Spontaneous bacterial peritonitis laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Shivani Chaparala M.B.B.S [2]

Overview

Early Diagnostic paracentesis (needle drainage of the ascitic fluid performed in < 72hrs) is recommended in all cirrhotic patients with ascites. Paracentesis reveals an ascitic fluid with a total white cell count of up to 500 cells/mcL, a high polymorphonuclear (PMN) cell count (250/mm3 more). Ascitic fluid analysis and culture must be performed before initiating antibiotic therapy by bedside inoculation of ascitIc fluid ≥ 10 mL into blood culture bottles. Ascitic fluid analysis is the gold standard for the confirmation of the diagnosis of spontaneous bacterial peritonitis. Ascitic fluid culture is negative in up to 60% of patients with clinical manifestations of spontaneous bacterial peritonitis (SBP). Therefore, the diagnosis of SBP is based on the neutrophil count, which reaches its highest sensitivity with a cutoff neutrophil count of > 250/mm3.[1] Leukocytosis and acidosis may be present but are non-specific. If reasonable doubt still persists, an exploratory peritoneal lavage may be performed (e.g. in the case of trauma, in order to look for white blood cells, red blood cells, or bacteria).

Laboratory Findings

Laboratory tests for the diagnosis and differential diagnosis of SBP
Ascitic fluid analysis Spontaneous Bacterial Peritonitis Secondary bacterial peritonitis Hepatic ascites[2] Cardiac ascites[3] Nephrogenic ascites Pancreatic ascites Tuberculous ascites Malignant ascites[4]
Gross appearance cloudy or turbid turbid or purulent clear straw or milky clear to pale yellow straw colored or chylous milky or cloudy or turbid milky or normal milky or bloody
Leukocyte count and differential (cells/mm3) ≥ 250 PMN > 1000 WBC

predominantly

PMN

< 500 WBC

≥ 250 PMN or normal

< 500 WBC

< 250 PMN

< 500 WBC

< 250 PMN

< 500 WBC

≥ 250 PMN

≥ 250 PMN or normal ≥ 500 WBC
Total protein ≥ 25 g/L > 25 g/ L < 25 g/L ≥ 25 g/L < 25 g/L ≥ 25 g/L ≥ 25 g/L ≥ 25 g/L
Serum-ascites albumin gradient[5][6] ≥ 1.1 g/dL ≥ 1.1 g/dL ≥ 1.1 g/dL ≥ 1.1 g/dL < 1.1 g/dL < 1.1 g/dL < 1.1 g/dL < 1.1 g/dL
LDH(lactate dehydrogenase) ↑or normal > upper limit of normal for serum LDH ↓ or normal ↑or normal ↑or normal
Glucose < 50 mg/dL normal normal
Amylase - - normal - - - ↑or normal
Tumor markers - - ↑or normal normal - ↑or normal ↑or normal
Confirmatory tests single organism in culture, total protein < 1 g/dL, glucose > 50 mg/dl, LDH < 225 units/ L. poly-microbial infection including anaerobes , total protein > 1 g/dL, glucose < 50 mg/dL, LDH ≥ 225 units/ L. Upright abdominal x-ray, water soluble contrast studies of GI tract ultrasound and/or liver biopsy chest x-ray and ekg 24-hour urine protein excretion Abdominal CT scan mycobacterial growth on culture of laparoscopic biopsy specimen of peritoneum search for primary tumor
Additional comments good clinical response to antibiotics. Consider surgery if perforation of gut is suspected.

CEA >5 ng/ml.[7]

Alkaline phosphatase > 240 units/ L.[7]

ascitic fluid amylase > 100 units/ L laparoscopy, peritoneal biopsy, bacteriology, PCR. cytology
Relative frequency - - 81% 3% Dialysis associated- 1% 1% 2% 10%

Approach to the diagnosis and treatment of spontaneous bacterial peritonitis

 
 
 
 
 
 
 
 
 
Diagnostic Paracentesis
❑ Perform ascitic fluid cell count and differential
❑ Perform ascitic fluid culture (Inoculated at bedside)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PMN ≥ 250cells/mm³
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If YES
❑ Presumptive SBP
❑ Begin empiric antibiotic therapy(eg:Cefotaxime 2g IV q8H and
❑ IV Albumin on day 1 & day 3
IF serum creatinine 1mg/dl, BUN > 30mg/dl or total albumin > 4mg/dl
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IF NO
❑ Look for the signs/symptoms of Infection
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is Culture Positive ?
 
 
 
 
 
 
 
Absent Symptoms
❑ Is Culture Positive?
 
