今日の臨床サポート

特発性細菌性腹膜炎

著者: 栃谷健太郎 京都市立病院 感染症科

監修: 山本舜悟 京都市立病院 感染症科/京都大学 医療疫学(非常勤講師) 

著者校正/監修レビュー済:2021/07/14
患者向け説明資料

概要・推奨   

  1. 腹水検査のための腹腔穿刺に際して、出血予防の習慣的な新鮮凍結血漿や血小板の使用は推奨されない(推奨度3)。
  1. 特発性細菌性腹膜炎を疑い腹水検査を行う際には、細胞数(分画)、アルブミン、総蛋白、一般細菌培養(血液培養ボトルを用いる)、グラム染色、糖、LDH、アミラーゼを提出する(推奨度1)。
  1. SBPにおいて腹水培養陽性率を上げるために抗菌薬前に培養を採取し、採取した腹水をベッドサイドで速やかに血液培養ボトルに10mL注入する(推奨度2)。
  1. 腹水中の多核白血球が250/mm3以上あり二次性腹膜炎が疑われる場合、SBPと二次性腹膜炎の鑑別のため腹水の総蛋白、LDH、糖、グラム染色、CEA、ALPを検査する(推奨度2)。
  1. 腹水中の多核白血球が250/mm3以上ある場合は速やかに経験的治療を開始する。250/mm3以下の場合でも感染徴候(38℃以上の発熱や腹痛、腹部圧痛)がある場合は、腹水の培養結果を待つ間、経験的治療を開始する(推奨度1)。
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  1. 腹水の多核白血球が250/mm3以上ありSBPが疑われる患者で、血清Cr値 が1 mg/dL以上、BUN 30 mg/dL以上、総ビリルビン値 4 mg/dL以上――の3つのうちどれかを満たす場合は診断から6時間以内にアルブミン1.5g/kgを、3日目に1.0g/kgを、経静脈的に投与する(推奨度2)。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
栃谷健太郎 : 特に申告事項無し[2021年]
監修:山本舜悟 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、「難治症例の治療」を削除し、「予防」の項目を追加した。また一部加筆修正を行なった。

病態・疫学・診察

疾患情報  
  1. 特発性細菌性腹膜炎(spontaneous bacterial peritonitis、SBP)は、外科的介入を要する腹腔内感染によらない腹水の感染と定義され、腹水培養が陽性で腹水中の多核白血球が250/mm3以上といった特徴を持つ。単一菌による感染がほとんどで、複数菌による感染では二次性腹膜炎を考慮する。
  1. 心不全やネフローゼ症候群などにも起こり得るが、多くは進行した肝硬変患者で肝機能がひどく低下したときの症状として起こる。
  1. SBP発症には門脈圧亢進、腸内細菌の異常増殖、腸管粘膜の透過性亢進、bacterial translocation、免疫応答システムの機能低下、細網内皮系の貪食細胞活性低下、腹水の防御能低下などさまざまな要素が関わっている。一過性の菌血症から腹水に細菌が播種し、これを排除することができないため腹水中で細菌が増殖する結果、SBPが起こるとされている。
  1. SBPの亜型として以下の3つがある。
  1. CNNA(culture-negative neutrocytic ascites):腹水中の多核白血球が250/mm3以上で腹水培養陰性。臨床的特徴、予後、治療はSBPと同様。
  1. MNB(monomicrobial bacterial peritonitis):腹水中の多核白血球が250/mm3未満で、腹水細菌培養が陽性。臨床所見や症状が感染を示唆する場合、治療はSBPと同様。
  1. Polymicrobial bacterascites:腹水中の多核白血球が250/mm3未満で腹水グラム染色や腹水細菌培養で複数の細菌感染が存在。腹腔穿刺の際、誤って腸管を刺した結果として生じる。免疫状態が保たれている(腹水蛋白量正常)場合は自然治癒する。
  1. 二次性細菌性腹膜炎は腹水中の多核白血球が250/mm3以上で、腹水培養で複数の細菌が陽性となり、外科的介入を要する腹腔内感染巣(消化管穿孔など)により生じる。通常、①腹水中総蛋白が1g/dL以上 ②糖が50mg/dL未満 ③LDHが血清LDHの正常上限以上――のいずれかを満たす。
問診・診察のポイント  
  1. 腹水のある肝硬変患者ではSBPの頻度が高い。感染症として常に考慮する。

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文献 

著者: B A Runyon
雑誌名: Arch Intern Med. 1986 Nov;146(11):2259-61.
Abstract/Text A prospective study of 229 abdominal paracenteses performed on 125 patients with ascites revealed only two major complications (transfusion-requiring abdominal wall hematomas) in a single patient (0.9% of paracenteses and 0.8% of patients), and two minor complications (non-transfusion-requiring hematomas) in two patients (0.9% of paracenteses and 1.6% of patients). No paracentesis resulted in bacterial peritonitis or death. Abdominal paracentesis in patients with ascites is a safe procedure. Fear of complications of the procedure should not preclude performing a paracentesis, provided certain precautions are taken.

