狂犬病疫苗-接種對象-目前建議動物咬傷之後打四劑

2023-10-04
疾管署 狂犬病 Q&A
狂犬病Q&A我國疫苗接種時程?
依據世界衛生組織(WHO)公布之狂犬病專家諮詢指引建議，狂犬病疫苗由原先5劑修訂為4劑時程，分別於第0、3、7、14天各接種1劑。
最後更新日期 2018/7/27

哪些遭動物抓咬傷的人，才符合暴露後疫苗接種對象?
臺灣動物狂犬病疫情風險，目前侷限於中、南部及東部山區之野生動物，且以鼬獾為主要的感染動物，少數為白鼻心等，調整暴露後人用狂犬病疫苗適用對象為全國野生哺乳類動物抓咬傷者(除臺東市錢鼠外)，不符適用對象者可採自費接種。
依據農委會88-106年之流浪犬貓狂犬病監測資料，結果皆為陰性，且國內持續推動犬貓動物狂犬病疫苗注射，國內犬貓感染狂犬病毒風險極低，「流浪犬貓咬傷者」比照家犬貓咬傷者，暫不給予疫苗，動物觀察10日內出現疑似狂犬病症狀，並經動檢機關高度懷疑，則給予疫苗。
最後更新日期 2019/5/7

野外與登山醫學-處理撕裂傷(止血.沖洗.清創.縫合)使用無菌手套(相較於一般檢診手套)無法降低傷口感染率

2023-10-17 18:50 
WMS 2014 年發表的傷口基本處置指引
無菌技術無法降低傷口感染率. 使用一般檢診手套, 或使用手術用無菌手套. 之後感染率差不多. 

無菌手套無法降低傷口感染率. 
處理傷口只要選擇乾淨的環境. 不需要製造無菌環境. 
Aseptic technique There is no evidence that sterile, rather than clean, technique decreases the incidence of wound infection after management of lacerations. Studies comparing the use of sterile vs nonsterile gloves for the management of lacerations51,52 or for minor surgery53 have shown no difference in infection rates. 

Recommendation Wounds should be treated using a clean field, including gloves and instruments; sterility is not necessary. Recommendation grade: 1A
2014WMS指引. 引用的研究報告有三篇. 
51. Perelman VS, Francis GJ, Rutledge T, Foote J, Martino F, Dranitsaris G. Sterile versus nonsterile gloves for repair of uncomplicated lacerations in the emergency department: a randomized controlled trial. Ann Emerg Med. 2003;43:362–370. 

52. Creamer J, Davis K, Rice W. Sterile gloves: do they make a difference? Am J Surg. 2012;204:976–980. 

53. Rhinehart MB, Murphy MM, Farley MF, Albertini JG. Sterile versus nonsterile gloves during Mohs micrographic surgery: infection rate is not affected. Dermatol Surg. 2006;32:170–176.


A systematic review of the literature addressing asepsis in wound management
Volume 24 Number 4 – December 2016

下面是用google中文翻譯
過去幾十年來，關於無菌技術在傷口處理中的應用一直存在著廣泛的爭論，理論應用於臨床實踐的方式也經常改變。臨床醫生經常對各種技術的應用方式表示困惑，特別是在維持嚴格無菌本身就很困難的臨床環境中實踐時（例如，基於社區的傷口管理）。傷口清潔、使用開放式但未使用的傷口敷料以及傷口處理設備的存放是臨床醫生經常需要指導的問題。使用喬安娜布里格斯研究所的方法進行了系統性回顧，以確定該主題的科學文獻的現狀，並為該領域實踐建議的製定提供資訊。審查中包含了所有層級的證據，包括意見文件。20 篇量化研究的結果以敘述性總結的形式報告，37 篇質性研究論文的結果以主題綜合的形式總結。儘管確定了關於傷口清潔解決方案的高水準證據，但審查得出的結論是，與傷口護理無菌相關的大多數主題都缺乏科學文獻。

ABSTRACT
There has been extensive ongoing debate on the application of aseptic technique in wound management over the previous decades and changes to the way in which theory is applied to clinical practice have occurred regularly. Clinicians often express confusion over the way various techniques should be applied, particularly when practising in clinical settings in which maintenance of strict asepsis is inherently difficult (for example, community-based wound management). Wound cleansing, use of open but unused wound dressings and storage of wound management equipment are frequent issues on which clinicians request guidance. A systematic review using Joanna Briggs Institute methods was undertaken in order to establish the current state of the scientific literature on this topic and inform the development of recommendations for practice in this field. All levels of evidence were included in the review, including opinion papers. Findings from the 20 quantitative studies were reported in narrative summary and findings from 37 qualitative research papers were aggregated in a thematic synthesis. Although high-level evidence on wound cleansing solutions was identified, the review concluded that there is a paucity of scientific literature on most topics related to asepsis in wound care.

