猛爆性海洋霍乱弧菌坏死性筋膜炎课件

猛爆性海洋霍亂弧菌壞死性筋膜炎 Necrotizing Fasciitis and Sepsis as Initial Symptoms of Systemic Vibrio Infection,骨科系一般骨科 蔡燿鴻醫師 Yao-Hung Tsai, M.D. Department of Orthopaedic Surgery Division of General Orthopaedics Chang Gung Memorial Hospital, Chia-Yi,Special Thanks to,骨科同仁 許副院長、黃聰仁主任、黃國欽、李晏瑤、許維修、鄭錦昌、彭國狄、翁怡然 急診科同仁 蕭政廷主任、陳志聰醫師 整形外科同仁 楊文圭醫師、陳建銘主任 ICU 呂明憲主任 護理同仁 6D、6C、ICU、OR,Necrotizing Fasciitis,Group A beta-hemolytic streptococci (Streptococcus pyogens) - causes fulminating necrotizing fascitis Staphylococcus OSSA & ORSA (our hospital) 海洋霍亂弧菌一直存在溫暖海水中，大多生活在生蠔、蚵仔、魚和蝦蟹中，很少引起人類皮膚發炎感染，也不會像鏈球菌(Streptococcus pyogens) 容易引起壞死性筋膜炎和敗血症。 Vibrio 大部分為 cellulitis Vibrio necrotizing fascitis & progressive sepsis :Rare,Introduction,Vibrio species - warm sea waters and often in raw oyster, shellfish and other seafood. 主要症狀以腸胃炎 & Diarrhea 少數引起 Wound infection and primary septicemia. 有肝功能不好，如B型或C型肝炎、肝硬化或肝癌，糖尿病和慢性腎病等病症 Hepatic disease, diabetes, adrenal insufficiency and immunocompromised. 大部分為身上已有傷口或是被魚蝦剌傷過，再泡到海中，因而引起海洋霍亂弧菌引起的壞死性筋膜炎,海洋霍亂弧菌壞死性筋膜炎,內毒素 皮膚潰爛腫脹 - hemorrhagic bullae, subcutaneous bleeding, purpura, necrosis & gangrene 多重器官衰竭 - septicemia leads to rapid multi-organ failure Mortality was up to 50% in septic patients with hypotension (SBP 90 mm Hg) on admission Most of them dying within 48 hours of admission.,Vibrio 菌種,(1) V. cholerae O1 - GI problems (2) V. vulnificus - Skin infection (3) V. cholerae non-O1, V. parahaemolyticus, (4) V. fluvialis, V. alginolyticus, V. furnissii, V. mimicus, V. metschnikovii, V. hollisae,Vibrio Infection,Baffone ( Food Microbiology, 2001) High cytotoxicity: cholerae non-O1, vulnificus, parahaemolyticus, metschnikovii Moderate cytotoxicity: alginolyticus Low cytotoxicity: fluvialis, furnissii,Vibrio Species (USA 1999),Species GI Wound Septicemia V. Cholera Epidemic(O1) + (+) - Nonepidemic + + + V. mimicus + + - V. parahaemolyticus + + (+) V. fluvialis + + + V. vulnificus + + + V. alginolyticus - + - V. hollisae + + (+),Vibrio Species Enzymes,Species urease lipase Gelatinase V. Cholera Non-O1 - + + V. parahaemolyticus + + + V. fluvialis - + + V. vulnificus - + + V. alginolyticus + + + V. furnissii - + + V. metshnikovii + + + (Hm),Vibrio vulnificus soft tissue infection,最常見海洋霍亂弧菌壞死性筋膜炎 First described in 1979 存在 warm coastal water at salt concentrations of 0.7 to 1.6% Gulf of Mexico, South America, Asia (Thailand, Taiwan and Hong Kong) & Australia Severe sepsis in immunocompromised patients : underlying hepatic disease or diabetes.,Vibrio vulnificus soft tissue infection,First well-defined outbreak : 1996 Israel -62 pts, but no death Treatment : antibiotic therapy, intravenous fluid and debridement when tissue necrosis occurs. Early diagnosis and extensive debridement or 100% mortality (Seal, Current Opinion in Infect Dis 2001),2004 Nov - Journal of Bone and Joint Surgery (Am),Materials and Methods,June 2002 to Oct 2003 13 patients : 10 M, 3 F Mean age:61 y/o (46-74 y/o) Past history: 接觸過海水，抓過魚蝦或蚵的病史 9 legs, 4- hands,Materials and Methods,Past History -多數病患有喝酒習慣 8 - Hepatic dx: 3- DM & liver cirrhosis 2- Hepatitis B, 1- Hepatitis C, 1- HC+ DM & 1 - HCC 3- DM 1位洗腎，另一位則有吃類固醇病史,Materials and Methods,接觸時間 Contact ranged: 1 to 6 days prior to admission (with a mean of 3 days) The main presented complaints : (1) Pain and swelling of the involved limb (2) Chills and general malaise at ER PE: edematous, patchy erythematous, tenderness and bullous skin lesions,Materials and Methods,Three patients: BT than 38.5o C Eight patients: hypotensive with