PMID 2946271  Arch Intern Med. 1986 Nov;146(11):2259-61.
著者: Catherine M Grabau, Sharon F Crago, Linda K Hoff, Julie A Simon, Cheryl A Melton, Beverly J Ott, Patrick S Kamath
雑誌名: Hepatology. 2004 Aug;40(2):484-8. doi: 10.1002/hep.20317.
Abstract/Text Large-volume paracentesis, the preferred treatment for patients with symptomatic tense ascites due to cirrhosis, has traditionally been performed by physicians as an inpatient procedure. Our objectives were to determine (1) whether large-volume paracentesis could be performed safely and effectively by gastrointestinal endoscopy assistants and as an outpatient procedure, (2) whether the risk of bleeding was associated with either thrombocytopenia or prolongation of the prothrombin time, and (3) the resources used for large-volume paracentesis. Gastrointestinal endoscopy assistants performed 1,100 large-volume paracenteses in 628 patients, 513 of whom had cirrhosis of the liver. The preprocedure mean international normalized ratio for prothrombin time was 1.7 +/- 0.46 (range, 0.9-8.7; interquartile range, 1.4-2.2), and the mean platelet count was 50.4 x 10(3)/microL, (range, 19 x 10(3)/microL - 341 x 10(3)/microL; interquartile range, 42-56 x 10(3)/microL). Performance of 3 to 7 supervised paracenteses was required before competence was achieved. There were no significant procedure-related complications, even in patients with marked thrombocytopenia or prolongation in the prothrombin time. The mean duration of large-volume paracentesis was 97 +/- 24 minutes, and the mean volume of ascitic fluid removed was 8.7 +/- 2.8 L. In conclusion, large-volume paracentesis can be performed safely as an outpatient procedure by trained gastrointestinal endoscopy assistants. Ten supervised paracenteses would be optimal for training the operators carrying out the procedure. The practice guideline of the American Association for the Study of Liver Diseases which states that routine correction of prolonged prothrombin time or thrombocytopenia is not required is appropriate when experienced personnel carry out paracentesis.

Copyright 2004 American Association for the Study of Liver Diseases
PMID 15368454  Hepatology. 2004 Aug;40(2):484-8. doi: 10.1002/hep.2031・・・
著者: J Castellote, X Xiol, R Verdaguer, J Ribes, J Guardiola, A Gimenez, L Casais
雑誌名: Am J Gastroenterol. 1990 Dec;85(12):1605-8.
Abstract/Text The conventional method of ascitic fluid culture detects bacteria in only 50% of cirrhotic patients with neutrocytic ascites and suspected spontaneous bacterial peritonitis (SBP). We have prospectively compared two ascites culture methods in cirrhotic patients with spontaneous bacterial peritonitis: 1) conventional (on chocolate agar, blood agar, Mac Conkay agar, and thioglycolate broth), and 2) modified [inoculation of 10 ml of ascites in a tryptic soy broth (TSB) blood culture bottle at the patient's bedside]. In a 21-month period, 70 episodes of SBP were diagnosed according to our criteria in 60 cirrhotic patients. Both culture methods were performed simultaneously. The conventional grew bacteria in 40 episodes (57%), whereas the modified grew bacteria in 54 episodes (77%), a significantly higher sensitivity (p = 0.0001). In 16 cases (23%), ascitic culture was negative by both methods. The mortality rate was higher among patients with culture-positive SBP than those with culture-negative SBP (46% vs 37%), but did not reach statistical significance. We conclude that ascitic fluid inoculated into a TSB blood culture bottle at the patient's bedside should be used routinely for ascites culture in cirrhotic patients.

PMID 2252025  Am J Gastroenterol. 1990 Dec;85(12):1605-8.
著者: Bruce A Runyon, AASLD
雑誌名: Hepatology. 2013 Apr;57(4):1651-3. doi: 10.1002/hep.26359.
Abstract/Text
PMID 23463403  Hepatology. 2013 Apr;57(4):1651-3. doi: 10.1002/hep.263・・・
著者: E A Akriviadis, B A Runyon
雑誌名: Gastroenterology. 1990 Jan;98(1):127-33.
Abstract/Text To prospectively assess the value of an algorithm in differentiating spontaneous from secondary bacterial peritonitis, we performed serial paracenteses in 43 episodes of ascitic fluid infection (28 spontaneous and 15 secondary) in 40 patients. The algorithm involved identification of (a) secondary peritonitis associated with gut perforation, based on previously proposed criteria in patients with neutrocytic ascites (ascitic fluid total protein greater than 1 g/dl, glucose less than 50 mg/dl, and lactate dehydrogenase greater than the upper limit of normal for serum) and (b) separation of spontaneous from secondary peritonitis (unassociated with perforation) based on the response of the ascitic fluid cell count to antibiotic therapy. The perforation criteria had 100% sensitivity in detecting episodes of actual gut perforation; their specificity, however, was low (45%). After 48 h of treatment the concentration of ascitic fluid neutrophils was below the baseline pretreatment value in all episodes of spontaneous peritonitis but in only two thirds of the patients with secondary peritonitis. This algorithm is useful in (a) identifying patients who have infected ascites associated with perforation of an intraabdominal viscus, and (b) differentiating spontaneous from nonperforation secondary peritonitis on the basis of the response of the ascitic fluid cell count to appropriate antibiotic therapy. The optimal time for repeat paracentesis in patients with infected ascites appears to be 48 h after initiation of treatment.

