In Japan and other societies with rapidly aging populations, recurrent pneumonia (RP) is a major clinical problem yet only limited information exists regarding the burden of this disease. A prospective study of adult pneumonia was conducted to investigate the incidence of RP and potential risk factors. From February 1, 2012 to January 31, 2013, patients aged ≥ 15 years who were diagnosed with pneumonia were prospectively enrolled in a representative community hospital located in central Japan. Patients were followed for one-year to evaluate the recurrence of pneumonia and characteristics associated with RP. Cox proportional hazards models were constructed to compute adjusted hazard ratios (aHR) and ascertain risk factors significantly associated with RP. In total, 841 patients with a median age of 73 years (range 15–101 years) were enrolled totaling 1,048 person-years of observation with a median follow-up time of 475 days. A total of 137 patients had at least one recurrent episode with an incidence rate of 13.1 per 100 person-years (95% confidence interval: 11.1–15.5). In multivariate analysis, a past history of pneumonia (aHR 1.95, 95% CI: 1.35–2.8), chronic pulmonary disease (aHR 1.86, 1.24–2.78) and inhaled corticosteroid usage (aHR 1.78, 1.12–2.84) and hypnotic/sedative medication usage (aHR 2.06, 1.28–3.31) were identified as independent risk factors for recurrent pneumonia, whereas angiotensin converting enzyme-inhibitors usage was associated with a reduction of the risk of RP (aHR 0.22, 0.05–0.91). The detection of P. aeruginosa was significantly associated with RP even after adjusting for chronic pulmonary diseases (aHR = 2.37). Recurrent pneumonia constitutes a considerable proportion of the pneumonia burden in Japan. A past history of pneumonia, chronic pulmonary disease, inhaled corticosteroid and hypnotic/sedative medication usage and detection of P. aeruginosa were identified as independent risk factors for recurrent pneumonia and special attention regarding the use of medications in this vulnerable population is needed to reduce the impact of this disease in aging populations.

Rationale: Pneumonia due to Pseudomonas aeruginosa (PA) is associated with high mortality and requires antipseudomonal treatment. Because PA can colonize the respiratory tract, the diagnosis of pathogenic PA involvement is challenging. Objectives: To determine the prevalence of definitive and indeterminate PA infection in community-acquired pneumonia, to describe the clinical and microbiological profiles, and to estimate the burden of unnecessary antipseudomonal drug prescriptions. Methods: We prospectively enrolled 2,701 patients with community-acquired pneumonia. Using stringent criteria for diagnosing PA pneumonia, we generated the following three groups: 1) definitive PA, 2) indeterminate PA, and 3) non-PA pneumonia. Results: The prevalence of definitive PA pneumonia was 0.9% (n = 25), and that of indeterminate PA pneumonia was 4.9% (n = 131). Considerable clinical differences were observed among the groups. Patients with definitive PA pneumonia were more likely to have a history of tuberculosis and chronic obstructive pulmonary disease/bronchiectasis and had a higher 30-day mortality (28%) than patients with non-PA pneumonia. Patients with indeterminate PA pneumonia were more likely to have comorbidities than patients with non-PA pneumonia. More than half of the patients with indeterminate PA and 25% of the patients with non-PA pneumonia were treated with an antipseudomonal drug. No patients with definitive PA pneumonia had multidrug resistance. Conclusions: In this population, the prevalence of community-acquired pneumonia due to PA was low. The clinical features and 30-day mortality rates of patients with indeterminate PA pneumonia were different from those of patients with definitive PA pneumonia. Most of the prescribed antipseudomonal drugs for patients with community-acquired pneumonia were potentially unnecessary.

