One of the most controversial topics in the recommendations and consensus documents on antibiotic treatment in respiratory infections is the choice of outpatient treatment of pneumonia. The debate between monotherapy with a beta-lactam or combination with a macrolide leads to differences of opinion among clinicians, and even among scientific societies.1,2 There is some logic to the arguments, and several reasons to justify both approaches in the treatment of mild pneumonia. The first and most important is that no randomized trials with sufficient patient numbers have been conducted in different geographical areas and over long periods that include different seasons, comparing the use of a beta-lactam alone versus the combination of a beta-lactam with a macrolide. The few studies in non-hospitalized patients use mortality as a study variable, which is unhelpful since death rates are very low in this setting, and it is unlikely that significant differences will be detected. Other outcomes, such as therapeutic failure, complications or need for later admission, would be of greater interest. Secondly, because microbiological studies are not performed, there is a shortage of etiological information in mild pneumonia, so the percentage of intracellular microorganisms in which macrolides play an obvious role is unknown. The few studies that use microbiological molecular diagnostic techniques show that the prevalence of these intracellular bacteria, in particular Legionella pneumophila, is underestimated. Moreover, in the early stages of infection, urinary antigen testing for Legionella pneumophila may give false negatives, and this technique also only recognizes serotype i. In Spain, Legionella pneumophila occurs in up to 6% of cases in the outpatient setting and a beta-lactam in monotherapy is insufficient.3 Microbiological point-of-care testing in the outpatient setting that covers a range of bacteria and viruses would be very useful for improving etiological information; however, we are aware that these services are not available in standard practice and conventional microbiological studies are not recommended in the guidelines. The third factor is the possibility of pneumonia caused by mixed etiologies such as pneumococcus and intracellular bacteria or the possibility of bacteremia in mild pneumonias.4 For all these reasons, the therapeutic approach to mild pneumonias should always include a regimen offering complete cover that always includes pneumococcus and intracellular bacteria, in order to reduce the chance of failure. Efforts must be made to avoid continuing the macrolide for more than 3 or 5 days if the response is good.

Horita et al. published a meta-analysis5 analyzing the impact of the combination of beta-lactams and macrolides on mortality, but only 3 studies were included in the mild/moderate pneumonia subgroup. This is insufficient to properly address mortality, and the authors recognize the shortage of randomized and observational studies in their paper. Asadi et al.,6 in an observational study of 2,845 patients, compared macrolides with quinolones, and found fewer hospital admissions and lower mortality (0.2 vs. 3.0%, p = 0.02) in the macrolide group. In fact, macrolides have even shown good outcomes in patients with risk factors for pneumococcal resistance.7

When the decision has to be made between using fewer antibiotics or offering complete coverage of the most common microorganisms of mild pneumonia, the SEPAR update of the CAP guidelines leans towards the second option. We agree that a very large, well-designed randomized trial may provide an answer to this unresolved issue.