PMID 2293571  Gastroenterology. 1990 Jan;98(1):127-33.
著者: S S Wu, O S Lin, Y Y Chen, K L Hwang, M S Soon, E B Keeffe
雑誌名: J Hepatol. 2001 Feb;34(2):215-21.
Abstract/Text BACKGROUND/AIMS: In cirrhotic patients, spontaneous bacterial peritonitis (SBP) may be difficult to distinguish from secondary peritonitis with occult intestinal perforation; Runyon's criteria (based on ascitic fluid glucose, protein and lactate dehydrogenase levels) are sensitive but not specific. Ascitic fluid carcinoembryonic antigen (CEA) and alkaline phosphatase (AP) are potential markers for secondary peritonitis.
METHODS: Ascitic fluid CEA and AP levels were prospectively compared among three subject groups--cirrhotic patients with sterile ascites, cirrhotic patients with SBP, and patients (cirrhotic and non-cirrhotic) with perforation-related secondary peritonitis.
RESULTS: The secondary peritonitis group (n = 38 including 11 cirrhotic patients) had significantly higher mean CEA and AP levels than the SBP (n = 34) and sterile ascites patients (n = 63). Of secondary peritonitis patients, 92% fulfilled predetermined criteria (either CEA >5 ng/ml or AP >240 units/l) versus only 12% of SBP patients; sensitivity was 92% and specificity 88% for differentiating secondary peritonitis from SBP. Runyon's criteria had a sensitivity of 97% and specificity of 56%. Stratification of secondary peritonitis patients by the presence or absence of cirrhosis did not alter our results.
CONCLUSIONS: Ascitic fluid CEA or AP elevations appear to be sensitive and specific markers for perforation-related secondary peritonitis in cirrhotic as well as non-cirrhotic patients.

PMID 11281549  J Hepatol. 2001 Feb;34(2):215-21.
著者: Ilyas Tuncer, Nazan Topcu, Ahmet Durmus, M Kursad Turkdogan
雑誌名: Hepatogastroenterology. 2003 Sep-Oct;50(53):1426-30.
Abstract/Text BACKGROUND/AIMS: Cefotaxime or ceftriaxone were considered the first-choice antibiotic for empirical treatment in cirrhotic patients developing spontaneous bacterial peritonitis. It has been suggested that ciprofloxacin could be an alternative to cefotaxime or ceftriaxone in cirrhotic patients developing spontaneous bacterial peritonitis. The aim of the present study was to compare oral ciprofloxacin with cefotaxime and ceftriaxone in the treatment of spontaneous bacterial peritonitis in cirrhotic patients.
METHODOLOGY: Fifty-three hospitalized cirrhotic patients with spontaneous bacterial peritonitis were prospectively included and randomized into three groups: group A (n = 16); received orally 500 mg ciprofloxacin every 12 h, group B (n = 18); received intravenous cefotaxime 2 g every 8 h and group C (n = 19) received intravenous ceftriaxone 2 g every 24 h.
RESULTS: 15 patients from the ciprofloxacin group, 17 from the cefotaxime group and 17 patients from the ceftriaxone group were finally analyzed. Spontaneous bacterial peritonitis resolution in three groups was found to be 80%, 76%, and 83%, respectively (p = NS). Incidence of complications and hospital mortality was similar in the three groups. No adverse events were observed in any of the three groups. The cost of the treatment was statistically lower in the ciprofloxacin group than in the cefotaxime group and ceftriaxone group (p < 0.001).
CONCLUSIONS: These results suggest that orally ciprofloxacin is as effective as cefotaxime and ceftriaxone in the empirical treatment of spontaneous bacterial peritonitis in cirrhotic patients, and is also less expensive and can be administered orally.

PMID 14571754  Hepatogastroenterology. 2003 Sep-Oct;50(53):1426-30.
著者: B Bernard, J D Grangé, E N Khac, X Amiot, P Opolon, T Poynard
雑誌名: Hepatology. 1999 Jun;29(6):1655-61. doi: 10.1002/hep.510290608.
Abstract/Text In cirrhotic patients with gastrointestinal bleeding, antibiotic prophylaxis decreases the incidence of infections but most randomized trials have not shown an increase in survival. The aim of this meta-analysis was to assess the efficacy of antibiotic prophylaxis in the prevention of infections and its effect on survival rate in cirrhotic patients with gastrointestinal bleeding. Four end points were assessed: infection, bacteremia and/or spontaneous bacterial peritonitis (SBP), incidence of SBP, and death. For each end point, heterogeneity and treatment efficacy were assessed by Der Simonian and Peto methods. Five trials including 534 patients, 264 treated with antibiotic prophylaxis for 4 to 10 days and 270 without, were identified. Mean follow-up was 12 days. Antibiotic prophylaxis significantly increased the mean percentage of patients free of infection (32% mean improvement rate, 95% confidence interval [CI]: 22-42, P <.001), bacteremia and/or SBP (19% mean improvement rate, 95% CI: 11-26, P <.001), and SBP (7% mean improvement rate, 95% CI: 2.1-12.6, P =.006). Antibiotic prophylaxis also significantly increased the mean survival rate (9. 1% mean improvement rate, 95 % CI: 2.9-15.3, P =.004), without significant heterogeneity. In cirrhotic patients with gastrointestinal bleeding, short-term antibiotic prophylaxis significantly increases the mean percentage of patients free of infection and significantly increases short-term survival rate.

