to the same compound at concentrations above its MIC [47][48][49][50][51][52]. Similarly, increased bacterial susceptibility to phagocytosis or intracellular killing by leukocytes during the PAE phase was described by McDonald and collaborators, which defined this phenomenon as Post-antibiotic Leukocyte Enhancement (PALE) [53].…”

Section: Discussionmentioning

confidence: 99%

A synthetic peptide sensitizes multi-drug resistant Pseudomonas aeruginosa to antibiotics for more than two hours and permeabilizes its envelope for twenty hours

2020

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Background: Pseudomonas aeruginosa is a Gram-negative pathogen that frequently causes life-threatening infections in immunocompromised patients. We previously showed that subinhibitory concentrations of short synthetic peptides permeabilize P. aeruginosa and enhance the lethal action of co-administered antibiotics. Methods: Long-term permeabilization caused by exposure of multidrug-resistant P. aeruginosa strains to peptide P4-9 was investigated by measuring the uptake of several antibiotics and fluorescent probes and by using confocal imaging and atomic force microscopy. Results: We demonstrated that P4-9, a 13-amino acid peptide, induces a growth delay (i.e. post-antibiotic effect) of 1.3 h on a multidrug-resistant P. aeruginosa clinical isolate. Remarkably, when an independently P4-9-treated culture was allowed to grow in the absence of the peptide, cells remained sensitive to subinhibitory concentrations of antibiotics such as ceftazidime, fosfomycin and erythromycin for at least 2 h. We designated this persistent sensitization to antibiotics occurring in the absence of the sensitizing agent as Post-Antibiotic Effect associated Permeabilization (PAEP). Using atomic force microscopy, we showed that exposure to P4-9 induces profound alterations on the bacterial surface and that treated cells need at least 2 h of growth to repair those lesions. During PAEP, P. aeruginosa mutants overexpressing either the efflux pump MexAB-OprM system or the AmpC β-lactamase were rendered sensitive to antibiotics that are known substrates of those mechanisms of resistance. Finally, we showed for the first time that the descendants of bacteria surviving exposure to a membrane disturbing peptide retain a significant level of permeability to hydrophobic compounds, including propidium iodide, even after 20 h of growth in the absence of the peptide. Conclusions: The phenomenon of long-term sensitization to antibiotics shown here may have important therapeutic implications for a combined peptide-antibiotic treatment because the peptide would not need to be present to exert its antibiotic enhancing activity as long as the target organism retains sensitization to the antibiotic.

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Section: Discussionmentioning

confidence: 99%

A synthetic peptide sensitizes multi-drug resistant Pseudomonas aeruginosa to antibiotics for more than two hours and permeabilizes its envelope for twenty hours

2020

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“…Post-antibiotic effect (PAE) was estimated by incubating bacteria with drug for a period of time and then removal of drug [ 29 ]. First, the bacteria were incubated with 1MIC, 2MIC, 4MIC of drugs for 1 and 2 h; second, the drugs were removed by washing with new medium; third, 100 μL new incubation was sucked up at different time points and counted by plating on TSA.…”

Section: Methodsmentioning

confidence: 99%

PK-PD Modeling and Optimal Dosing Regimen of Acetylkitasamycin against Streptococcus suis in Piglets

Huang¹,

Mao²,

Huang³

et al. 2022

Antibiotics

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Streptococcus suis (S. suis) causes severe respiratory diseases in pigs and is also an important pathogen causing hidden dangers to public health and safety. Acetylkitasamycin is a new macrolide agent that has shown good activity to Gram-positive cocci such as Streptococcus. The purpose of this study was to perform pharmacokinetic–pharmacodynamic (PK-PD) modeling to formulate a dosing regimen of acetylkitasamycin for treatment of S. suis and to decrease the emergence of acetylkitasamycin-resistant S. suis. The minimal inhibitory concentration (MIC) of 110 S. suis isolates was determined by broth micro dilution method. The MIC50 of the 55 sensitive S. suis isolates was 1.21 μg/mL. The strain HB1607 with MIC close to MIC50 and high pathogenicity was used for the PK-PD experiments. The MIC and MBC of HB1607 in both MH broth and pulmonary epithelial lining fluid (PELF) was 1 and 2 μg/mL, respectively. The liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was used to determine the concentration change of acetylkitasamycin in piglet plasma and PELF after intragastric administration of a single dose of 50 mg/kg b.w. acetylkitasamycin. The PK parameters were calculated by WinNolin software. The PK data showed that the maximum concentration (Cmax), peak time (Tmax), and area under the concentration–time curve (AUC) were 9.84 ± 0.39 μg/mL, 4.27 ± 0.19 h and 248.58 ± 21.17 h·μg/mL, respectively. Integration of the in vivo PK data and ex vivo PD data, an inhibition sigmoid Emax equation was established. The dosing regimen of acetylkitasamycin for the treatment S. suis infection established as 33.12 mg/kg b.w. every 12 h for 3 days. This study provided a reasonable dosing regimen for a new drug used in clinical treatment, which can effectively be used to treat S. suis infection and slow down the generation of drug resistance.

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“…Prior to the emergence of S. suis strains, penicillin was the original choice of treatment 13) . Then, macrolides and fluoroquinolones, such as erythromycin, tylosin and enrofloxacin, were considered as the effective substitutes for penicillin because S. suis isolates are historically highly susceptible to these drugs 14) . However, some of the commonly used antibiotics such as erythromycin and enrofloxacin for treatment and prevention of S. suis infections in pigs are becoming less efficient, due to an increase in resistance among S. suis isolates in recent years 1,[15][16][17] .…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Effects of Galla Rhois Extract against Streptococcus suis Infection in Mice

Nam¹,

Yu²,

Park³

et al. 2013

Journal of Food Hygiene and Safety

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Streptococcus suis (S. suis) is a major swine pathogen and an emerging zoonotic agent and is an increasing public health problem across Asia. The present study was undertaken to estimate the antibacterial effect of GR extract and therapeutic effect of GR extract against S. suis infection in mice. At the concentration of GR extract 2.5 mg/ml, the antibacterial effect was not shown on S. suis. However, the antibacterial effect against S. suis was observed at the concentration of GR extract 5.0 mg/ml. Oral administration of GR extract at the dose of 10 mg/kg showed a therapeutic effect for S. suis infected BALB/c mice. The mortality of GR extract-treated mice at the concentration of 5, 10 and 20 mg/kg was 80%, 70%, and 50% at 12 days, respectively, while that of untreated mice was 100% at 8 days after a lethal dose of S. suis infection. The results of our study strongly indicate that GR extract has potential as an effective for S. suis infection in mice.

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Postantibiotic effects and postantibiotic sub-MIC effects of tilmicosin, erythromycin and tiamulin on erythromycin-resistant Streptococcus suis

Cited by 4 publications

References 12 publications

A synthetic peptide sensitizes multi-drug resistant Pseudomonas aeruginosa to antibiotics for more than two hours and permeabilizes its envelope for twenty hours

A synthetic peptide sensitizes multi-drug resistant Pseudomonas aeruginosa to antibiotics for more than two hours and permeabilizes its envelope for twenty hours

PK-PD Modeling and Optimal Dosing Regimen of Acetylkitasamycin against Streptococcus suis in Piglets

Antibacterial Effects of Galla Rhois Extract against Streptococcus suis Infection in Mice

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