As mentioned earlier, current knowledge about the clinical features of MC-CAP in adults is based on old studies, and most of these studies are descriptive [1,2,3,4,5]. In the current study, we used statistical inference to compare the clinical characteristics of CAP caused by M. catarrhalis infections with those with CAP cause by S. pneumoniae infections. In addition to reconfirming the previously known characteristics of MC-CAP, we found for the first time that co-infection with influenza virus was less common in MC-CAP patients compared to those with SP-CAP, even though half of MC-CAP patients were admitted during the influenza season. Furthermore, both MC-CAP and SP-CAP frequently caused asthma attacks.
As shown in previous studies [1, 3, 15], MC-CAP patients in the present study were frequently admitted in winter. The reason for this pattern is unknown. Some investigators have described an association with a preceding or concurrent viral infection [16, 17], but our data show that influenza virus infection is not common in MC-CAP. Infections with other respiratory viruses were not examined in this study; therefore, any associations with other respiratory viruses remain undetermined. Borges et al. [18] showed that the occurrence of MC-CAP in children in tropical regions was positively associated with low humidity and negatively associated with air temperature and sunshine, suggesting that climatic conditions might account for the seasonality of MC-CAP. Further studies are needed to address this question.
MC-CAP was more common in the elderly and more likely to complicate underlying pulmonary diseases in the present study, a result that is consistent with previous studies [19, 20]. Elderly patients’ propensity to develop MC-CAP might be explained by the asymptomatic carriage rate of M. catarrhalis. The carriage rate in those under 60 years old (5%) increases to 25% in those over 60 years old [19]. Past studies have shown that widespread use of pneumococcal vaccines increases the prevalence of M. catarrhalis colonisation in the respiratory tract [21, 22]. Therefore, we expect to see an increase in the incidence of MC-CAP, particularly among the elderly, as the global population ages and pneumococcal vaccine coverage increases. For this reason, we must pay attention to the epidemiological trends of MC-CAP in elderly patients.
To the best of our knowledge, no previous studies have investigated the rate of asthma attacks in MC-CAP patients. As M. catarrhalis adheres to mucosal surfaces and induces an inflammatory response in bronchial epithelial cells, it is not surprising that it can trigger an asthma attack [23, 24]. In addition, Alnahas et al. [25] demonstrated that M. catarrhalis infection induced IL-17 and TNF-α production in the airways and triggered asthma attacks in murine models. Thus, additional clinical studies are needed to clarify the relationship between asthma attacks and M. catarrhalis infection.
Studies of the radiological features of MC-CAP are limited. Additionally, no past studies have compared the radiological findings of MC-CAP and SP-CAP. Okada et al. [6] investigated 109 CT scans conducted on patients with M. catarrhalis pneumonia (only 34 of 109 patients had CAP) and found that the most common radiological findings were ground glass opacities (91%) followed by bronchial wall thickening (78%), centrilobular nodules (73%), and consolidation (49%). These findings were similar to our findings, suggesting that these findings are characteristic of M. catarrhalis respiratory infection regardless of the pneumonia classification as CAP or hospital-acquired pneumonia.
Gram stain examination is a simple and rapid diagnostic tool for the presumptive identification of causative bacteria in patients with CAP. Its diagnostic usefulness in the selection of appropriate antibiotics in clinical practice has been investigated in several previous studies [26, 27]. In the current study, the sensitivity of sputum Gram stain for MC-CAP diagnosis was lower than that for SP-CAP; however, the rate was relatively high. Fukuyama et al. [26] reported that the sensitivity of sputum Gram stain for MC-CAP diagnosis was higher than that for SP-CAP diagnosis (85.0% vs. 63.1%), although the number of patients included the study was small (20 and 76 patients with MC-CAP and SP-CAP, respectively). Our data show that Gram stain can guide the appropriate use of antibiotics; more than half the MC-CAP and SP-CAP patients were treated with penicillins. Drug-resistant bacteria are an increasingly serious problem worldwide, and we need conserve existing antibiotic drugs, particularly broad-spectrum antimicrobial agents. By having attending physicians perform a Gram stain, we could treat pneumonia patients with targeted, narrow-spectrum antibiotics in this study, rather than empirical, broad-spectrum antibiotics such as cephalosporins and quinolones.
The mortality rate of MC-CAP patients in this study was 0% even though previous studies have revealed rates ranging from 5 to 21.4% [1, 4, 6, 28]. In fact, most patients included in this study were not classified as having severe pneumonia according to the CURB-65 score. This might be because we excluded patients who were bedridden, residing in a nursing home, receiving an immunosuppressive therapy, or had other diseases complicating respiration, such as acute heart failure. We also excluded patients with concurrent bacterial co-infection; excluding these patients might affect the mortality. In addition, Gram stain-guided appropriate selection of antibiotics might reduce mortality. It is noteworthy that zero mortality was achieved with a penicillin-centred choice of antibiotics. Since Gram staining is generally performed by attending physicians for all patients in most hospitals in Okinawa [10], this study reconfirms the validity of Gram stain-guided prompt decision making in clinical practice.
The present study has several strengths. Firstly, the number of MC-CAP patients included in this study was larger than that in the previous studies. Additionally, we excluded MC-CAP patients co-infected with other respiratory bacteria; therefore, our study population was appropriate for evaluating the characteristics of MC-CAP. Secondly, rather than performing a descriptive study, we evaluated the characteristics of MC-CAP by comparing them with those of SP-CAP. Thirdly, our study is the first to determine the co-infection rate of MC-CAP with influenza virus as well as the rate of asthma attacks among MC-CAP patients.
Our study has certain limitations. Firstly, it was a retrospective study conducted in a single centre. Secondly, it is possible that some MC-CAP patients had co-infection with additional unidentified atypical pathogens and viruses. However, co-infection with atypical bacteria and respiratory viruses was not common in MC-CAP [29]; therefore, this limitation may not significantly affect our results. Finally, we did not perform chest CT examinations in all pneumonia patients. However, only one study in the literature examined the characteristics of chest CT findings in MC-CAP patients, and our results were similar to the findings of that study [6].