Aetiological agents of adult community-acquired pneumonia in Japan: systematic review and meta-analysis of published data.

OBJECTIVE: Epidemiological information is essential in providing appropriate empiric antimicrobial therapy for pneumonia. This study aimed to clarify the epidemiology of community-acquired pneumonia (CAP) by conducting a systematic review of published studies in Japan. DESIGN: Systematic review. DATA SOURCE: PubMed and Ichushi web database (January 1970 to October 2022). ELIGIBILITY CRITERIA: Clinical studies describing pathogenic micro-organisms in CAP written in English or Japanese, excluding studies on pneumonia other than adult CAP, investigations limited to specific pathogens and case reports. DATA EXTRACTION AND SYNTHESIS: Patient setting (inpatient vs outpatient), number of patients, concordance with the CAP guidelines, diagnostic criteria and methods for diagnosing pneumonia pathogens as well as the numbers of each isolate. A meta-analysis of various situations was performed to measure the frequency of each aetiological agent. RESULTS: Fifty-six studies were included and 17 095 cases of CAP were identified. Pathogens were undetectable in 44.1% (95% CI 39.7% to 48.5%). Streptococcus pneumoniae was the most common cause of CAP requiring hospitalisation or outpatient care (20.0% (95% CI 17.2% to 22.8%)), followed by Haemophilus influenzae (10.8% (95% CI 7.3% to 14.3%)) and Mycoplasma pneumoniae (7.5% (95% CI 4.6% to 10.4%)). However, when limited to CAP requiring hospitalisation, Staphylococcus aureus was the third most common at 4.9% (95% CI 3.9% to 5.8%). Pseudomonas aeruginosa was more frequent in hospitalised cases, while atypical pathogens were less common. Methicillin-resistant S. aureus accounted for 40.7% (95% CI 29.0% to 52.4%) of S. aureus cases. In studies that used PCR testing for pan-respiratory viral pathogens, human enterovirus/human rhinovirus (9.4% (95% CI 0% to 20.5%)) and several other respiratory pathogenic viruses were detected. The epidemiology varied depending on the methodology and situation. CONCLUSION: The epidemiology of CAP varies depending on the situation, such as in the hospital versus outpatient setting. Viruses are more frequently detected by exhaustive genetic searches, resulting in a significant variation in epidemiology.

The Clinical Significance of Anaerobic Coverage in the Antibiotic Treatment of Aspiration Pneumonia: A Systematic Review and Meta-Analysis.

INTRODUCTION: Aspiration pneumonia is increasingly recognised as a common condition. While antibiotics covering anaerobes are thought to be necessary based on old studies reporting anaerobes as causative organisms, recent studies suggest that it may not necessarily benefit prognosis, or even be harmful. Clinical practice should be based on current data reflecting the shift in causative bacteria. The aim of this review was to investigate whether anaerobic coverage is recommended in the treatment of aspiration pneumonia. METHODS: A systematic review and meta-analysis of studies comparing antibiotics with and without anaerobic coverage in the treatment of aspiration pneumonia was performed. The main outcome studied was mortality. Additional outcomes were resolution of pneumonia, development of resistant bacteria, length of stay, recurrence, and adverse effects. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: From an initial 2523 publications, one randomised control trial and two observational studies were selected. The studies did not show a clear benefit of anaerobic coverage. Upon meta-analysis, there was no benefit of anaerobic coverage in improving mortality (Odds ratio 1.23, 95% CI 0.67-2.25). Studies reporting resolution of pneumonia, length of hospital stay, recurrence of pneumonia, and adverse effects showed no benefit of anaerobic coverage. The development of resistant bacteria was not discussed in these studies. CONCLUSION: In the current review, there are insufficient data to assess the necessity of anaerobic coverage in the antibiotic treatment of aspiration pneumonia. Further studies are needed to determine which cases require anaerobic coverage, if any.

Usefulness of the Legionella Score for differentiating from COVID-19 pneumonia to legionella pneumonia.