文獻中的定量結果 清潔解決方案和技術 SR 以及探索沖洗液的研究在定量研究中受到了最多的關注。補充資料中的表 1 提供了納入研究的詳細信息，包括其品質和證據水平，可訪問 www.woundsaustralia.com.au/journal/2404.php。由於表 1 中的各個研究 18,19,21,23,26,29 已包含在已確定的 SR 中，因此下面僅報告 SR 結果；然而，沒有一項單獨的隨機對照試驗顯示用無菌溶液清洗的傷口與用自來水清洗的傷口之間的感染率有顯著差異18,19,21,23,26,29。高品質 SR36 對無菌鹽水 (n=326) 和自來水 (n=257) 在清潔撕裂傷、急性和慢性傷口方面進行了比較。兩個隨機對照試驗的總結果顯示，傷口感染率沒有顯著差異，自來水導致感染的可能性稍低（比值比[OR] 0.79，95% 信賴區間[CI] 0.36 至1.72，p=0.55）36 。中等品質的 Cochrane SR33 比較了撕裂傷、開放性骨折、慢性傷口和手術傷口的清潔方法。所有傷口類型（3 個隨機對照試驗）的感染率在自來水清洗和不清洗之間沒有顯著差異（相對風險 [RR] 1.06，95% CI 0.07 至 16.50，p=不顯著 [ns]）。在所有急性縫合傷口（3 個隨機對照試驗）中，自來水與無菌生理食鹽水沖洗之間的感染率沒有差異（RR 0.66，95% CI 0.42 至 1.04，p=ns）。成本效益分析有利於自來水33。這項 Cochrane 綜述得出了與同一研究團隊早期系統綜述相同的結論34,35。低品質 SR 將自來水與無菌鹽水進行了比較。無菌鹽水清洗的傷口明顯較多出現臨床感染（鹽水為 7.1%，自來水為 4.3%，RR 0.62，95% CI 0.39 至 1.01，p=0.05）。培養物呈陽性的傷口沒有顯著差異（鹽水 3.1% 與自來水 4.4%，RR 1.53，95% CI 0.79 至 2.99，p=0.21）31。低品質 SR 比較了術後足部傷口洗澡與不洗澡的情況。正常衛生組在術後 1-5 天進行淋浴 (n=1,639)。放棄足部衛生的患者等到縫線/釘書針拆除後才進行足部衛生（n=511）。任何研究中手術部位感染率均無顯著差異32。儘管注意到了混雜因素（例如，當控制這些因素時，結果並沒有改變。高級證據的結果31,33-36 表明，用自來水清洗傷口不會增加傷口感染率。

Quantitative results from the literature Cleansing solutions and technique SRs and studies exploring irrigation fluids received the most attention in quantitative research. Details of the included studies, including their quality and level of evidence, are provided in Table 1 in the supplementary material accessible at www.woundsaustralia.com.au/journal/2404.php. As the individual studies18,19,21,23,26,29 in Table 1 were included in identified SRs, only SR results are reported below; however, none of the individual RCTs established significant differences in infection rates between wounds cleansed with sterile solutions versus tap water18,19,21,23,26,29. A high quality SR36 compared sterile saline (n=326) to tap water (n=257) for cleansing lacerations, acute and chronic wounds. Pooled results from two RCTs showed no significant difference in wound infection rates, with tap water slightly less likely to result in infection (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.36 to 1.72, p=0.55)36. A moderate quality Cochrane SR33 compared cleansing methods for lacerations, open fractures, chronic and surgical wounds. Infection rate in all wound types (3 RCTs) was not significantly different between tap water cleansing and no cleansing (relative risk [RR] 1.06, 95% CI 0.07 to 16.50, p=not significant [ns]). There was no difference in infection rates in all acute sutured wounds (3 RCTs) between tap water versus sterile saline irrigation (RR 0.66, 95% CI 0.42 to 1.04, p=ns). Cost-effective analyses favoured tap water33. This Cochrane review reached the same conclusions as earlier systematic reviews by the same research team34,35. A low quality SR compared tap water to sterile saline. Significantly more wounds cleansed with sterile saline became clinically infected (saline 7.1% versus tap water 4.3%, RR 0.62, 95% CI 0.39 to 1.01, p=0.05). There was no significant difference in wounds with positive cultures (saline 3.1% versus tap water 4.4%, RR 1.53, 95% CI 0.79 to 2.99, p=0.21)31. A low quality SR compared bathing to no bathing for postsurgical foot wounds. Normal hygiene groups showered at 1–5 days postoperative (n=1,639). Patients abstaining from foot hygiene waited until sutures/staples removal (n=511). There were no significant differences in surgical site infection rates in any study32. Although confounding factors are noted (for example, administration of saline at cooler temperatures than water) when controlled for these factors the outcomes did not change. Findings from the high-level evidence31,33-36 indicated no increase in wound infection rates associated with cleansing wounds in tap water.

