Abstract
Purpose :
Netilmicin is an aminoglycoside antibiotic indicated for the treatment of bacterial ocular infections of the anterior segment of the eye and ocular adnexa. Combined with dexamethasone, it’s indicated in inflammatory ocular conditions including post-operative cases. Marketed formulations with netilmicin and dexamethasone have a dosing schedule of 4 administrations per day. To predict clinical efficacy of netilmicin when administered 2 (b.i.d.) or 4 (q.i.d.) times a day, killing kinetic experiments were performed against S. aureus (S.a.) and S. epidermidis (S.e.) using a standard and a pulsed protocol to mimic the posology scheme used in human.
Methods :
S.a. 6538 and S.e. 12228 ATCCs grown to reach 108 cfu/ml on supplemented Mueller-Hinton (MH) broth were then diluted to 106 cfu/ml in the same broth containing 32 µg/ml netilmicin. An antibiotic-free control was similarly inoculated.
Standard protocol: at 0, 1, 2, 6, 12 and 24h, 0.1ml was diluted in phosphate-buffered saline, inoculated onto MH agar plates and incubated at 37°C for 24h, to determine viable cfu/ml.
Pulsed protocol: in the b.i.d. regimen, bacteria were exposed to netilmicin at 0 and 12h while in the q.i.d. regimen, 4 exposures were carried out every 4h along the 12h. In both protocols, contact time of bacteria with netilmicin was 2h. At the end of this period, 0.1ml of each sample were processed as above. Data represent mean±SEM of log10 cfu/ml. Statistical analysis were sought by unpaired t-test.
Results :
In the standard protocol, netilmicin showed a bactericidal effect against S.a. at 6h (5 log10 decrease) and this activity is stronger at 12 and 24h (6 log10 decrease). Moreover, netilmicin confirmed bactericidal effect against S.e., and importantly this activity starts 1h after exposure (3 log10 decrease). Data obtained in the pulsed protocol, showed that netilmicin retains its bactericidal effect against S.a. (Fig.1A) and S.e. (Fig.1B) when administered b.i.d. or q.i.d. within 12h (6 log10 decrease) and also at 24h, i.e. after 12h washout.
Conclusions :
Interestingly, pulsed protocol demonstrated that bactericidal effect of netilmicin against Staphylococci is maintained unchanged when administered 2 or 4 times a day. Therefore, in order to reduce the antibiotic resistance and improve the patient’s compliance, the hypothesis to reduce the posology of marketed products containing netilmicin could be taken into account.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.