 
 
 
 
 
 
 
Symptoms Present
❑ Begin Empiric Antibiotic Therapy for SBP
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Negative Culture Culture Negative Neutrocytic Ascites ( CNNA )
❑ morbidity and mortality same as SBP
❑ Treat as SBP
❑ Complete 5 day Antibiotic Course
 
Confirmed SBP
❑ Narrow the spectrum based on the susceptibility to complete the 5 day course
 
 
Culture Negative
❑ No Antibiotics indicated
 
 
 
 
Culture Positive
Monomicrobial nonneutrocytic Bacterascites: ❑ Followup paracentesis recommended when the culture growth is discovered
❑ ~ 60% spontaneous resolution, ❑ ~ 40% turn to SBP. Polymicrobial bacterascites: ❑ Low morbidity ❑ Majority from traumatic tap
❑ Clinical followup +/- antibiotics is recommended
 
 
 

Routine laboratory studies for spontaneous bacterial peritonitis include:


Diagnostic paracentesis:

Performed usually within 72 hrs of admission.[10]

Indications for diagnostic paracentesis
  • Upon admission to the hospital

Given the similarities in presentation between the variants of ascitic fluid infection and the inability to clinically distinguish spontaneous from secondary peritonitis, the diagnosis of SBP should be through abdominal paracentesis as it has been shown to be safe with a low risk for complication, even in patients with marked coagulopathy and thrombocytopenia.

Ascitic Fluid Analysis

Ascitic fluid analysis is the gold standard and is required for the confirmation of the diagnosis of spontaneous bacterial peritonitis.[11]

Tests Diagnostic Values
Cell count with differential Leukocyte count > 500 cells/mm3 Absolute neutrophil count >250 cells/mm3
Bacterial culture[12] Usually positive for gram-negative bacteria (mainly Escherichia coli and Klebsiella) and gram-positive cocci (usually Streptococcus spp. and enterococci).[13][14]
Protein concentration 1 g/dL (10 g/L) or less

Ascitic fluid Culture

  • Performed before initiating antibiotic therapy by bedside inoculation of ascitIc fluid ≥ 10 mL into blood culture bottles, instead of sending the fluid to the laboratory in a syringe or container, since immediate inoculation improves the yield on bacterial culture from approximately 65% to 90%, when the ascitic fluid cell count is at least 250 cells/mm3.[15]
  • Separate and simultaneous blood cultures should also be obtained, as up to 50% of patients with SBP have concomitant bacteremia.
  • Neither sensitive/specific
  • But is indicated to rule out secondary peritonitis caused by many organisms usually anaerobes and also to guide and narrow down the appropriate antibiotic of choice based on the culture and sensitivity results.

The following tests are recommended for suspected infection of the ascitic fluid.[16]

  1. Gram stain: To identify the number of organisms causing peritonitis, most helpful in the diagnosis of free perforation of the intestine, where many different organisms are found including gram negative bacteria and anaerobes, fungi.
  2. Total protein: 20% of ascitic samples in patients with cirrhosis will have a protein concentration greater than 2.5 g/dL
  3. Lactate dehydrogenase: In SBP, the ascitic fluid LDH rises because of the release of LDH from neutrophils, and the concentration will be more than serum concentration. In secondary peritonitis, the levels are even more elevated than in SBP.
  4. Glucose: Under normal conditions, and in early SBP, the ascitic fluid glucose concentration is similar to that of serum. By contrast, in SBP detected later in its course, and as well as in the setting of intestinal perforation into ascitic fluid, the ascitic fluid concentration drops to 0 mg/dL because of consumption of glucose by increased numbers of neutrophils and bacteria.
  5. Amylase: In uncomplicated ascites in the setting of cirrhosis, the ascitic fluid amylase concentration usually one half that of the serum value. In patients with acute pancreatitis or intestinal perforation (with release of luminal amylase into the ascitic fluid), the fluid amylase concentration is elevated markedly, and approximately five-fold greater than simultaneous serum values.
  6. Albumin: It is important for the calculation of serum-ascites albumin gradient , and helps us in identifying the portal hypertension and associated prognosis.
  7. Serum-ascites albumin gradient (if not calculated before): SAAG > 1.1 g/dL indicates the presence of portal hypertension. Peritoneal carcinomatosis is the most common cause of a low SAAG.
  8. AFB smear and culture: Helps in the identification of tuberculous peritonitis which presents similarly to SBP, with fever, abdominal pain and one half of patients have cirrhosis.
  9. Bilirubin: AF bilirubin > 6 mg/dL suggests biliary or small intestinal perforation into AF.
  10. Triglyceride: A triglyceride level should be measured in opalescent or frankly milky ascitic fluid. Chylous ascites has a triglyceride concentration greater than serum (200 mg/dL).
  11. Cytology: Expensive and is only revealing in the setting of peritoneal carcinomatosis, typically in patients with a history of breast, colon, gastric or pancreatic carcinoma.
  • Paracentesis reveals an ascitic fluid with, most commonly:[17]
    • Decreased ascitic opsonic activity.
    • Some patients may have an ascitic neutrophil count <250 cells/mm3 with positive cultures. This is known as "bacterascites". These patients should undergo a repeat paracentesis.
    • Patients with signs of Systemic inflammatory response syndrome (SIRS) or in whom the repeat ascitic neutrophil count is >250 cells/mm3 should receive antibiotic therapy.
    • If not, they should be followed up.[1]

