Spontaneous bacterial peritonitis ( SBP ) in adults - Diagnosis and management of
|Next review: 25/10/2022|
|Approved By: Improving Antimicrobial Prescribing Group|
|Copyright© Leeds Teaching Hospitals NHS Trust 2019|
This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
Update on aztreonam injection shortage - now only restricted outside of CF and UTI (protected antibiotic codes no longer required for these indications). See alternatives - 22 August 2018
Guideline for diagnosis and management of spontaneous bacterial peritonitis (SBP) in adults
Spontaneous bacterial peritonitis ( SBP ) in adults
SBP may be suspected on clinical grounds but confirmation and classification is a laboratory diagnosis.
Table 1. Ascitic fluid tests required.
If genuine penicillin allergy –Tigecycline IV 100mg loading dose followed by 50mg 12-hourly. If Child Pugh C liver disease reduce to 25mg 12-hourly IV.
For directed therapy regimens, duration of treatment, switch to oral agent(s) see full guideline
Table 3. Adapted from Sleisenger’s & Fordtran’s Gastrointestinal & Liver Disease, 7th Ed, Elsevier.
Many of the features of liver failure make the recognition of sepsis difficult. For example, the reduced peripheral neutrophil count due to hypersplenism, elevated basal heart rate and relative hypotension due to the hyperdynamic circulation and basal hyperventilation due to encephalopathy (Wong et al., 2005). A high index of suspicion must be maintained. [Evidence level C]
SBP may be suspected on clinical grounds but confirmation and classification is a laboratory diagnosis (see investigations below).
SBP can only be diagnosed by examining a sample of ascitic fluid. Abdominal paracentesis (ascitic tap) is safe (Runyon 1986, Lin et al., 2005).
Recommendation: A routine diagnostic paracentesis should be performed PRIOR to starting antimicrobial therapy within 6 hours in all patients:
A number of ascitic fluid parameters have been evaluated for the diagnosis of SBP. The highest accuracy for a diagnosis of SBP can be made from a pH ≤ 7.34 or a blood-ascitic fluid gradient ≥ 0.10 in combination with an ascitic fluid neutrophil count > 500/mm3 (0.5 x 109/l) (Stassen et al., 1986). An ascitic fluid neutrophil count ≥ 250/mm3 (0.25 x109/l) is consistent with a diagnosis of SBP (Garcia-Tsao 1992, Arroyo et al., 2000). The total white cell count can also be used to diagnose SBP. Runyon et al. (2006) suggest a WCC > 500mm3 (0.5 x 109/l) is diagnostic, irrespective of the differential. The ascitic cell count and differential is performed by automated techniques in the laboratory.
Recommendation: Samples of ascitic fluid should be routinely sent to haematology for a differential white cell count [Evidence level B].
Recommendation: an ascitic fluid neutrophil count ≥ 250/mm3 (or 0.25 x109/l) should be considered diagnostic for SBP in an appropriate clinical situation. [Evidence level B]
Leukocyte esterase reagent strips have a high sensitivity (64 to 100%) and specificity (92.5 to 100%) in the detection of an elevated ascitic fluid neutrophil count (Castelote et al., 2002, Sapey et al., 2005). Although these are cheap, rapid and readily available on wards (urine dipsticks) microscopy is an absolute requirement so bedside testing will not alter management and is not therefore recommended.
Recommendation: use of Leukocyte esterase reagent strips is not recommended for the diagnosis of SBP. [Evidence level D]
Recommendation: 10ml ascitic fluid should be inoculated directly into both an aerobic and anaerobic blood culture bottle according to Standard operating procedure. [Evidence level D]
Recommendation: When an ascitic culture unexpectedly yields an organism known to cause SBP in a patient without clinical signs of infection or with a low ascitic WCC the ascitic tap must be repeated to reassess the neutrophil count and re-culture (Rimola et al., 2000). [Evidence level C]
Recommendation: When an ascitic culture yield a potential contaminant (e.g. coagulase-negative staphylococcus or “diphtheroid” the ascitic tap should be repeated to reassess the neutrophil count and re-culture (Rimola et al., 2000). [Evidence level C]
Recommendation: If mixed organisms are seen on Gram-stain or cultured – (particularly anaerobes and Candida species). Consider a surgical cause or sampling from gut lumen. [Evidence level C]
Recommendation: consider secondary bacterial peritonitis if ascitic fluid neutrophil count is climbing despite 48 hours of antibiotics. [Evidence level C]
Paracentesis may be repeated after 48 hours of treatment to assess the response to antibiotics. [Evidence level D]
|Empirical Antimicrobial Treatment|
The initial decision to treat suspected ascitic fluid infection is based on an elevated fluid neutrophil count and/or the clinical setting. A high index of suspicion is essential. CNNA and SBP have comparable mortality rates so similar management is warranted.
