The aim of our study was to verify the validity, applicability, and efficacy of the guidelines proposed in 2000 by the International Ascites Club for the treatment of SBP. The applicability in the clinical practice of a guideline derived from randomized controlled investigations is very important. Moreover, such analysis is also justified by the evidence that the type and etiology of bacterial infections in cirrhosis may have changed during recent years[14–18
]. For this purpose, the results of patients’ management according to these guidelines were evaluated in an unselected group of cirrhotic patients with SBP consecutively observed in the last three-year period.
Our study suggests that, in clinical practice, an approach to SBP based on ascitic fluid PMN cell count is correct and valid for starting the antibiotic treatment and evaluating its efficacy as well. On the other hand, the suggestion of using third-generation cephalosporins (cefotaxime) as the first-line antibiotic treatment is not equally valid, since a switch to another antibiotic was necessary in more than 40% of our cases.
Infections may frequently occur in patients with liver cirrhosis, especially when decompensated, and may be a cause of death per se
; but, they can also act as a trigger for a number of severe complications, such as hepatic encephalopathy and renal failure[23
]. Moreover, infection has been related to variceal bleeding both in terms of pathogenesis of portal pressure increment and severity of bleeding episodes[24,25
], since the related mortality was reduced by prompt antibiotic therapy[26
]. SBP is one of the most frequent infections in patients with cirrhosis[6
]. Fever, leukocytosis, and abdominal symptoms are rare (recorded in 20% only of our series); the identification of the infection of ascitic fluid is, therefore, based only on the result of the diagnostic paracentesis. A PMN cell count > 250 cell/mm3
has been proposed as the most important parameter for the diagnosis of SBP, as we isolated responsible bacteria in the ascitic fluid culture very infrequently (recorded in only 24% of the episodes observed in our cohort). The low proportion of positive ascitic fluid cultures is probably due to the relatively low concentration of bacteria in the ascitic fluid as compared with the infections in other organic fluids (e.g. urine)[12
]. For the same reason, a therapy based on the isolation of the responsible bacteria is seldom achievable and the antibiotic treatment cannot be delayed to the moment when microbiological results are available[12,13
]. In these conditions, the efficacy of the empiric antibiotic treatment can rarely be based on the amelioration of the symptoms or on microbiological results. Therefore, a reduction of PMN cell count below 250 cell/mm3
or of 25% of the initial value has been suggested as the main criterion for establishing the efficacy of the antibiotic and the need for switching the therapy. Our study confirms the validity of such an approach. Based on PMN cell count, we were, in fact, able to identify the failure of the initial therapy on time, and the consequent change of the antibiotic therapy allowed us to control the infection in the majority of cases, with in-hospital mortality rate of less than 15%. This result is similar to that reported in the literature and is particularly good when considering the severe conditions of our patients.
In our study, the presence of arterial hypotension or renal failure at admission was the only independent predictor of mortality for SBP. To our knowledge, this observation is similar to the findings of other studies[27
]. According to the 2000 Ascites Club guidelines the use albumin, as suggested by the paper of Sort et al[28
], was not included in our protocol for SBP management. Even the most recent guidelines for the prevention and treatment of HRS[29
] suggest that albumin administration may reduce the incidence of renal failure and mortality in patients with SBP, but recommended further studies to define the optimal doses and the subgroup of patients for whom albumin is highly indicated. In our study, renal dysfunction was independently related with mortality and this finding supports the importance of improving the systemic hemodynamics and, thus, of renal function during the treatment of SBP.
According to the PMN cell count carried out at 48-h diagnostic paracentesis, cefotaxime-suggested as the first-line empiric antibiotic treatment-failed in more than 40% of SBP episodes. The need for changing antibiotic treatment is higher than that reported in previous studies[30–35
Although the cases with a positive culture were few (only 9 out of 29 patients), in these episodes the percentage of treatment failure of the initial therapy with cefotaxime was similar to that of the entire series (44%). In these patients, cefotaxime failed because the isolated organisms were intrinsically resistant to cefotaxime (as enterococci) or capable of degrading the expanded-spectrum cephalosporins (as ESBL-producing E. coli
or Amp C β-lactamase producing Enterobacter
species) or bacteria with a inherent insufficient susceptibility to cefotaxime (as Staphylococcus aureus
). If this small subgroup is to be considered representative of the organisms currently involved in the development of SBP, our study supports the possibility that, in recent years, the microbial etiology of SBP is changing, as it seems to have more generally occurred for bacterial infections of these kinds of patients[14
]. In our hospital, a recent survey[36
] on 4769 samples collected for bacterial isolation from April to September 2006, showed a high prevalence of ESBL-producing enterobacteriacae as an emergent cause of infections. In particular, among the ESBL-positive E. coli
, strains with CTX-M -lactamases, specifically able to hydrolyze cefotaxime, were the most diffused. It is interesting to note that, although in the majority of our patients SBP was defined as “community-acquired” and nosocomial infections-defined as an infection of ascitic fluid diagnosed after a first negative ascitic fluid analysis-were not prevalent in the group resistant to cefotaxime, the above organisms are typically nosocomial. In other words, the episodes of SBP resistant to cefotaxime may be considered as healthcare-related infections[37
], probably due to the fact that compromised patients, as the cirrhotic patients included in the present study, have the frequent need of hospital assistance including outpatient visits, diagnostic invasive examinations, day-hospital admissions, etc
., which may facilitate contact with nosocomial antibiotic-resistant pathogens. These considerations should induce a change in our approach aimed not only at changing the first line antibiotic therapy in SBP, but also at reducing and making the patients’ access to the hospital more appropriate and rational.
In conclusion, an approach to SBP based on ascitic fluid PMN cell count is correct and valid in the clinical practice for both starting promptly the antibiotic treatment and evaluating its efficacy. However, the initial treatment with cefotaxime failed more frequently than expected. These results should promote investigations aimed at identifying different approaches. The antibiotics used for the empiric initial treatment should be chosen among those able to control infections which are often healthcare-related and thus sustained by antibiotic-resistant bacteria. The characteristics of bacterial infection in a given geographical area and community should be taken into account. Therefore, the generalization of our findings, which are derived by a monocentric study, deserves further investigations.