PMID 10347104  Hepatology. 1999 Jun;29(6):1655-61. doi: 10.1002/hep.51・・・
著者: G Soriano, C Guarner, A Tomás, C Villanueva, X Torras, D González, S Sainz, A Anguera, X Cussó, J Balanzó
雑誌名: Gastroenterology. 1992 Oct;103(4):1267-72.
Abstract/Text To assess the efficacy of selective intestinal decontamination with norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage, 119 patients were included in a prospective randomized study. Group 1 (n = 60) received norfloxacin orally or through a nasogastric tube, 400 mg twice daily for 7 days beginning immediately after emergency gastroscopy; group 2 (n = 59) was the control group. We found a significantly lower incidence of infections (10% vs. 37.2%; P = 0.001), bacteremia and/or spontaneous bacterial peritonitis (3.3% vs. 16.9%; P less than 0.05), and urinary infections (0% vs. 18.6%; P = 0.001) in patients receiving norfloxacin, as a consequence of decrease in the incidence of infections caused by aerobic gram-negative bacilli. The decrease in mortality observed in the treated group (6.6% vs. 11.8%) did not reach statistical significance. The cost for antibiotic treatment showed a 62% reduction in the treated group compared with the control group. The results show that selective intestinal decontamination with norfloxacin is useful in preventing bacterial infections in cirrhotics with gastrointestinal hemorrhage.

PMID 1397884  Gastroenterology. 1992 Oct;103(4):1267-72.
著者: Javier Fernández, Luis Ruiz del Arbol, Cristina Gómez, Rosa Durandez, Regina Serradilla, Carlos Guarner, Ramón Planas, Vicente Arroyo, Miguel Navasa
雑誌名: Gastroenterology. 2006 Oct;131(4):1049-56; quiz 1285. doi: 10.1053/j.gastro.2006.07.010.
Abstract/Text BACKGROUND & AIMS: Oral norfloxacin is the standard of therapy in the prophylaxis of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage. However, during the last years, the epidemiology of bacterial infections in cirrhosis has changed, with a higher incidence of infections caused by quinolone-resistant bacteria. This randomized controlled trial was aimed to compare oral norfloxacin vs intravenous ceftriaxone in the prophylaxis of bacterial infection in cirrhotic patients with gastrointestinal bleeding.
METHODS: One hundred eleven patients with advanced cirrhosis (at least 2 of the following: ascites, severe malnutrition, encephalopathy, or bilirubin >3 mg/dL) and gastrointestinal hemorrhage were randomly treated with oral norfloxacin (400 mg twice daily; n = 57) or intravenous ceftriaxone (1 g/day; n = 54) for 7 days. The end point of the trial was the prevention of bacterial infections within 10 days after inclusion.
RESULTS: Clinical data were comparable between groups. The probability of developing proved or possible infections, proved infections, and spontaneous bacteremia or spontaneous bacterial peritonitis was significantly higher in patients receiving norfloxacin (33% vs 11%, P = .003; 26% vs 11%, P = .03; and 12% vs 2%, P = .03, respectively). The type of antibiotic used (norfloxacin), transfusion requirements at inclusion, and failure to control bleeding were independent predictors of infection. Seven gram-negative bacilli were isolated in the norfloxacin group, and 6 were quinolone resistant. Non-enterococcal streptococci were only isolated in the norfloxacin group. No difference in hospital mortality was observed between groups.
CONCLUSIONS: Intravenous ceftriaxone is more effective than oral norfloxacin in the prophylaxis of bacterial infections in patients with advanced cirrhosis and hemorrhage.

PMID 17030175  Gastroenterology. 2006 Oct;131(4):1049-56; quiz 1285. d・・・
著者: Javier Fernández, Miquel Navasa, Ramón Planas, Silvia Montoliu, David Monfort, German Soriano, Carmen Vila, Alberto Pardo, Enrique Quintero, Victor Vargas, Jose Such, Pere Ginès, Vicente Arroyo
雑誌名: Gastroenterology. 2007 Sep;133(3):818-24. doi: 10.1053/j.gastro.2007.06.065. Epub 2007 Jul 3.
Abstract/Text BACKGROUND & AIMS: Norfloxacin is highly effective in preventing spontaneous bacterial peritonitis recurrence in cirrhosis, but its role in the primary prevention of this complication is uncertain.
METHODS: Patients with cirrhosis and low protein ascitic levels (<15 g/L) with advanced liver failure (Child-Pugh score > or = 9 points with serum bilirubin level > or = 3 mg/dL) or impaired renal function (serum creatinine level > or = 1.2 mg/dL, blood urea nitrogen level > or = 25 mg/dL, or serum sodium level < or = 130 mEq/L) were included in a randomized controlled trial aimed at comparing norfloxacin (35 patients) vs placebo (33 patients) in the primary prophylaxis of spontaneous bacterial peritonitis. The main end points of the trial were 3-month and 1-year probability of survival. Secondary end points were 1-year probability of development of spontaneous bacterial peritonitis and hepatorenal syndrome.
RESULTS: Norfloxacin administration reduced the 1-year probability of developing spontaneous bacterial peritonitis (7% vs 61%, P < .001) and hepatorenal syndrome (28% vs 41%, P = .02), and improved the 3-month (94% vs 62%, P = .003) and the 1-year (60% vs 48%, P = .05) probability of survival compared with placebo.
CONCLUSIONS: Primary prophylaxis with norfloxacin has a great impact in the clinical course of patients with advanced cirrhosis. It reduces the incidence of spontaneous bacterial peritonitis, delays the development of hepatorenal syndrome, and improves survival.

