급성 담낭염 2018 도쿄 가이드라인... jama

[문형철]

원대 병원 교수시절에 

000 원장님.. 은사님이 급성 담낭염으로 10일간 입원치료

급성담낭염 가이드라인은 담낭제거술을 했을때 항생제 필요하지 않다.

수술이 필요하지 않은 3등급 담낭염에서는 4-7일간만 항생제가 필요하다. 

반코마이신(그람 양성균)

메로페넴(그람 양성균, 음성균) 두가지 항생제만 써도 된다.

그런데..... 

000은사님은 10일간 입원치료를 하면서 항생제를 과도하게 투여한듯하고

퇴원해서도 10일간 항생제 처방을 받으셨다고 한다. 

당연히... 

장내 유익균이 대부분 죽었을 것이고

장내 유익균이 만들어내는 뷰티르산, 프로피온산, 세로토닌 합성, 비타민 b12, 비타민 k 등이 만들어지지 못할 것이다.

무기력하고, 피로하고

하루에 5회씩 허열이 오르면서 잠을 못주무신다고 한다.

건생병사로 어렵지 않게 치료될 것으로 추정된다. 

• When selecting antimicrobial agents, targeted organisms, local antibiograms, pharmacokinetics and pharmacodynamics, renal and hepatic function, any history of prior antimicrobial usage, allergy, and other adverse events should be considered (strong recommendation, very low QOE).

• The optimum duration of antimicrobial therapy for patients with acute cholangitis is 4 to 7 days once source control is obtained (strong recommendation, low QOE).

• For patients with grade I and II acute cholecystitis, antimicrobial therapy only before and at the time of surgery is recommended (strong recommendation, moderate QOE). For patients with grade III acute cholecystitis, antimicrobial therapy for 4 to 7 days is recommended once source control is obtained (weak recommendation, very low QOE). For patients with pericholecystic abscesses or gallbladder perforation, antimicrobial treatment should be continued until the patient is afebrile, has a normal white blood cell count, and is without abdominal findings (strong recommendation, very low QOE)

- 항균제를 선택할 때는 표적 유기체, 국소 항생제, 약동학 및 약력학, 신장 및 간 기능, 이전 항균제 사용 이력, 알레르기 및 기타 부작용을 고려해야 합니다(강력 권고, 매우 낮은 QOE).

- 급성 담관염 환자에 대한 항균 치료의 최적 기간은 원인균을 통제한 후 4~7일입니다(강력 권고, 낮은 QOE).

- 1등급 및 2등급 급성 담낭염 환자의 경우, 수술 전과 수술 시에만 항균 치료를 권장합니다(강력 권고, 중간 정도의 QOE). 3등급 급성 담낭염 환자의 경우, 원인균을 통제한 후 4~7일 동안 항균 치료를 권장합니다(약한 권고, 매우 낮은 QOE). 담낭 주위 농양 또는 담낭 천공이 있는 환자의 경우, 환자가 열이 없고 백혈구 수가 정상이며 복부 소견이 없을 때까지 항균 치료를 계속해야 합니다(강력 권고, 매우 낮은 QOE).

Summary of the Clinical Problem

Timely treatment of acute cholecystitis and cholangitis is necessary to prevent unwanted outcomes. The most important aspect of treatment is source control, but antimicrobial treatment is a necessary and important adjunct. The primary goal of antimicrobial therapy is to limit the systemic septic response and local inflammation and prevent surgical site infection and intrahepatic abscess formation.1 Increasing antimicrobial resistance, particularly owing to extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae, complicates selection of anti-infective agents, making knowledge of local epidemiological data important. Provision of antimicrobial therapy calls for a balance between ensuring adequate treatment of the pathogen(s) and minimizing risk of collateral damage due to excessive antimicrobial administration. Stratifying antimicrobial use based on severity of infection and whether it is a community-acquired or health care–associated infection, deescalating therapy once definitive culture results are available, and limiting duration of therapy when appropriate promote optimal antimicrobial use.

임상 문제 요약

급성 담낭염과 담관염은 

원치 않는 결과를 예방하기 위해 

적시에 치료하는 것이 필요합니다. 

치료의 가장 중요한 측면은 

원인균을 통제하는 것이지만 

항균 치료는 필요하고 중요한 보조 수단입니다. 

항균 치료의 주요 목표는 

전신 패혈증 반응과 국소 염증을 제한하고 

수술 부위 감염과 간내 농양 형성을 예방하는 것입니다.1 

특히 

확장 스펙트럼 β- 락타마제(ESBL)를 생성하는 

장내 세균으로 인한 항균제 내성 증가는 

항감염제 선택을 복잡하게 만들므로 

지역 역학 데이터에 대한 지식이 중요합니다. 

항균 치료를 제공하려면 

병원균에 대한 적절한 치료와 

과도한 항균제 투여로 인한 부수적 피해의 위험을 최소화하는 것 사이의 

균형이 필요합니다. 

