Initial choice of antibiotic in recurrent spontaneous bacterial peritonitis: A retrospective study.

CONTEXT: Spontaneous bacterial peritonitis (SBP) is a commonly encountered infection seen in the setting of ascites secondary to advanced liver disease. Recurrence of SBP is common and is associated with high mortality. This study was designed to recognize a better initial choice of antibiotic in case of recurrent SBP - a third-generation cephalosporin or a carbapenem. AIMS: This study aims to determine a better initial choice of antibiotic in case of recurrent SBP and to compare the all-cause mortality among two different groups of patients treated with a third-generation cephalosporin and a carbapenem. SETTINGS AND
DESIGN: This study was conducted among fifty patients presenting with recurrent SBP visiting the emergency department (ED) at a tertiary care center and who were subsequently admitted in a gastroenterology intensive care unit, during a period of 1 year. SUBJECTS AND METHODS: This is a retrospective, observational study conducted among patients with chronic liver disease and diagnosed with recurrent SBP visiting the ED at a tertiary care center in South India treated with either of two classes of antibiotics - third-generation cephalosporins or carbapenems, and their outcomes were compared. Recurrence is defined as an episode of SBP after resolution of the first index case of SBP within 1 year. STATISTICAL ANALYSIS USED: Statistical analysis was done using IBM SPSS version 23.0 (SPSS Inc., Chicago, IL, USA). All categorical variables were represented as percentages, and all continuous variables were represented as mean ± standard deviation. To test the statistical significance of the association of categorical variables with the outcome, Chi-square test was used. P <0.05 was considered statistically significant.
RESULTS: A total of fifty patients with recurrent SBP were included in the study, of which 44 (88%) patients were male and 6 patients were female (12%). Twenty-nine (58%) patients survived and 21 (42%) patients expired within 28 days. Twenty-seven (54%) patients were treated with third-generation cephalosporins and 23 (46%) were treated with carbapenems. It was observed that mortality was statistically significantly lower among patients treated with carbapenem (P = 0.001). The incidence of acute kidney injury was also lower among patients treated with a carbapenem than patients treated with a third-generation cephalosporin (40.7% vs. 59.25%, respectively).
CONCLUSIONS: Initiation of a carbapenem significantly reduced the all-cause mortality when compared to a third-generation cephalosporin as an initial antibiotic of choice in recurrent SBP. Copyright:

INTRODUCTION

Spontaneous bacterial peritonitis (SBP) is a commonly encountered complication seen in the setting of ascites mostly in the background of chronic liver disease (CLD) when there is no other intra-abdominal source of infection.[1] The incidence of SBP in patients with ascites is approximately 10%–30%, with a mortality rate of about 20%. Recurrence within 1 year is quite common after the index episode of SBP and is associated with a high mortality rate. Risk factors for recurrence include advanced Child-Pugh score,[2] a low ascitic protein concentration (≤1 g/dL), high serum bilirubin >4 mg/dL, and occasionally paracentesis Itself is a risk factor.[345] SBP is believed to occur as a result of overgrowth of specific organism in the intestine and translocation of the organism into the mesenteric lymph nodes and subsequently into the ascitic fluid, resulting in bacterascites.[67]

It is characterized by fever, abdominal pain, generalized malaise, and slight change in mental status.[8] Clinical signs include presence of ascites, abdominal tenderness, and rebound tenderness in some patients. It is diagnosed when an ascitic fluid analysis shows >250 polymorphonuclear (PMN) leukocytes per cubic millimeter.[9] Ascitic fluid culture may or may not show a positive growth.[10] The most commonly encountered organisms are Escherichia coli, Klebsiella pneumonia, Streptococcus pneumonia, Proteus and other Streptococcus species, Staphylococcus, Pseudomonas, etc.[911]

Existing literature recommends that all patients with SBP should receive intravenous empirical antibiotics (preferably cefotaxime or any other third-generation cephalosporin),[12] but there is no such recommendation in case of recurrent SBP. The purpose of this study was to determine whether the initial antibiotic of choice had any effect on patient mortality in case of recurrent SBP.

