Spontaneous bacterial peritonitis is a sequela of ascites resulting from infection of the ascitic fluid in the absence of any primary focus of intraabdominal inflammation.
Presentation
Although a significant 30% of patients proven to have SBP via positive paracentesis may present asymptomatically [15], any acute change in the ascitic patient's clinical status warrants suspicion for SBP. Being an infection it may present with varied signs and symptoms and it is therefore important to rule out other possible causes by conducting thorough investigative laboratory and imaging tests. One particular study on SBP reported the most common clinical features to be abdominal tenderness (46%), altered mental status (61%) and fever (68%) [16].
Patients with SBP are likely to present with the following symptoms:
- Fever and chills (80%)
- Abdominal pain: mild to moderate in intensity, not localized, and persistent (70%)
- Diarrhea
- Gastrointestinal bleeding
- Nausea and vomiting
- Body malaise
- Other features of ascites
On physical examination patients will show characteristic signs that may be attributed to the underlying cirrhosis and/or ascites. In addition, other signs may be elicited dependent on whether there is an asymptomatic bacteriascites or a more severe sepsis syndrome with possible fatality [17]. Common signs include:
- Stigmata of chronic hepatic failure including jaundice and angiomata
- Hypotension (5%-14%)
- Abdominal tenderness: mild to severe with possible signs of guarding and rebound tenderness (>50%). Although these may be masked by the effect of ascitic fluid.
- Altered mental status with possible new onset or worsening encephalopathy
- Ileus
Of importance, suspicion for SBP should be raised when the patient develops a new onset renal failure or a worsening renal/hepatic failure.
Entire Body System
- Fever
Cirrhotic patients with ascites and clinical suspicion for SBP-abdominal pain or tenderness, fever or altered mental status-should have a diagnostic paracentesis. [ncbi.nlm.nih.gov]
Fever on presentation, or in the last 24 hours, is highly specific for SBP (Table 1 ) [16]. [doi.org]
Signs of SBP may include fever, malaise, encephalopathy, worsening hepatic failure, and unexplained clinical deterioration. [merckmanuals.com]
- Recurrent Infection
[…] is of concern, there is a higher risk of infection due to Candida and Enterococcus species, Fluconazole is warranted in patients who have a malignancy, transplant, inflammatory disease, recurrent intra-abdominal infection, gastric ulcer on acid suppression [uspharmacist.com]
Gastrointestinal
- Abdominal Pain
Cirrhotic patients with ascites and clinical suspicion for SBP-abdominal pain or tenderness, fever or altered mental status-should have a diagnostic paracentesis. [ncbi.nlm.nih.gov]
- Vomiting
In each instance it started abruptly with sudden fever and shaking chills, accompanied by nausea, vomiting, and progressive abdominal discomfort. Hypotension, which was present in each patient, was usually severe. [doi.org]
[…] grams every 8 hours Nosocomial source of infection may require broadening of antibiotic coverage Oral antibiotics Oral agents Ofloxacin 400 mg orally twice daily Amoxicillin -Clavulanate ( Augmentin ) Indications for oral therapy Tolerating oral (no Vomiting [fpnotebook.com]
Vomiting precedes pain and is followed by diarrhea (gastroenteritis) Delayed vomiting, absent bowel movement and flatus (acute intestinal obstruction; the delay increases with a lower site of obstruction) Severe vomiting precedes intense epigastric, left [msdmanuals.com]
- Abdominal Tenderness
The patient complained of fever, abdominal tenderness, and loose stools and showed all of the signs of peritonitis on physical examination. [ncbi.nlm.nih.gov]
Peritoneal signs (eg, abdominal tenderness and rebound) are present but may be somewhat diminished by the presence of ascitic fluid. [merckmanuals.com]
On physical exam, there is abdominal distension, diffuse abdominal tenderness to palpation, flank dullness, and a positive fluid wave. [medbullets.com]
Spontaneous bacterial peritonitis is defined as the presence of an infection in a previously sterile ascites in the absence of an intra-abdominal source of infection or malignancy. [clinicaltrials.gov]
- Nausea