Legionella pneumophila is a major causative pathogen of community-acquired pneumonia (CAP), but recently the novel coronavirus disease 2019 (COVID-19) became the most common causative pathogen of CAP. Because L. pneumophila CAP is clinically distinct from bacterial CAPs, the Japan Society for Chemotherapy (JSC) developed a simple scoring system, the Legionella Score, using six parameters for the presumptive diagnosis of L. pneumophila pneumonia. We investigated the clinical and laboratory differences of L. pneumophila CAP and COVID-19 CAP and validated the Legionella Score in both CAP groups. We analyzed 102 patients with L. pneumophila CAP and 956 patients with COVID-19 CAP. Dyspnea and psychiatric symptoms were more frequently observed and cough was less frequently observed in patients with L. pneumophila CAP than those with COVID-19 CAP. Loss of taste and anosmia were observed in patients with COVID-19 CAP but not observed in those with L. pneumophila CAP. C-reactive protein and lactate dehydrogenase levels in L. pneumophila CAP group were significantly higher than in the COVID-19 CAP group. In contrast, sodium level in the L. pneumophila CAP group was significantly lower than in the COVID-19 CAP group. The median Legionella Score was significantly higher in the L. pneumophila CAP group than the COVID-19 CAP group (score 4 vs 2, p < 0.001). Our results demonstrated that the JSC Legionella Score had good diagnostic ability during the COVID-19 pandemic. However, physicians should consider COVID-19 CAP when loss of taste and/or anosmia are observed regardless of the Legionella Score.

Evaluation of a novel urinary antigen test kit for diagnosing Legionella pneumonia.

OBJECTIVES: The aim of this study was to evaluate the diagnostic utility of a novel test kit that could theoretically detect all serogroups of Legionella pneumophila for diagnosing Legionella pneumonia, in comparison with existing kits. METHODS: This study was conducted in 16 hospitals in Japan from April 2016 to December 2018. Three urinary antigen test kits were used: the novel kit (LAC-116), BinaxNOW Legionella (Binax), and Q-line Kyokutou Legionella (Q-line). In addition, sputum culture and nucleic acid detection tests and serum antibody tests were performed where possible. The diagnostic accuracy and correlations of the novel kit with the two existing kits were analyzed. RESULTS: In total, 56 patients were diagnosed with Legionella pneumonia. The sensitivities of LAC-116, Binax, and Q-line were 79%, 84%, and 71%, respectively. The overall match rate between LAC-116 and Binax was 96.8% and between LAC-116 and Q-line was 96.4%. One patient had L. pneumophila serogroup 2, and only LAC-116 showed a positive result, whereas Binax and Q-line did not. CONCLUSIONS: The novel Legionella urinary antigen test kit was useful for diagnosing Legionella pneumonia. In addition, it could detect Legionella pneumonia caused by non-L. pneumophila serogroup 1.

Human immunodeficiency virus-associated pulmonary sarcoidosis in a Japanese man as a manifestation of immune reconstitution inflammatory syndrome.

Asymptomatic pulmonary sarcoidosis can develop after starting antiretroviral therapy. The decision on whether to treat sarcoidosis with corticosteroids should be based on the disease severity.

Use of steroids to treat anti-tumor necrosis factor α induced tuberculosis-associated immune reconstitution inflammatory syndrome: Case report and literature review.

INTRODUCTION: Individuals with tuberculosis (TB) who are being treated with anti-tumor necrosis factor α (anti-TNFα) for coexisting conditions may experience unexpected exacerbations of TB after the initiation of antituberculous therapy, so-called anti-TNFα-induced TB-immune reconstitution inflammatory syndrome (anti-TNFα-induced TB-IRIS). Anti-TNFα-induced TB-IRIS is often treated empirically with corticosteroids; however, the evidence of the effectiveness of corticosteroids is lacking and the management can be a challenge. PATIENT CONCERNS: A 32-year-old man on long-term infliximab therapy for Crohn disease visited a clinic complaining of persistent fever and cough that had started 1 week previously. His most recent infliximab injection had been administered 14 days before the visit. A chest X-ray revealed a left pleural effusion, and he was admitted to a local hospital. DIAGNOSIS: A chest computed tomography (CT) scan revealed miliary pulmonary nodules; acid-fast bacilli were found in a sputum smear and a urine sediment sample; and polymerase chain reaction confirmed the presence of Mycobacterium tuberculosis in both his sputum and the pleural effusion. He was diagnosed with miliary TB. INTERVENTIONS: Antituberculous therapy was started and he was transferred to our hospital for further management. His symptoms initially improved after the initiation of antituberculous therapy, but 2 weeks later, his symptoms recurred and shadows on chest X-ray worsened. A repeat chest CT scan revealed enlarged miliary pulmonary nodules, extensive ground-glass opacities, and an increased volume of his pleural effusion. This paradoxical exacerbation was diagnosed as TB-IRIS associated with infliximab. A moderate-dose of systemic corticosteroid was initiated [prednisolone 25 mg/day (0.5 mg/kg/day)]. OUTCOMES: After starting corticosteroid treatment, his radiological findings improved immediately, and his fever and cough disappeared within a few days. After discharge, prednisolone was tapered off over the course of 10 weeks, and he completed a 9-month course of antituberculous therapy uneventfully. He had not restarted infliximab at his most recent follow-up 14 months later. CONCLUSION: We successfully managed a patient with anti-TNFα-induced TB-IRIS using moderate-dose corticosteroids. Due to the limited evidence currently available, physicians should consider the necessity, dosage, and duration of corticosteroids for each case of anti-TNFα-induced TB-IRIS on an individual patient-by-patient basis.