a systolic blood pressure of 90 mm Hg or less. 11-WBC band form increase, 2- Leukocytosis with increase of PMN form,Materials and Methods,Culture:wound- five, blood- three, both in five Two-combined antibiotics at ER :7- ceftriaxone and doxycycline, 5- ceftazidime and doxycycline, and 1- penicillin with gentamycin Student t-test and chi-square test for statistical significance of relationships among factors.,Results,12 pts: Fasciotomy or limb amputation 1 patient died before surgery A. 11 - fasciotomy and debridement 3- AK amputation, 2- AE amputation 3 Skin graft B. 1 AK amputation 5 patients died 8 patients survived ( Mortality rate 38%),Results,Species 9 - Vibrio vulnificus: the most common 2 - Vibrio cholerae non-O1 1 - Vibrio fluvialis 1 - Vibrio parahemolyticus,Results,5 patients died: within 2-6 days of admission (mean:3 Days) 8 surviving patients - hospital stays from 15 to 54 days (mean: 30 days) Between death and BP of 90 mm Hg or less (P 0.05) Between death and the WBC 5200 upon arrival at ER were statistically significant (P 0.05),Case Reports,Case 3:70 y/o fishman with HC,Case 3: Mortality,4 days before admission - fish sting Sepsis at ER Fasciotomy Expired the next day Culture: V. cholerae non-O1,Case 9: 66 y/o female with ESRD,Case 9: AE Amputation,Fasciotomy 20 days later - AE amputation HBO therapy Culture: V. vulnificus,Case 11: 46 Y/O male,Right leg contusion and swelling due to TA on 92-10-3, then 10-4 went to fish pond for fishing PH: Alcohol intake, Hepatitis B 92-10-4 because of pain ,he went to other hospital, and 10-7 11AM transfer to our ER PE: right whole leg bullous lesions with pain,Case Presentation,Lab 1. WBC-21900,seg -89.5, Band-4.5, 2. Platelet-11000, INR-1.19 3.Alb-2.1, CR-1.7,CRP-249 4. AST-128 5. BP:110/80, Temp: 37.4 Imp: right leg necrotizing fascitis 15:00 fasciotomy Wound culture: Vibrio fluvialis, B/C: no growth,4 days later after fasciotomy,Vibrio fluvialis infection,Patient still had septic sign WBC increase 10-14 debridement 2nd culture- Ps. and Acineto. infection 92-10-17 Rt AK amputation 10-21 Debridement 10-24 STSG 11-5 discharge,Vibrio fluvialis,Vibrio fluvialis : halophilic enteric bacterial pathogen diarrhea and GI illness Strains: 6,6a,7,15a,15b - Lipase, Gelatinase Vibrio fluvialis hemolysin: enterotoxigenic and against erythrocyte (Kothary, Infection and Immunity, 2003) Cytotoxicity: low Injury 2005; E36:546-549,Vibrio infection 文獻報告,Howard( Ann Surg. 1993): 11 (45.8%) of the 24 patients required debridement & died Fujisawa (J Infect. 1998):3 of five patients died,Vibrio infection 文獻報告,Halow (J Am Coll Surg. 1996 ): no mortality in seven patients with operative exploration within 46 hours of admission Seven case reports of fasciotomy or amputation : 5- Vibrio vulnificus, 1- Vibrio cholerae non-O1, and 1- Vibrio parahaemolyticus Six patients survived, and one patient with Vibrio vulnificus infection died,Vibrio infection文獻報告,奇美-莊銀清主任 (Clin Infect Dis. 1992) : underlying chronic illness such as cirrhosis, alcoholic liver disease, gouty arthritis, chronic renal failure, diabetes mellitus, or the use of chronic steroids was present in 55 percent of patients with primary wound infection and 94.7 percent of patients with primary bacteremia. Patients underwent debridement: 28% mortality Pts did not debride: 66% mortality rate. Bonner (Ann Int Med. 1983): mortality rate of debridement / none 25% / 100%.,In Our Study,All cases - caught and raised oysters, fish or other seafood History: alcohol intake, diabetes