清潔溶液與技術 十八個類別被匯總為與傷口清潔相關的六種綜合。合成10：理想的傷口清潔劑應該充分清潔傷口，不會造成細胞損傷或敏感，並且具有較長的保質期。強調無傷害和預防感染的原則作為傷口清潔劑的選擇9。強調了對清潔劑的毒性及其引起敏感性的可能性的考慮42,63。應避免使用過期產品57，選擇保存期限長的傷口清潔劑42,63。有效去除有機材料和減少生物負荷的能力是其他考慮因素42,63。綜合 11：跨專業團隊應進行評估，以確定是否應清潔創床，如果需要，應採用何種清潔流程。並非所有傷口床都需要清潔，因為如果沒有視覺污染物或感染跡象，傷口可以在不受損的情況下癒合39,58。傷口管理團隊可以共同努力確定針對個別患者的最佳方法9,39,58。合成12：生理食鹽水、飲用水、無菌水和低濃度抗菌溶液是安全有效的傷口清潔劑。抗菌劑不是清潔傷口的好選擇。無菌生理食鹽水是一種等滲溶液，對組織修復過程沒有影響42,46；因此，它是一種安全且傳統的選擇62，特別是在醫院環境中46或對於脆弱的傷口9。自來水、無菌水和生理食鹽水均報告為安全；然而，這些解決方案都沒有減少傷口中的生物負荷42,46,56,57,67。抗菌解決方案可減少生物負荷63,67, 儘管應根據潛在的細胞毒性仔細選擇濃度63,67。警告不要在傷口清潔中使用皮膚清潔劑和防腐劑39,42,58,63。細胞毒性42,58,63、潛在致癌性41、與傷口接觸時間不足而無法有效降低細菌水平39以及與抗生素抗藥性細菌39的關聯都是人們關注的問題。合成 13：考慮到交叉感染的可能性，在微溫的溫度下使用傷口清潔劑並使用低壓沖洗創面床 建議使用注射器或水龍頭管在低壓（4 至 15 磅/平方英寸）下沖洗促進碎片清除而不破壞肉芽組織42,56,62,65。在微溫的溫度下塗抹液體可以避免血管收縮，從而降低組織癒合能力9,45,46,54,62,66。淋浴時要考慮病人之間交叉感染的可能性，或是髒身體部位的污染水流過傷口的可能性9,54,58。灌溉時適當引導液體流動54被認為是預防交叉感染的另一種策略。合成 14：優質自來水對於清潔髒傷口、慢性傷口以及閉合或縫合邊緣的傷口來說是一種經濟有效的選擇，儘管它可能會引起疼痛。討論了自來水的優點和缺點39,42,46,54,56,58,62,66。對於縫合傷口 39、骶骨/會陰傷口 56、開放性創傷傷口 56 和慢性傷口 56 以及邊緣密封的傷口 39，水是可以接受的。確保高品質的水很重要54,56,62,66，儘管評論員指出，在擁有受監控和可飲用的自來水的城市中，它對傷口來說足夠安全54,56,62,66。文字建議使用自來水至少 30 秒62 或將傷口浸泡在桶中58。更高、恆定壓力62、大液體量62、病人滿意度66 和減少時間66 是水的優點。缺乏額外的設備（例如注射器）有助於提高水的成本效益46,54,62,66。然而，水可能會因滲透壓增加而引起疼痛46。綜合 15：可以採取預防措施來降低水源潛在污染的風險。另一個缺點是自來水可能受到污染9,41。一位評論員提出，醫院水中存在感染劇毒病原體或生物膜的風險41。對於免疫功能低下的患者來說，這種風險可能更高41。然而，可以採取預防措施41,42,56。水過濾器41、