Distribution of Legionella species and serogroups in patients with culture-confirmed Legionella pneumonia.

Legionella species are consistently identified as some of the most common causative agents of severe community-acquired pneumonia (CAP) or nosocomial pneumonia. Although the number of reported Legionella infection cases is gradually increasing in Japan, most cases are diagnosed by a urinary antigen test, which identifies only L. pneumophila serogroup 1. Therefore, assessment of pneumonia-causing Legionella species and serogroups would be important. The Japan Society for Chemotherapy Legionella committee has collected the isolates and clinical information on cases of sporadic community-acquired Legionella pneumonia throughout Japan. Between December 2006 and March 2019, totally 140 sporadic cases were identified, in which L. pneumophila was the most frequently isolated species (90.7%) followed by L. bozemanae (3.6%), L. dumofii (3.6%), L. micdadei (1.4%), and L. longbeachae (0.7%). Among 127 isolates of L. pneumophila, 111 isolates were of serogroup 1, two of serogroup 2, four of serogroup 3, one of serogroup 4, one of serogroup 5, seven of serogroup 6, and one was of serogroup 10. We also assessed in vitro activity of antibiotics against these isolates and showed that quinolones and macrolides have potent anti-Legionella activity. Our study showed that pneumonia-causing Legionella species and serogroup distribution was comparable to that reported in former surveillances. L. pneumophila was the most common etiologic agent in patients with community-acquired Legionella pneumonia, and L. pneumophila serogroup 1 was the predominant serogroup.

Diagnostic performance of serum interferon gamma, matrix metalloproteinases, and periostin measurements for pulmonary tuberculosis in Japanese patients with pneumonia.

Serum markers that differentiate between tuberculous and non-tuberculous pneumonia would be clinically useful. However, few serum markers have been investigated for their association with either disease. In this study, serum levels of interferon gamma (IFN-γ), matrix metalloproteinases 1 and 9 (MMP-1 and MMP-9, respectively), and periostin were compared between 40 pulmonary tuberculosis (PTB) and 28 non-tuberculous pneumonia (non-PTB) patients. Diagnostic performance was assessed by analysis of receiver-operating characteristic (ROC) curves and classification trees. Serum IFN-γ and MMP-1 levels were significantly higher and serum MMP-9 levels significantly lower in PTB than in non-PTB patients (p < 0.001, p = 0.002, p < 0.001, respectively). No significant difference was observed in serum periostin levels between groups. ROC curve analysis could not determine the appropriate cut-off value with high sensitivity and specificity; therefore, a classification tree method was applied. This method identified patients with limited infiltration into three groups with statistical significance (p = 0.01), and those with MMP-1 levels < 0.01 ng/mL and periostin levels ≥ 118.8 ng/mL included only non-PTB patients (95% confidence interval 0.0-41.0). Patients with extensive infiltration were also divided into three groups with statistical significance (p < 0.001), and those with MMP-9 levels < 3.009 ng/mL included only PTB patients (95% confidence interval 76.8-100.0). In conclusion, the novel classification tree developed using MMP-1, MMP-9, and periostin data distinguished PTB from non-PTB patients. Further studies are needed to validate our cut-off values and the overall clinical usefulness of these markers.