mellitus or chronic steroid intake chronic hepatic dysfunction and adrenal insufficiency Altered neutrophil and macrophage function, resulting in immunosupression sepsis SBP of 90mm Hg or less & leukopenia (WBC5200) at ER - a significantly higher mortality rate,In Our Study,12 surgical patients 11 pts - Fascitomy and 1 pt - AK amputation 4 pts died on mean 3 days with multi-organ failures The mortality of surgical pts : 33% Immediate limb amputation did not decrease the mortality rate of acute septic patients such as in cases 1 and 5 Limb amputation can still save a patients life if the sepsis is progressive after fasciotomy in case 13.,Vibrio vulnificus 創傷弧菌病例調查,嘉義長庚醫院臨床病理科收集2002年1月到2005年6月- 36病例 男性26位(72.2%)，平均64y/o 嘉義縣東石鄉27.7%，雲林縣口湖鄉16.7% 血液培養52.2% 潛在病77.8%；DM、Liver disease，renl insuffiency 海鮮刺傷35.7%，傷口接觸海水64.3%,Vibrio vulnificus 創傷弧菌病例調查,GI sepsis 5, UTI 1 ER 切割傷 2 ENT 之Deep neck infection - 2 Cellulitis 24 Finger cellulitis with debridement 3 Cellulitis with antibiotics 7 NF with operation 14 ( 兩人2次), death 4,Vibrio vulnificus 創傷弧菌病例,Vibrio vulnificus 創傷弧菌病例,Vibrio vulnificus 創傷弧菌病例,Farmer, Vibrio infection ?,2007 Mar JBJS(Am),海洋創傷弧菌及單孢產氣菌株引起之壞死性軟組織感染之比較,Necrotizing Soft Tissue Infections and Sepsis Caused by Vibrio vulnificus Compared with that Caused by Aeromonas Species 蔡燿鴻 李晏瑤 黃聰仁 黃國欽 許維修 彭國狄 許文蔚 嘉義長庚醫院1 長庚大學2,Introduction of Vibrio and Aeromonas,Members of the Vibrionaceae family and thrive in aquatic environments GI illness, soft-tissue infections and primary septicemia Vibrio vulnificus - gram-negative, motile, curved, and rod-shaped bacteria endemic to warm coastal waters and raw seafood,Introduction of Vibrio and Aeromonas,Aeromonads - gram-negative, facultative, unipolar, and anaerobic bacillus that are -hemolytic on blood agar and ferment carbohydrates with acid and gas production Aeromonas are often located in fresh or brackish water, sewage, soil, tap water and non-fecal organic materials,Introduction of Vibrio and Aeromonas,Both produce necrotizing fasciitis and sepsis in patients with hepatic diseases, diabetes mellitus, adrenal insufficiency and immunocompromised conditions Similar skin lesions -hemorrhagic bullae, subcutaneous bleeding, purpura, necrosis and gangrene The purposes of this study - compare the fulminating clinical characteristics of the two group infections, and to identify the risk factors of outcomes.,Material and Methods,From June 2002 to November 2005: 32 patients with necrotizing soft tissue infections and sepsis Chief complaints - pain and swelling of involved limbs with patchy, edematous, erythematous, and bullous skin lesions at time of consultation in the ER or ward. Broad-spectrum antibiotic therapy ceftriaxone or ceftazidime combined with doxycycline or gentamycin,Material and Methods,Vibrio vulnificus -17 patients 12 men and 5 women (mean 60 y/o, 36 to 77 ); all had a history of contact with raw seafood or exposure to warm sea water, and most occurred in the summer months (May to September) 8 hepatic dx : 3-LC+DM, 2-LC+DM+Hepatitis, 1-LC, 1-HBC, 1-HC+DM 4-DM, 2-CRI, 1-RA, 1- Good health, 1-Drug abuse,Aeromonas species in 15 cases,12 men and 3 women ( mean 62 y/o, 22 to 79) 12 - farmers Polymicrobial infection - 7 patients (47%). Pathogens : Enterococcus, Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa, Klebsiella oxytoca, Clostridium and Serratia marcescens. 