Cleansing solutions and technique 

Eighteen categories were aggregated into six syntheses related to wound cleansing. Synthesis 10: An ideal wound cleanser should adequately clean the wound, not cause cell damage or sensitivity and have a long shelf life. The principle of doing no harm and preventing infection were highlighted as guiding the choice of wound cleanser9 . Consideration to the toxicity of a cleanser and its potential to cause sensitivity was highlighted42,63. Using an expired product should be avoided57 by selecting a wound cleanser with a long shelf life42,63. The ability to effectively remove organic material and reduce bioburden are other considerations42,63. Synthesis 11: An assessment should be conducted by the interdisciplinary team to determine if a wound bed should be cleansed, and if so, the cleansing process to use. Not all wound beds require cleansing as a wound may heal without disruption if there are no visual contaminants or signs of infection39,58. The wound management team could work together to determine the best approach for individual patients9,39,58. Synthesis 12: Normal saline, potable tap water, sterile water and low concentration antimicrobial solutions are safe and effective wound cleansers. Antiseptics are not a good choice for wound cleansing. Sterile saline is an isotonic solution that has no impact on tissue repair processes42,46; therefore it is a safe and traditional option62, particularly in hospital environments46 or for vulnerable wounds9 . Tap water, sterile water and normal saline were all reported as safe; however, none of these solutions reduces bioburden in the wound42,46,56,57,67. Antimicrobial solutions reduce bioburden63,67, although concentrations should be selected carefully in light of potential cell toxicity63,67. Use of skin cleaners and antiseptics in wound cleansing is warned against39,42,58,63. Cell toxicity42,58,63, potential carcinogenicity41, insufficient contact time with the wound to effectively reduce bacteria levels39 and association with antibiotic-resistant bacteria39 were concerns. Synthesis 13: Apply a wound cleanser at a lukewarm temperature with consideration to the potential for crossinfection and using low pressure to irrigate the wound bed Irrigation at a low pressure (4 to 15 pounds per square inch) using a syringe or faucet tubing is suggested for promoting debris removal without disrupting granulating tissue42,56,62,65. Applying fluid at lukewarm temperature avoids vasoconstriction that lowers tissue healing capacity 9,45,46,54,62,66. The potential for cross-infection between patients, or contaminated water from dirty body areas flowing over a wound are considerations when washing in a shower9,54,58. Directing fluid flow appropriately when irrigating54 was noted as another strategy to prevent cross-infection. Synthesis 14: Good quality tap water is a cost-effective option for cleansing dirty wounds, chronic wounds and wounds with closed or sutured edges, although it may cause pain. Benefits and disadvantages of tap water were discussed39,42,46,54,56,58,62,66. Water was noted as acceptable for sutured39, sacral/perineal56, open traumatic56, and chronic56 wounds, and wounds with sealed edges39. Ensuring high quality water is important54,56,62,66, although commentators noted that in cities with monitored and drinkable tap water it is sufficiently safe for wounds54,56,62,66. Texts suggested using running tap water for at least 30 seconds62 or soaking wounds in a bucket58. Higher, constant pressure62, large fluid volumes62, patient satisfaction66 and reduced time66 are advantages of water. Lack of additional equipment (for example, syringes) contributes to the cost-effectiveness of water46,54,62,66. However, there is potential that water may cause pain due to increasing osmotic pressure46. Synthesis 15: Precautions can be taken to reduce the risk of potential contamination of water sources. Another disadvantage is the potential for contaminated tap water9,41. One commentator suggested a risk of acquiring virulent pathogens or biofilm from hospital water41. This risk may be higher for immunocompromised patients41. However, precautions can be taken41,42,56. Water filters41, running taps for a few minutes before using the water42 and evaluating the water storage and delivery before use9 were suggested.