In each instance it started abruptly with sudden fever and shaking chills, accompanied by nausea, vomiting, and progressive abdominal discomfort. Hypotension, which was present in each patient, was usually severe. [doi.org]
It's often accompanied by loss of appetite, nausea, vomit and diarrhea. 3. Peritoneal irritation. Abdominal tenderness is what patients' feel. 4. Ascites. The speed of ascites accelerates. Patients feel anabatic abdominal distension. [cirrhosis-treatment.net]
Patients will complain of fever, chills, nausea and vomiting, abdominal pain and sometimes change in the level of consciousness. In order to confirm diagnosis laboratory tests on the ascitic fluid have to be carried out. [symptoma.com]
Signs and symptoms of spontaneous bacterial peritonitis (SBP) include fevers, chills, nausea, vomiting, abdominal pain and tenderness, general malaise, altered mental status, and worsening ascites. [en.wikipedia.org]
- Abdominal Distension
On physical exam, there is abdominal distension, diffuse abdominal tenderness to palpation, flank dullness, and a positive fluid wave. [medbullets.com]
Abdominal tenderness is what patients' feel. 4. Ascites. The speed of ascites accelerates. Patients feel anabatic abdominal distension. The diuretic does not work. Even patients breath with difficulty. [cirrhosis-treatment.net]
Signs and symptoms of SBP can include any constellation of the following: Abdominal pain and guarding Abdominal distension Diarrhea Emesis Encephalopathy Fever Lethargy Poor feeding Sepsis There are no reliable signs/symptoms that indicate a definitive [pediatriceducation.org]
Ascites causing moderate symmetrical distension of the abdomen. Grade 3 (large). Ascites causing marked abdominal distension. [doi.org]
Cardiovascular
- Heart Disease
Chemical Immunology, 74, 42-60. http://dx.doi.org/10.1159/000058760 [ 10 ] Lequier, L.L., Nikaidoh, H., Leonard, S.R., Bokovoy, J.L., White, M.L. and Scannon, .P.J. (2000) Preoperative and Postoperative Endotoxemia in Children with Congenital Heart Disease [scirp.org]
[…] failure in those with pre-existing heart disease. 117 TIPS insertion should be considered as a treatment option for patients who require frequent paracentesis (generally >3 a month). [doi.org]
Musculoskeletal
- Arthritis
Child-Turcotte-Pugh classification score of ≥7) and other liver diseases (ie, alcoholic liver disease, alpha-antitrypsin deficiency, viral hepatitis, and primary sclerosing cholangitis), and autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis [ncbi.nlm.nih.gov]
Neurologic
- Altered Mental Status
Cirrhotic patients with ascites and clinical suspicion for SBP-abdominal pain or tenderness, fever or altered mental status-should have a diagnostic paracentesis. [ncbi.nlm.nih.gov]
Altered mental status is also highly sensitive for SBP, and SBP should, therefore, be considered in the evaluation of altered mental status, along with hepatic encephalopathy. [doi.org]
Critical Essential Core Tested Community Questions (2) (M2.GI.4694) A 56-year-old African American male presents with altered mental status, abdominal pain, and a fever of 100.4F. [medbullets.com]
Patients with SBP may present with abdominal distention, pain, fever (or hypothermia), tachycardia, hypotension, or altered mental status. [clinicaladvisor.com]
One particular study on SBP reported the most common clinical features to be abdominal tenderness (46%), altered mental status (61%) and fever (68%). [symptoma.com]
- Meningism
Microbiologic features of adult community-acquired bacterial meningitis in Taiwan.. J Formos Med Assoc. 2000 Apr;99(4):300-4. 16. Cheng DL, Liu YC.. Array. J Infect Dis Soc ROC. 1997 Jan;8(1):2-5. 17. Chang WN, Huang CR, Lu CH, Chien CC.. [oapublishinglondon.com]
Workup
A mandatory test indicated for all patients with suspected SBP is peritoneal fluid analysis, preferably done at the emergency department on initial encounter of the patient. The specific procedure to obtain peritoneal fluid varies: For patients that routinely undergo peritoneal dialysis and have a peritoneal catheter in situ, an aseptic technique should be employed to extract peritoneal fluid. For patients without an indwelling peritoneal catheter, the usual diagnostic paracentesis is done. In some cases, ascitic fluid may be minimal or negligible and such will benefit from an ultrasound guided paracentesis in order to obtain fluid for analysis.
