Spontaneous Bacterial Peritonitis (SBP) Workup

All patients suspected of having spontaneous bacterial peritonitis (SBP) must undergo peritoneal fluid analysis while in the emergency department. Diagnostic paracentesis should be performed in all patients who do not have an indwelling peritoneal catheter and are suspected of having spontaneous bacterial peritonitis. In peritoneal dialysis patients with a peritoneal catheter, fluid should be withdrawn with sterile technique. Ultrasonography may aid paracentesis if ascites is minimally detectable or questionable. Growing evidence supports early diagnostic paracentesis (defined as occurring within the first 11 hours of presentation). This, combined with early antibiotic treatment, leads to decreased ICU and hospital length of stay, in-hospital mortality, and 3-month mortality. ^{[11, 12]}

In patients with advanced cirrhosis, SBP may develop insidiously and remain unrecognized, and has been associated with a poor prognosis (one-year mortality rate: 65-93%). ^[14] One promising biomarker for SBP (in patients with cirrhosis) is Calprotectin, a diagnostic marker of inflammation; it is a calcium and zinc-binding protein that is found exclusively in neutrophils. ^[15]  Its level in any bodily fluid is proportional to the level of neutrophils present in that fluid; therefore a high calprotectin level indicates an inflammatory or infectious process. ^{[16, 17]}  It is available as a bedside test whose result can be known in minutes, resulting in quick diagnosis and prompt treatment. ^[18]

Blood and urine cultures should be obtained in all patients suspected of having spontaneous bacterial peritonitis. Blood culture results are positive for the offending agent in as many as 33% of patients with spontaneous bacterial peritonitis and may help guide antibiotic therapy. Urine culture may also prove useful, since asymptomatic bacteruria has been suggested to predispose to the development of spontaneous bacterial peritonitis.

If there is clinical suspicion of a perforated viscus, imaging should be strongly considered. Although plain radiographs (including abdominal flat plate, abdominal upright, and chest) may be obtained, CT scanning of the abdomen should be considered, as it is much more sensitive for a small perforation.

Peritoneal fluid analysis must be performed in any patient in whom spontaneous bacterial peritonitis (SBP) is considered. In patients undergoing peritoneal dialysis (PD), this can be accomplished by obtaining a sample of the dialysate. In patients without a peritoneal catheter, diagnostic paracentesis must be performed.

The examination of ascitic fluid for SBP has routinely involved sending the fluid for cell count, differential, and culture. It has been accepted that the results of aerobic and anaerobic bacterial cultures, used in conjunction with the cell count, are beneficial in guiding therapy for those with SBP. ^[19]

Recent data, though, suggest that ascitic fluid cultures have generally been shown to be of low yield with respect to altering management of patients with ascites. In addition, positive culture and sensitivity results obtained from emergency department testing have not been shown to result in appropriate adjustment of antibiotic therapy by inpatient physicians. The reasons for this may include inpatient physicians' distrust of the culture results and the difficulty in determining what constitutes a true pathogen in ascitic fluid cultures. ^[20]

The sensitivity of microbiologic studies has been reported to increase significantly with the direct inoculation of routine blood culture bottles at the bedside with 10 mL of ascitic fluid.

Ascitic fluid neutrophil count

An ascitic fluid neutrophil count of more than 500 cells/µL is the single best predictor of spontaneous bacterial peritonitis, with a sensitivity of 86% and specificity of 98%. Lowering the ascitic fluid neutrophil count to more than 250 cells/µL results in an increased sensitivity of 93% but a lower specificity of 94%. (For simplicity, a threshold of 250 cells/µL is used for the remainder of this discussion.)

An exciting new development in the rapid diagnosis of spontaneous bacterial peritonitis is the proposed use of reagent strips that detect leukocyte esterase, which can be read at the bedside using a portable spectrophotometric device. In a pilot study that compared the reagent strips with the manual laboratory polymorphonuclear leukocyte count, the strips achieved a 100% sensitivity in diagnosis of spontaneous bacterial peritonitis. ^[21]

This diagnostic method holds promise in replacing manual cell counting, which is time-consuming and is often unavailable in many laboratories "after hours". Use of these reagent strips may result in a significant reduction of the time from paracentesis to presumptive diagnosis and antibiotic treatment of spontaneous bacterial peritonitis.

In a small cohort, the average time saved from dipstick to laboratory results ranged from 2.73 hours (dipstick to validated result from automated counter) to 3 hours (dipstick to validated manual cell count of ascitic fluid). Although promising, this diagnostic method has not been investigated in a large-scale study.

Ascitic Calprotectin

Ascitic calprotectin is a biomarker that is gaining traction and interest for use in earlier detection and more expedient treatment. It has been shown to reliably predict PMN count > 250/uL, which may prove useful in diagnosis of SBP. ^[22]

Other ascitic fluid studies

Other studies of ascitic fluid to be considered include the following:

• Cytology

• Lactate level

• pH

An ascites lactate level of more than 25 mg/dL was found to be 100% sensitive and specific in predicting active spontaneous bacterial peritonitis in a retrospective analysis. In the same study, the combination of an ascites fluid pH below 7.35 and polymorphonuclear neutrophil count above 500 cells/µL was 100% sensitive and 96% specific for spontaneous bacterial peritonitis.

A 2012 study investigated using leukocyte reagent strips in the emergency department as a means of expediting the diagnosis of spontaneous bacterial peritonitis. ^[23] In this prospective study, 223 patients presenting with ascites and who had paracentesis performed in the emergency department had their peritoneal fluid sent for the usual diagnostic tests, but they also had the fluid dipped with both a Uri-Quick Clini 10 strip and Multistix 10SGA. Both had at least 90% positive predictive value and 94% negative predictive value for spontaneous bacterial peritonitis when compared with the criterion standard of peritoneal fluid Gram stain and culture—thus allowing a shorter interval between diagnosis and initiation of treatment.

Combined ascitic fluid neutrophil count and culture

Combining the results of the ascitic fluid polymorphonuclear neutrophil (PMN) count and the ascitic fluid culture yields the following subgroups:

• Spontaneous bacterial peritonitis

• Culture-negative neutrocytic ascites (probable spontaneous bacterial peritonitis)

• Monomicrobial nonneutrocytic bacterascites

Spontaneous bacterial peritonitis is noted when the PMN count is 250 cells/µL or higher, in conjunction with a positive bacterial culture result. As mentioned previously, one organism is usually identified on the culture in most cases. Obviously, these patients should receive antibiotic therapy.

Culture-negative neutrocytic ascites (probable spontaneous bacterial peritonitis) is noted when the ascitic fluid culture results are negative, but the PMN count is 250 cells/µL or higher. This may happen in as many as 50% of patients with SBP and may not actually represent a distinctly different disease entity. It may be the result of poor culturing techniques or late-stage resolving infection. Nonetheless, these patients should be treated just as aggressively as those with positive culture results.

Monomicrobial nonneutrocytic bacterascites exists when a positive culture result coexists with a PMN count of 250 cells/µL or fewer. Although this may often be the result of contamination of bacterial cultures, one study found that 38% of these patients subsequently develop spontaneous bacterial peritonitis. ^[24] Therefore, monomicrobial nonneutrocytic bacterascites may represent an early form of spontaneous bacterial peritonitis.

All study patients described that eventually developed spontaneous bacterial peritonitis were symptomatic. ^[24] For this reason, any patient suspected clinically of having spontaneous bacterial peritonitis in this setting must be treated.