1-HCC+DM+LC, 6 -DM, 2- health, 2-Alcoholic, 1-steroid, 1-DM+gout, 1-gout, 1-CRI 5-cutting, 1-handle fish, 4-MVA and fell into ditch, 4-did not recall any injuries, 1- HCC post TAE,Results,All- Surgical debridement or immediate limb amputation Ten patients died- mortality rate of 31% The death had significantly lower albumin than surviving pts Patients with hepatic dysfunction and diabetes mellitus have higher mortality than hepatic disease or diabetes mellitus alone,Results - Vibrio vulnificus infection,10- forearms, 7 legs 16- fasciotomy, 1-immediate AK amputation 6 death, 11 survivals, mortality rate 35% 16 post fasciotomy 2 AE & 2 AK amputation, 9- STSG or flap 3 had fever (18%), 12 BP90mmHg(71%),Vibrio vulnificus infection,Vibrio vulnificus infection,Vibrio vulnificus Case 12- 57 female,Result -Aeromonas Infection,13- legs, 2-forearm 11- fasciotomy, 2 immediate AK amputation, 2- bimalleolar open type II fractures -BK 4- death, 11-survivals, mortality 26.7% 2nd operation of 11 pts : 2 AK & 1 BK amputataion, 6-STSG,Result -Aeromonas Infection,none had fever, 3- BP90mmHg 10-Aeromonas hydrophila 4-Aeromonas sobria 1- Aeromonas caviae ( case 9 - W/C:Aeromonas sobria B/C: Aeromonas caviae),Aeromonas Infection,Aeromonas Infection,Aeromonas Case 4- 66 male, farmer,Result - Comparison between the Vibrio vulnificus group and Aeromonas group,Age, fever, interval between injury and admission, the increase in white cell count, the platelet count, and serum albumin were not significantly different The Aeromonas patients who died had a significantly decreased white blood cell count and segmented white blood cells. The Vibrio vulnificus group patients who died had significant systolic blood pressure 90 mm Hg in the emergency room. The surviving patients in the Aeromonas group had significantly lower banded white blood cells than those in the Vibrio vulnificus group.,Discussion,Vibrio vulnificus and Aeromonas species, members of the Vibrionaceae family - gram-negative with positive oxidase activity and glucose fermentation Vibrio vulnificus is arginine dehydrogenase (ADH) negative, lysine decarboxylase (LDC) positive and orinithine decarboxylase (ODC) positive. Aeromonas species -ADH positive and sensitive to vibrio-static agent O129 Vibrio vulnificus and Aeromonas species can produce extracellular virulence factors into blood to cause fulminant courses of sepsis.,Discussion,Mortality rate of Vibrio infection - 25% to 33% among patients with chronic illnesses who underwent debridement and 66% to 100% among those who did not Fatality rate of Aeromonas soft tissue infections and bacteremia has been reported to be as high as 28% to 73% Vibrio vulnificus haemolysin - disrupt various eukaryotic erythrocytes and mast cells. The Vibrio vulnificus protease also enhances vascular permeability by activating the Hageman factir-plasma kallikrein-kinin cascade and/or exocytotic histamine release,Aeromonas Soft Tissue Infection,Highly toxic exotoxins- cytolysin, -haemolysin, -haemolysin, cytotoxic enterotoxin, and cholera toxin-like factor - extensive muscular necrosis (Minnaganti 2000, Kohashi 1995) Aeromonas soft-tissue infections, such as A. hydrophila and A. sobria, can be severe with myonecrosis and gas production resembling those caused by clostridia. (Itoh 1999) A. hydrophila is frequently with polymicrobial infection and in synergistic necrotizing fasciitis with gram-negative bacilli and Clostridium species Vibrio vulnificus seldom - polymicrobial infection,In Our Study identified differences between Vibrio vulnificus and Aeromonas Infection,Contact mechanisms Vibrio vulnificus patients lived on the coast and had the history of