Peritoneal fluid analysis usually includes bacterial culture, total and differential cell count as well as a number of biochemical markers; pH and lactate levels. It is of utmost importance as these results have been shown to be beneficial in guiding treatment of patients with SBP [18]. For instance, an ascitic fluid neutophil count of greater than 500 cells/µL is indicates SBP. It has a sensitivity and specificity of 86% and 98% respectively. On the other hand, an ascitic fluid neutrophil count of 250 cells/µL is associated with a higher sensitivity (93%) but a lower specificity (98%).
Generally, a polymophonuclear count of greater than 250 cells/µL is considered diagnostic of SBP. On the other hand, a count of 250 cells/µL or lesser occurring in the setting of a positive culture correlates with monomicrobial non-neutrocytic bacterascites. This may however be owed to a contamination of the bacterial culture.
According to one retrospective analysis study, an ascites lactate level greater than 25mg/dl was found to give 100% sensitivity and specificity in the prediction of active SBP. The same study revealed that a neutrophil count of more than 500 cells/µL obtained from ascitic fluid with a pH of less than 7.35 was 100% sensitive and 96% specific for SBP [19].
Apart from peritoneal fluid analysis, there are other important diagnostic tests that patients with suspected SBP need to undergo. Blood culture has been shown to be positive in about 33% of patients with SBP. These blood culture results usually reveal a single organism. In case multiple organisms are cultured, the possibility of a contaminated culture or a perforated abdominal viscus needs to be considered.
Urine culture results are also important in the prediction of SBP since asymptomatic bacteruria has been linked to the development of SBP.
Diagnostic imaging is considered in case of a suspected perforated viscus. The imaging of choice is an abdominal computed tomography (CT) scan because of its sensitivity towards small perforations. Chest and abdominal radiographs may be obtained as well.
Serum
- Neutrophilia
Shiratori B, Leano S, Nakajima C, Chagan-Yasutan H, Niki T, et al. (2014) Elevated OPN, IP-10, and neutrophilia in loop-mediated isothermal amplification confirmed tuberculosis patients. Mediators Inflamm 2014: 513263. [aclr.com.es]
Microbiology
- Listeria Monocytogenes
A case of Listeria monocytogenes induced spontaneous bacterial peritonitis (SBP) is reported in a patient with primary biliary cirrhosis. It is an indolent illness and may not show a neutrophil reaction in peritoneal fluid. [ncbi.nlm.nih.gov]
- Blood Culture Positive
culture positive for A. niger and 1 patient had ascitic culture positive for C. albicans and blood culture positive for C. albicans and C. tropicalis. [doi.org]
Laboratory
- Leukocytosis
In peripheral leukocytosis and in the ascites fluid, low hemoglobin can be considered predictors of mortality in patients with PBS. [ncbi.nlm.nih.gov]
Total PMNs ≥ 250 + culture from peritoneal fluid In general only occurs in pts with ascites 2/2 advanced cirrhosis and significant ascites Most common symptoms: fever, AMS, abd pain/tenderness (approx 10% have no symptoms) Clinical features include leukocytosis [errolozdalga.com]
Thus, if the patient presents to their follow-up appointment with infectious symptoms, the outpatient provider can repeat a CBC to check for worsening leukocytosis. [clinicaladvisor.com]
Clinical suspicion cannot be used to rule out SBP and a diagnostic paracentesis should be performed in any patient admitted to the hospital or with worsening clinical status, fever, leukocytosis, or renal failure. [emdocs.net]
The poor prognostic indicators found in this study were; low ascitic protein, hepatic encephalopathy, coagulopathy, renal dysfunction (creatinine >2mg/dl) and leukocytosis (all having p < 0.05). [panafrican-med-journal.com]
Treatment
The mainstay of treatment in SBP is pharmacotherapy. It is advised to apply empirical antibiotic therapy immediately since waiting for culture results may result in mortality due to severe sepsis [20]. A recommended therapy guideline as published by the International Ascites Club in 2000 indicates that antibiotics should be administered for a minimum of 5 days [21]. The club's recommendation was largely influenced by results from a comparative trial study that showed the same level of efficacy achieved in using 2g cefotaxime every eight hours for 5 days and in using the same regimen for 10 days. The measures of efficacy compared in this study included hospital mortality rates, resolution of infection and recurrence of SBP [22]. As a result, SBP once diagnosed but awaiting culture results would be treated with IV cefotaxime 2g every 4 to 8 hrs for a minimum of 5 days and up until the ascitic fluid cell count decreases to less than 250 cells/μL. In order to curb recurrence which occurs in up to 70% of patients within a year, prophylactic antibiotics (preferably quinolones) would be used.