The recommended empirical regimen for SBP is Piperacillin/tazobactam 4.5g 8-hourly iv. [Evidence level D]
If genuine penicillin allergy –Tigecycline IV 100mg loading dose followed by 50mg 12-hourly IV*. If Child Pugh C liver disease reduce to 25mg 12-hourly IV [Evidence level D]
Note: Tigecycline is not active against Pseudomonas species; call Microbiology if there are any concerns about this.
Up to 10% of infections are caused by Gram-positive cocci (particularly Enterococcus species). Ampicillin-Tobramycin and Co-Amoxiclav (Amoxicillin-Clavulanate) have been used with the assumption that they would provide adequate Gram-positive cover.
The Cochrane review made no firm conclusions from the randomised controlled trials. Although third generation cephalosporins have been established as the standard treatment of SBP in many centres, current concerns about Clostridium difficile infection, selection of extended-spectrum beta-lactamase (ESBL) producing coliforms and adequacy of spectrum have raised questions about the wisdom of this approach.
Piperacillin/tazobactam was chosen in order to provide appropriate antimicrobial cover (including enterococci, streptococci, and resistant gram-negative including Pseudomonas species) and to avoid the use of cephalosporins, quinolones (whose activity can no longer be relied upon for empirical treatment) and Gentamicin (to reduce the risk of toxicity). Tigecycline has an appropriate spectrum of activity (active against Staphylococus aureus, enterococci and many Gram negatives but not Pseudomonas). Tigecycline is licensed for use in intra-abdominal infections but data specific for spontaneous bacterial peritonitis are lacking.
N.B. Co-Amoxiclav (Amoxicillin-Clavulanate) susceptibility was not been routinely tested in the laboratory during the review period so data are not available. Cefuroxime can be used as a reasonable marker of Co-Amoxiclav (Amoxicillin-Clavulanate) susceptibility. This antimicrobial is less broad spectrum than Piperacillin/tazobactam against Gram-negatives and lacks antipseudomonal activity.
|Directed Antimicrobial Treatment (when microbiology results are known)|
If ascitic fluid culture results are positive then antimicrobials should be changed to optimise effectiveness and reduce adverse effects - this will usually be the most narrow spectrum effective agent available.
Directed therapy should be determined on a case by case basis with discussion with Microbiology if required.
|Duration of Treatment|
In most studies the length of treatment was based on disappearance of symptoms and signs. One study demonstrated no difference in either mortality or resolution of SBP with 5 or 10 days treatment with intravenous Cefotaxime .
Recommendation: To reduce adverse events including selection for resistant bacteria five days should be the standard duration, extended up to 10 days if clinical response is slow. [Evidence level B]
|Switch to oral agent(s)|
There is some evidence to support a switch from intravenous to oral antibiotics early in patients who show an improvement after a short IV course. Oral therapy alone may be possible from the start of treatment in those without systemic inflammatory response or renal failure. Oral Ciprofloxacin /Ofloxacin , Co-Amoxiclav (Amoxicillin-Clavulanate) , and oral 3rd generation cephalosporins demonstrated non-inferiority when compared to IV therapies. Oral Ofloxacin was compared with IV Cefotaxime in 123 patient with uncomplicated SBP (no encephalopathy, renal failure, vomiting, ileus, shock or GI haemorrhage) - no difference in the number of deaths, resolution of SBP or presence of adverse effects was seen. Two 3rd generation cephalosporins were compared in 38 patients - oral Cefixime vs. IV Ceftriaxone , but no significant differences were found for any of the outcomes provided. No difference in effectiveness or mortality was demonstrated when oral Ciprofloxacin was compared to IV Ciprofloxacin in 80 cirrhotic patients with SBP.
Recommendation: Switch to oral antimicrobials should be considered when patients are clinically improving, afebrile and inflammatory markers falling. [Evidence level C]
If patients have been commenced on Piperacillin/tazobactam then oral Co-Amoxiclav (Amoxicillin-Clavulanate) 625mg 8-hourly is appropriate for oral switch unless culture results indicate otherwise. [Evidence level B]
|Please contact Microbiology if the patient is not responding to the recommended antimicrobial regimens.|
|Target patient group:||all adult patients with SBP|
|Target professional group(s):||Secondary Care Doctors
Secondary Care Nurses
Arroyo V et al. Spontaneous Bacterial Peritonitis, Eds. O’Grady and Lake’s comprehensive clinical hepatology, 1st Ed. Barcelona: Mosby, 2000:7.10-7.14.
Bobadilla et al. Improved method for bacteriological diagnosis of spontaneous bacterial peritonitis. J Clin Microbiol 1989; 27:2145-7.
Campillo B et al. Epidemiology of severe hospital-acquired infections in patients with liver cirrhosis: effect of long term administration of norfloxacin. Clin Infect Dis 1998; 26:1066-70.