contact with seawater through their occupation, which involved catching and raising oysters, fish, or other seafood. Most Aeromonas patients were farmers and had the history of contact with soil, wood, brackish water and dirty ditches.,In Our Study identified differences between Vibrio vulnificus and Aeromonas Infection,Soft-tissue infections in both groups had similar hemorrhagic bullae, subcutaneous bleeding, purpura, necrosis and gangrene The appearance of Aeromonas infection had markedly more myonecrosis and a foul odor. fractured limb - quickly invaded the bony fragment. Gold (1993) reported 9 cases (82%) had polymicrobial infection by wound culture, and no deaths in 11 Aeromonas patients. Ko (2000) had reported 19 Aeromonas bacteremic episodes (32%) were polymicrobial and the fatality rate was 49% (9/19 episodes),In Our Study identified differences between Vibrio vulnificus and Aeromonas Infection,Patients with hepatic dysfunction and diabetes mellitus have higher mortality than hepatic disease or diabetes mellitus alone. The death patients had significantly lower albumin level than surviving patients at the time of presentation. Patients with severe hypoalbuminemia might be associated with malnutrition or immunocompromised conditions, which can quickly lead to fatal sepsis. Overall clinical course of the Vibrio vulnificus group was more fulminant than that of the Aeromonas group, especially in the case of low systolic blood pressure and high band forms of white blood cells.,Conclusion,Necrotizing soft tissue infections and sepsis caused by Vibrio vulnificus and Aeromonas species are surgical emergencies due to the high mortality rates. Early fasciotomy and culture-directed antimicrobial therapy should be applied to patients with hypotensive shock, leukopenia, severe hypoalbuminemia and underlying chronic illness, particularly hepatic dysfunction and diabetes mellitus.,Conclusion,The contact history of patients with rapid onset of cellulitis can alert clinicians to an early differential diagnosis of Vibrio (contact with seawater or raw seafood) and Aeromonas (contact with fresh or brackish water, soil or wood) soft tissue infections. Treatment should be aggressive in patients with necrotizing fasciitis and fulminating sepsis.,Necrotizing Fasciitis and Primary Sepsis Caused by Vibrio vulnificus and Vibrio cholerae non-O1 海洋創傷弧菌及non-O1海洋弧菌引起之壞死性筋膜炎及敗血症,Introduction,Vibrio vulnificus : the most rapid fatal soft-tissue infection and surgical emergency Patients with hepatic dysfunction, diabetes mellitus, adrenal insufficiency and immunocompromised status Mortality rate - 25% to 38% among patients with chronic illnesses who underwent debridement and 66% to 100% among those who did not,Introduction,Vibrio cholerae non-O1 - Most cause endemic diarrhea Clinical features similar to those of Vibrio vulnificus necrotizing fasciitis with high mortality rates Both organisms feature hemorrhagic bullae, subcutaneous bleeding, purpura, necrosis and gangrene, and cause severe sepsis This study examined the fulminating clinical characteristics of Vibrio vulnificus and Vibrio cholerae non-O1 soft tissue infections and risk factors related to outcome.,Materals and Methods,From June 2002 to May 2007, retrospectively reviewed 30 patients with necrotizing fasciitis and sepsis caused by Vibrio vulnificus and cholerae non-O1 Vibrio necrotizing fasciitis was suspected due to a recent history of exposure to seawater or raw seafood at ER Excisional debridement of necrotic fascia or