수술부위 감염 및 예방

* 예방적 항생제
- 대부분의 수술 : Cefazolin
- 복부 수술 : Cefoxitin
- MRSA 관련 수술부위감염 발생률 높거나 페니실린 알레르기 있는 경우 : Vancomycin or Fluoroquinolone
- 수술부위 절개 전 1 시간 이내에 투여 (Vancomycin or Fluoroquinolone 제제는 2시간 이내)
- 대부분의 수술에서 예방적 항생제는 단회 투여가 적합한 것으로 권장됨
- 조직 내 적정 농도를 유지하기 위해 약물의 반감기에 근거하여 재투여 고려

Ref) APSIC SSI Prevention guideline_Korea_Jan 2019

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* 수술 전 투여를 위한 최적의 시간은 수술 절개 전 60분 이내
* fluoroquinolone, vancomycin이나 fluoroquinolone 제제는 1~2시간에 걸쳐 투여해야 하므로 이들 제제의 투여는 수술 절개 전 120분 이내에 시작되어야 함 
* 수술 시간이 약물 반감기의 2배를 초과하거나 과도한 혈액의 손실(>1500ml)이 있는 경우 적절한 혈청 및 조직 농도를 유지하기 위해 수술 중 재투여가 필요

* 수술 예방을 위한 항생제의 공통 원칙: 수술 부위 감염 예방, 수술 부위와 관련된 질병률과 사망률 예방, 의료 비용과 기간 감소, 부작용 없음, 환자나 병원 미생물총에 부작용이 없어야 함
 → 이러한 목표를 이루기 위한 항생제는 수술부위를 오염시킬 가능성이 가장 높은 병원체에 대해 항균력을 가져야 하며, 잠재적 오염 가능한 기간 동안 적절한 용량과 시간에 혈청 및 조직 내 농도를 보장, 안전해야 함, 부작용 및 내성 발생을 최소화하기 위해 최단기간 동안 투여
* 청결 시술 후 수술부위 감염을 일으키는 주요 미생물: S. aureus, Coagulase-negative staphylococci(ex. S.epidermidis)
* 복부 시술 및 심장, 신장 등을 포함 한 청결오염 시술에서는 피부상재균 이외에도 G(-) 및 enterococci에 대해 고려해야 함
* MRSA의 위험이 높을 때 Vancomycin이 흔히 사용되지만, MSSA에 대한 수술부위 예방적 항생제로는 cefazolin이 효과적임.
* 베타락탐계에 알레르기 있는 경우 vancomycin이나 clindamycin 사용 가능
* Staphylococci, Streptococci 이외의 병원체가 있을 가능성이 있는 수술의 경우, 해당 병원체에 대해 활성을 갖는 추가 제제를 고려(그람음성균이 연관된 경우 aminoglycoside(gentamicin or tobramycin), aztreonam, or fluoroquinolone 병용투여)
* 수술 예방적 항생제는 개인 및 기관의 세균총을 변화시킬 수 있고, C. difficile 관련 대장염 발병이 높아질 수 있음. 수술 예방적 항생제의 기간을 수술 전 단일 용량으로 제한하면, C. difficile 관련 대장염의 위험을 감소시킬 수 있음
* 약물 투여
 - 수술 유형에 따라 선호되는 투여 방법이 다르지만, 대부분의 수술에서는 IV투여가 이상적임.
 - Initial dose의 투여는 수술 부위에서 오염이 일어나기 전에 투여되어야 하고, 수술 과정 중 병원체에 대한 최소억제농도(MIC)를 초과하는 혈청 및 조직에서의 농도에 도달할 수 있도록 하는 시점에 미리 투여.
* 약물 용량
 - 소아의 경우 체중 기반의 용량을 설정하지만, 성인의 경우 표준화된 용량으로 투여(비만환자의 경우 증량 가능)
 - gentamicin의 경우 metronidazole과 병용 투여 시 분할 투여보다는 단회 투여가 더 효과적
 - 재투여(redosing) 간격은 수술 시작시점이 아니라 수술 전 용량을 투여한 시점부터 계산. 반감기가 연장된 환자(ex. 신부전 환자)에서는 재투여가 필요하지 않을 수도 있음.
* 약물 투여기간
 - 수술부위 예방적 항생제의 투여 기간은 알려져 있지 않으나, 대부분의 수술에서 투여기간은 24시간 이내여야 함
* S.aureus에 대한 수술 전 검사 및 탈집락화 전략은 수술부위 감염의 발생률을 낮추는 보조적 수단으로 이용(ex. 집락화 환자에게 수술 전 비강 내 mupirocin 투여)
* MRSA 집락화 환자에게 vancomycin 사용 중 그람 음성균에 의한 감염이 일어나면 aztreonam, aminoglycoside 등을 병용 투여(베타락탐계에 알레르기 있는 경우, fluoroquinolone 투여)

