Postantibiotic effect and postantibiotic sub-minimum inhibitory concentration effect of valnemulin against Staphylococcus aureus isolates from swine and chickens

Abstract

Significance and Impact of the Study: In this study, valnemulin demonstrated prolonged postantibiotic effects and postantibiotic sub-MIC effects on strains of Staphylococcus aureus. The strains with identical MICs of valnemulin exhibited different PAEs and PA-SMEs. Staphylococcus aureus isolated from different species has little impact on the postantibiotic effect of valnemulin. The result suggests a longer dosing interval while formulating a daily administration dosage, and it may play a valuable role of valnemulin in treating Staph. aureus infections in animals. AbstractThe postantibiotic effect (PAE) and postantibiotic sub-minimum inhibitory concentration (MIC) effect (PA-SME) of valnemulin against Staphylococcus aureus were investigated in vitro using a spectrophotometric technique and classic viable count method. A standard curve was constructed by regression analysis of the number of colonies and the corresponding optical density (OD) at 630 nm of the inoculum. After exposure to valnemulin at different concentrations for an hour, the antibiotic was removed by centrifuging and washing. The PA-SMEs were measured after initial exposure to valnemulin at 4 9 the MIC, and then, valnemulin was added to reach corresponding desired concentrations in the resuspended culture. Samples were collected hourly until the culture became turbid. The results were calculated by converting the OD values into the counts of bacteria in accordance with the curve. The MIC of valnemulin against eight strains was identically 0Á125 lg ml À1 . The mean PAEs were 2Á12 h (1 9 MIC) and 5Á06 h (4 9 MIC), and the mean PA-SMEs were 6Á85 h (0Á1 9 MIC), 9Á12 h (0Á2 9 MIC) and 10Á8 h (0Á3 9 MIC). The results showed that the strains with identical MICs exhibited different PAEs and PA-SMEs. Valnemulin produced prolonged PAE and PA-SME periods for Staph. aureus, supporting a longer dosing interval while formulating a daily administration dosage.

In vitro activity and post-antibiotic effects of linezolid in combination with fosfomycin against clinical isolates of <em>Staphylococcus aureus</em>

“…In comparison with the contribution of PAE, PA-SME possibly reveals more useful clinical information as a period of subinhibitory concentrations would always exist in vivo, while the drug concentrations in plasma would be less than the MIC because of the process of elimination. 24 …”

Antibacterial Activity and Pharmacokinetic Profile of a Promising Antibacterial Agent: 22-(2-Amino-phenylsulfanyl)-22-Deoxypleuromutilin

“…It could also be observed that amphenmulin showed potent activity against all Gram-positive bacteria, except E. faecalis (ATCC 29212), and pretty weak activity against the Gram-negative bacteria E. coli (ATCC 25922) and S. typhimurium (ATCC 14028). Previous study has shown that valnemulin only showed bacteriostatic effect on Staphylococcus aureus [25]. According to the time-kill curve, amphenmulin belongs to bacteriostatic agents as well.…”

“…As shown in Table 3, amphenmulin displayed a concentration-independent PAE and performed a comparable or longer PAE than tiamulin against MRSA. It indicated that amphenmulin may possess longer dosing intervals, fewer adverse effects, and lower costs while formulating a daily administration dosage [25].…”

Dosage assessment of valnemulin in pigs based on population pharmacokinetic and Monte Carlo simulation

“…Recent studies have clearly shown that the area under the concentration–time curve (AUC) divided by the minimum inhibitory concentration (MIC) (AUC/MIC) is the most important predictive parameter of clinical and microbiological response for glycopeptides (Revilla et al ., ) and quinolones (Tanigawara et al ., ). Previous studies for valnemulin focused on its structure (Tang et al ., ), antibacterial mechanism (Zhang et al ., ), PK (Yuan et al ., ; Xiao et al ., ), antimicrobial activity (Zhao et al ., ) and resistance (Long et al ., ). However, dosage regimen for valnemulin based on PK/PD principles has not been carefully considered.…”