PMID 17854593  Gastroenterology. 2007 Sep;133(3):818-24. doi: 10.1053/・・・
著者: G Soriano, C Guarner, M Teixidó, J Such, J Barrios, J Enríquez, F Vilardell
雑誌名: Gastroenterology. 1991 Feb;100(2):477-81.
Abstract/Text In a prospective randomized study, selective intestinal decontamination with norfloxacin was performed during hospitalization in 32 cirrhotic patients with low ascitic fluid total protein levels. The incidence of infections was compared with that in a control group of 31 nontreated cirrhotic patients of similar characteristics. We found a significantly lower incidence of infections [1/32 (3.1%) vs. 13/31 (41.9%); P less than 0.005] and spontaneous bacterial peritonitis [0/32 (0%) vs. 7/31 (22.5%); P less than 0.05] in patients receiving norfloxacin. The lower incidence of extraperitoneal infections [1/32 (3.1%) vs. 7/31 (22.5%); P = 0.052] in the treated group did not reach statistical significance. The incidence of infections [1/28 (3.6%) vs. 9/22 (40.9%); P less than 0.01] and spontaneous bacterial peritonitis [0/28 (0%) vs. 5/22 (22.7%); P less than 0.05] in cirrhotic patients admitted because of ascites was also significantly lower in the treated group. The decrease in the rate of mortality observed in the group undergoing selective intestinal decontamination did not reach statistical significance. These data show that selective intestinal decontamination is useful to prevent spontaneous bacterial peritonitis and extraperitoneal infections in hospitalized cirrhotic patients with low ascitic fluid total protein levels.

PMID 1985045  Gastroenterology. 1991 Feb;100(2):477-81.
著者: N Singh, T Gayowski, V L Yu, M M Wagener
雑誌名: Ann Intern Med. 1995 Apr 15;122(8):595-8.
Abstract/Text OBJECTIVE: To assess the efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis and ascites.
DESIGN: A randomized controlled trial.
SETTING: University-affiliated Veterans Affairs medical center.
PATIENTS: 60 consecutive patients with cirrhosis and ascites.
INTERVENTIONS: Consecutive patients were randomly assigned to receive either no prophylaxis or trimethoprim-sulfamethoxazole, one double-strength tablet daily, five times a week (Monday through Friday). Patient entry was stratified by serum bilirubin (> 51 mumol/L [> 3 mg/dL]), ascitic fluid protein (< 1 g/dL), and serum creatinine (> 177 mumol/L [> 2 mg/dL]) levels to ensure that high-risk patients would be similarly distributed in the two groups. The median duration of follow-up for the study patients was 90 days.
MAIN OUTCOME MEASURES: Spontaneous bacterial peritonitis or spontaneous bacteremia as defined by objective criteria.
RESULTS: Spontaneous bacterial peritonitis or spontaneous bacteremia developed in 27% (8 of 30) of patients who did not receive prophylaxis compared with 3% (1 of 30) of patients receiving trimethoprim-sulfamethoxazole (P = 0.025). Overall, infections developed in 9 of 30 patients (30%) not receiving prophylaxis and in 1 of 30 patients (3%) receiving trimethoprim-sulfamethoxazole (P = 0.012). Death occurred in 6 of 30 patients (20%) who did not receive prophylaxis and in 2 of 30 patients (7%) who received trimethoprim-sulfamethoxazole (P = 0.15). Side effects--particularly, hematologic toxicity--could not be attributed to trimethoprim-sulfamethoxazole in any patient.
CONCLUSIONS: Trimethoprim-sulfamethoxazole was efficacious, safe, and cost-effective for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis.

PMID 7887554  Ann Intern Med. 1995 Apr 15;122(8):595-8.
著者: Gaurav Mehta, Kenneth D Rothstein
雑誌名: Med Clin North Am. 2009 Jul;93(4):901-15, viii-ix. doi: 10.1016/j.mcna.2009.03.005.
Abstract/Text Caring for patients with cirrhosis requires special consideration. The role of the hepatologist is to assist the primary care physician in caring for such patients. This involves an active role in immunizations, lifestyle modifications, and providing instructions on when to go to the emergency room (ER). There are also specific recommendations geared toward the patient with cirrhosis relating to slowing down the disease process, maintaining quality of life, and improving survival.

