Infections of respiratory or abdominal origin in ICU patients: what are the differences?

The SOAP study was a prospective multicenter observational study designed to evaluate the epidemiology and characteristics of sepsis in European countries and was initiated by a working group of the European Society of Intensive Care Medicine. Full details of recruitment, data collection and management have been provided elsewhere [6]. Briefly, all adult patients (> 15 years old) admitted to a participating center (see Additional file 1 for a list of participating countries and centers) between 1 and 15 May 2002 were included, except patients who stayed in the ICU for less than 24 hours for routine postoperative surveillance. Due to the observational character of the study which did not require any deviation from routine medical care, institutional review board approval was either waived or expedited in participating institutions and informed consent was not required. Patients were followed up until death, hospital discharge, or for 60 days.

Data were collected prospectively using pre-printed case report forms and entered centrally by medical personnel. Data collection on ICU admission included demographic data, comorbid diseases, admission category, source of admission and admission diagnosis. Clinical and laboratory data needed to calculate the Simplified Acute Physiology Score II (SAPS II) were reported as the worst value within 24 hours after hospital admission [16]. Evaluation of organ function was made using the Sequential Organ Failure Assessment (SOFA) score, based on the most abnormal value for each of the six organ systems [17]. Daily collection of data included infection characteristics, organ function and the need for special supportive modalities such as mechanical ventilation, hemofiltration and hemodialysis.

Infection was defined as the presence of a pathogenic microorganism in a sterile milieu and/or clinically suspected infection, plus the administration of antibiotics. Clinically suspected infection was diagnosed at the discretion of the attending physician. Sepsis and severe sepsis and septic shock were defined by standard criteria [18]. Organ failure was defined as a Sequential Organ Failure Assessment (SOFA) score > 2 for the organ in question [17]. Early organ failure and late organ failure were defined as those occurring within and after 48 hours of a diagnosis of sepsis, respectively. For the purposes of this substudy, two groups were identified: Patients with abdominal infection (microbiologically proven or clinical diagnosis) on admission to the ICU without any concurrent respiratory infection and those with respiratory infections (microbiologically proven or clinical diagnosis) on ICU admission without concurrent abdominal infection. Secondary infections were defined as infections occurring more than 24 hours after onset of a preexisting infection, at a site other than the abdominal or respiratory system for patients in the abdominal or respiratory groups, respectively.

Data were analyzed using the Statistical Package for Social Sciences (SPSS) for Windows, version 17.0 (SPSS Inc., Chicago, IL, USA). A Kolmogorov-Smirnov test was used, and histograms and normal-quantile plots were examined to verify the normality of distribution of continuous variables. Discrete variables are expressed as counts (percentage) and continuous variables as means ± SD or median (25^th to 75^th percentiles). For demographic and clinical characteristics of the study groups, differences between groups were assessed using a chi-square, Fisher's exact test, Student's t-test or Mann-Whitney U test, as appropriate. We performed a multivariate logistic regression analysis with development of secondary infection as the dependent factor to investigate the influence of length of ICU stay on the development of secondary infection in abdominal and respiratory groups. Variables considered for the analysis included, demographic data, co-morbidities, SAPS II score on admission, type of microorganism, organ failure assessed by the SOFA score. Only variables associated with a higher risk of development of secondary infection (P < 0.2) on a univariate basis were modeled. All variables included in the model were tested for colinearity. Interaction terms involving combinations between length of ICU stay and presence in the abdominal or respiratory group were tested. A Hosmer and Lemeshow goodness of fit test was performed and odds ratios and their corresponding 95% confidence intervals were calculated [19]. We also performed a multivariate Cox proportional hazard model with time to in-hospital death as the dependent factor. Variables included in the Cox regression analysis were: age, gender, comorbid diseases, SAPS II and SOFA scores on admission, the type of admission (medical or surgical), source of admission, admission diagnosis, the presence of sepsis, early organ failure, and the need for mechanical ventilation or renal replacement therapy during the ICU stay. Variables were introduced in the model if significantly associated with a higher risk of in-hospital death on a univariate basis at a P-value < 0.2. Colinearity between variables was excluded prior to modeling. The time dependent covariate method was used to check the proportional hazard assumption of the model; an extended Cox model was constructed, adding interaction terms that involve time, that is, time dependent variables, computed as the by-product of time and individual covariates in the model (time × covariate). Individual time-dependent covariates were introduced one by one and in combinations in the extended model, none of which was found to be significant. A stepwise approach was used and presence in the abdominal or respiratory group variable was forced as the last step in the model. A Kaplan-Meier survival analysis was performed and survival between groups was compared using a Log rank Test. All statistics were two-tailed and a P < 0.05 was considered to be statistically significant.