The rickettsial diseases Japanese spotted fever (JSF) and scrub typhus (ST) are caused by Rickettsia japonica and Orientia tsutsugamushi, respectively. The diseases share clinical symptoms, such as fever, rash, and eschar. However, there are no systematical investigations of the serological cross-reactivity between R. japonica and O. tsutsugamushi. Also, the serological cross-reactivity among O. tsutsugamushi serotypes is still unclear. We analyzed 1406 cases tested by indirect immunoperoxidase assay using seven rickettsial antigens—one R. japonica and six O. tsutsugamushi serotypes—between 2003 and 2016 at two reference centers in Japan. Of these, 167 JSF and 190 ST cases were serologically diagnosed. None of the ST cases had a significant increase in IgM titers against R. japonica. Six JSF cases showed IgG titers of ≥40 against O. tsutsugamushi, but no IgG titer showed a significant elevation in the convalescent phase sample. We observed a substantial degree of cross-reactivity between O. tsutsugamushi serotypes. Cross-reactivity was significant among Karp, Hirano/Kuroki, and Kato types and between Gilliam and Irie/Kawasaki types in IgM, while the Shimokoshi type was less cross-reactive than the others. In conclusion, there is no serological cross-reaction between R. japonica and O. tsutsugamushi. The cross-reactivity among O.tsutsugamushi varies depending on serotypes.

We examined the frequency of cross-reactions to Rickettsia typhi in patients with Japanese spotted fever (JSF) and evaluated the differences between two rickettsiae using antibody endpoint titers. Patients' immunoglobulin (Ig)M and IgG titers against Rickettsia japonica and Rickettsia typhi in two phases were measured using an indirect immunoperoxidase assay at two reference centers for rickettsiosis in Japan. Cross-reaction was defined as a higher titer against R. typhi in convalescent sera than in acute sera among patients fulfilling the criteria for JSF diagnosis. The frequencies of IgM and IgG were also evaluated. Approximately 20% of cases showed positive cross-reactions. A comparison of antibody titers revealed the difficulty in identifying some positive cases. Cross-reactions of 20% in serodiagnosis may lead to the misclassification of rickettsial diseases. However, with the exception of some cases, we were able to successfully differentiate JSF from murine typhus using each endpoint titer.

Mortality prediction of pneumonia by severity scores in patients with multiple underlying health conditions has not fully been investigated. This prospective cohort study is to identify mortality-associated underlying health conditions and to analyse their influence on severity-based pneumonia mortality prediction. Adult patients with community-acquired pneumonia or healthcare-associated pneumonia (HCAP) who visited four community hospitals between September 2011 and January 2013 were enrolled. Candidate underlying health conditions, including demographic and clinical characteristics, were incorporated into the logistic regression models, along with CURB (confusion, elevated urea nitrogen, tachypnoea, and hypotension) score as a measure of disease severity. The areas under the receiver operating characteristic curves (AUROC) of the predictive index based on significant underlying health conditions was compared to that of CURB65 (CURB and age ≥ 65) score or Pneumonia severity index (PSI). Mortality association between disease severity and the number of underlying health conditions was analysed. In total 1772 patients were eligible for analysis, of which 140 (7.9%) died within 30 days. Six underlying health conditions were independently associated: home care (adjusted odds ratio, 5.84; 95% confidence interval, CI, 2.28–14.99), recent hospitalization (2.21; 1.36–3.60), age ≥ 85 years (2.15; 1.08–4.28), low body mass index (1.99, 1.25–3.16), neoplastic disease (1.82; 1.17–2.85), and male gender (1.78; 1.16–2.75). The predictive index based on these conditions alone had a significantly or marginally higher AUROC than that based on CURB65 score (0.78 vs 0.66, p = 0.02) or PSI (0.78 vs 0.71, p = 0.05), respectively. Compared to this index, the AUROC of the total score consisting of six underlying health conditions and CURB score (range 0–10) did not improve mortality predictions (p = 0.3). In patients with one or less underlying health conditions, the mortality was discretely associated with severe pneumonia (CURB65 ≥ 3) (risk ratio: 7.24, 95%CI: 3.08–25.13), whereas in patients with 2 or more underlying health conditions, the mortality association with severe pneumonia was not detected (risk ratio: 1.53, 95% CI: 0.94–2.50). Mortality prediction based on pneumonia severity scores is highly influenced by the accumulating number of underlying health conditions in an ageing society. The validation using a different cohort is necessary to generalise the conclusion.