대한정형외과학회지 : 제 38 권제 7 호 2003 J. of Korean Orthop. Assoc. 2003; 38: 771-5 정형외과수술후감염환자의균동정 조명래 김철 손정환 김재도 고신대학교의과대학정형외과학교실 목적 : 수술후감염환자의균동정을통하여항생제투여에있어서 Cephalosporin 단독투여에대한문제점과균배양결과가없는환자에서항생제선택에대해관찰해보고자한다. 대상및방법 : 1998년 1월부터 2002년 5월까지인공관절이나종양대치물로수술적처치를시행받은환자와타의료기관에서수술후급성감염으로본원에전원된환자 18예를대상으로하였다. 수술전항생제는수술 1시간전에제 1세대세파계항생제를정맥주사하였고, 수술후급성또는만성으로감염이발생한전예에서균동정과균의항생제에대한감수성검사를실시하였다. 결과 : 그람양성균이 15예 (83%) 였으며그중황색포도상구균이 13예 (72%) 로가장많았다. 수술후급성으로발생한감염환자에서는그람양성균이 8예 (80%) 로가장많았으며만성감염환자에서는황색포도상구균이 7예 (88%) 로가장많았다. 항생제감수성검사결과 Vancomycin, Teicoplanin, Ciprofloxacin이광범위한감수성을보였다. 결론 : 수술후감염의원인균은주로포도상구균이므로감염방지를위하여는포도상구균에감수성이높은항생제를투여하는것이바람직하다. 그러나감염이발생한경우에는세파제는감수성이떨어지고, Ciprofloxacin에대한감수성은높았으므로, 특히균이동정되지않는감염에서는 Ciprofloxacin의선택이유용하리라판단된다. 색인단어 : 감염, 포도상구균, 셰파계항생제, Ciprofloxacin Identification of Bacteria in Postoperative Infections after Orthopaedic Surgery Myung Rae Cho, M.D., Chul Kim, M.D., Jung Wan Son, M.D., and Jae Do Kim, M.D. Department of Orthopaedic Surgery, Kosin University Gospel Hospital, Busan, Korea Purpose: By identifying micro-organism in postoperative patients, we evaluated problems associated with the use of cephalosporin for the prevention of infection, and antibiotic choice in cases, in which causative micro-organisms cannot be islolated. Materials and Methods: Eighteen patients, from January 1998 to May 2002, who received arthroplasty, were studied. All cases were administered preoperative first generation cephalosporin one hour before operation. All patients with infection had micro-organisms identified received an antibiotic sensitivity test. Results: Gram positive cocci were identified in fifteen cases (83%) (staphylococcus was the most common (72%)), and there were eight cases (80%) in acute infections and seven (88%) in chronic. 78-83% were sensitive to vancomycin, teicoplanin and ciprofloxacin, but only 17% were sensitive to cephalothin. Conclusion: Staphylococcus was found to be the most common organism in postoperative infection, and ciprofloxacin was more effective than cephalosporin. Ciprofloxacin is considered to be an effective antibiotic in patients with unidentified causative organisms. Key Words: Infection, Staphylococcus, Cephalosporin, Ciprofloxacin 정형외과수술에있어서수술전, 수술후항생제사용은감염의방지를위해매우중요하다. 수술후에급성으로발생하는감염의중요한원인은세균이환자자신또는수술실내의공기로부터수술부위로침투되며, 특히수술할때에존재할수있는괴사물 (necrotic materials), 허혈 (ischemia), 출혈 (hemorrhage), 파편 (debris) 등이감염의가능성을증가시킨다. 