PMID 19577121  Med Clin North Am. 2009 Jul;93(4):901-15, viii-ix. doi:・・・
著者: F Donato, A Tagger, U Gelatti, G Parrinello, P Boffetta, A Albertini, A Decarli, P Trevisi, M L Ribero, C Martelli, S Porru, G Nardi
雑誌名: Am J Epidemiol. 2002 Feb 15;155(4):323-31.
Abstract/Text The authors investigated the dose-effect relation between alcohol drinking and hepatocellular carcinoma (HCC) in men and women separately, also considering hepatitis B and hepatitis C virus infections. They enrolled 464 subjects (380 men) with a first diagnosis of HCC as cases and 824 subjects (686 men) unaffected by hepatic diseases as controls; all were hospitalized in Brescia, northern Italy, in 1995-2000. Spline regression models showed a steady linear increase in the odds ratio of HCC for increasing alcohol intake, for values of >60 g of ethanol per day, with no substantial differences between men and women. Duration of drinking and age at start had no effect on the odds ratio when alcohol intake was considered. Former drinkers who had stopped 1-10 years previously had a higher risk of HCC than current drinkers did. The effect of alcohol drinking was evident even in the absence of hepatitis B or hepatitis C virus infection. In addition, a synergism between alcohol drinking and either infection was found, with approximately a twofold increase in the odds ratio for each hepatitis virus infection for drinkers of >60 g per day.

PMID 11836196  Am J Epidemiol. 2002 Feb 15;155(4):323-31.
著者: C De Bac, T Stroffolini, G B Gaeta, G Taliani, G Giusti
雑誌名: Hepatology. 1994 Nov;20(5):1225-30.
Abstract/Text We designed a multicenter cross-sectional study to evaluate the role of alcohol abuse, the hepatitis viruses and other pathogenic factors in cirrhosis and hepatocellular carcinoma. A total of 1,829 consecutive cirrhosis patients, with or without HCC, was enrolled over 6 mo in 21 centers throughout Italy. The etiological categories and diagnostic criteria were preestablished. The median age of the patients was 59 yr (range, 13 to 85 yr); 63.6% of the patients were graded as Child class A, 23.4% as Child class B and 13% as Child class C. Hepatitis C virus antibodies were found in 72.1% of cases (47.7% alone, 21.2% with alcohol abuse, 3.2% with hepatitis B virus); HBsAg was present in 13.8% (4.2% alone, 3.2% with hepatitis D virus, 3.2% with hepatitis C virus, 3% with alcohol abuse), alcohol abuse with no concomitant viral infection was recorded in 8.7%, primary biliary cirrhosis was found in 1.8%, other causes were found in 1.4% and cryptogenic cirrhosis was only present in 5.3%. Hepatocellular carcinoma was detected in 11.9% of patients (217 cases). The presence of hepatocellular carcinoma was more frequent in males than females (14.7% vs. 7.3%; p < 0.001) and increased with worsening Child class (8.3% in Child class A, 16.9% in Child class B, 19.9% in Child class C, p < 0.001). The highest prevalences of hepatocellular carcinoma were observed in hepatitis B virus infection, with or without alcohol abuse (20% and 16%, respectively) and in hepatitis C virus cirrhosis, with or without alcohol abuse (16% and 10.3%, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 7523273  Hepatology. 1994 Nov;20(5):1225-30.
著者: A Oshima, H Tsukuma, T Hiyama, I Fujimoto, H Yamano, M Tanaka
雑誌名: Int J Cancer. 1984 Dec 15;34(6):775-9.
Abstract/Text In order to confirm the close association between chronic hepatitis B virus (HBV) infection and primary hepatocellular carcinoma (PHC) in Japan, 8,646 male hepatitis B surface antigen (HBs Ag)-positive blood donors (GPT less than or equal to 35 Karmen units) were followed up. Twenty liver cancer cases were observed during the follow-up period (average 6.2 years), the expected number calculated on the basis of age-specific incidence rates among the general population being 3.03. Therefore, the observed to expected ratio of liver cancer was 6.60, that is significantly higher than 1.0. During the same follow-up period, a total of 76 deaths were observed, of which 20 were due to liver cancers and 9 to liver cirrhoses, meaning that nearly 40% of deaths among the study subjects due to chronic liver diseases. Drinking and smoking habits in the liver cancer cases were compared with those observed in healthy male HBV carriers. A strong positive association between drinking habits and liver cancer was observed and there was a significant dose-response relationship after adjustment for cigarette smoking habits. A high risk of liver cancer was also observed among heavy smokers, but a significant dose-response relationship could not be found between smoking habits and liver cancer, partly because of the limited number of the study subjects. These findings suggest that HBV is a major etiologic agent of PHC in Japan where the HBs Ag prevalence rate is about 2%, and alcohol drinking and cigarette smoking may promote the process of HB viral hepato-carcinogenesis.

