藥物警訊

Over-the-Counter Topical Antiseptic Products: Drug Safety Communication - FDA Requests Label Changes and Single-Use Packaging to Decrease Risk of Infection

AUDIENCE: Healthcare Professional, Risk Manager, Pharmacy

ISSUE: The U.S. Food and Drug Administration (FDA) is requesting label and packaging changes to enhance the safe use of certain over-the-counter (OTC) topical antiseptic products. This request is the result of our ongoing evaluation of infrequent but continuing reports of infections resulting from antiseptic products labeled for preoperative or preinjection skin preparation. When used properly, topical antiseptics are safe and effective products to reduce the number of bacteria on patients’ skin prior to surgery or injections. However, most often, contamination of topical antiseptics occurs when organisms are introduced into the product by users. Therefore, health care professionals and patients should follow all label directions to decrease the chances of infection.

Outbreaks associated with the use of contaminated topical antiseptics have been reported in the medical literature and to the Centers for Disease Control and Prevention (CDC). Clinical infections have also been reported to FDA, leading to some product recalls. The reported outcomes ranged from localized infections at injection sites to systemic infections that resulted in death. FDA has reviewed reports of four deaths, five cases of wound infection, seven cases of peritonitis, 10 cases of septic arthritis, 14 cases of indwelling catheters requiring replacement, 16 cases of injection site infection, and 32 cases of bacteremia. These infections have been confirmed to be caused by contaminated antiseptic products. Affected products included all commonly used antiseptic ingredients, including alcohol, iodophors, chlorhexidine gluconate, and quaternary ammonium products. Organisms implicated in the outbreaks included Bacillus cereus, Burkholderia cepacia, Pseudomonas aeruginosa, Achromobacter xylosoxidans, Ralstonia pickettii, Serratia marcescens, and Mycobacterium abscessus.

BACKGROUND: Over-the-counter (OTC) topical antiseptic drugs for use according to the label instructions to reduce the number of bacteria on the skin prior to surgery or injections. When used properly, over-the-counter (OTC) topical antiseptics are safe and effective products to reduce the number of bacteria on the skin prior to surgery or an injection. Commonly used products contain isopropyl or ethyl alcohol, povidone iodine, poloxamer iodine, benzalkonium chloride, benzethonium chloride, or chlorhexidine gluconate as a single agent or in combination with alcohol. These products are marketed as solutions, swabs, pads saturated with a solution, and applicators containing a solution. Currently available as both single-use and multiple-use products. Topical antiseptics are not required to be manufactured as sterile and so may become contaminated with bacteria during manufacturing. Labeling stating a product is sterile means it was treated with a process during manufacturing to eliminate all potential microorganisms. However, even topical antiseptics manufactured with a sterile process, can become contaminated if proper care is not taken when using them. The term nonsterile on the product label means it was not sterilized during manufacturing; it does not mean the product contains harmful bacteria.

RECOMMENDATION: To further reduce the risk of infection with improper topical antiseptic use and the possibility of these products becoming contaminated with bacteria during use, we are requesting that manufacturers package antiseptics indicated for preoperative or preinjection skin preparation in single-use containers.

‧ To reduce the risk of infection, ensure the products are used according to the directions on the label. 

‧ The antiseptics in these single-use containers should be applied only one time to one patient. 

‧ We also recommend that health care professionals and patients do not dilute antiseptic products after opening them. 

‧ Applicators and any unused solution should be discarded after the single application.

For Complete MedWatch Safety Alert including link to Drug Safety Communication and Q&A: 

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHuma...

因手術前或注射前使用皮膚外用消毒劑而感染之報告，雖為罕見但持續出現，因此，美國FDA要求非處方藥之外用消毒劑更改仿單說明及包裝以加強用藥安全。此類產品若適當使用可安全且有效的減少術前或注射前之病人皮膚的細菌數量，然而，若不當使用反可能造成產品汙染。醫療人員以及病人應遵循仿單指示使用以降低感染機會。

醫學文獻及CDC（Centers for Disease Control and Prevention）皆曾有使用受汙染的外用消毒劑而導致感染的報告。FDA也有接獲臨床使用感染之案例，導致部分產品回收。此感染範圍包括注射處產生局部感染到全身性感染，甚至死亡。FDA已接獲4名死亡、5名傷口感染、7名腹膜炎、10名細菌性關節炎、14名需更換導管，16名注射處感染及32名菌血症之案例；這些皆已確認是因為使用了受汙染之消毒劑，如酒精、優碘、氯己定葡萄糖酸鹽（chlorhexidine gluconate）、四級銨（quaternary ammonium）化合物等產品。造成感染的菌種有Bacillus cereus, Burkholderia cepacia, Pseudomonas aeruginosa, Achromobacter xylosoxidans, Ralstonia pickettii, Serratia marcescens, 及Mycobacterium abscessus。

非處方藥之外用消毒劑目前可分為單次和多次劑量使用兩種包裝。此類產品不需無菌，故可能在製程中受到汙染。若仿單說明產品為無菌，表示於製造過程中已去除可能存在的微生物。然而即使為已滅菌處理的外用消毒劑，仍可能因不當使用而受到汙染。未滅菌代表在製程中沒有經過無菌處理，但不表示其含有病菌。

為了進一步減少因不當使用外用消毒劑所造成之感染風險，FDA要求廠商針對用於術前或注射前之外用消毒劑，以單次劑量包裝規格生產。

1. 為了減少感染的風險，請務必依照仿單指示使用。

2. 單次劑量包裝的消毒劑僅限一名病人使用，且只能使用一次。

3. FDA建議醫療人員和病人，勿稀釋開封後之消毒劑。

4. 單次使用後，塗藥工具和剩餘溶液應立即丟棄。

相關訊息與連結請參考FDA網址：http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm374892.htm

資料來源：美國FDA之藥物安全警訊

資料提供：台大醫院藥劑部