따라서수술후감염환자에서처음균접촉시점은대부분의경우에서수술중에발생하기때문에수술전에항생제를투여하여수술중적절한농도를유지함으로써감염의가능성을감소시킨다는것은이미여 러연구에서보고되었다 1,4,10,12). 그러나균의내성발생빈도를감소시키기위한최대한의노력으로수술전에이용되고있는항생제는그람양성균및다양한그람음성균에효과적인것으로알려져있는제 1세대세파계를주로투여한다. 저자들은관절치환술과종양대치물삽입술을시술받은후감염된환자에서균동정과균에대한항생제감수성검사결과를조사하여예방적인목적으로투여되는항생제인세파계단독투여의문제점과감염환자의항생제선택에대하여알아보고자한다. 통신저자 : 조명래부산광역시서구암남동 34 고신대학교복음병원정형외과 TEL: 051-990-6467 FAX: 051-243-0181 E-mail: cmr0426@lycos.co.kr Address reprint requests to Myung Rae Cho, M.D. Department of Orthopaedic Surgery, Kosin University Gospel Hospital 34 Amnam-dong, Suh-gu, Busan 602-702, Korea Tel: +82.51-990-6467, Fax: +82.51-243-0181 E-mail: cmr0426@lycos.co.krr 771
772 조명래 김철 손정환외 1 인 대상및방법 1998년 1월부터 2002년 5월까지본원정형외과교실에서종양대치물치환술과고관절및슬관절치환술을시술받은환자 272 예중감염이확인되어수술적처치를받은 16예와타의료기관에서수술을받은후급성감염으로본원으로전원된 2예 (Table 1. 증례 15, 17) 를포함하여 18예를대상으로하였다. 모든환자는수술시작 1시간전에세파계인 shincef 1.5 g ( 소아 : 25-30 mg/kg) 또는 cefmetazone을 1회정맥주사하였다. 남자가 9예, 여자가 9예였으며연령별분포는다양하였고, 평균연령은 38세였다. 내원당시환자의진단은종양이 10예로가장많았으며그중골육종이 6예였고, 연골육종, 유잉육종, 거대세포종, 연골아세포종이각각 1예였다. 그리고슬관절골관절염이 2예, 대퇴골두무혈성괴사 2예, 류마티스관절염, 방사선조사후골괴사, 전자간골절, 대퇴경부골절이각각 1예였다 (Table 1). 수술적처치는모든종양환자는광범위절제술및종양대치물 HMRS (Howmedica Modular Resection System, Rutherford, New Jersey) 삽입술을시술받았고, 골관절염, 대퇴골두무혈성괴사, 류마티스관절염, 방사선조사후골괴사, 전자간골절, 대퇴경부골절환자들은모두인공관절치환술을시술받았다. 골육종6예와유잉육종 1예는수술전과수술후에항암화학요법을시행하였고, 수술은수술전혈액검사에서백혈구, 혈소판등수술시행기준에부합된상태에서시행하였다. 감염발현시기는 10예에서는수술후급성감염이었고, 8예는만성혈액성감염이었다. 감염의진단은부종, 동통, 열감, 배농, 발적등임상적인소견과백혈구수치, ESR, CRP 등의혈액검사와관절천자, 조직검사에의한균동정및조직학적소견에따랐다 (Table 3). 모든환자에서균동정및항생제감수성검사를실시하였고, 치료도중에균검사결과에서균의종류가바뀐경우에는처음동정된균과항생제감수성검사의결과에따랐다. 감염이발생한환자는수차례소파술, 변연절제술, 세척술등여러가지방법을시술받았으며, 급성, 만성감염의모든환자에서결국구조물을제거한후항생제를포함한시멘트를삽입하고재건술을시술받았다. 다만방사선조사후발병한골괴사환자 1예에서는구조물제거술만시행하였고재건술은시행하지않았다. 혈액검사상백혈구수치와 CRP가정상이며, ESR이정상또는감소하는상태에서, 또수술시에동결조직검사에서중성백혈구개수가 400배확대상에 5개미만인것을확인하고시행하였다. 재건술은항생제사용은감수성검사결과에따랐고, 수술후항생제는혈액검사가정상으로될때까지정맥주사하였고, 경구투여는최소 6주이상실시하였다. 재삽입술을시행받은 17예중종양대치술을시술받은 3예는계속적인재발로현재재삽입된구조물을다시제거하고항생제를혼합한골시멘트가삽입된상태로관찰중이다. 결과그람양성균이 15예 (83%) 였고, 그중포도상구균이 13예 (72%) 였다. Coagulase 음성인포도상구균이 8예 (44%) 였고, 황색포도상구균이 5예였으나, MRSA나 VRSA (superbacteria) 는없었다. 녹농균이 4예, Burkholderia cepacia가 2예, 연쇄상구균이 2예였고, 혼합감염 ( 황색포도상구균과 Burkholderia cepacia, 황색포도상구균과녹농균 ) 이 5예였으며, 1예에서는수차례의배양검사에도불구하고균이검출되지않았다. 