PMID 6511124  Int J Cancer. 1984 Dec 15;34(6):775-9.
著者: H Kuper, A Tzonou, E Kaklamani, C C Hsieh, P Lagiou, H O Adami, D Trichopoulos, S O Stuver
雑誌名: Int J Cancer. 2000 Feb 15;85(4):498-502.
Abstract/Text During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of hepatocellular carcinoma (HCC), as well as from 360 controls who were hospitalized for eye, ear, nose, throat or orthopedic conditions in Athens, Greece. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays, and information on smoking habits and beverage consumption was obtained. We found a significant dose-response, positive association between smoking and HCC risk [>/= 2 packs per day, odds ratio (OR)=2.5]. This association was stronger in individuals without chronic infection with either HBV or HCV (>/= 2 packs per day, OR=2.8). Consumption of alcoholic beverages above a threshold of 40 glasses per week increased the risk of HCC (OR=1.9). We also found evidence of a strong, statistically significant and apparently super-multiplicative effect of heavy smoking and heavy drinking in the development of HCC (OR for both exposures=9.6). This interaction was particularly evident among individuals without either HBsAg or anti-HCV (OR for both exposures=10.9). Coffee intake was not positively associated with HCC risk, but the reverse could not be excluded for the subgroup of chronically infected individuals. In conclusion, tobacco smoking and heavy alcohol consumption are associated with increased risk of HCC, especially when these 2 exposures occur together.

Copyright 2000 Wiley-Liss, Inc.
PMID 10699921  Int J Cancer. 2000 Feb 15;85(4):498-502.
著者: P Ginés, A Rimola, R Planas, V Vargas, F Marco, M Almela, M Forné, M L Miranda, J Llach, J M Salmerón
雑誌名: Hepatology. 1990 Oct;12(4 Pt 1):716-24.
Abstract/Text Eighty cirrhotic patients who had recovered from an episode of spontaneous bacterial peritonitis were included in a multicenter, double-blind trial aimed at comparing long-term norfloxacin administration (400 mg/day; 40 patients) vs. placebo (40 patients) in the prevention of spontaneous bacterial peritonitis recurrence. At entry, both groups were similar with respect to clinical and laboratory data, ascitic fluid protein and polymorphonuclear concentrations, number of previous episodes of spontaneous bacterial peritonitis and causative organisms of the index spontaneous bacterial peritonitis. Norfloxacin administration produced a selective intestinal decontamination (elimination of aerobic gram-negative bacilli from the fecal flora without significant changes in other microorganisms) throughout the study in six patients in whom the effect of norfloxacin on the fecal flora was periodically assessed. Fourteen patients from the placebo group (35%) and five from the norfloxacin group (12%) developed spontaneous bacterial peritonitis recurrence during follow-up (chi 2 = 5.97; p = 0.014) (mean follow-up period = 6.4 +/- 0.6 mo; range = 1 to 19 mo). Ten of the 14 spontaneous bacterial peritonitis recurrences in the placebo group and only one of the five spontaneous bacterial peritonitis recurrences in the norfloxacin group were caused by aerobic gram-negative bacilli (chi 2 = 8.87; p = 0.0029). The overall probability of spontaneous bacterial peritonitis recurrence at 1 yr of follow-up was 20% in the norfloxacin group and 68% in the placebo group (p = 0.0063) and the probability of spontaneous bacterial peritonitis recurrence caused by aerobic gram-negative bacilli at 1 yr of follow-up was 3% and 60%, respectively (p = 0.0013).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 2210673  Hepatology. 1990 Oct;12(4 Pt 1):716-24.
著者: Samuel H Sigal, Carmen M Stanca, Javier Fernandez, Vicente Arroyo, Miguel Navasa
雑誌名: Gut. 2007 Apr;56(4):597-9. doi: 10.1136/gut.2006.113050.
Abstract/Text
PMID 17369392  Gut. 2007 Apr;56(4):597-9. doi: 10.1136/gut.2006.113050・・・
著者: P Sort, M Navasa, V Arroyo, X Aldeguer, R Planas, L Ruiz-del-Arbol, L Castells, V Vargas, G Soriano, M Guevara, P Ginès, J Rodés
雑誌名: N Engl J Med. 1999 Aug 5;341(6):403-9. doi: 10.1056/NEJM199908053410603.
Abstract/Text BACKGROUND: In patients with cirrhosis and spontaneous bacterial peritonitis, renal function frequently becomes impaired. This impairment is probably related to a reduction in effective arterial blood volume and is associated with a high mortality rate. We conducted a study to determine whether plasma volume expansion with intravenous albumin prevents renal impairment and reduces mortality in these patients.
METHODS: We randomly assigned 126 patients with cirrhosis and spontaneous bacterial peritonitis to treatment with intravenous cefotaxime (63 patients) or cefotaxime and intravenous albumin (63 patients). Cefotaxime was given daily in dosages that varied according to the serum creatinine level, and albumin was given at a dose of 1.5 g per kilogram of body weight at the time of diagnosis, followed by 1 g per kilogram on day 3. Renal impairment was defined as nonreversible deterioration of renal function during hospitalization.
RESULTS: The infection resolved in 59 patients in the cefotaxime group (94 percent) and 62 in the cefotaxime-plus-albumin group (98 percent) (P=0.36). Renal impairment developed in 21 patients in the cefotaxime group (33 percent) and 6 in the cefotaxime-plus-albumin group (10 percent) (P=0.002). Eighteen patients (29 percent) in the cefotaxime group died in the hospital, as compared with 6 (10 percent) in the cefotaxime-plus-albumin group (P=0.01); at three months, the mortality rates were 41 percent (a total of 26 deaths) and 22 percent (a total of 14 deaths), respectively (P=0.03). Patients treated with cefotaxime had higher levels of plasma renin activity than those treated with cefotaxime and albumin; patients with renal impairment had the highest values.
CONCLUSIONS: In patients with cirrhosis and spontaneous bacterial peritonitis, treatment with intravenous albumin in addition to an antibiotic reduces the incidence of renal impairment and death in comparison with treatment with an antibiotic alone.