綜合 17：可以使用非無菌但清潔的設備、溶液和手套對低風險患者進行簡單的傷口處理程序。更複雜的手術或高風險患者的手術需要手術無菌非接觸技術，使用無菌手套、溶液和設備。文本發現涉及清潔技術/標準 ANTT 和無菌技術/手術技術/手術 ANTT。第一種技術適用於常規換藥，無需手術保守性清創和持續不到 20 分鐘的簡單手術37,61,68。據報道，該技術涉及清潔的表面、非無菌手套、清潔的設備和沖洗液（例如自來水）37,61,68。手術 ANTT 需要無菌手套和設備以及無菌沖洗液，並具有嚴格的無菌區域37,56,57，61,68。研究結果表明，該手術適合感染風險高的患者、需要手術保守清創的傷口、具有許多關鍵部位的複雜/侵入性手術或持續時間超過 20 分鐘的手術56,57,61,68。一位評論員建議這應該成為標準做法56。

Synthesis 17: Simple wound management procedures on low-risk patients can be performed with non-sterile but clean equipment, solutions and gloves. More complex procedures or procedures in higher risk patients require surgical aseptic non-touch technique, using sterile gloves, solutions and equipment. Textual findings referred to clean technique/standard ANTT and aseptic technique/surgical technique/surgical ANTT. The first technique is appropriate for routine dressing changes without surgical conservative debridement and simple procedures lasting less than 20 minutes37,61,68. This technique was reported to involve a clean surface, non-sterile gloves and clean equipment and irrigation fluids (for example, tap water)37,61,68. The surgical ANTT requires sterile gloves and equipment and a sterile irrigation fluid, with a strict aseptic field37,56,57,61,68. The findings suggested this procedure was appropriate for patients at high infection risk, wounds requiring surgical conservative debridement, complex/ invasive procedures with many key parts or procedures lasting longer than 20 minutes56,57,61,68. One commentator suggested that this should be standard practice56.

黴菌感染-傳統與新知 Onychomycosis: Old and New 治療時間-劑量-治癒率

2023-10-03 17:28

健保給付規定: 10.6.4. Terbinafine ( 如 Lamisil tab )：(85/1/1、91/4/1、98/8/1)限 1.手指甲癬及足趾甲癬病例使用， 每日 250 mg，手指甲癬限用 42 顆，需於 8 週內使用完畢。足趾 甲癬限用 84 顆，需於 16 週內使 用完畢。治療結束日起算，各在 6 及 12 個月內不得重複使用本品或 其他同類口服藥品。(98/8/1) 2.其他頑固性體癬及股癬病例使 用，每日一次，最長使用 2 週， 治療期間不得併用其他同類藥 品。 3.頭癬病例使用，每日一次，最長使 用 4 週，若確需延長治療時間，須 於病歷詳細載明備查。(98/8/1)

下面使用GOOGLE中文翻譯

口腔治療
甲真菌病的治療有多種選擇（表 2）。口服特比萘芬是美國食品藥物管理局（FDA）核准的治療甲癬最有效的藥物[ 54 ]。對於手指甲和腳趾甲灰指甲，特比萘芬的治療持續時間通常分別至少為六週和十二週。特比萘芬對趾甲甲真菌病患者的完全治癒率在 35% 至 78% 之間變化 [ 16 , 17 , 18 , 55 ]。特比萘芬在涉及非皮癬菌黴菌或酵母菌的甲真菌病中的敏感性尚未得到充分研究[ 56 ]。
特比萘芬脈衝給藥方案的劑量、持續時間和頻率可能有所不同。常見的治療方案是每日兩次特比萘芬 250 mg 脈衝治療方案，持續 4 週，然後停藥 4 週。

Gupta 等人的統合分析。確定連續特比萘芬治療方案在真菌學治癒方面通常優於脈衝給藥。然而，連續給藥和脈衝給藥的完全治癒率相似[ 57 , 58 ]。

口服特比萘芬的其他衝擊療法包括每天 500 mg，持續一周，然後三週不治療，每月重複一次，持續三個月[59 ]。評估成本[ 60 ]和合規性[ 61]的研究] 沒有發現連續療法和脈衝療法之間的差異。然而，由於患者偏好、副作用、共病以及潛在藥物交互作用的風險，脈衝給藥可能是首選[ 57 , 60 ]。
特比萘芬使用的禁忌症包括其與其他由細胞色素 P-450 酶 2D6 代謝的藥物的相互作用。最值得注意的是，美托洛爾屬於此類 cP450 2D6 代謝藥物，因此不鼓勵服用美托洛爾的患者進行特比萘芬治療。

