Community-acquired pneumonia (CAP) in children is associated with significant morbidity in developed countries and a high mortality in developing countries, with an annual incidence of 30 to 40 cases per 1000 children aged less than 5 years and an annual incidence of hospitalization of 15.7 cases per 10000 children under 18 years.1

The inclusion in the routine immunization schedule of the Haemophilus influenzae type b vaccine and later the pneumococcal conjugate vaccine has caused a shift in the epidemiology of paediatric CAP. The importance of Mycoplasma pneumoniae (MP) as the aetiological agent has increased, especially in children aged 5 years or older.2

Although several clinical rules have been proposed, there are no signs or symptoms with a good enough predictive value for the aetiological diagnosis of pneumonia.3 The introduction of polymerase chain reaction (PCR) for diagnosis of MP has led to a breakthrough in its management, as it offers quick results with a high sensitivity and specificity that can guide treatment.4

The aim of our study was to describe the epidemiology, clinical manifestations and treatment of community-acquired MP pneumonia (CAMP) in a paediatric population over a period of 6 years.

The sample consisted of patients aged less than 14 years who underwent microbiological testing for MP (PCR for detection of MP in nasopharyngeal swab samples and/or serological testing for MP in the acute phase) due to clinical suspicion of CAMP at the discretion of the paediatrician in charge in an urban paediatric emergency department in Valencia (Spain) between January 1, 2010 and December 31, 2015. We performed a retrospective review of the health records and the findings of chest radiographs for these patients.

The inclusion criteria were having undergone a chest X-ray examination in the emergency department in the previous 72h or at the time of diagnosis. We excluded patients in whom the radiographic findings ruled out CAP, as determined by a paediatrician–researcher that was blinded to the patient's demographic and clinical information. Patients underwent additional microbiological studies and other diagnostic tests at the discretion of the physician. At the time of diagnosis of CAP, a sample was collected for measurement of the white blood cell (WBC) count and the serum levels of C-reactive protein (CRP) and procalcitonin.

We defined a CAMP case as a patient presenting with the following two criteria: (1) MP infection confirmed by positive PCR for MP in nasopharyngeal swab samples (Progenie Molecular RealCycler®) or detection of antibodies against MP through a MP-specific IgM assay during the acute phase of disease (ELISA IgM, Vircell®) and (2) radiographic evidence of pneumonia.5 The radiographic criteria included presence of consolidation (lung opacity with or without air bronchograms), other infiltrates (alveolar or interstitial densities) and pleural effusion. We did not consider peribronchial thickening or atelectasis criteria for pneumonia.

The exclusion criteria were relevant chronic illness (neoplasia, transplant, lung disease other than asthma, immunodeficiency or severe heart disease), recent hospitalization (within the past 7 days), residency in an extended-care facility, and previous inclusion in the study in the past 28 days.

We obtained follow-up data on the patients following the collection of the sample for MP detection from the electronic health records, which include information for all health care services received in the public health system of the province of Valencia (emergency, inpatient, primary and hospital outpatient care).

To date, many studies have described the clinical manifestations of CAMP in hospitalized children,6–13 but as far as we know, this is one of the largest studies describing the characteristics of CAMP in children, including outpatients. Despite its retrospective nature, the high proportion of patients for which we could obtain follow-up data allowed us to establish the course of this infection in a representative sample from the general population, as opposed to only patients that required admission.

We found two incidence peaks in the period under study: the first one in 2011, which had already been described in other populations in Europe,14–16 and the second in 2015. This is consistent with the cyclic epidemic pattern of CAMP, with outbreaks known to occur every 4–7 years. The reason for this is not fully understood yet. Outbreaks may be facilitated by the waning of herd immunity and shifts in the MP serotypes circulating in the human population.4

The seasonal prevalence differs depending on the population under study. In countries with temperate climates, outbreaks of MP infection tend to occur in the summer or early autumn, when other respiratory infectious pathogens are less prevalent.9 In our sample, we found a higher proportion of positive cases in summer. However, there were incidence peaks in July, November and December. A higher incidence of respiratory tract infections in November and December combined with a smaller proportion of MP infections could explain the higher number of cases of pneumonia but with a lower positivity rate for MP in these months.

Although theoretically MP is a pathogen that predominantly infects school-aged children, we found the largest number of cases in the 2-to-5-years age group. Most studies in the literature have reported peaks in the 5-to-9-years age group.8,9,12,17 The positivity rate in children with lower respiratory tract infection and its distribution by age was similar to those reported in a recently published single centre study conducted in Denmark.18 A multicentre, population-based study of community-acquired pneumonia in children in the United States found that the distribution of cases of MP was fairly across age groups, although its proportion out of the total cases of pneumonia steadily increased with age.2 This is similar to what we found in our sample, with a higher positivity rate in older patients. In light of these results, physicians may consider empiric treatment of CAP with a macrolide in older children and reserving testing for detection of MP for younger children, since detection of MP may result in treatment changes.