SUBJECTS AND METHODS

This is a retrospective, observational study conducted among fifty patients with CLD and diagnosed with recurrent SBP visiting the emergency department (ED) and who were subsequently admitted in the gastroenterology intensive care unit (ICU) at a tertiary care center in South India. The period of study was during the years 2017–2018.

SBP was diagnosed based on clinical features and ascitic fluid analysis showing >250 PMN leukocytes per cubic millimeter or more, with or without a positive ascitic fluid culture.[913] ICU admission criteria were based on the treating physician's decision. General ICU admission guidelines include critically ill, hemodynamically unstable patients requiring intensive monitoring; patients requiring ventilator support and requiring vasoactive agents for maintaining systemic perfusion; patients having chronic comorbid conditions; patients with altered mentation caused by hepatic encephalopathy (HE); and patients with a high likelihood of benefit from ICU stay.[14]

Details of patients diagnosed with SBP were retrospectively analyzed, and the antibiotic initiated from the ED was noted.

Based on the initial antibiotic administered, patients were included in either of two groups covering treatment with an intravenous third-generation cephalosporin and a carbapenem. The antibiotics used in the third-generation cephalosporin group were cefotaxime, ceftriaxone, and cefoperazone and in the carbapenem group, the antibiotics used were meropenem and imipenem. The same antibiotic was continued in the ICU until culture, and sensitivity reports were available and modified accordingly. All-cause mortality after 28 days of initiation of treatment was studied in both groups and compared.

Statistical analysis was done using IBM SPSS version 23.0 (SPSS Inc., Chicago, IL, USA). All categorical variables were represented as percentages, and all continuous variables were represented as mean ± standard deviation. To test the statistical significance of the association of categorical variables with the outcome, Chi-square test was used. P < 0.05 was considered statistically significant.

RESULTS

A total of 50 patients were included in the study, of which 44 (88%) were male and 6 (12%) were female, showing a strong male predominance. The mean age group of patients included in the study was 53.32 ± 11.67 years. All patients in the study were belonging to Child-Pugh Class B and above. In the study, 29 (58%) survived and 21 (42%) patients expired within 28 days. All the fifty patients in the study were initiated with either of the two antibiotics – a third-generation cephalosporin or a carbapenem from the ED itself.

It was observed that all-cause mortality within 28 days in patients with recurrent SBP was statistically significantly lower among patients treated with intravenous carbapenem (82.6% survived, P< 0.001) as initial antibiotic than patients treated with a third-generation cephalosporin (37% survived, P< 0.001) [Table 1 and Figure 1]. The cause of mortality was multifactorial, among which septic shock and multiorgan dysfunction syndrome were the predominant causes. The incidence of acute kidney injury (AKI) was also significantly lower among patients initiated with an intravenous carbapenem than patients initiated with an intravenous third-generation cephalosporin in case of recurrent SBP.

Table 1

Initial antibiotic and treatment outcome in recurrent spontaneous bacterial peritonitis

Initial Antibiotic group	n	Survived		Expired		P
		n	%	n	%
3rd gen Cephalosporin	27	10	37	17	63	<0.001
Carbapenem	23	19	82.6	4	17.4

Figure 1

Initial antibiotic and treatment outcome in recurrent spontaneous bacterial peritonitis

It was also observed that 27 (54%) patients developed AKI, among which 11 (40.7%) patients belonged to the carbapenem group and 16 (59.25%) patients belonged to the third-generation Cephalosporin group [Table 2]. Twenty-three out of 27 patients who developed AKI expired.

Table 2

Initial antibiotic and incidence of acute kidney injury (AKI) in recurrent spontaneous bacterial peritonitis

Initial antibiotic group	Incidence of AKI		Total
	n	%
3rd generation Cephalosporin	16	59.25	27 (54%)
Carbapenem	11	40.7

Comorbidities commonly encountered in the study population were type 2 diabetes mellitus, systemic hypertension, chronic kidney disease (CKD), coronary artery disease, chronic hepatitis B, chronic hepatitis C, chronic obstructive pulmonary disease, hepatocellular carcinoma, etc., These comorbidities may have skewed the results.[15]

