Causative agents and outcome of spontaneous bacterial peritonitis in cirrhotic patients: community-acquired versus nosocomial infections

Spontaneous bacterial peritonitis (SBP) is a well-recognized and prevalent complication seen in cirrhotic patients with ascites, occurring in 10–25% of these patients [1‐4]. It leads to more severe liver function damage, multi-organ failure and sepsis, thus affecting the prognosis of such patients [5‐7]. Once SBP is diagnosed, appropriate antibiotic treatment must be started as soon as possible, without prior knowledge of the causative organisms or their in vitro drug sensitivities [1, 2]. Because Gram-negative Enterobacteriaceae members are recognized as the most common causative organisms of SBP, third-generation cephalosporins (TGCs) have been recommended as the first-line therapies for this condition [1, 2, 8]. However, as cirrhotic patients require frequent hospitalization, undergo numerous invasive procedures, and are subject to antibiotic prophylaxis, some studies have suggested that the bacterial spectrum and resistance profiles of the causative pathogens of SBP have changed and show huge regional variation [4, 9, 10]. Thus, the latest guidelines from the European Association for the Study of Liver (EASL) recommend that for empirical treatment of SBP in cirrhotic patients with ascites, distinguishing nosocomial SBP from community-acquired SBP is necessary [11]. Moreover, whether the infection site is community-acquired or nosocomically acquired will influence the clinical outcome for patients with SBP, but large differences exist in the data from different studies [4, 12, 13].

This study aimed to determine whether differences exist between the clinical and microbiological characteristics of nosocomial and community-acquired SBP. We also explored the use of a comprehensive approach to determine the possible prognostic factors for hospital mortality in relation to SBP.

SBP is a serious complication and common cause of death in patients with liver cirrhosis, but early diagnosis and the timely application of antibiotic therapy can significantly decrease its mortality rate [1, 2]. However, the etiological patterns of peritonitis show huge regional differences [4, 9, 10]. Thus, studying the epidemiology of SBP should be conducted at a local level with regard to the use of empirical therapy.

Gram-negative bacteria like E. coli and K. pneumonia are the most common causes of SBP [1, 2]. But several studies in recent years have shown that the major pathogens responsible for SBP have shifted from Gram-negative bacteria to Gram-positive cocci [14‐17]. In contrast to these findings, and in agreement with the traditional model, our results show that Gram-negative bacteria (53.3%) remain the main etiological agents of SBP and that E. coli (24.3%) was its most common cause. Notably, Gram-negative bacteria were predominant in the community-acquired infections, whereas Gram-positive organisms were predominant in the nosocomial infections. This result is consistent with the data obtained from other investigations in mainland China [18, 19], indicating that no significant changes in the proportion of Gram-negative to Gram-positive infections occurred in the Chinese patients with SBP.

In recent years, some studies have reported on the emergence of resistance to TGCs in SBP [20‐22]. Indeed, nosocomial infections are considered an independent predictor of resistance to these agents [4, 23]. In the present study, the resistant organisms cultured from ascites fluid mainly included Enterococci, ESBL-producing Enterobacteriaceae and some other naturally resistant bacteria (Stenotrophomonas maltophilia and Listeria monocytogenes). We found that ESBL production was higher in the samples from the nosocomial infection cases. Consequently, TGC resistance in the major Gram-negative bacteria was higher in the nosocomial group than in the community-acquired group. However, in a recent meta-analysis, Fiore et al found no significantly higher risk of TGC-resistant strains in nosocomial SBP compared with community-acquired SBP in China, although the total rate of TGC resistance was much higher than that seen in other countries [24]. This discrepancy may be partly explained by differences in the study populations. Beijing Youan Hospital is one of the largest liver disease treatment centers in China, with patients coming from all over the country. Some of these patients might have been undergoing antibiotic therapy in other hospitals. In addition, the E. coli strains obtained from the patients with nosocomial SBP showed much higher resistance to piperacillin/tazobactam (12.2% vs. 0.0%) and levofloxacin (71.9% vs. 42.9%), than those from patients with community-acquired SBP. K. pneumoniae, however, was more resistant to cefepime when it was isolated from the nosocomial cases than from the community-acquired cases (28.8% vs. 0.0%). There was also a significant difference in the distribution of Enterococci between the two groups (nosocomial, 6.1% vs. community-acquired, 27.7%). Enterococci are resistant to a variety of antibacterial agents, including TGC, but are highly sensitive to vancomycin, linezolid and teicoplanin. This suggests that when choosing the treatment for empiric therapy of patients with SBP medics should consider both the acquisition site of infection (nosocomial or community-acquired infection) and the local epidemiological situation. The new guidelines from EASL also mention another epidemiological entity; specifically, health-care associated SBP, which requires the same therapeutic approach as that used for nosocomial SBP [11]. However, as there is still controversy about its utility [25], health-care associated SBP was not divided into a separate group in the present study.

Continual progress in health technology has markedly improved the prognosis for cirrhotic patients with SBP. But the one-year survival rate after recovery from the first episode of SBP is only 30–40% [26, 27]. A number of studies have sought to identify prognostic factors in patients with SBP [4, 10, 12, 23, 28, 29]. Consistent with other studies [4, 28, 29], our results show that the Child-Pugh classification, concomitant hepatocellular carcinoma, renal failure presentation and hepatic encephalopathy are all significant risk factors for the 30-day mortality associated with SBP. As for nosocomial infections being a prognostic factor for SBP, some divergent opinions still exist. In our study, even after adjusting for the other prognostic factors associated with mortality, nosocomial SBP (p = 0.044; HR, 1.514; 95% CI, 1.012–2.267) was still identified as an independent risk factor for mortality. This view is consistent with the study findings of Cheong et al, [4] but differs from other studies in Korea [12, 13], which have all highlighted that the acquisition site of infection does not affect the clinical outcomes for patients with SBP. Differences in the study populations and variable therapeutic regimens may play a part in this discrepancy. But researchers also think that the high mortality rate for patients with SBP reflects both the presence of infectious diseases and the underlying illness itself. In general, patients with nosocomial SBP have more severe underlying illnesses than those with community-acquired SBP [14]; hence, it is not surprising that nosocomial SBP has a worse prognosis. Previous studies [4, 23, 28, 29] have also reported that resistance to TGC is an independent predictor of mortality in patients with SBP. However, the effects of such resistance could not be confirmed in our study. The difference between these other studies and our own may result from heterogeneity in the pathogens. Clearly, a bigger sample size will be needed in future research to verify this.

Our study has some limitations. First, the study comprised a single-center retrospective design and a relatively small sample size, and this may have compromised its statistical power. Second, the 2 groups are not completely comparable in their baseline characteristics (i.e., the higher prevalence of HCC in nosocomial infections reflect that these patients had a more advanced liver disease), to some extent, these selective bias could have influenced the higher mortality rate in the nosocomial SBP group. Third, only patients with SBP based on positive cultures were included in this study; we excluded patients with culture-negative neutrocytic ascites. Thus, selection bias may have occurred.