Polymicrobial aetiology was found in 11% of all patients with CAP admitted to the ICU, 20% considering those with defined aetiology only. Although S. pneumoniae was the most frequent pathogen in both groups, we found MRSA, P. aeruginosa, GNEB, H. influenzae, M. catarrhalis and respiratory viruses more frequently identified in polymicrobial pneumonia than in monomicrobial pneumonia. Chronic respiratory disease and ARDS criteria were independent predictors of polymicrobial aetiology. Although an independent predictor of hospital mortality such as inappropriate treatment was more frequent in the polymicrobial aetiology group, the trend for higher hospital mortality in patients from this group was not statistically significant.
In general populations of hospitalised patients with CAP, we have previously reported lower rates of polymicrobial pneumonia (5%) [3
] than in this series of ICU patients. Other studies on patients with CAP found 5.7% and 38.4% rates of polymicrobial aetiology in their series [4
]. These wide variations might be explained by differences in the populations studied, epidemiological settings, rate of antimicrobial pretreatment, microbiological workup and definitions of aetiology. A typical limitation of many studies dealing with microbial aetiology in CAP is that not all microbiological tests are applied systematically for all patients. This issue means that the real frequency of polymicrobial aetiologies could possibly be higher if a complete microbiological investigation was performed in all cases. In view of these methodological problems, it seems difficult to indicate precisely the extent of the problem of polymicrobial aetiology. Analysing the potential impact of polymicrobial aetiology is therefore more important, particularly in the most severely ill patients and in those at highest risk of death.
was not only the most frequent pathogen but also by far the most frequent co-pathogen in polymicrobial infections. This finding underlines the importance of pneumococcal coverage in any initial antimicrobial treatment regimen. The most frequent polymicrobial pattern was S. pneumoniae
and viral infection, particularly influenza virus. Pneumococci have been identified as the most frequent bacterial superinfection in both seasonal [13
] and novel H1N1 [14
] influenza virus-associated pneumonia.
Interestingly, whereas S. pneumoniae
was by far the most frequent single pathogen, the rate of this pathogen was similar among patients with monomicrobial aetiology and those with polymicrobial aetiology. Among the pathogens more frequently identified in polymicrobial pneumonia, respiratory viruses were the most frequent. We did not find that polymicrobial aetiology was associated with higher mortality. Viruses were the most frequent microorganisms associated with polymicrobial aetiology. Except for influenza A H1N1, viruses are not a cause of excess mortality-as recently pointed out by two recent studies [13
]. The role of viruses in the aetiology of pneumonia is unclear, since they may be regarded either as primary infection or, with bacteria, as representing superinfection [17
]. None of our patients received antiviral treatment. We feel that at least during the influenza season, however, patients could benefit from antiviral treatment.
The role of MRSA in CAP is limited in Europe, even if patients meeting criteria for healthcare-associated pneumonia remain included [18
]. Although for our series we excluded patients with healthcare-associated pneumonia, the frequent association of this pathogen with severe underlying illness [19
] may explain the higher rate of this pathogen in the polymicrobial aetiology group, since these patients were more severe at admission than those with monomicrobial aetiology. The exact role of MRSA in polymicrobial CAP is difficult to assess, however, because even a high bacterial load of MRSA may still represent colonisation rather than infection [20
]. The higher rate of P. aeruginosa
and GNEB in polymicrobial pneumonia may also be related to the higher rate of chronic respiratory diseases in this group, since identification of these pathogens occurs more frequently in those with chronic lung disease [21
]. As for MRSA, the identification of P. aeruginosa
does not necessarily mean this is the causative pathogen of acute exacerbation in all chronic obstructive pulmonary disease patients colonised by the pathogen [22
], and similarly MRSA eventually may represent colonisation rather than infection in patients with pneumonia.
We identified chronic respiratory disease and ARDS criteria as independent predictors of polymicrobial aetiology. In chronic obstructive pulmonary disease, this finding can be explained by the previous colonisation of different bacteria these patients may have in their lower airways. On the contrary, ARDS may be the consequence of a mixed infection with higher pulmonary insult. In both chronic obstructive pulmonary disease and ARDS with severe CAP, our recommendation is to give a broad empirical antibiotic treatment from the beginning of therapy because mixed infections are more frequent [23
A relevant issue in polymicrobial aetiology of severe CAP refers to its potential prognostic implications. We found a strong association between polymicrobial aetiology and initial inappropriate antimicrobial treatment, which in turn was an independent predictor of increased hospital mortality. Inappropriate empiric treatment has already been associated with poor outcome in patients with severe infections [25
]. Although crude mortality was near double in patients with polymicrobial aetiology, this difference did not reach statistical significance-probably due to the insufficient number of patients included. These results indicate that the impact of initial inappropriate antimicrobial treatment is crucial for survival, and that polymicrobial aetiology is an important determinant for such inappropriateness.
To the best of our knowledge, this is the first study addressing the issue of multiple aetiologies of CAP in a large population of ICU patients. We decided to include all patients admitted to the ICU regardless of whether they met IDSA/ATS severity criteria. We think that clinical decisions for ICU admission may be valid, while the IDSA/ATS severity criteria have proven to be overly sensitive [1
Several limitations have to be addressed. First, the complete diagnostic workup and microbiological sampling could not be applied in every patient. Second, the true incidence of polymicrobial aetiology may be underestimated since 21% patients had received prior antimicrobial treatment. Finally, viral infections may have been missed since paired serology is frequently not available in nonsurvivors. We did not include molecular techniques such as PCR for bacterial detection. We believe that the systematic use of qualitative and quantitative PCR for the diagnosis of respiratory infections may increase substantially the number of identified bacterial pathogens [7
]. Moreover, these new techniques could play a crucial role in the determination of the clinical impact of polymicrobial aetiology in CAP. Unfortunately, the use of molecular techniques is not yet part of the routine diagnostic workup in CAP.