감염의 중증도와 지역사회 획득 감염인지 

의료 관련 감염인지에 따라 항균제 사용을 계층화하고, 

확실한 배양 결과가 나오면 

치료를 단계적으로 축소하며, 

적절한 경우 치료 기간을 제한하는 것이 

최적의 항균제 사용을 촉진합니다.

Characteristics of the Guideline Source

This guidelinewas developed by the TokyoGuidelines Revision Committee with support from the Japanese Society of Hepato-BiliaryPancreaticSurgery, JapaneseSociety ofAbdominal EmergencyMedicine, Japanese Society of Surgical Infection, and Japan Biliary Association. A formal conflict of interest policy was followed.

Evidence Base

The guideline committee performed a systematic literature review using PubMed, Cochrane Clinical Controlled Trials, and CochraneDatabase of Systematic Reviews in addition to integrating literature cited in the Tokyo Guidelines 2007 and Tokyo Guidelines 2013. The Tokyo Guidelines Revision Committee then made recommendations using a consensus process and GRADE (Grades of RecommendationAssessment,Developmentand Eval‎uation)methodology. The document provides a thorough literature review generalizable across all patients with acute cholecystitis and cholangitis (Table).

가이드라인 출처의 특징

이 가이드라인은 일본간담도췌장외과학회, 일본복부응급의학회, 일본외과감염학회, 일본담도협회의 지원을 받아 도쿄 가이드라인 개정위원회에서 개발했습니다. 공식적인 이해 상충 정책을 따랐습니다.

증거 기반

가이드라인 위원회는 도쿄 가이드라인 2007 및 도쿄 가이드라인 2013에 인용된 문헌을 통합하는 것 외에도 PubMed, 코크란 임상 대조 시험 및 코크란 체계적 고찰 데이터베이스를 사용하여 체계적 문헌 고찰을 수행했습니다. 그 후 도쿄 가이드라인 개정 위원회는 합의 과정과 GRADE(권고안 평가, 개발 및 평가) 방법론을 사용하여 권고안을 만들었습니다. 이 문서는 모든 급성 담낭염 및 담관염 환자에게 일반화할 수 있는 철저한 문헌 검토를 제공합니다(표).

Benefits and Harms

The Tokyo Guidelines 2018 continue the approach of prior guidelines in recommending a stratified approach to antimicrobial selection and duration of therapy. Regimens having broad-spectrum activity are recommended only for gradeIII community-acquired biliary infections and for health care–associated infections; narrowerspectrum agents are recommended for grade I and II communityacquired infections. The guidelines also emphasize a shorter course of antimicrobial therapy. Both antimicrobial stratification and limited duration of therapy promote antimicrobial stewardship. The guidelines recognize the need for alternative therapies in locales where there is an increased incidence of ESBL-producing and carbapenemase-producing Enterobacteraciae.2The guidelinesalso note that administration of appropriate empirical antibiotics within 1 hour of diagnosis is important in patients with sepsis and septic shock.3

혜택과 해로움

도쿄 가이드라인 2018은 

항균제 선택과 치료 기간에 대한 계층화된 접근 방식을 권장하는 

이전 가이드라인의 접근 방식을 이어갑니다. 

광범위한 활성을 가진 요법은 3등급 지역사회 획득 담도 감염과 의료 관련 감염에만 권장되며, 1등급 및 2등급 지역사회 획득 감염에는 좁은 스펙트럼의 약제가 권장됩니다. 

이 지침은 또한 

항균제 치료 기간을 

단축할 것을 강조합니다. 

항균제 계층화와 제한된 치료 기간 모두 

항균제 관리를 촉진합니다. 

가이드라인은 

ESBL 생성 및 카바페네마제 생성 장내세균의 발생이 증가하는 지역에서는 

대체 요법의 필요성을 인정합니다.2 

또한 패혈증 및 패혈성 쇼크 환자에게는 

진단 후 1시간 이내에 

적절한 경험적 항생제를 투여하는 것이 중요하다고 지적합니다.3

Although the guidelines support theconcept ofantibioticdeescalation once definitive culture results are available, this was not explicitly stated in the actual recommendations. This might lead practitioners to continue broad-spectrum antimicrobial therapy when not necessary,potentiallyharming thepatientand thecommunityatlarge. The recommended use ofvancomycin plus piperacillin-tazobactam in patientswithhealthcare–associatedbiliaryinfectionsmaybedetrimental, as this combination has been shown to be associated with increased nephropathy.4 The guidelinealsomentions using piperacillintazobactam to treat resistant ESBL-producing Escherichia coli and Klebsiella spp. However, in 2018, piperacillin-tazobactam was shown not tobenoninferior for 30-daymortalitycomparedwithmeropenem forbacteremiadue toESBL-producingEcoliorKlebsiellapneumoniae. 5 Therefore,acombinationofvancomycinandmeropenemmaybeabetter alternative for those patients in whom these are concerns.

가이드라인은 확정적인 배양 결과가 나오면 

항생제 증량이라는 개념을 지지하지만, 

실제 권고안에는 명시적으로 언급되지 않았습니다. 