* 흉부수술의 경우 cefazolin 또는 ampicillin/sulbactam 단회 투여를 권장

* 맹장수술(충수절제술)의 경우 수술부위 감염에서 분리되는 가장 흔한 미생물은 혐기성 및 호기성 그람음성 장내 세균( Bacteroides fragilis는 일반적으로 배양되는 혐기균, E.coli는 가장 빈번한 호기성균)
 → 혐기성균에 효과 있는 cephalosporin계(cefoxitin 또는 cefotetan 등) 단독 사용 혹은 1세대 cephalosporin(cefazolin)+ Metronidazole 병용
 → 베타락탐 알레르기 환자의 경우 clindamycin과 gentamicin or aztreonam or fluoroquinolone/ metronidazole과 gentamicin or fluoroquinolone
* 소장 수술의 경우 폐쇄의 증거가 없으면 cefazolin, 폐쇄의 경우 cefazolin+metronidazole 혹은 cefoxitin or cefotetan

 

* 수술별 권고 요법

• Cardiac procedures:
  - a single preincision dose of cefazolin or cefuroxime with appropriate intraoperative redosing
  - Clindamycin or vancomycin is an acceptable alternative in patients with a documented b-lactam allergy
• Device implantation or generator replacement in a permanent pacemaker, implantable cardioverter defibrillator, or cardiac resynchronization device:
  - a single dose of cefazolin or cefuroxime
  - Clindamycin or vancomycin is an acceptable alternative in patients with a documented b-lactam allergy
• Thoracic procedures:
  - a single dose of cefazolin or ampicillin–sulbactam is recommended
  - Clindamycin or vancomycin is an acceptable alternative in patients with a documented b-lactam allergy
  - risk of gram negative contamination of the surgical site → combine cefazolin or clindamycin or vancomycin with another agent (aztreonam, aminoglycoside, or single-dose fluoroquinolone if the patient is b-lactam allergic)
• Gastroduodenal procedures:
  - A single dose of cefazolin is recommended
  - Alternative regimens for patients with b-lactam allergy include clindamycin or vancomycin plus gentamicin, aztreonam, or a fluoroquinolone
• Open biliary tract procedures:
  - A single dose of cefazolin should be administered
  - Alternatives include ampicillin–sulbactam and other cephalosporins (cefotetan, cefoxitin, and ceftriaxone).
  - Alternative regimens for patients with b-lactam allergy include clindamycin or vancomycin plus gentamicin, aztreonam, or a fluoroquinolone; or metronidazole plus gentamicin or a fluoroquinolone
• Uncomplicated appendicitis:
  - the recommended regimen is a single dose of a cephalosporin with anaerobic activity (cefoxitin or cefotetan) or a single dose of a first-generation cephalosporin (cefazolin) plus metronidazole
  - For b-lactam-allergic patients, alternative regimens include (1) clindamycin plus gentamicin, aztreonam, or a fluoroquinolone and (2) metronidazole plus gentamicin or a fluoroquinolone (ciprofloxacin or levofloxacin)
• Small bowel surgery without obstruction:
  - the recommended regimen is a firstgeneration cephalosporin (cefazolin)
• Small bowel surgery with intestinal obstruction:
  - the recommended regimen is a cephalosporin with anaerobic activity (cefoxitin or cefotetan) or the combination
  of a first-generation cephalosporin (cefazolin) plus metronidazole
  - For b-lactam-allergic patients, alternative regimens include (1) clindamycin plus gentamicin, aztreonam, or a fluoroquinolone and (2) metronidazole plus gentamicin or a fluoroquinolone (ciprofloxacin or levofloxacin)
• hernioplasty and herniorrhaphy:
  - the recommended regimen is a single dose of a first-generation cephalosporin (cefazolin)
  - For patients known to be colonized with MRSA, it is reasonable to add a single preoperative dose of vancomycin to the recommended agent
  - For b-lactam allergic patients, alternative regimens include clindamycin and vancomycin.
• Colon procedures:
  - A single dose of second-generation cephalosporin with both aerobic and anaerobic activities (cefoxitin or cefotetan)
  or cefazolin plus metronidazole is recommended
  - An alternative regimen is ampicillin–sulbactam
  - Alternative regimens for patients with b-lactam allergies include (1) clindamycin plus an aminoglycoside, aztreonam, or a fluoroquinolone and (2) metronidazole plus an aminoglycoside or a fluoroquinolone. Metronidazole plus aztreonam is not recommended as an alternative because this combination has no aerobic gram-positive activity
