Bactericidal concentration of povidone–iodine

We read with great interest the article by Silas et al.1 and would like additional information regarding the methods used and to further discuss the bactericidal concentration of povidone–iodine. Several studies2–4 have used liquid media, such as a balanced salt solution, and have found povidone–iodine’s bactericidal activity at very dilute concentrations, including concentrations of 0.1% and lower. In addition, the effect was very rapid, with marked bactericidal activity observed after only 15 seconds. Compared with the typical 5.0% preoperative preparation, povidone–iodine 1.0% is certainly more dilute, although much higher than the bactericidal concentration required in these single-application studies using liquid media. Organic substances have been shown to inhibit povidone–iodine,5 and the culture medium (agar plates) could have reduced the available iodine in the more dilute preparations, exhausting its supply before the bacteria were killed. Was a blood agar plate system chosen to better simulate the in vivo environment in which the povidone–iodine is exposed to the organic tissues of the eye? In previous in vitro studies, the povidone–iodine was inactivated using sodium thiosulfate after the dedicated exposure time elapsed; was the povidone–iodine inactivated in the study by Silas et al.? The presence of residual povidone–iodine in the agar plate after the liquid was decanted could have increased the apparent bactericidal activity of the more concentrated solutions by releasing more bactericidal-free iodine over the 24-hour incubation period. Furthermore, the delivery of povidone–iodine to the bacterial cell membrane might be more difficult in an agar plate system, and although some bactericidal-free iodine remained in solution, it might have been unable to reach the bacteria. Did a significant amount of the 2 mL applications of povidone–iodine absorb into the agar plate, or was most of it discarded? Evaluating the decanted fluid to determine its free iodine concentration could help determine whether the iodine was “used up” in the more dilute solutions or was unable to kill the bacteria for some other reason. In addition to factors related to the pharmacokinetics of povidone–iodine in this system, microorganism-specific factors could play a role. The organism used in this study, Staphylococcus epidermidis (RPG2A), is a stock strain originally isolated from a patient with catheter-associated sepsis. It is a virulent organism and an avid slime producer. This might not be representative of the S epidermidis that commonly lives on the eyelids. Hosseini et al. in 2012,6 however, found that several clinical isolates of S epidermidis from endophthalmitis cases could survive exposure to povidone–iodine for extended periods. Was this S epidermidis strain selected to specifically test the ability of povidone–iodine to kill a “high-risk” organism regarding development of endophthalmitis?