Figure 1Hospital mortality for subgroups according to cultures and bacteremia. Overall P value for comparison between three subgroups was 0.03. Listed P values refer to comparisons between two subgroups. aSignificant after Bonferroni correction.Figure 2Hospital mortality for subgroups according to cultures and receipt of appropriate http://www.selleckchem.com/products/mek162.html antibiotics. Overall P value for comparison between three subgroups was 0.005. Listed P values refer to comparisons between two subgroups. aSignificant after Bonferroni …DiscussionTo the best of our knowledge, no previous study has focused on the differences between culture-negative and culture-positive severe sepsis. The main findings of this study are that patients with culture-negative sepsis had fewer comorbidities and lower severity of illness than those with culture-positive sepsis.

Although culture-negative patients had a shorter hospitalization and lower ICU mortality and hospital mortality than culture-positive patients, culture positivity per se was not independently associated with mortality on multivariable analysis.Causative microorganisms were not found in 41.5% of our patients. Multicenter studies published in the last decade found that culture-negative patients accounted for 28%, 35%, 38%, and 48% of all cases of severe sepsis in North American, Spanish, French, and Canadian ICUs, respectively [10,16-18]. The corresponding figure was 40% in the pan-European Sepsis Occurrence in Acutely Ill Patients (SOAP) study [11]. In the United States, 49% of hospitalized patients with sepsis were culture-negative [3].

Meanwhile, the Extended Prevalence of Infection in Intensive Care (EPIC) II study, which reported prevalence – and not incidence – found that 30% of all infections in ICUs worldwide were culture-negative [19]. While we found more Gram-negative pathogens, others have found a predominance of Gram-positive microorganisms [3,11].Despite the high prevalence of culture-negative sepsis, studies which focus on the outcomes of such patients are surprisingly limited. In the 1990s, Rangel-Frausto and colleagues found a mortality of 25% among 577 patients with severe sepsis and septic shock in a teaching hospital and no difference in outcomes between culture-negative and culture-positive patients [9]. Mortality was also similar among 310 culture-negative and 742 culture-positive patients with severe sepsis in a multicenter study by Brun-Buisson and colleagues [8].

In the 2000s, a North American study led by Kumar and colleagues found similar mortality among 608 culture-negative Anacetrapib and 1,546 culture-negative patients [10], while the pan-European SOAP study found similar ICU mortality rates (40% versus 39%) between 468 culture-negative and 454 culture-positive septic patients [11]. Our study, on the other hand, found a significantly lower hospital mortality rate for culture-negative than for culture-positive severe sepsis (35.9% versus 44.0%).