The results of our study show that among patients admitted for CAP, a threefold decreased chance of having a S. pneumoniae infection and a threefold increased probability of having pneumonia of atypical aetiology were associated with the patient having received an initial beta-lactam treatment as an outpatient. These findings indicate that information on prior outpatient antimicrobial therapy has a predictive value in the diagnostic workup aimed at identifying the causative pathogen and planning the corresponding treatment in patients with pneumonia.
The initial management of patients hospitalised with pneumonia has been under constant study in different settings during the past decades. The choice of antimicrobial treatment, time to first antimicrobial drug administration and route of administration have all appeared to be relevant factors associated with the outcome of pneumonia [15–17]. A knowledge of the predominant microbial patterns in CAP is therefore essential when choosing an essential empirical antimicrobial treatment. Previous studies have found that S. pneumoniae, H. influenzae, Influenza virus A and B, Legionella spp. and C. pneumoniae are the most frequent pathogens in CAP , which is in accordance with our results. Because S. pneumoniae is the most frequently appearing pathogen, the administration of beta-lactam antibiotics is the initial empirical antimicrobial treatment of choice in the treatment guidelines on CAP [3, 12, 13]. Beta-lactam antibiotics, however, do not cover Legionella spp., C. pneumoniae and M. pneumoniae, the so-called atypical pathogens. Therefore, patients with pneumonia of atypical aetiology who are treated with beta-lactam antibiotics as an outpatient will probably not respond to treatment, with the possible consequence being a deterioration of the situation and subsequent hospital admission. Our finding of an increased prevalence of atypical pathogens in patients with prior outpatient beta-lactam treatment supports such an explanation, but also confirms what has already been suggested in the different guidelines for the management of community-acquired pneumonia in adults [13, 18]. These guidelines state that following the failure of the initial empirical treatment with beta-lactam antibiotics, the microbiological examination should be reassessed with a view to excluding the less common pathogens, such as atypical pathogens, and that antimicrobial treatment covering atypical pathogens should be considered. Our study supports the choice of antimicrobial treatment covering atypical pathogens (e.g. macrolides) for all patients with CAP who are admitted to hospital after prior treatment with beta-lactam antibiotics. However, whether this protocol will result in improved clinical outcome should be subject to additional study.
The observed reduction in the frequency of S. pneumoniae in patients who received prior outpatient antimicrobial treatment could also be due to a failure to detect the organisms in cultures. This could mask S. pneumoniae as the causative pathogen. However, we believe that this explanation is less plausible, especially since we also used antigen testing to identify the causative pathogen . In addition, such a mechanism can not explain the finding of an increased probability of pneumonia caused by atypical pathogens. To the best of our knowledge, our study is the first to specifically document and quantify the failure of initial outpatient antibiotic treatment as a predictor of the microbial aetiology of CAP.
This study was conducted in a single teaching hospital in The Netherlands, but we believe that the conclusions drawn will apply to other settings. First, the percentage of identified aetiology (64% in this study) is in agreement with that of other studies using similar microbiological techniques [20–22]. Second, our patient characteristics comply to a great extent with a previous nationwide study on prior outpatient antibacterial therapy as a prognostic factor for mortality in patients hospitalised for pneumonia . In that large database study, the percentage of patients hospitalised after initial outpatient antimicrobial treatment was almost identical to that observed in our study (27 vs. 23%, respectively). In addition, age distribution, co-morbidities and the antibiotic utilisation profile of the outpatients were very similar as were the median duration of hospital stay and in-hospital mortality. Unfortunately, due to limited numbers, we were unable to study an association between prior outpatient antimicrobial treatment and mortality in our study. A very reassuring finding was that 85% of all outpatient antibiotic prescriptions complied with national guidelines on the initial treatment of adults with suspected pneumonia. This reduces the possibility that the findings, rather than being associated with antibiotics, might reflect the diagnostic acumen of the physicians who saw the patients in primary care. However, we cannot rule out the possibility that typical signs of infection with atypical pathogens may have been missed by primary care physicians.
As well as finding a relation between prior antimicrobial treatment and aetiology, we also found an association between aetiology and age and pulmonary co-morbidity. Patients aged <60 years without co-morbidities were more likely to have an aetiology comprising viral or atypical bacterial pathogens, and pulmonary co-morbidity was independently associated with S. pneumoniae and H. influenzae as causative pathogens. These findings confirm the results of previous studies on the impact of age and co-morbidity on the microbial aetiology of CAP . A limitation of the present study, however, is that we were not able to adjust for smoking habits and alcohol intake of the patients. Previous studies on determinants for pneumonia aetiology found that these factors are significant predictors of pneumococcal infection [6, 7]. On the other hand, we do not expect prior antimicrobial therapy and smoking and alcohol intake to coincide in such a way that this would result in a null effect when all the information is available.
In conclusion, among patients admitted for pneumonia, whether or not a patient has received prior antimicrobial therapy as an outpatient provides relevant information in the diagnostic workup, in particular in terms of identifying the causative pathogen and planning the initial treatment at the time of hospital admission. This finding supports a further strengthening of the continuity of care at the interface between the extramural and hospitalised settings.