수술후에급성으로감염이발생한 10예에서는그람양성균과그람음성균의단독감염이각각 6예 (60%), 2예 (20%) 였고, 혼합감염 2 Table 1. Patient Data Cases Age Diagnosis Index Operation Interval* 1 24 Osteosarcoma, Tibia Wide Excision and Tumor Prosthesis (HMRS) 72 Months 2 21 Osteosarcoma, Femur Wide Excision and Tumor Prosthesis (HMRS) 27 Months 3 18 Osteosarcoma, Tibia Wide Excision and Tumor Prosthesis (HMRS) 3 Weeks 4 10 Osteosarcoma, Tibia Wide Excision and Tumor Prosthesis (HMRS) 4 Weeks 5 19 Osteosarcoma, Femur Wide Excision and Tumor Prosthesis (HMRS) 12 Months 6 16 Osteosarcoma, Femur Wide Excision and Tumor Prosthesis (HMRS) 13 Months 7 42 Chondrosarcoma, Tibia Wide Excision and Tumor Prosthesis (HMRS) 9 Months 8 18 Ewing s Sarcoma, Femur Wide Excision and Tumor Prosthesis (HMRS) 24 Months 9 30 Giant cell Tumor, Femur Wide Excision and Tumor Prosthesis (HMRS) 6 Weeks 10 60 Chondroblastoma, Tibia Excision and Tumor Prosthesis (HMRS) 4 Weeks 11 75 Osteoarthritis, Knee Total Knee Arthroplasty 3 Weeks 12 33 Osteoarthritis, Knee Total Knee Arthroplasty 7 Months 13 54 AVN, Femoral Head Total Hip Arthroplasty 4 Weeks 14 42 AVN, Femoral Head Total Hip Arthroplasty 5 Months 15 42 Rheumatoid Arthritis, Hip Total Hip Arthroplasty 4 Weeks 16 49 Osteoradionecrosis, Hip Total Hip Arthroplasty 3 Weeks 17 60 Intertrochanteric Fracture Bipolar Arthroplasty 3 Weeks 18 75 Fracture, Femoral Neck Bipolar Arthroplasty 5 Weeks Abbreviation: HMRS, Howmedica Modular Resection System. *Interval means the period between index operation and infection, Index operation was performed at other hospital.
정형외과수술후감염환자의균동정 773 Table 2. Patient Data Cases Signs of Infection Micro-organisms Sensitivity Treatment Clin.* Lab. Procedures 1 + + + Coagulase (-) Staph. Van., Tei., Clin. Staged Operation 2 + + + Coagulase (-) Staph. Van., Tei., Clin., Cip., Bac., Fus., Imi., Staged Operation Pseudomonas aeruginosa Cip., Cef., Ceft., Pip., Gam. 3 + + + Staphylococcus aureus Van., Tei., Fus., Oxa. Staged Operation 4 + + + Staphylococcus aureus Van., Tei., Clin., Cip., Cep., Staged Operation Bac., Ery., Fus., Pip., Oxa. 5 + + + Coagulase (-) Staph. Van., Tei., Clin., Cip. Staged Operation 6 + + + No Growth Staged Operation 7 + + + Coagulase (-) Staph. Van., Tei., Clin., Cip., Bac. Staged Operation 8 + + + Coagulase (-) Staph. Van., Tei., Clin., Cip., Ery., Oxa. Staged Operation Pseudomonas aeruginosa Ami., Cip., Cef., Ceft., Pip., Bac. 9 + + + Burkholderia cepacia Cip., Cef., Imi., Pip., A/S., Gam. Staged Operation 10 + + + Streptococcus agalactiae Van., Tei., Cep., Ery. Staged Operation 11 + + + Streptocccus durans Van., Tei. Staged Operation 12 + + + Coagulase (-) Staph. Van., Tei., Clin., Cip., A/S., Ery. Staged Operation Pseudomonas aeruginosa Cip., Cef., Ceft., Pip., A/S. 13 + + + Coagulase (-) Staph. Van., Tei., Cip., Imi., A/S. Staged Operation 14 + + + Coagulase (-) Staph. Van., Tei., Cip. Staged Operation 15 + + + Staphylococcus aureus Van., Tei., Clin. Staged Operation Burkholderia cepacia Bac., Pip., Oxa. 16 + + + Comanos acidovorans Cip., Cef., Ceft., Imi., Pip. Resection Arthroplasty 17 + + + Staphylococcus aureus Van., Tei., Bac., Fus. Staged Operation Pseudomonas aeruginosa Cip., Imi., Oxa. 18 + + + Staphylococcus aureus Van., Tei., Clin., Cip., Imi., Oxa. Staged Operation Abbreviations: Ami., amikacin; A/S, ampicillin/sulbactam; Bac., bactrim; Cep., cephalothin; Cef., cefoperazone; Ceft., ceftazidime; Cip., ciprofloxacin; Clin., clindamycin; Ery., erythromycin; Fus., fusidic acid; Gam., gentamycin; Imi., imipenem; Oxa., oxacillin; Pip., piperacillin; Tei., teicoplanin; Van., vancomycin. *Clin.: Clinical symptoms such as swelling, heatness, fistula, and erythematous change. Lab.: Laboratory findings (ESR, CRP, Leukocyte count). Procedures include aspiration (with Gram stain and culture) and biopsy. + means the existence of clinical symptoms and elevation of inflammatory reactants. Staged operation: Implant removal, insertion of cement with antibiotics and reimplantation. Table 3. Identification of the micro-organisms in acute post-operative and chronic infections Micro-organisms Acute (No.*) Chronic (No.) Total (No.) Staphylococcus aureus 5 5 coagulase negative 1 7 8 Pseudomonas aeruginosa 1 3 4 Burkholderia cepacia 2 2 Streptococcus agalactiae 1 1 durans 1 1 Comanos acidovorans 1 1 No growth 1 1 Mixed infection 2 3 5 *No.: Number. 예를포함시킨경우에그람양성균의감염은 8예 (80%) 였다. 만성감염환자 8예에서는그람양성균의단독감염이 5예 (63%) 였으나그람음성균의단독감염은없었고, 혼합감염 3예를포함한경우에그람양성균은 7예 (88%), 그람음성균은 3예 (38%) 였다. 특히만성감염환자에서배양된그람양성균은모두 Coagulase 음성인포도상구균이었다 (Table 3). 동정된균의항생제감수성 Table 4. Antibiotic sensitivity of micro-organisms in acute and chronic infection Antibiotics Acute organisms Chronic organisms Vancomycin 8 7 Teicoplanin 8 7 Ciprofloxacin 5 9 Clindamycin 3 6 Piperacillin 4 3 Bactrim 3 3 Cefoperazone 2 3 Ceftazidime 2 3 Table 5. Antibiotic sensitivity of micro-organisms Antibiotics Number Vancomycin 15 Teicoplanin 15 Ciprofloxacin 14 Clindamycin 9 Cephalothin 3 Cefoperazone 5 Ceftazidime 5