Validation of a diagnostic score model for the prediction of Legionella pneumophila pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) due to Legionella has a high mortality rate in patients who do not receive adequate antibiotic therapy. In a previous study, we developed a simple Legionella Score to distinguish patients with Legionella and non-Legionella pneumonia based on clinical information at diagnosis. In the present study, we validated this Legionella Score for the presumptive diagnosis of Legionella CAP. METHODS: This validation cohort included 109 patients with Legionella CAP and 683 patients with non-Legionella CAP. The Legionella Score includes six parameters by assigning one point for each of the following items: being male, absence of cough, dyspnea, C-reactive protein (CRP) ≥ 18 mg/dL, lactate dehydrogenase (LDH) ≥ 260 U/L, and sodium < 134 mmol/L. RESULTS: When the Legionella CAP and non-Legionella CAP were compared by univariate analysis, most of the evaluated symptoms and laboratory test results differed substantially. The six parameters that were used for the Legionella Score also indicated clear differences between the Legionella and non-Legionella CAP. All Legionella patients had a score of 2 points or higher. The median Legionella Scores were 4 in the Legionella CAP cases and 2 in the non-Legionella CAP cases. A receiver operating characteristics curve showed that the area under the curve was 0.93. The proposed best cutoff, total score ≥3, had sensitivity of 93% and specificity of 75%. CONCLUSION: Our Legionella Score was shown to have good diagnostic ability with a positive likelihood of 3.7 and a negative likelihood of 0.10.

A Therapeutic Strategy for All Pneumonia Patients: A 3-Year Prospective Multicenter Cohort Study Using Risk Factors for Multidrug-resistant Pathogens to Select Initial Empiric Therapy.

BACKGROUND: Empiric therapy of pneumonia is currently based on the site of acquisition (community or hospital), but could be chosen, based on risk factors for multidrug-resistant (MDR) pathogens, independent of site of acquisition. METHODS: We prospectively applied a therapeutic algorithm based on MDR risks, in a multicenter cohort study of 1089 patients with 656 community-acquired pneumonia (CAP), 238 healthcare-associated pneumonia (HCAP), 140 hospital-acquired pneumonia (HAP), or 55 ventilator-associated pneumonia (VAP). RESULTS: Approximately 83% of patients were treated according to the algorithm, with 4.3% receiving inappropriate therapy. The frequency of MDR pathogens varied, respectively, with VAP (50.9%), HAP (27.9%), HCAP (10.9%), and CAP (5.2%). Those with ≥2 MDR risks had MDR pathogens more often than those with 0-1 MDR risk (25.8% vs 5.3%, P < .001). The 30-day mortality rates were as follows: VAP (18.2%), HAP (13.6%), HCAP (6.7%), and CAP (4.7%), and were lower in patients with 0-1 MDR risks than in those with ≥2 MDR risks (4.5% vs 12.5%, P < .001). In multivariate logistic regression analysis, 5 risk factors (advanced age, hematocrit <30%, malnutrition, dehydration, and chronic liver disease), as well as hypotension and inappropriate therapy were significantly correlated with 30-day mortality, whereas the classification of pneumonia type (VAP, HAP, HCAP, CAP) was not. CONCLUSIONS: Individual MDR risk factors can be used in a unified algorithm to guide and simplify empiric therapy for all pneumonia patients, and were more important than the classification of site of pneumonia acquisition in determining 30-day mortality. CLINICAL TRIALS REGISTRATION: JMA-IIA00146.

Clinical Features of Human Metapneumovirus Pneumonia in Non-Immunocompromised Patients: An Investigation of Three Long-Term Care Facility Outbreaks.

Background: Several studies have reported outbreaks due to human metapneumovirus (hMPV) in long-term care facilities (LTCF) for the elderly. However, most of these reports are epidemiological studies and do not investigate the clinical features of hMPV pneumonia. Methods: Three independent outbreaks of hMPV occurred at separate LTCF for intellectually challenged and elderly residents. A retrospective evaluation of hMPV pneumonia and its clinical and radiological features was conducted using available medical records and data. Results: In 105 hMPV infections, 49% of patients developed pneumonia. The median age of pneumonia cases was significantly higher than non-pneumonia cases (P < .001). Clinical manifestations of hMPV pneumonia included high fever, wheezing in 43%, and respiratory failure in 31% of patients. An elevated number of white blood cells as well as increased levels of C-reactive protein, creatine phosphokinase, and both aspartate and alanine transaminases was also observed among pneumonia cases. Evaluation of chest imaging revealed proximal bronchial wall thickenings radiating outward from the hilum in most patients. Conclusions: The aforementioned characteristics should be considered as representative of hMPV pneumonia. Patients presenting with these features should have laboratory testing performed for prompt diagnosis.