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References

  1. 1.0 1.1 European Association for the Study of the Liver (2010). "EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis". J Hepatol. 53 (3): 397–417. doi:10.1016/j.jhep.2010.05.004. PMID 20633946.
  2. Moore CM, Van Thiel DH (2013). "Cirrhotic ascites review: Pathophysiology, diagnosis and management". World J Hepatol. 5 (5): 251–63. doi:10.4254/wjh.v5.i5.251. PMC 3664283. PMID 23717736.
  3. Runyon BA (1988). "Cardiac ascites: a characterization". J Clin Gastroenterol. 10 (4): 410–2. PMID 3418089.
  4. Runyon BA, Hoefs JC, Morgan TR (1988). "Ascitic fluid analysis in malignancy-related ascites". Hepatology. 8 (5): 1104–9. PMID 3417231.
  5. Mauer K, Manzione NC (1988). "Usefulness of serum-ascites albumin difference in separating transudative from exudative ascites. Another look". Dig Dis Sci. 33 (10): 1208–12. PMID 3168691.
  6. Runyon BA, Montano AA, Akriviadis EA, Antillon MR, Irving MA, McHutchison JG (1992). "The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites". Ann Intern Med. 117 (3): 215–20. PMID 1616215.
  7. 7.0 7.1 Wu SS, Lin OS, Chen YY, Hwang KL, Soon MS, Keeffe EB (2001). "Ascitic fluid carcinoembryonic antigen and alkaline phosphatase levels for the differentiation of primary from secondary bacterial peritonitis with intestinal perforation". J Hepatol. 34 (2): 215–21. PMID 11281549.
  8. Terg, Rubén; Gadano, Adrian; Cartier, Mariano; Casciato, Paola; Lucero, Romina; Muñoz, Alberto; Romero, Gustavo; Levi, Diana; Terg, Gonzalo; Miguez, Carlos; Abecasis, Raquel (2009). "Serum creatinine and bilirubin predict renal failure and mortality in patients with spontaneous bacterial peritonitis: a retrospective study". Liver International. 29 (3): 415–419. doi:10.1111/j.1478-3231.2008.01877.x. ISSN 1478-3223.
  9. Wu, Hongli; Chen, Lin; Sun, Yuefeng; Meng, Chao; Hou, Wei (2016). "The role of serum procalcitonin and C-reactive protein levelsin predicting spontaneous bacterial peritonitis in patients with advanced liver cirrhosis". Pakistan Journal of Medical Sciences. 32 (6). doi:10.12669/pjms.326.10995. ISSN 1681-715X.
  10. Rimola, Antoni; García-Tsao, Guadalupe; Navasa, Miquel; Piddock, Laura J.V.; Planas, Ramon; Bernard, Brigitte; Inadomi, John M. (2000). "Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document". Journal of Hepatology. 32 (1): 142–153. doi:10.1016/S0168-8278(00)80201-9. ISSN 0168-8278.
  11. Riggio O, Angeloni S (2009). "Ascitic fluid analysis for diagnosis and monitoring of spontaneous bacterial peritonitis". World J Gastroenterol. 15 (31): 3845–50. PMC 2731245. PMID 19701963.
  12. Runyon BA, Canawati HN, Akriviadis EA (1988). "Optimization of ascitic fluid culture technique". Gastroenterology. 95 (5): 1351–5. PMID 3049220.
  13. Caly WR, Strauss E (1993). "A prospective study of bacterial infections in patients with cirrhosis". J Hepatol. 18 (3): 353–8. PMID 8228129.
  14. Sajjad M, Khan ZA, Khan MS (2016). "Ascitic Fluid Culture in Cirrhotic Patients with Spontaneous Bacterial Peritonitis". J Coll Physicians Surg Pak. 26 (8): 658–61. doi:2399 Check |doi= value (help). PMID 27539758.
  15. Runyon BA, Antillon MR, Akriviadis EA, McHutchison JG (1990). "Bedside inoculation of blood culture bottles with ascitic fluid is superior to delayed inoculation in the detection of spontaneous bacterial peritonitis". J Clin Microbiol. 28 (12): 2811–2. PMC 268281. PMID 2280015.
  16. Lippi G, Danese E, Cervellin G, Montagnana M (2014). "Laboratory diagnostics of spontaneous bacterial peritonitis". Clin Chim Acta. 430: 164–70. doi:10.1016/j.cca.2014.01.023. PMID 24508989.
  17. Orman ES, Hayashi PH, Bataller R, Barritt AS (2014). "Paracentesis is associated with reduced mortality in patients hospitalized with cirrhosis and ascites". Clin Gastroenterol Hepatol. 12 (3): 496–503.e1. doi:10.1016/j.cgh.2013.08.025. PMC 3944409. PMID 23978348.


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