Of the 3,147 patients enrolled in the SOAP study, 777 (25%) had sepsis on admission to the ICU; of these, 162 (21%) had abdominal infection without concurrent respiratory infection and 380 (49%) had respiratory infection without concurrent abdominal infection. The baseline characteristics of the patients are summarized in Table 1. Age, sex, SAPS II and SOFA scores were similar in the two groups. Patients with abdominal infections were more likely to be surgical admissions and to have been referred from the operating room or recovery room; they were more likely than patients with respiratory infections to have cancer but less likely to have chronic obstructive pulmonary disease (COPD) or hematologic cancer. Patients with respiratory infection were admitted mainly because of respiratory (57%), cardiovascular (19%) and neurologic diagnoses (13%), while patients with abdominal infection were primarily admitted because of digestive/liver (40%) and cardiovascular diagnoses (34%).

Table 2 shows the major microbiological data. Microbiologic cultures were positive in 46% of the patients. Diagnostic criteria for infection and the overall rates of Gram-positive, Gram-negative, or fungal infection were similar in the two groups. The most commonly isolated organisms in patients with abdominal infections were Staphylococcus aureus and Streptococcus group D, and in patients with respiratory infections, the most commonly isolated organisms were S. aureus and Pseudomonas species. Streptococcus pneumoniae infections were more common in patients with respiratory than in those with abdominal infections (4.7% vs. 0.6%, P = 0.02), while Streptococcus group D (18.5% vs. 6.3%, P < 0.001) and any streptococcal (24.1% vs. 12.9%, P < 0.001) infections were more common in patients with abdominal infections. Escherichia coli (15.4% vs. 7.6%, P = 0.006) and Candida non-albicans (6.2% vs. 2.4%, P = 0.027) infections were also more common in patients with abdominal infections than in those with respiratory infections.

Secondary infections were more common in patients with abdominal infections (70 patients, 43%), than in those with respiratory infections (119 patients, 31%), P = 0.010. Thirty-five patients (22%) with abdominal infections developed respiratory infections later during the ICU stay and 15 patients (4%) with respiratory infections developed abdominal infections (Table 3). Patients with abdominal infection on admission were more likely to develop secondary skin/wound infection (16% vs. 5.5%, P < 0.001) whereas patients with respiratory infections were more likely to develop secondary urinary infections (9.2% vs. 1.9%, P < 0.001). Patients in the abdominal group who developed secondary infections had a longer ICU stay than those who did not (12 (5.7 to 27.3) days versus 9.8 (4.6 to 21.9), P < 0.05). Multiple logistic regression analysis showed that the relationship between the abdominal group and the development of secondary infection was related to ICU stay (interaction parameter = 0.069, P = 0.011 (Table 4). Specifically, the odds ratio of developing secondary infections increased with increasing duration of ICU stay in the abdominal group (Figure 1).

Although the incidence of severe sepsis on admission was similar in the two groups (around 70%), more patients with abdominal infection had septic shock on admission than patients with respiratory infection (40.1% vs. 29.5%, P = 0.016). However, when considering the incidence of sepsis syndromes during the whole ICU stay, these differences lost statistical significance (Table 5).

Patients with abdominal infection also had a greater incidence of early coagulation failure (17.3% vs. 9.5%, P = 0.01) and early acute renal failure (38.3% vs. 29.5%, P = 0.04), and more needed hemofiltration than patients with respiratory infection. Patients with respiratory infection were more likely to have early neurological failure than patients with abdominal infection (30.5% vs. 9.9%, P < 0.001).

The median duration of ICU stay was the same in the two groups, but the median duration of hospital stay was longer for patients with abdominal infection (27 days vs. 20 days, P = 0.02). ICU (29.0% vs. 28.9%) and hospital (37.5% vs. 38.1%) mortality rates were remarkably similar in the two groups of patients. In a Kaplan Meier survival analysis, 60-day survival was similar between groups (Log Rank = 0.267, P = 0.605; Figure 2). In Cox regression analysis (Table 6), age, cancer, septic shock on admission, early coagulation failure, acute renal failure, and neurological failure were all associated with an increased risk of death, but abdominal or respiratory infection were not.