Legionella pneumophila contamination of hospital dishwashers.

In a tertiary hospital, Legionella spp were isolated from taps and from ward dishwashers connected to contaminated tap piping. Our investigation revealed favorable conditions for growth of Legionella, and showed that Legionella pneumophila SG6 isolates from the taps and dishwashers were all genetically identical by repetitive-element polymerase chain reaction. These results suggest that contaminated dishwashers might be a potential reservoir for the spread of Legionella in health care facilities.

In vitro activity of various antibiotics against clinical strains of Legionella species isolated in Japan.

The activities of various antibiotics against 58 clinical isolates of Legionella species were evaluated using two methods, extracellular activity (minimum inhibitory concentration [MIC]) and intracellular activity. Susceptibility testing was performed using BSYEα agar. The minimum extracellular concentration inhibiting intracellular multiplication (MIEC) was determined using a human monocyte-derived cell line, THP-1. The most potent drugs in terms of MICs against clinical isolates were levofloxacin, garenoxacin, and rifampicin with MIC90 values of 0.015 µg/ml. The activities of ciprofloxacin, pazufloxacin, moxifloxacin, clarithromycin, and azithromycin were slightly higher than those of levofloxacin, garenoxacin, and rifampicin with an MIC90 of 0.03-0.06 µg/ml. Minocycline showed the highest activity, with an MIC90 of 1 µg/ml. No resistance against the antibiotics tested was detected. No difference was detected in the MIC distributions of the antibiotics tested between L. pneumophila serogroup 1 and L. pneumophila non-serogroup 1. The MIECs of ciprofloxacin, pazufloxacin, levofloxacin, moxifloxacin, garenoxacin, clarithromycin, and azithromycin were almost the same as their MICs, with MIEC90 values of 0.015-0.06 µg/ml, although the MIEC of minocycline was relatively lower and that of rifampicin was higher than their respective MICs. No difference was detected in the MIEC distributions of the antibiotics tested between L. pneumophila serogroup 1 and L. pneumophila non-serogroup 1. The ratios of MIEC:MIC for rifampicin (8) and pazufloxacin (2) were higher than those for levofloxacin (1), ciprofloxacin (1), moxifloxacin (1), garenoxacin (1), clarithromycin (1), and azithromycin (1). Our study showed that quinolones and macrolides had potent antimicrobial activity against both extracellular and intracellular Legionella species. The present data suggested the possible efficacy of these drugs in treatment of Legionella infections.

Do infections with disseminated Mycobacterium avium complex precede sweet's syndrome? A case report and literature review.

Sweet's syndrome is reportedly associated with preceding nontuberculous mycobacterial infections (NTMIs). Here, we report on a systemic Mycobacterium intracellulare infection in a patient on corticoid therapy for Sweet's syndrome. Literature searches show that 69.1% of patients with Sweet's syndrome and NTMIs developed this syndrome later than NTMIs and 89.3% of them developed during the clinical course of a rapidly growing mycobacterial infection. The residual cases were associated with slow-growing mycobacteria (14.3%), but only three cases of Mycobacterium avium complex (MAC) infections before the onset of Sweet's syndrome have been reported, and all of them were caused by disseminated MAC disease. One of these cases developed during corticoid therapy for Sweet's syndrome, while another case had underlying diabetes mellitus. Hence, the occurrence of systemic MAC disease may be an inevitable consequence of long-term steroid use and underlying diseases. Literature searches also show that cervical lymphadenitis was a predominant symptom in NTMIs (90.5%). The present case did not have cervical lymphadenitis although the previously reported MAC cases did experience it. Therefore, lymphadenitis from NTMIs may be related to the pathogenesis of Sweet's syndrome. Hence, should a patient have systemic infection without lymphadenitis, it will be more difficult to clinically confirm that MAC disease is a predisposing factor for Sweet's syndrome.

Clinical presentation of Legionella pneumonia: Evaluation of clinical scoring systems and therapeutic efficacy.

