CAP-associated morbidity and mortality are considerable and particularly common in patients hospitalized with CAP
]. The REACH study gathered data on underlying characteristics and treatment patterns in patients hospitalized with CAP in a variety of clinical settings across 128 hospitals in ten EU countries. We found an unexpectedly high overall rate of initial antibiotic treatment modification (28.9%), with the majority of the patients treated empirically. Rates of initial antibiotic treatment modification and associated outcomes, such as overall mortality, were increased in patients with more complicated or more severe illness, such as those patients with a PORT/PSI score of V or ‘severe’ CURB-65 score, immunocompromised/immunosuppressed patients and patients with recurrent infections or comorbidities. Additionally, patients with HCAP had a much higher mortality rate of 16.3% compared with 5.5% in patients with CAP. Total mortality in REACH appears low at 7.2% but is consistent with data published previously for patients with PORT scores
]. However, it may be that REACH patients without a measure of severity (PORT/PSI or CURB-65) actually had less severe disease globally.
Comparison with previous studies is complicated because different definitions of treatment modification and treatment failure are employed. Indeed, a 2009 review of treatment failure in patients with CAP across Europe found a wide variation (2.4–31%) in reported rates (including both early and late failure)
]. In studies with treatment failure defined as per the definition of initial antibiotic treatment modification used in REACH, treatment failure rates align closely with the rate of initial antibiotic treatment modification observed
A health economic analysis of our study showed that initial antibiotic treatment modification is associated with higher use of resources compared with no modification of initial antibiotic treatment (Ostermann et al. submitted). Therefore, it is critically important that management decisions for patients with CAP incorporate measures that reduce the likelihood of initial antibiotic treatment modification, including selection and rapid initiation of the most effective antibiotic agent, efficient diagnostic methods and early identification of patients with additional concerns. Initiatives aimed at improving empiric treatment strategies and microbiological stewardship may help in this respect.
The broad range of potential pathogens implicated in CAP and the difficulty in obtaining a precise microbiological diagnosis complicate treatment of CAP. In this study, initial treatment decisions were empiric in 94.1% of patients. A further complication is the wide range of treatment options: 48 different antibiotic regimens were reported in this study.
Although almost every patient underwent a microbiological test, the diagnosis rate was only 28.5%. The most common organism identified was S. pneumoniae
, which follows previous studies
]. Interestingly, high percentages of less common pathogens, such as S. aureus
(7.2%) and Pseudomonas aeruginosa
(7.0%), were observed. A Swedish study found that these pathogens were more common in patients with higher CRB-65 scores
], and a European review of patients with CAP admitted to intensive care
] observed S. aureus
(7.0%) and Gram-negative enteric bacilli (8.6%) more frequently than in the whole population
]. In patients with bacteraemia in REACH, the spectrum of pathogens was more homogeneous, being dominated by S. pneumoniae
74; 63.8%). Compared with previous studies
], a low proportion of resistant pathogens was reported in our study (two patients with penicillin-resistant S. pneumoniae
[0.3%] and 12 with methicillin-resistant S. aureus
Previous studies show that adherence to guidelines for antibiotic therapy for CAP
] can reduce hospital length of stay
] and mortality
]. The European Respiratory Society (ERS), in collaboration with The European Society for Clinical Microbiology and Infectious Disease (ESCMID), recommends penicillins, with or without β-lactamase inhibitors, or cephalosporins, administered in combination with newer macrolides for patients hospitalized with CAP
]. Although there were a large number of different initial antibiotic regimens used in REACH, the majority of treatment decisions were consistent with these guidelines.
Interestingly, several of the most common antibiotic classes (penicillins plus macrolide, 32.3%; cephalosporin [excluding cefuroxime] plus fluoroquinolone, 31.3%) were associated with initial antibiotic treatment modification rates slightly higher than the average for all treatments. This may reflect inappropriate initial treatment choices for the infecting pathogen. A further possible explanation is higher use of certain antibiotics in patients with more severe illness, who may have been predisposed to initial antibiotic treatment modification. It should be noted that the initial antibiotic treatment modification rates reported for antibiotic classes may not generalize to individual agents within that class.
Our study had a number of limitations. The retrospective design may have resulted in inconsistent outcomes assessment between investigators due to differences in interpretation. However, the potential problem of incomplete information in some patient records was not common, generally occurring in ≤7% of patients (although the reason for initial antibiotic treatment modification was ‘Other’, ‘Unknown’ or was not reported in 14.8% of patients). The small patient numbers in some of the subgroups limit the possibility of making firm conclusions. Patient recruitment varied widely between countries owing to differences in ethical requirements. Also, the included countries were mainly western European, and so may not be fully representative of Europe as a whole.
In summary, this large, Europe-wide study provides the most current data to further describe patient characteristics and clinical management of patients hospitalized with CAP in this region. The findings reveal the enormous heterogeneity in clinical management patterns. Initial antibiotic treatment modification occurred in almost one-third of affected patients, and was more common in patients with comorbidities than in those without. Therefore, the authors believe that a reassessment of optimal management regimens should be undertaken and new therapies may be required to address this unmet need.