이로 인해 

의료진이 필요하지 않은 경우에도 

광범위한 항균 치료를 계속하여 

환자와 지역사회에 해를 끼칠 수 있습니다. 

의료 관련 담도 감염 환자에게 

반코마이신과 피페라실린-타조박탐을 병용하는 것은 

신증 증가와 관련이 있는 것으로 밝혀졌기 때문에 해로울 수 있습니다.4 

가이드라인에서는 

내성 ESBL 생성 대장균 및 클렙시엘라균 치료에 

피페라실린타조박탐을 사용할 것을 권고하고 있습니다. 

그러나 

2018년에 피페라실린타조박탐은 

메로페넴에 비해 

ESBL 생성 에코리엘라 폐렴균에 대한 30일 사망률에 대해 비열등하지 않다는 것이 밝혀졌습니다. 5 

따라서 

반코마이신과 메로페넴을 병용하는 것이 

이러한 우려가 있는 환자에게 더 나은 대안이 될 수 있습니다.

Discussion

The TokyoGuidelines 2018 on antimicrobial therapy for patientswith biliary infections represent an ongoing evolution of the 2007 and 2013 guidelines. Stratification of antimicrobial therapy is emphasized, recommending that patients with grade III communityacquired and health care–associated acute cholecystitis and cholangitis be treated with broad-spectrum therapy, including agents with activity againstPseudomonas aeruginosa and enterococci. The increasing preval‎ence of resistant Enterobacteriaceae in many locales necessitates knowledge of local resistance patterns to ensure optimal empirical antibiotic choice. Although newer antimicrobial agents are now available, these have not been well studied in biliary tract infections. Although not explicitly stated, antimicrobial deescalation is important when using broader-spectrum regimens to limit development of resistance. For most patients, limited duration of antimicrobial therapy should now be the standard. Patients who undergo cholecystectomy for grade I and II acute cholecystitis usually do not need postoperative antibiotics.6 Postoperative antibiotics are recommended for 4 to 7 days for patients with grade III cholecystitis, although 4 days should be adequate based on the results of the Study to Optimize Peritoneal Infection Therapy trial.7 Patients with cholangitis should be treated for 4 to 7 days following biliary decompression if source control is achieved, but there are few data to support duration of therapy in these patients.

Areas in Need of Future Study or Ongoing Research

Ongoing research is needed to assess the efficacy of new antibiotic regimens in the treatment of acute cholecystitis and cholangitis, especially in areas with high levels of bacterial resistance. In addition, while the duration of antimicrobial therapy is shorter than previously used, further studies should test if this can be decreased further without causing harm while also identifying patients who might warrant longer therapy. This should be investigated in patients undergoing subtotal cholecystectomy who may have continued external bile drainage for several days after the procedure.

담도 감염 환자의 항균 치료에 관한 도쿄 가이드라인 2018은 2007년과 2013년 가이드라인을 지속적으로 발전시킨 것입니다. 항균 치료의 계층화가 강조되어 3등급 지역사회 획득 및 의료 관련 급성 담낭염 및 담관염 환자는 녹농균 및 장구균에 대한 활성이 있는 약제를 포함한 광범위한 요법으로 치료할 것을 권장합니다. 

많은 지역에서 내성 장내세균의 유병률이 증가함에 따라 

최적의 경험적 항생제 선택을 보장하기 위해 

지역 내성 패턴에 대한 지식이 필요합니다. 

현재 새로운 항균제가 출시되었지만, 담도 감염에 대한 연구는 제대로 이루어지지 않았습니다. 명시적으로 언급되지는 않았지만, 내성 발생을 제한하기 위해 광범위한 요법을 사용할 때는 항균제 감량 요법이 중요합니다. 

대부분의 환자에게는 

이제 항생제 치료 기간을 제한하는 것이 표준이 되어야 합니다. 

1, 2등급 급성 담낭염으로 담낭 절제술을 받은 환자는 일반적으로 수술 후 항생제가 필요하지 않습니다.6 

3등급 담낭염 환자의 경우 수술 후 항생제는 4~7일 동안 투여하는 것이 권장되지만, 복막 감염 치료 최적화 연구 시험 결과에 따르면 4일이 적절할 수 있습니다.7 

담관염 환자는 담도 감압 후 원천 조절이 달성되면 4~7일 동안 치료해야 하지만 이러한 환자에서 치료 기간을 뒷받침하는 데이터는 거의 없습니다.

향후 연구 또는 지속적인 연구가 필요한 분야

급성 담낭염 및 담관염 치료, 특히 박테리아 내성이 높은 영역에서 새로운 항생제 요법의 효능을 평가하기 위해서는 지속적인 연구가 필요합니다. 또한 항균 치료 기간이 이전에 비해 짧아졌지만, 추가 연구를 통해 해를 끼치지 않고 더 줄일 수 있는지 테스트하는 동시에 더 긴 치료가 필요할 수 있는 환자를 식별해야 합니다. 이는 담낭절제술을 받은 환자 중 시술 후 며칠 동안 외부 담즙 배액을 계속할 수 있는 환자를 대상으로 조사해야 합니다.