774 조명래 김철 손정환외 1 인 검사에서는반코마이신과 Teicoplanin이감염된증례의 83% 에서감수성을가졌고, Ciprofloxacin이 78% 에서감수성을보였으나, 제 1세대세파제인 Cephalothin은 17% 에서만감수성이있었다. 수술후급성으로감염된환자에서는반코마이신과 Teicoplanin 이 80%, Ciprofloxacin은 50% 에서감수성을보였고, 만성감염환자에서는 Ciprofloxacin이전예에서감수성이나타났고반코마이신과 Teicoplanin도 88% 에서감수성을보였다 (Table 4, 5). 고찰수술후감염의주원인은환자의피부, 비뇨생식기계통, 수술실내의공기로부터발생하는데청결수술에서는감염률이 5% 미만이고, 청결-오염 (clean-contaminated) 수술의경우는감염률이 10% 정도가되며, 청결- 불결 (contaminated-dirty) 수술의경우는 20-40% 의감염률을보고하고있다 7). 수술후감염의방지를위해서는 Laminar flow system, 개개인격리, 자외선소독, 이중장갑착용, 수술실내의대인접촉주의, 대화금지등공기로부터균의접촉을막기위한방법과항생제사용이있다. 감염의예방을위한항생제사용은초기에는논란이많았으나 Burke 등의보고에따르면수술적처치를시행할때균의접촉에대한환자의균에대한저항을고려하여항생제의예방적처치가필요하며현재까지널리이용되고있다 2,4). 또한수술후감염의처음시작은수술중에균의접촉으로발생하므로수술전에항생제를투여하여수술시균의접촉이있을때균의증식을막도록수술중에적당한항생제의농도가유지되어야하는데수술전 60분에주사하는것이적당한것으로보고되고있다 7). 사용되는항생제의종류와항생제사용기간에대하여도논란이많다. 광범위항생제를장기간사용함으로부터발생하는이차적인균의과증식과항생제사용으로부터발생되는인체의독성등의문제로특이한균에적극적으로작용하는협의의항생제가이상적이다. 그러나현재로는다양한균에작용할수있는광범위항생제를짧은기간사용함으로써이차적인균의증식을감소시키고, 장시간사용함으로부터오는항생제의독성을감소할수있는세파계항생제를수술전투여되는항생제로주로사용한다. 특히항생제는골내에충분한농도를유지할수있어야하며, 경제적인사정도고려되어일세대세파계인 Cefazolin 2그람을수술전투여하는것이많이보고되고있다 12). 항생제의사용기간에대해서는 Nelson 등의보고에의하면수술후하루, 일주일간사용한경우에서로차이가없었으며 9), 오히려감염을일으키는균의접종이수술중에발생하므로균의오염시점에항생제의체내농도유지가가장중요하다고하였다 11). 본연구에서모든환자는수술 1시간전에세파계항생제를주사하였고, 수술후항생제는세파계와 Aminoglycosides계를혼합투여하였으며, 사용기간은평균 17일이었다. 국외여러연구결과에비해사용기간이긴것은악성골육종환자와유잉육종환자의경우에수술전항생제투여로어느정도의면역기능저하가있을수있다는가정과종양의근치적제거를위해서시행될수밖에없는 수술로인한광범위한조직의손상과수술시간의지연등으로인하여일반적인관절치환술의경우보다장시간항생제의투여가요구되었다. 그리고타의료기관에비해 Laminar flow system, 개개인격리 (Personal isolator system) 등여러가지감염위험인자의존재에대한치료의의보상심리로설명될수있지만, 항생제투여기간을줄여야할것이다. 그리고수술후감염환자에서동정된균이세파계에감수성이떨어지는것도항생제투여기간이매우긴것과관련이있을수있다고여겨진다. 18예중 15예 (83%) 가그람양성균이었고그중13예가포도상구균이었다. 1940년페니실린이임상적으로사용된이래로포도상구균은많은항생제에저항을나타내었고, 1996년에는포도상구균에가장확실한항생제인반코마이신에내성을가진포도상구균의출현으로 3,5,6,8) 또다른항생제의개발이절실하다 14), 본연구에서는모든포도상구균은반코마이신과 Teicoplanin에감수성을보였고, 특히반코마이신과 Teicoplanin은감염된환자에서균의종류에관계없이 83%, Ciprofloxacin이 78%, 제 1세대세파계인 Cephalothin은 17% 에서감수성을보였다. Teicoplanin은잦은내성발현을가지기때문에사용에상당한주의가필요하며, 반코마이신은페니실린에알레르기를가진환자에서선택될수있는항생제이나, 남용으로인한저항균의출현때문에 MRSA나확실하게균이항생제감수성을가진경우를제외하고일반적으로예방적투여에는사용에주의를요한다. 그러나관절치환술후의감염은조절하기가심히어렵고, 치명적일수있다. 그래서초기의항생제선택이중요한데장기간항생제투여로인한균의병인성약화로균이검출되지않는경우와확실한염증의증상이있으나균검출결과가나오기전까지사용할수있는항생제의선택에 Ciprofloxacin의일차적인선택과반코마이신은고려해볼수있으리라판단된다. 특히만성감염환자에서균이검출된환자의전례에서검출된균은그람양성균이었고, 모두반코마이신과 Ciprofloxacin은감수성을보여만성감염환자에서균검출이되지않은환자나균배양결과가나오기전에사용할항생제를선택할경우에상기항생제의선택이의미가있으리라판단된다. 수술후급성감염의원인균으로그람양성균이 80% 였는데, 반코마이신과 Teicoplanin이전례에서감수성을보였다. 특히균종류에관계없이수술후감염환자에서반코마이신과 Teicoplanin은 80%, Ciprofloxacin은 50% 에서감수성을보여수술전 Cephalosporin과반코마이신의복합투여는수술후의감염방지에의미가있을것으로판단된다. 그러나인공관절수술후감염의빈도가 1% 이하로낮기때문에반코마이신과세파계복합투여와세파계단독투여로인한수술후감염의발생빈도에대한전향적비교조사가어려울수있으나필요하리라판단된다. 반코마이신사용으로발생할수있는포도상구균의내성발현빈도에대해서는이미감염된환자에서치료목적으로반코마이신을장기간투여한경우와수술후감염의빈도를감소시키기위해수술전에반코마이신의 1회투여하는경우어느쪽이내성발현빈도가높은가에대하여는계속의
