社區發作泌尿道感染病人之抗生素治療分析

Retrospective study of antibiotics treatment for patients with community onset urinary tract infection

陳可欣(Ko-Hsin Chen)

指導教授 ： 張上淳

國立臺灣大學/醫學院/臨床藥學研究所/碩士(2013年)

https://doi.org/10.6342/NTU.2013.10185

摘要

研究背景：
泌尿道感染為最常見之感染症之ㄧ。美國與歐洲已發表相關之治療指引，2000年臺灣感染症醫學會也針對臺灣之泌尿道感染制定治療準則，然而與國外之建議多有出入。另一方面，菌種抗藥性比例的上升以及各種醫療照護相關感染的出現，使得病人較容易接受不適當的抗生素治療，導致治療的失敗。此外，急診病人具有某些與門診病人不同之特性，但針對急診泌尿道感染之研究並不多。為了提供臨床上適合於急診泌尿道感染病人之使用抗生素選擇的參考依據，進一步以急診病人作為研究群族是必要的。

研究目的：
分析臺大醫院急診部對於泌尿道感染病人治療，所使用之經驗性抗生素處方型態、致病菌種分布與抗生素敏感性試驗結果，並進一步探討治療結果、比較社區型與醫療照護型感染之差別，最後探討治療失敗之相關因子，以期能找出合理且適合於急診病人使用之經驗性抗生素。

研究方法：
本研究為病歷回溯性研究，研究之病人族群為大於或等於20歲，於2011年3月至5月間曾於臺大醫院急診部就診，經診斷碼且進一步篩選後確認為泌尿道感染，並使用抗生素治療者。紀錄並分析醫師之處方型態、菌種培養結果及抗生素敏感性試驗結果，並比較社區型感染與醫療照護相關型感染於菌種分布及抗生素抗藥性之差別。治療結果以第三天(Day 3, D3)、第七天(Day7, D7) 以及療程結束時(end of therapy, EOT) 之臨床治療反應評估。比較使用不同經驗性抗生素以及使用適當的經驗性抗生素與否之治療結果。最後分析第D3治療失敗之相關因子及cefazolin抗藥性之危險因子。

研究結果：
本研究共收入424人，其中急診返家者為242人，急診住院者為182人。醫師之經驗性抗生素處方中，54%為第一代cephalosporins，19.3%為第二代cephalosporins。急診返家病人中，醫師最常處方cephalexin三天療程；急診住院病人中，醫師最常處方cefazolin治療，然而使用cefazolin的病人，醫師最容易因推定失敗 (含細菌培養結果為cefazolin抗藥之菌種) 而換藥。若病人年齡較大、為醫療照護型感染或複雜型感染、有慢性腎臟病、懷疑合併肺炎或蜂窩性組織炎時醫師可能會優先考慮選用cefazolin及cefmetazole以外的抗生素。
醫療照護相關型感染Escherichia coli比例較社區型感染為低 (41.0% vs 66.1%, p<0.0001)，但感染Pseudomonas aeruginosa (16.7% vs 1.3%, p<0.0001) 與yeast (5.1% vs 0.4%, p=0.0145) 之比例較高。醫療照護相關型感染之菌株在amoxicillin/clavulanate、cefmetazole、cefotaxime、 gentamicin、cefepime、ceftazidime、levofloxacin的抗藥性比例較高。然而兩組病人在D3、D7、EOT之治療結果無顯著差別。
雖然菌株對cefazolin之抗藥性達72%，但使用cefazolin或cefmetazole或其他抗生素作為經驗性抗生素，在D3、D7、EOT之治療結果無顯著差別；使用不適當經驗性抗生素治療的病人，在D3治療成功的比例較低 (51.7% vs 76.4%, p=0.0215)，有70%的病人因治療效果不佳或於得知敏感性試驗結果後換藥，於D7與EOT之治療結果與使用適當經驗性抗生素者無差別。
病人於D3治療失敗的顯著相關因子為阻塞性尿路疾病 (OR=4.395, p=0.0129)、不適當的經驗性抗生素 (OR=4.624, p=0.0126) 及三天內因為推定失敗而換藥(OR=7.051,p<0.0001)。對cefazolin抗藥性之危險因子為存在泌尿道系統外來裝置(OR=10.549, p=0.0223) 或於前一個月使用過第一代cephalosporins (Chi-square, p=0.0221)。

結論：
本研究顯示使用不同經驗性抗生素做治療無顯著差別，推論至急診就醫之病人，可使用cefazolin作為第一線經驗性抗生素治療。但本研究顯示不適當的經驗性抗生素治療會造成早期治療的失敗，因此若病人存在有cefazolin抗藥性菌種之危險因子，如泌尿道系統外來裝置或於前一個月使用過第一代cephalosporins，可考慮使用第二代cephalosporins為第一線治療，以提早讓病人症狀獲得改善。