在這些情況下，甲癬的口服治療選擇包括伊曲康唑，一種替代的廣譜抗真菌藥物。伊曲康唑經 FDA 核准用於治療甲真菌病，可有效對抗皮癬菌、酵母菌和非皮癬菌黴菌。

劑量選擇包括

每日 200 毫克的連續治療方案，持續三個月，

或每日 400 毫克的四脈衝治療方案，持續一周，然後暫停藥物治療三週。

伊曲康唑治療的完全治癒率在 14-43% 之間 [ 16, 17、18、19、20 ] 。 _ _ _ _ _ 

另一種二線治療選擇包括口服抗真菌氟康唑。FDA 未核准氟康唑用於治療甲真菌病。然而，臨床試驗已證實其對皮癬菌指甲感染的功效。

氟康唑的典型給藥方案是每週一次 150–450 mg，治療指甲的療程為 6 個月，治療腳趾甲的療程為 12 個月或更長時間 [ 22 , 62 ]。完全治癒率範圍為 21% 至 48%，取決於劑量和治療持續時間 [ 21 , 22 ]。表 2. 目前的口服抗黴菌療法。
抗真菌抗藥性是選擇治療方案時也應考慮的變數。隨著皮癬菌感染隨著時間的推移而演變，口服抗真菌藥物的功效也可能會改變。在最近的一項臨床試驗中，對常用的抗真菌藥物（包括特比萘芬、伊曲康唑和氟康唑）進行了針對慢性和慢性復發性體癬、股癬和麵癬的測試[ 25]。

經過 4 週的治療，所有藥物的治癒率都在 8% 左右或更低。

治療八週後，特比萘芬、伊曲康唑和氟康唑的治癒率分別為 28%、66% 和 42%。

這項研究顯示了抗真菌抗藥性的現實，以及顯示伊曲康唑在特比萘芬抗藥性皮癬菌病中有效的證據。歐洲也有關於毛癬菌屬特比萘芬抗藥性增加的類似報導[ 23 , 24 ]。需要更多的研究來進一步評估多重抗藥性病例的治療方案。

由於口服抗真菌藥物的全身性，在處方這些藥物時應考慮副作用和藥物交互作用。特比萘芬與肝損傷有關。因此，建議在開始治療之前進行肝功能檢查，儘管一些醫生建議在整個特比萘芬治療過程中評估肝功能[ 20 ]。伊曲康唑治療具有很高的藥物交互作用風險，由於其存在心臟衰竭和心律不整的風險，因此在患有心臟病的患者中應謹慎使用[ 63 ]。氟康唑也與高風險交互作用（用作脈衝治療時不多）心血管風險有關，並且據報道可延長 QT 間期 [ 64]。氟康唑的其他副作用包括明顯的先天缺陷，強烈建議在懷孕期間避免使用這種藥物[ 65 ]。

對於沒有預先存在血液學或肝臟異常的成人和兒童，口服抗真菌治療的間隔監測是不必要的[ 66 ]。此後，FDA 取消了在接受口服抗真菌藥物治療時繼續監測肝功能的建議。由於在已有肝臟疾病的患者中藥物性肝損傷的發生率較高，因此劑量調整和持續的間隔監測對這些病例是有益的。

甲下角化症超過 2 毫米且真菌感染涉及外側指甲或超過整個指甲單位 50% 的個體對治療反應較差的比例較高 [15 ]。最近的一些研究表明，艾夫康唑局部治療在這種情況下可能有用[ 51 , 52 ]。鑑於特比萘芬對皮癬菌敏感，混合感染或抗藥性微生物引起的甲癬也與不良預後相關。據報告，在周邊循環減少的情況下，如老年或糖尿病患者，一線口服抗真菌藥物的治療反應不佳。