• Clean surgical procedures of the head and neck:
  - Antimicrobial prophylaxis is not required
  - If there is placement of prosthetic material, a preoperative dose of cefazolin or cefuroxime is reasonable
  - A reasonable alternative for patients with b-lactam allergies is clindamycin
• Clean-contaminated head and neck procedures:
  - (1) cefazolin or cefuroxime plus metronidazole and (2) ampicillin–sulbactam.
  - Clindamycin is a reasonable alternative in patients with a documented b-lactam allergy. The addition of an aminoglycoside to clindamycin may be appropriate when there is an increased likelihood of gram-negative contamination of the surgical site.
• Clean neurosurgical procedures, CSF-shunting procedures, or intrathecal pump placement:
  - A single dose of cefazolin is recommended
  - Clindamycin or vancomycin should be reserved as an alternative agent for patients with a documented b-lactam allergy (vancomycin for MRSA-colonized patients)
• All women undergoing cesarean delivery:
  - a single dose of cefazolin administered before surgical incision
  - For patients with b-lactam allergies, an alternative regimen is clindamycin plus gentamicin
• Women undergoing vaginal or abdominal hysterectomy, using an open or laparoscopic approach:
  - a single dose of cefazolin. Cefoxitin, cefotetan, or ampicillin–sulbactam may also be used.
  - Alternative agents for patients with a b-lactam allergy include (1) either clindamycin or vancomycin plus an aminoglycoside, aztreonam, or a fluoroquinolone and (2) metronidazole plus an aminoglycoside or a fluoroquinolone
• Clean orthopedic procedures, including knee, hand, and foot procedures, arthroscopy, and other procedures without
  instrumentation or implantation of foreign materials:
  - Antimicrobial prophylaxis is not recommended
• Orthopedic spinal procedures with and without instrumentation:
  - The recommended regimen is cefazolin
  - Clindamycin and vancomycin should be reserved as alternative agents
  - If gram-negative organisms are a cause of SSIs for the procedure → combining clindamycin or vancomycin with another agent (cefazolin if the patient is not b-lactam allergic; aztreonam, gentamicin, or single-dose fluoroquinolone
  if the patient is b-lactam allergic)
  - Mupirocin should be given intranasally to all patients known to be colonized with S. aureus.
• Hip fracture repair or other orthopedic procedures involving internal fixation:
  - The recommended regimen is cefazolin
  - Clindamycin and vancomycin should be reserved as alternative agents
  - If gram-negative organisms are a cause of SSIs for the procedure → combining clindamycin or vancomycin with another agent (cefazolin if the patient is not b-lactam allergic; aztreonam, gentamicin, or single-dose fluoroquinolone
  if the patient is b-lactam allergic)
  - Mupirocin should be given intranasally to all patients known to be colonized with S. aureus.
• Total hip, elbow, knee, ankle, or shoulder replacement:
  - The recommended regimen is cefazolin
  - Clindamycin and vancomycin should be reserved as alternative agents
  - If gram-negative organisms are a cause of SSIs for the procedure → combining clindamycin or vancomycin with another agent (cefazolin if the patient is not b-lactam allergic; aztreonam, gentamicin, or single-dose fluoroquinolone
  if the patient is b-lactam allergic)
  - Mupirocin should be given intranasally to all patients known to be colonized with S. aureus.
• Clean urologic procedures in patients without risk factors for postoperative infections:
  - No antimicrobial prophylaxis is recommended
• Lower urinary tract instrumentation with risk factors for infection:
  - a fluoroquinolone or trimethoprim–sulfamethoxazole (oral or i.v.) or cefazolin (i.v. or intramuscular) is recommended