關鍵字

泌尿道感染 ； 急診 ； 社區發作 ； 經驗性抗生素 ； 醫療照護相關型 ； 治療結果

並列摘要

Background:
Urinary tract infection (UTI) is one of the most common infections. Some treatment guidelines for UTI have already been published by American and European associations. In 2000, The Infectious Diseases Society of Taiwan published guidelines for antimicrobial therapy of UTI in Taiwan, but there are some discrepancies between the recommendations of these guidelines. On the other hand, the increasing resistance of the etiological pathogens and the emergence of healthcare-associated infections may lead to inappropriate antibiotic treatment and treatment failure. Furthermore, there are some significant differences in characteristics and UTI management between outpatients and patients in emergency room (ER), but research in ER patients are rare. So it is crucial to conduct a research of antibiotic treatment of UTI in ER patients.

Objectives:
The aims of this study were to describe the prescription pattern of empirical antibiotics, distribution of the etiological pathogens and their antibiotic resistant rate for UTI patients visiting ER.We also evaluated the treatment outcome of the empirical antibiotic therapy, compared the differences between community-acquired (CA) and healthcare-associated (HCA) UTI, and tried to identify the risk factors for treatment failure. Our final goal is to determine the appropriate empirical antibiotics for UTI patients visiting ER.

Methods:
This is a retrospective, chart-review study. Patients above 20 years old who visited our ER with UTI-related diagnosis and antibiotic treatments during March 1,2011 to May 31, 2011 were included. The prescription pattern, urine culture results, and sensitivity tests were recorded and analyzed. Clinical response rate as treatment outcome were evaluated at Day 3 (D3), Day 7 (D7) and end of therapy (EOT).Treatment outcomes were compared between patient groups with different empirical antibiotics, and between patient groups with appropriate and inappropriate empirical antibiotic use. The risk factors for treatment failure at D3 and cefazolin resistance were conducted by logistic regression.

Results:
Total 424 patients were included, with 242 patients stayed in ER for <48 hours and 182 patients stayed in ER for≧48 hours or admitted to wards. Among the 424 patients, 54% patients received first generation cephalosporins treatment and 19.3% patients received second generation cephalosporins treatment empirically. For patients stayed in ER for <48 hours, physicians frequently prescribed cephalexin for 3 days with the diagnosis of cystitis. For patients stayed in ER for≧48 hours or admitted to ward, physicians frequently prescribed cefazolin with the common diagnosis of acute pyelonephritis. However, physicians tended to upgrade antibiotics from cefazolin to other antibiotics due to presumed failure. In patients who were older or had complicated UTI, HCA UTI, chronic kidney disease, and suspected coinfections such as pneumonia and cellulitis, physicians tended to prescribe antibiotics other than cefazolin and cefmetazole.
Escherichia coli was less common in HCA UTI patients than in CA UTI patients(41.0% vs 66.1%, p<0.0001), but Pseudomonas aeruginosa(16.7% vs 1.3%, p<0.0001) and yeast(5.1% vs 0.4%, p=0.0145) were more frequent in HCA UTI patients. Amoxicillin/clavulanate,cefmetazole, cefotaxime,gentamicin,cefepime, ceftazidime and levofloxacin resistance were more common in HCA UTI bacteruria . However, the treatment outcome at D3, D7 and EOT were not significantly different between CA UTI and HCA UTI patients.
Regarding treatment outcome at D3, D7 and EOT, there were no significant differences between groups with different empirical antibiotics. In the subgroup analysis, there was a lower treatment successful rate at D3 when inappropriate empirical antibiotics were given (51.7% vs 76.4%, p=0.0215). Of patients with inappropriate empirical antibiotics, 70% had changed to another antibiotic according to urine culture sensitivity tests or clinical response. At D7 and EOT, the treatment outcomes were not different between patients received inappropriate empirical treatment and those received appropriate empirical treatment.
Risk factors associated to D3 treatment failure were obstructive uropathy(OR=4.395, p=0.0129), inappropriate empirical antibiotic(OR=4.624, p=0.0126), and change in initial antimicrobial therapy for presumed failure within 3 days(OR=7.051,p<0.0001). Risk factors associated to cefazolin resistance were foreign instruments (OR=10.549, p=0.0223) and first generation cephaslosporins use within previous 1 month (Chi-square, p=0.0221).

Conclusion:
The results showed the treatment outcomes were not different between patient groups with different empirical antibiotics. For UTI patients presenting to ER, cefazolin as the empirical antibiotic is acceptable. Because inappropriate empirical antibiotics may lead to early treatment failure, if patients with risk factors for cefazolin-resistant pathogens, such as foreign instruments or previous use of first generation cephalosporin within 1 month, second generation cephalosporin may be an alternative choice if we want patients to get improved earlier.

並列關鍵字

Urinary tract infection ； emergency department ； community-onset ； empirical antibiotic ； healthcare-associated ； treatment outcome

參考文獻

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