Castelote J et al. Rapid diagnosis of SBP by the use of reagent strips. Hepatology 2002; 37:893-6.
Cirera I et al. Bacterial translocation of enteric organisms in patients with cirrhosis. J Hepatol 2001; 34:32-7.
Conn H, Fessel J. Spontaneous bacterial peritonitis in cirrhosis: variations on a theme. Medicine 1971; 50:161-97.
Fernandez J et al. Bacterial infections in cirrhosis: Epidemiological changes with invasive procedures and norfloxacin prophylaxis. Hepatology 2002; 35:140-8.
Fernandez J et al. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and haemorrhage. Gastroenterology 2006. 131(4): 1049-56.
Frances R et al. Bacterial DNA activates cell mediated immune response and nitric oxide overproduction in peritoneal macrophages from patients with cirrhosis and ascites. Gut 2004; 53:860-4.
Friedman LS, Keeffe EB. Handbook of Liver Disease. 2nd Ed. Elsevier Inc 2004.
Garcia-Tsao G. Spontaneous bacterial peritonitis. Gastroenterol Clin N Am 1992; 21:257-75.
Garcia-Tsao G. Current management of the complications of cirrhosis and portal hypertension: variceal haemorrhage, ascites and spontaneous bacterial peritonitis. Gastroenterology 2001; 120:726-48.
Garcia-Tsao G. Spontaneous Bacterial Peritonitis: a historical perspective. J Hepatol 2004; 41: 522-7.
Gines P, Rimola A, Planas R, et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. Hepatology 1990; 12:716–24.
Guarner C et al. Intestinal bacterial overgrowth and bacterial translocation in an experimental model of cirrhosis in rats. J Hepatol 1997; 26:1372-8.
Guarner C et al. Bacterial translocation and its consequences in patients with cirrhosis. Eur J Gastroenterol Hepatol 2005; 17:27-31.
Jalan R, Hayes P. UK guidelines on the management of variceal haemorrhage in cirrhotic patients. British Society of Gastroenterology 2000.
Lin Y et al. Prophylactic antibiotics with upper gastrointestinal haemorrhage: a prospective, controlled trial. Chinese Medical Journal 2002; 65(8): 365-371.
Lin C et al. Pre-procedure coagulation tests are unnecessary before abdominal paracentesis in emergency departments. Hepatology 2005; 41:402-3.
Moore K, Aithal G. Guidelines on the management of ascites in cirrhosis. Gut 2006; 55; 1-12.
Rimola A et al. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. J Hepatol 2000; 32:142-53.
Rolachon A, Cordier L, Bacq Y, et al. Ciprofloxacin and long-term prevention of spontaneous bacterial peritonitis: results of a prospective controlled trial. Hepatology 1995; 22:1171–4.
Ruiz-del-Arbo L et al. Cardiovascular, renal and hepatic haemodynamic derangement in cirrhotic patients with spontaneous peritonitis. Hepatology 2003; 38:1210-8.
Runyon B. Paracentesis of ascitic fluid: a safe procedure. Arch Intern Med 1986; 146:2259-61.
Runyon B. Ascites and spontaneous bacterial peritonitis. In: Feldman M et al. Sleisenger and Fordran’s gastrointestinal and liver disease, 8th Ed. Philadelphia: Saunders 2006:1935-64.
Sapey T et al. Rapid diagnosis of spontaneous bacterial peritonitis with leukocyte esterase reagent strips in an European and in an American centre. J Gastroenterol Hepatol 2005; 20:187-92.
Sherlock S, Dooley J. Spontaneous Bacterial Peritonitis. In: Sherlock and Dooley’s diseases of the liver and biliary system, 11th Ed. Oxford: Blackwell, 2002:132-4.
Singh N et al. Trimethoprim-Sulfamethoxazole for the prevention of Spontaneous Bacterial peritonitis in cirrhosis. Annals of Internal medicine 1995; 122: 595-598.
Sleisenger’s & Fordtran’s Gastrointestinal & Liver Disease, 7th Ed, Elsevier Inc.
Soares-Weiser K, Brezis M, Tur-Kaspa R, Leibovici L. Antibiotic prophylaxis for cirrhotic patients with gastrointestinal bleeding. The Cochrane Collaboration 2005; 1:1-34.
SongJ et al. Prognostic significance of infection acquisition sites in spontaneous bacterial peritonitis: nosocomial vs. community acquired. J Korean Med Sci 2006; 21:666-71.
Sort P et al. Effects of intravenous albumin on renal impairment and mortality in patients with cirrhosis and SBP. N Engl J Med 1999; 341:403-9.
Stassen W et al. Immediate diagnostic criteria for bacterial infection of ascitic fluid – evaluation of ascitic fluid polymorphonuclear leukocyte count, pH, and lactate concentration, alone and in combination. Gastroenterology 1986; 90:1247-54.
Wong F et al. Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club. Gut 2005; 54:718-25.
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