• Clean urologic procedures without entry into the urinary tract:
  - cefazolin is recommended
  - vancomycin or clindamycin as an alternative for those patients allergic to b-lactam antimicrobials
• Clean urologic procedures with entry into the urinary tract:
  - cefazolin is recommended
  - alternative antimicrobials to include a fluoroquinolone, the combination of an aminoglycoside plus metronidazole, or an aminoglycoside plus clindamycin
• Clean-contaminated procedures of the urinary tract (often entering the gastrointestinal tract):
  - the combination of cefazolin with or without metronidazole, cefoxitin
  - for patients with b-lactam allergy, a combination of either a fluoroquinolone or aminoglycoside given with either metronidazole or clindamycin.
  - The medical literature does not support continuing antimicrobial prophylaxis until urinary catheters have been removed.
• Vascular procedures associated with a higher risk of infection, including implantation of prosthetic material :
  - The recommended regimen is cefazolin
  - Clindamycin and vancomycin should be reserved as alternative agents
  - If gram-negative organisms are a cause of SSIs for the procedure → combining clindamycin or vancomycin with another agent (cefazolin if the patient is not b-lactam allergic; aztreonam, gentamicin, or single-dose fluoroquinolone
  if the patient is b-lactam allergic)
• Lung transplantation:
  - The recommended regimen is a single dose of cefazolin
  - Alternatives include vancomycin with or without gentamicin, aztreonam, and a single fluoroquinolone dose.
  - The prophylactic regimen may also include antifungal agents for Candida and Aspergillus species based on patient
  risk factors for infection (e.g., cystic fibrosis) and colonization, pretransplantation and posttransplantation cultures, and local fungus epidemiology. Patients undergoing lung transplantation for cystic fibrosis should receive treatment for at least seven days with antimicrobials selected according to pretransplantation culture and susceptibility results
• Liver transplantation:
  - (1) piperacillin–tazobactam and (2) cefotaxime plus ampicillin
  - For patients who are allergic to b-lactam antimicrobials, clindamycin or vancomycin given in combination with gentamicin, aztreonam, or a fluoroquinolone is a reasonable alternative.
  - The duration of prophylaxis should be restricted to 24 hours or less.
  - For patients at high risk of Candida infection, fluconazole adjusted for renal function may be considered
• Pancreas or SPK transplantation, Kidney transplantation :
  - The recommended regimen is cefazolin
  - For patients who are allergic to b-lactam antimicrobials, clindamycin or vancomycin given in combination with gentamicin, aztreonam, or a fluoroquinolone is a reasonable alternative.
  - The duration of prophylaxis should be restricted to 24 hours or less.
  - The use of aminoglycosides in combination with other nephrotoxic drugs may result in renal dysfunction and should be avoided unless alternatives are contraindicated.
  - For patients at high risk of Candida infection, fluconazole adjusted for renal function may be considered.
• Clean-contaminated procedures, breast cancer procedures, and clean procedures with other risk factors:
  - a single dose of cefazolin or ampicillin–sulbactam
  - Alternative agents for patients with b-lactam allergy include clindamycin and vancomycin.
  - If gram-negative organisms cause SSIs for the procedure, the practitioner may consider combining clindamycin or vancomycin with another agent (cefazolin if the patient is not b-lactam allergic; aztreonam, gentamicin, or single-dose fluoroquinolone if the patient is b-lactam allergic)
  - Postoperative duration of antimicrobial prophylaxis should be limited to less than 24 hours, regardless of the presence of indwelling catheters or drains.

 
Ref) Clinical practice guidelines for antimicrobial prophylaxis in surgery