DISCUSSION

SBP is the infection of the ascitic fluid occurring almost exclusively in the setting of advanced liver disease and related ascites. SBP needs to be suspected when such a patient presents with the symptoms of fever, abdominal pain and distension, generalized malaise, altered mentation, clinical signs of peritonism, and abdominal tenderness.[8] Altered mentation is most commonly seen in the context of patients with a Child-Pugh score C. Altered mentation in a cirrhotic patient generally points to HE. Decreased serum albumin level may facilitate the development of HE and accelerate the death of a cirrhotic patient with HE.[1617] Diagnosis is confirmed after ascitic fluid analysis (PMN >250 cells/mm3). It has also been described in many studies that the occurrence of SBP is independent of the etiology of CLD.[1] The most commonly encountered organisms in causing SBP include E. coli, K. pneumoniae, Pseudomonas species, Proteus species, and Streptococcus species.[1117]

Risk factors of SBP include patients with advanced liver disease with a low ascitic fluid protein concentration, paracentesis itself, and presence of any other systemic source of infection such as respiratory tract infection and urinary tract infection also rarely in cases of complement deficiency and reticuloendothelial system dysfunction. Gastrointestinal hemorrhage is an independent risk factor for SBP, which is often underrecognized.[16]

SBP is associated with high sepsis-related mortality in cirrhotic patients.[18] Early antibiotics is warranted in cirrhosis-related SBP.[9]

Recurrence of SBP within 1 year of index presentation of SBP is reported to be 10%–30% and is associated with a very high mortality.[18192021] A study by Titó et al. describes that patients with a serum bilirubin >4 mg/dL, prothrombin ≤45%, and protein concentration in ascitic fluid ≤1 g/dL were associated with a high risk or recurrence of SBP.[317] Mortality is most commonly due to sepsis and multiorgan dysfunction syndrome, especially deteriorating renal function.[22] Serum albumin before discharge is a useful single parameter to predict the recurrence of SBP and long-term survival.[18] Long-term human albumin administration prolongs overall survival and might act as a disease-modifying treatment in patients with decompensated cirrhosis.[23] Proton pump inhibitor use is not a risk factor for recurrent SBP in cirrhotic patients.[24]

The treatment of index presentation of SBP includes ascitic fluid analysis and culture along with the administration of empirical intravenous antibiotics (preferably a third-generation cephalosporin such as cefotaxime) and standard sepsis treatment.[2021] There are no current recommendations of the type of antibiotic to be initiated in case of recurrence of SBP.[20] Most patients require ICU admission in view of the high propensity of associated HE, sepsis, and multiorgan dysfunction syndrome, especially renal involvement.[1721]

Renal impairment develops in 30%–40% of patients with liver cirrhosis and SBP, and is a significant prognostic factor in these patients.[917]

In this retrospective study, we observed that fifty patients who presented with recurrent SBP to the ED in a period of 1 year had a high mortality (42%) within 28 days. A comparison was made between the two groups of patients based on the class of antibiotics initially administered, a third-generation cephalosporin and a carbapenem. It was observed that the patients treated with a carbapenem had a higher survival rate (82.6%), in recurrent SBP (P = 0.001) than patients treated with a third-generation cephalosporin. In addition, the incidence of AKI was lower in patients initiated on a carbapenem than on a third-generation cephalosporin (40.7% vs. 59.25%).

A study by Jindal et al. revealed that in hospitalized cirrhotic patients with SBP and risk factors for treatment failure, cephalosporin showed comparable efficacy and survival to carbapenem.[25] This was in contrast to our study in which the use of a carbapenem was associated with improved survival and decreased incidence of AKI compared to a cephalosporin in recurrent SBP.

CONCLUSIONS

This study emphasizes the pivotal role of initiating a higher antibiotic in the ED itself for improving the overall outcome among patients with cirrhosis and recurrent SBP. Patients presenting with recurrent SBP to the ED may be initiated on a carbapenem than a third-generation cephalosporin. Further research needs to be carried out in larger population to confirm the results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical conduct of research

This study was approved by the Institutional Review Board / Ethics Committee. The authors followed applicable EQUATOR Network (http://www.equator-network.org/) guidelines during the conduct of this research project.