Introduction
The concept that Povidone-Iodine (PVP-I), can support microbial contamination, appears to be a contradiction in terms. After all, how can organisms survive in the very solutions that were created to kill them? The literature indicates that a number of incidences of contaminated Iodophor solutions have occurred over the last 25 years, leading to microbiological investigations.

Action of PVP-I
PVP-I has been classified as Category I (generally considered safe and effective and not misbranded) by the U.S. Food and Drug Administration. The term ‘Povidone-Iodine’ denotes iodophors representing complexes of Polyvinylpyrrolidone (PVP) and Iodine. Free Iodine, the active ingredient in PVP-I, is rapidly lethal to bacteria, fungi, viruses and protozoa. These microbial effects are the result of cell wall penetration, oxidation and substitution of microbial contents with free iodine¹. Combining the free iodine with PVP, allows the solution to be used on skin surfaces without irritation or sensitization.

Incidences of Contamination
The literature reports at least six (6) cases where the presence of Pseudomonas cepacia, or as it is now known, Burkholderia cepacia, as well as other organisms have been isolated from commercially produced iodophor solutions.

1. In 1980, Pseudomonas cepacia was recovered from the blood cultures of 52 patients in four (4) hospitals in New York over seven (7) months.²
2. In 1981, Craven et al, reported on a unique pseudobacteremia in sixteen (16) patients and thirty-five (35) blood cultures in a Boston hospital caused by a 10% PVP-I solution contaminated with P. cepaci.³
3. In 1982, five (5) dialysis patients at an Atlanta Hospital became infected with P. aeruginosa. All patients had indwelling peritoneal catheters which had been wiped with a 4 X4 soaked with a PVP-I solution.⁴
4. In 1989, four (4) more patients had Pseudomonas cepacia isolated from peritoneal fluid and two (2) others had it isolated from their blood at a children's hospital in Texas.⁵
5. In 1999 twenty (20) lots of 3/4 oz PVP-I pouches were recalled for microbial contamination with Pseudomonas putida, Poly D, and Aeromonas sobrai.⁶
6. The most recent and by far the most widely spread incident occurred in March, 2000. This extensive recall involved six (6) different product lines (including PVP-I) in multiple packaging variations. The recalling company confirmed bacterial contamination in some lots of products with Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and coagulase negative Staphylococcus.⁷

In all of these cases, the bacteria were traced to both open and unopened packages and/or bottles of 10% U.S.P. PVP-I solution that had not been terminally sterilized.

Mode of Contamination
How could an effective, broad spectrum, antiseptic solution, such as PVP-I support live, disease causing bacteria?; The most likely mode of contamination is via a manufacturer's water handling system. Although PVP-I manufacturers rely on complex water purification systems that sanitize the water used in formulating PVP-I solution, bacteria can colonize in water distribution pipes, filters, and pumps. Once affixed, P. cepacia and P. aeruginosa can form a biofilm and become protected by a glycocalyx film, or slime layer.⁸ This slime layer can randomly become dislodged and travel with the PVP-I solution to the finished product during the packaging process. Once in the package, this slime layer protects the bacteria from the lethal affects of the Iodine solution.

Prevention
Since the dislodging of this type of bacteria cannot be predicted, the most effective way to address this accidental solution contamination is through a validated terminal sterilization process. Terminal sterilization refers to a process that is performed on every unit of use package manufactured after it has been hermetically sealed. This process renders the solution and applicator (if present) sterile until the package is opened or damaged, thereby eliminating the chance that any viable organisms would be delivered to the patient via the antiseptic agent. Aplicare is currently the only manufacturer that terminally sterilizes every unit dose PVP-I product it manufactures. This includes prep pads, swabsticks and pouches.

These sterile antiseptics are also found extensively in sterile kits and trays, used for procedures requiring aseptic technique. Because the inner contents of packages are not rendered sterile during the kit sterilization process, all aspects of the inner contents of the kit are NOT sterile unless sterile antiseptics are used. Manufacturers are required to state this on their labels as a disclaimer. In other words, the outer packaging of the PVP-I swabstick may be sterile in a dressing change kit, but if the label does not include the word "sterile", the inside is not.

Recently, an outbreak of Burkholderia cepacia was traced to a contaminated hospital water supply which was used to dilute alcohol solutions. Over the course of seven (7) years, 411 cases of B.cepacia bloodstream infections had occurred in 361 patients. The initial outbreak occurred when this contaminated solution was used prior to IV catheter insertion.⁹

Virtually all antiseptic solutions can be subject to bacterial contamination. Terminal sterilization of unit of use packages, wherever possible, is one way to prevent these organisms from finding their way to already compromised patients.