Onychomycosis: Old and New
Oral Treatments
Several treatment options exist for the treatment of onychomycosis (Table 2). Oral terbinafine is the most effective Food and Drug Administration (FDA)-approved treatment for onychomycosis [54]. Terbinafine treatment duration is typically a minimum of six weeks and twelve weeks for fingernail and toenail onychomycosis, respectively. Terbinafine complete cure rates vary between 35% and 78% in patients with toenail onychomycosis [16,17,18,55]. Terbinafine sensitivity is not well studied in onychomycosis involving non-dermatophyte molds or yeast [56].
Terbinafine pulse dosing regimens can vary in dose, duration, and frequency. A common regimen is two pulse regimens of terbinafine 250 mg daily for four weeks, followed by four weeks off. A meta-analysis by Gupta et al. determined that continuous terbinafine regimen is generally superior to pulse dosing for mycologic cure. However, both continuous and pulse dosing had similar complete cure rates [57,58]. Other pulse regimens for oral terbinafine include 500 mg daily for one week, followed by three weeks of no treatment, repeated every month for three months [59]. Studies assessing cost [60] and compliance [61] did not identify a difference between continuous and pulse regimens. However, pulse dosing may be preferred due to patient preference, side effects, comorbidities, and risk of potential drug–drug interactions [57,60].
Contraindications to terbinafine use include its interaction with other pharmaceuticals that are metabolized by cytochrome P-450 enzyme 2D6. Most notably, metoprolol is among this category of cP450 2D6 metabolized drugs, making terbinafine treatment discouraged in patients taking metoprolol. In these cases, oral treatment options for onychomycosis include itraconazole, an alternative broad-spectrum antifungal. Itraconazole is FDA-approved for the treatment of onychomycosis and is effective against dermatophytes, yeasts, and non-dermatophyte molds. Dosing options include a continuous treatment regimen of 200 mg daily for three months or a four-pulse treatment regimen of 400 mg daily for one week, followed by a three-week pause in drug treatment. Complete cure rate with itraconazole treatment ranges between 14–43% [16,17,18,19,20].
An additional second-line treatment option includes the oral antifungal fluconazole. Fluconazole is not FDA approved for the treatment of onychomycosis. However, clinical trials have established its efficacy in dermatophyte nail infections. Typical dosing regimen of fluconazole is 150–450 mg once weekly for a duration of six months for fingernails and 12 months or more for toenails [22,62]. Complete cure rates range from 21% to 48%, depending on dosage and treatment duration [21,22].
Table 2. Current oral antifungal therapies.
Antifungal resistance is a variable that also should be considered when choosing treatment options. As dermatophytic infections evolve over time, the efficacy of oral antifungals may change, as well. In a recent clinical trial, commonly prescribed antifungals, including terbinafine, itraconazole, and fluconazole, were tested against chronic and chronic relapsing tinea corporis, cruris, and faciei [25]. After four weeks of treatment, all drugs demonstrated a cure rate around 8% or less. After eight weeks of treatment, cure rates with terbinafine, itraconazole, and fluconazole were reported as 28%, 66%, and 42%, respectively. This study indicates the reality of antifungal resistance, as well as evidence suggesting the effectiveness of itraconazole in terbinafine-resistant dermatophytosis. Similar reports of increasing terbinafine resistance in Trichophyton species have been reported in Europe [23,24]. More studies are needed to further assess treatment regimens in multi-drug resistant cases.
Due to the systemic nature of oral antifungal medications, side effects and drug–drug interactions should be considered when prescribing each of these medications. Terbinafine has been associated with hepatic injury. Therefore, liver function tests are recommended prior to starting treatment, although some doctors recommend evaluating liver function throughout the course of terbinafine treatment [20]. Itraconazole therapy carries a high risk of drug interactions and should be used cautiously in patients with cardiac conditions due to its risk of heart failure and arrythmias [63]. Fluconazole is also associated with high risk of interactions (not much when used as pulse treatment) cardiovascular risk and has been reported to prolong the QT interval [64]. Additional side effects with fluconazole include significant congenital defects, and avoidance of this medication during pregnancy is strongly advised [65].
Interval monitoring in oral antifungal treatment is unnecessary in adults and children without preexisting hematologic or hepatic abnormalities [66]. The recommendation for continued hepatic function monitoring while receiving treatment with an oral antifungal has since been removed by the FDA. Due to higher incidence rates of drug-induced liver injury seen in patients with preexisting hepatic conditions, dosing adjustments and continued interval monitoring is beneficial in these cases.
Poor response to treatment is seen at higher rates in individuals with subungual keratosis measuring more than 2 mm and fungal infection involving the lateral nail or over 50% of the entire nail unit [15]. Recently a few studies showed that topical treatment with efinaconazole can be useful in this setting [51,52]. Given the terbinafine sensitivity to dermatophytes, onychomycosis caused by mixed infection or resistant organisms are also associated with poor prognostic outcomes. In the setting of decreased peripheral circulation, as in elderly or diabetic patients, poor treatment response to first-line oral antifungals has been reported.