정형외과수술후감염환자의균동정 775 문이존재하리라판단된다. 결론수술후감염된환자에서동정된원인균으로포도상구균이가장많았다. 그러므로감염방지를위한항생제로는포도상구균에감수성이높은항생제를써야하며비교적부작용이적은제 1세대세파계항생제가유용할것으로여겨진다. 그러나항생제에대한감수성검사에서세파계항생제에대한내성을갖는균이많은것은항생제투여기간과도연관이있을것으로여겨져, 예방적인항생제투여기간을줄이고, 감염된환자에서는감수성이있는항생제를투여하여야한다. 균이검출되지않은감염환자에서는비교적감수성이높은 Ciprofloxacine의투여를고려할수있다. 참고문헌 1. Burke JF: The effective period of preventative antibiotic action in experimental incisions and dermal lesion. Surgery. 50: 161-167, 1961. 2. Crossley K and Gardner LC: Antimicrobial prophylaxis in surgical patients. J.A.M.A. 245: 772-784, 1981. 3. Emslie KR and Nade S: Acute hematogenous staphylococcal osteomyelitis. A description of the natural history in an avian model. Am J Pathol. 110: 333-345, 1983. 4. Fry DE, Harbrecht PJ and Polk HC: Systemic prophylactic antibiotics. Arch Surg, 116: 466-469, 1981. 5. Garvin KL and Urban JA: Emerging multiresistant strains: recommended precautions in the emergency room and surgical setting. Instr Course Lect. 49: 605-614, 2000. 6. Hanaki H and Hiramatatsu K: Combination effect of teicoplanin and various antibiotics against hetero-vrsa and VRSA. J Japanese Asso. infectious Disease. 73: 1048-1053, 1999. 7. Mader JT and George C III: The Principle of the use of Preventive antibiotics. Clin Orthop, 190: 75-82, 1984. 8. Nehrer S, Thalhammer F, Schwameis E, Breyer S and Kotz R: Teicoplanin is the prevention of infection in total hip replacement. Archives of Orthopaedic & Trauma Surgery. 118: 32-36, 1998. 9. Nelson CL, Green TG, Porter RA and Warren BS: One day versus seven days of preventive antibiotic therapy on orthopedic surgery. Clin Orthop, 176: 258-263, 1983. 10. Petty W, Bryan RS, Coventry MB and Peterson LFA: Infection after total knee arthroplasty. Orthop Clin Am. 6: 1005-1013, 1975. 11. Williams DN, Gustilo RB, Beverly R and Kind AC: Bone and serum concentration of five cephalosporin drugs.relevance to prophylaxis and treatment in orthopaedic surgery. Clin Orthop, 179: 253-265, 1983. 12. William DN and Gustilo RB: The use of preventive antibiotics in orthopaedic surgery. Clin Orthop, 190: 83-88, 1984. 13. Young LS: Infection in the compromised host. Hosp. Prac. 16: 73-81, 1981.