In 2009, another guideline was submitted by the American Association for the Study of Liver Diseases. According to this guideline empiric antibiotic therapy with intravenous 3rd generation cephalosporins such as cefotaxime 2g every 8 hours is initiated in adult cirrhotic patients found to have ascitic fluid cell counts of 250 cells/µL or more in a community acquired setup. If the same category of patients is found in a hospital setup, antibiotic therapy will be applied based only on susceptibility testing of cultured bacteria. This latter approach also applies to patients who have received beta-lactam antibiotics in the recent past [20] [23].
Hospital admission and prompt antibiotic therapy is indicated for patients with an ascitic fluid cell count of more than 500 cells/μL regardless of the ascitic fluid gram stain results. To treat SBP, antibiotic therapy for 10 to 14 days is recommended. With this therapy, clinical improvement is expected within 48 hours of onset.
In case the patient's condition does not improve possible complications such as intrabdominal abscess or gut perforation have to be considered and need to be ruled out by the use of imaging studies or surgical exploration.
Prognosis
Owing to recent advancements in the field of medicine, there have been great improvements towards the approach to diagnosis and treatment of SBP. As a result mortality due to SBP has been on the decrease in all patient categories. In adult cirrhotic patients, the mortality rate lies between 40% and 70%. Initiation of antibiotic therapy early in the disease course has also proven to significantly improve the prognosis. The most opportune time to initiate antibiotics is before shock and set in of renal failure [11] [12].
Despite this progress in lowering mortality directly associatied to SBP, the presence of an underlying chronic liver disease predisposes to mortality due to other non-infectious causes at rates as high as 20% to 40% [11] [12]. Furthermore, if such patients survive initial hospitalization, they still stand at a risk of mortality within the subsequent two years, the rates being as high as 70% and 80% [13].
Other factors shown to impair the prognosis include SBP occurring concurrently with renal insufficiency as well as the use of non-selective beta blockers which have been reported to increase the risk of developing SBP, hepatorenal syndrome and eventual death in patients with cirrhosis [14].
Etiology
Over 90% of spontaneous bacterial peritonitis cases are attributed to a single bacterial species. SBP rarely occurs due to polymicrobial causes.
The highest susceptibility to SBP is seen in cirrhotic patients in a decompensated state [4]. Analysis of protein levels in ascitic fluid also reveals whether a patient is at high or low risk for developing SBP. Patients with protein levels of more than 1g/dl are considered to be at low risk while their counterparts with levels of less than 1 g/dl are ten times more likely to develop SBP. Previous treatment for SBP as well as gastrointestinal hemorrhage are factors associated with recurrence.
Anaerobic bacteria rarely cause SBP because of their inability to thrive in environments with high oxygen tension such as that of the ascitic fluid. Aerobic bacteria are the main causative agents with about 75% of infections linked to gram negatives. 50% of the aerobic gram negative causative agents are Escherichia coli. Only about 25% of infections are caused by gram positive aerobes, the greater amount being streptococci. However, the proportion of gram positive aerobes linked to SBP is on the rise [5] [6].
Epidemiology
Spontaneous bacterial peritonitis occurs both in children and adults with the incidence rate in the two age groups being nearly the same. The disease processes leading to hepatic failure in children and adults are quite different, but once ascites sets in, predisposition to SBP is almost equal with the frequency being as high 18%. In adults, SBP is almost always associated with the presence of ascites while the majority of children with SBP do not present ascites, a phenomenon that is still under investigation.
In children, SBP peaks during the neonatal period and around the age of 5 years. Generally, there has been an increased frequency of SBP cases in the recent past owing to the fact that more and more diagnostic paracenteses are being carried out and awareness of the condition has significantly improved.