PMID 10432325  N Engl J Med. 1999 Aug 5;341(6):403-9. doi: 10.1056/NEJ・・・
著者: B A Runyon, J G McHutchison, M R Antillon, E A Akriviadis, A A Montano
雑誌名: Gastroenterology. 1991 Jun;100(6):1737-42.
Abstract/Text In an attempt to determine the optimal duration of therapy of spontaneous bacterial peritonitis, 100 patients with neutrocytic ascites and suspected spontaneous bacterial peritonitis were randomized to short-course vs. long-course treatment groups. Empiric therapy was initiated before the results of ascitic fluid culture were available. Of the 90 patients who met strict criteria for spontaneous bacterial peritonitis or culture-negative neutrocytic ascites, 43 were randomized to a group receiving 5 days and 47 to a group receiving 10 days of single-agent cefotaxime, 2 g IV every 8 hours. Infection-related mortality (0% vs. 4.3%), hospitalization mortality (32.6% vs. 42.5%), bacteriologic cure (93.1% vs. 91.2%), and recurrence of ascitic fluid infection (11.6% vs. 12.8%) were not significantly different between the 5- and 10-day treatment groups, respectively. Recurrence rates were comparable to the values reported in the literature. The cost of antibiotic and antibiotic administration were significantly lower in the short-course group. Short-course treatment of spontaneous bacterial peritonitis is as efficacious as long-course therapy and significantly less expensive.

PMID 2019378  Gastroenterology. 1991 Jun;100(6):1737-42.
著者: M Bhuva, D Ganger, D Jensen
雑誌名: Am J Med. 1994 Aug;97(2):169-75.
Abstract/Text Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with cirrhotic ascites. Greater understanding of the pathogenesis and risk factors for the development of SBP recently has improved our ability to prevent and treat the infection. The decreased threshold for performing diagnostic paracentesis in cirrhotic patients coupled with the use of non-nephrotoxic antibiotics have resulted in decreasing mortality rates for patients with SBP. Despite these advances, recurrence is common and often fatal. Thus, the prevention of SBP by diuresis and oral antibiotic prophylaxis has recently been studied. This review summarizes the recent developments in SBP, with an emphasis on patient management and prevention of SBP.

PMID 8059783  Am J Med. 1994 Aug;97(2):169-75.
著者: M Navasa, A Follo, J M Llovet, G Clemente, V Vargas, A Rimola, F Marco, C Guarner, M Forné, R Planas, R Bañares, L Castells, M T Jimenez De Anta, V Arroyo, J Rodés
雑誌名: Gastroenterology. 1996 Oct;111(4):1011-7.
Abstract/Text BACKGROUND & AIMS: Treatment of spontaneous bacterial peritonitis currently involves intravenous antibiotic administration. To test the possibility of treating spontaneous bacterial peritonitis with oral antibiotics, oral ofloxacin was compared with intravenous cefotaxime in this infection.
METHODS: One hundred twenty-three cirrhotics with uncomplicated spontaneous bacterial peritonitis (no septic shock, grade II-IV hepatic encephalopathy, serum creatinine level of > 3 mg/dL, and gastrointestinal hemorrhage or ileus) were randomly given oral ofloxacin (64 patients) or intravenous cefotaxime (59 patients).
RESULTS: Infection resolution rate was 84% in the ofloxacin group and 85% in the cefotaxime group. Peak serum levels and trough serum and ascitic fluid levels of ofloxacin and cefotaxime measured on days 3 (23 patients) and 6 (11 patients) of therapy were greater than the minimal inhibitory concentration of isolated organisms. Hospital survival rate was 81% in each group of patients. Blood urea nitrogen and hepatic encephalopathy at diagnosis were associated with prognosis. None of the 36 nonazotemic patients with community-acquired spontaneous bacterial peritonitis and without hepatic encephalopathy developed complications during hospitalization, and all were alive at time of discharge.
CONCLUSIONS: Oral ofloxacin is as effective as intravenous cefotaxime in uncomplicated spontaneous bacterial peritonitis. Nonazotemic cirrhotic patients with uncomplicated community-acquired spontaneous bacterial peritonitis and without hepatic encephalopathy have an excellent prognosis and may be treated with oral ofloxacin without requiring hospitalization.

PMID 8831596  Gastroenterology. 1996 Oct;111(4):1011-7.

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