Although current guidelines recommend PCR and single-sample serological testing to diagnose MP infections,19,20 the gold standard for diagnosis remains a fourfold increase in the antibody titre measured in paired sera.21 There are drawbacks to this approach in clinical practice, as it may hinder decision-making regarding treatment initiation and may be only useful as a retrospective confirmatory test. The development of PCR has been a breakthrough in this regard. The data in our study showed a clear shift from the use of serological methods to the use of PCR for diagnosis. However, some concerns remain unresolved, such as the presence of asymptomatic carriers, previously described in children, which complicates the interpretation of PCR results.22

We also found a changing trend in the use of clarithromycin, which was displaced by azithromycin in the second period (91.5% vs. 3.1% of azithromycin out of all macrolide prescriptions), a treatment that has a more convenient dosing schedule. In fact, the 2011 United States guidelines recommended azithromycin as the antibiotic of choice.19

The laboratory characteristics of CAMP were remarkable. We ought to highlight the low elevation of CRP, with levels that were very similar to those reported in other studies.9,17,23 The main concern about treating a child with CAMP with a macrolide in monotherapy is the possibility of co-infection with S. pneumoniae and the drug resistance associated with this pathogen. An article published by Chiu et al. reported higher levels of CRP in cases of MP with S. pneumoniae coinfection compared to MP monoinfection (66.5±24.0mg/L vs. 296.1±114.3mg/L; P<.01).12 In the sample under study, there was only 1 detected case of bacterial coinfection (C. pneumoniae). Other authors have reported proportions of bacterial coinfection of up to 2% in patients with CAMP.24 This difference could be explained by several reasons: local epidemiology influenced by vaccination coverage, the setting of the sample under study, the kind of samples used for testing or the microbiological criteria used in the case definition.

We found differences in the clinical presentation between age groups. Wheezing associated with CAMP was significantly more common in younger children, although there are limitations to our study due to the low frequency of testing for viral coinfections. Nevertheless, the stratified analysis that included the patients in whom viral detection tests had been performed in nasopharyngeal swab samples found a higher prevalence of wheezing in patients with viral coinfection, although the difference was not statistically significant (71.4% vs. 56.5%; P=.481). The highest fevers corresponded to older children, in whom the diagnosis occurred after a longer time had elapsed from onset of fever. Of all patients with CAMP, 14.2% were afebrile at the time of diagnosis. This is similar to the findings of a study of 257 episodes of pneumococcal pneumonia in children, of whom 10% presented without fever.25

Unlike other studies that found that diarrhoea, vomiting and upper respiratory tract involvement were more common in younger children,9,17 we did not find differences in these variables. Cutaneous manifestations develop in up to 25% of MP infections.4 In our study, 1 out of every 10 patients with CAMP presented with a rash.

Some studies have found evidence of different manifestations in children with CAMP and viral coinfection.12,13 In our sample, the analysis of patients in whom testing was performed for viral detection in nasopharyngeal swab samples found that, compared with patients with negative results, patients with viral coinfection tended to be younger (median age 2.6 vs. 5.1 years; P=.033) and were more likely to be hospitalized (100% vs. 60.9%; P=.048).

The need of treatment in CAMP is still under debate.26,27 In our sample, most patients received a macrolide before or after the results of testing for detection of MP became available. A previous Cochrane review21 concluded that there is insufficient evidence about the efficacy of antibiotics in the treatment of MP-related lower respiratory tract infections in children.

There are some limitations to our study. First of all, a positive PCR or IgM test does not rule out the possibility of a past infection or the presence of coinfection. This is a common limitation of similar studies.7–12 However, this allowed us to describe the management of these infections in clinical practice with the tests available for use in the acute phase, and the follow-up and treatment chosen based on the results of these tests. Secondly, the retrospective nature of the study precluded the collection of samples for assessment of other microbial coinfection or for follow-up in all patients. Finally, the lack of routine testing for mutations that confer macrolide resistance prevented us from establishing the rate of drug resistance in our sample. It is well known that there has been a worldwide increase in the circulation of macrolide-resistant MP strains.28–30

In conclusion, according to this study, among the children with CAP, the proportion of infection by MP is highest in those who are older, have milder symptoms and have lower levels of inflammatory markers, so these subsets could benefit from empiric treatment with a macrolide. Thus, knowledge of the epidemiology in a given geographical area may be important for the management of CAP in children.