SBP is not associated with any racial predilection and specifically in patients with ascites, it has no gender predisposition.
Pathophysiology
Several theories attempt to explain the pathophysiological process of spontaneous bacterial peritonitis. One theory suggests that inoculation of bacteria into ascitic fluid is a result of bacterial translocation from the gut transmurally. In SBP, it was detected that enteric bacteria as well as endotoxins were cultured in large quantities in both ascitic fluid and blood. This theory has however been refuted in the recent past in light of experimental evidence that suggests this mechanism plays an almost negligible role in the development of SBP [7].
Another proposed theory suggests that ascitic bacterial inoculation is likely to occur when hematogenous transmission of bacteria from a distant site or the gut takes place in the presence of immunocompromise. The exact process by which this transmission proceeds remains unclear.
The majority of SBP cases in adults is associated with cirrhosis and ascites. These conditions enhance certain factors that work to trigger ascitic bacterial inoculation and subsequent development of SBP. The factors include:
- Impaired bactericidal activity within the ascitic fluid [8]
- Bacterial overgrowth in the gut due to increased intestinal transit time
- Prolonged bacteremia due to concurrent immunocompromise as evidenced by a state of hypocomplementemia and impaired activity of the reticuloendothelial system.
- Intrahepatic shunting of colonized blood
Moreover, serum bilirubin levels and ascitic protein levels can be used to predict whether cirrhotic patients are facing an increased risk of developing SBP. High bilirubin levels of greater than 2.5 mg/dl and low ascitic protein levels under 1.0 g/dl have been associated with new onset as well as recurrent SBP [9] [10].
Prevention
Outpatient antibiotic prophylaxis is recommended for certain patient groups. By decontaminating the gastrointestinal tract the risk of developing SBP may be reduced. In order to avoid bacterial antibiotic resistance this prophylaxis is not carried out routinely but reserved for patients who face a great risk of developing SBP. These include those with previous SBP, and ascitic patients that present with either gastrointestinal bleeding or ascitic fluid protein levels of less than 1 g/dl.
The above guidelines were recommended in 2012 by the American Association for the Study of Liver Diseases [23]. For this long-term outpatient prophylaxis, the recommended antibiotics include
- Oral Ciprofloxacin 750 mg weekly
- Oral Norfloxacin 400mg once a day
- Double strength trimethoprim-sulfamethoxazole 5 times a week.
Summary
Spontaneous bacterial peritonitis (SBP) is largely associated with liver cirrhosis whether alcohol related or due to any other cause. It occurs in up to 30% of cirrhotic patients and its presence in this condition indicates poor prognosis [1]. Certain patients are also at a higher risk of developing SBP including those undergoing dialysis and suffering from conditions such as cardiac failure and Budd-Chiari syndrome which may lead to the development of ascites.
Diagnosis of SBP is only qualified when infection of the ascitic fluid cannot be attributed to any intra-abdominal focus that is amenable to surgery [2] [3]. Furthermore, the infection's etiological basis is rarely polymicrobial; generally only one type of enteric bacteria is implicated.
A few patients may be asymptomatic but the majority present with characteristic clinical features. Laboratory analysis of the ascitic fluid tapped through paracentesis remains the mainstay of diagnosis. Medical therapy for SBP entails use of antibiotics.
Patient Information
Spontaneous bacterial peritonitis (SBP) is a complication that occurs in a condition known as ascites. Ascites refers to an accumulation of fluid within the abdominal cavity as a result of certain liver diseases such as alcoholic cirrhosis and viral hepatitis. Infection of this fluid by bacteria leads to SBP. Patients on peritoneal dialysis face a high risk of developing this condition.
SBP affects men and women equally and may occur in both adults and children. Patients will complain of fever, chills, nausea and vomiting, abdominal pain and sometimes change in the level of consciousness. In order to confirm diagnosis laboratory tests on the ascitic fluid have to be carried out. This is the infected fluid in the abdominal cavity, that is extracted via a procedure called paracentesis. Analysis of this fluid serves to identify the type of the causative bacteria and its total number within the fluid as this will influence the choice of treatment.
SBP is mainly treated using antibiotics for about 10 to 14 days. There is a 70% chance of recurrence within a year. Long-term antibiotic therapy is only recommended in patients at highest risk.
References
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