To evaluate scoring systems to predict Legionella pneumonia and therapeutic efficacy against Legionella pneumonia, the Japanese Society of Chemotherapy Legionella committee has collected data on cases of Legionella pneumonia from throughout Japan. We analyzed 176 patients with Legionella pneumonia and compared them with 217 patients with Streptococcus pneumoniae pneumonia and 202 patients with Mycoplasma pneumoniae pneumonia. We evaluated four scoring systems, the Winthrop-University Hospital score, Community-Based Pneumonia Incidence Study Group score, and Japan Respiratory Society score, but they demonstrated limited sensitivity and specificity for predicting Legionella pneumonia. Using six clinical and laboratory parameters (high fever, high C-reactive protein, high lactate dehydrogenase, thrombocytopenia, hyponatremia, and unproductive cough) reported by Fiumefreddo and colleagues, only 6% had Legionnella pneumonia when less than 2 parameters were present. The efficacy rates of antibiotics at the time of termination were 94.6% for intravenous antibiotics, including ciprofloxacin and pazufloxacin, and 95.5% for oral antibiotics, including ciprofloxacin, levofloxacin, garenoxacin, moxifloxacin, and clarithromycin. Our results suggested that the previously reported clinical scoring systems to predict Legionnella pneumonia are not useful, but 6 simple diagnostic score accurately ruled out Legionnella pneumonia, which may help to optimize initial empiric therapy. Quinolones and clarithromycin still showed good clinical efficacy against Legionella pneumonia.

Etiological analysis and epidemiological comparison among adult CAP and NHCAP patients in Okinawa, Japan.

BACKGROUND: Etiological epidemiology and diagnosis are important issues for CAP and NHCAP. Despite the availability of effective therapies, significant morbidity and mortality ensues. METHODS: We retrospectively analyzed the etiology of 200 pneumonia patients at the University of the Ryukyus Hospital. Patients were categorized into CAP (n = 97) or NHCAP (n = 103), according to the Japanese Respiratory Society guidelines. Diagnoses were made using clinical tests including, Gram stain, bacterial culture, serum and urinary tests. RESULTS: Pathogens were detected in 71% of patients, and identified as the source of infection in 52% (104/200). The majority of patients suffered from Streptococcus pneumoniae (32/200), Haemophilus influenzae (22/200), and Moraxella catarrhalis (16/200). Gram stain guided pathogen-oriented therapy decisions for 38 of 96 patients with unknown pathogens. Atypical pathogens were only diagnosed in CAP patients (n = 5). Severity of pneumonia was related to male sex (p = 0.006), and preexisting conditions, such as chronic heart failure (p < 0.001) and COPD (p < 0.001). Risk factors associated with increased length of stay included chronic heart failure, chronic renal failure, other pulmonary diseases and diabetes. Mortality for NHCAP patients was associated with lung cancer and bronchiectasis. CAP patients were more frequently admitted during winter months, while NHCAP patients were admitted during all other seasons. Seasonal patterns for individual pathogens could not be determined. CONCLUSION: Gram staining remains useful to guiding diagnostics. Pathogens affecting CAP and NHCAP patients were not significantly different; as such, attention should be focused on the management of underlying conditions. Clinical outcomes were not affected by guideline discordant therapy.

An Epidemiological Analysis of Summer Influenza Epidemics in Okinawa.

Objective This study evaluates the difference between winter influenza and summer influenza in Okinawa. Methods From January 2007 to June 2014, weekly rapid antigen test (RAT) results performed in four acute care hospitals were collected for the surveillance of regional influenza prevalence in the Naha region of the Okinawa Islands. Results An antigenic data analysis revealed that multiple H1N1 and H3N2 viruses consistently co-circulate in Okinawa, creating synchronized seasonal patterns and a high genetic diversity of influenza A. Additionally, influenza B viruses play a significant role in summer epidemics, almost every year. To further understand influenza epidemics during the summer in Okinawa, we evaluated the full genome sequences of some representative human influenza A and influenza B viruses isolated in Okinawa. Phylogenetic data analysis also revealed that multiple H1N1 and H3N2 viruses consistently co-circulate in Okinawa. Conclusion This surveillance revealed a distinct epidemic pattern of seasonal and pandemic influenza in this subtropical region.

Comparative epidemiology of influenza A and B viral infection in a subtropical region: a 7-year surveillance in Okinawa, Japan.

BACKGROUND: The epidemic patterns of influenza B infection and their association with climate conditions are not well understood. Influenza surveillance in Okinawa is important for clarifying transmission patterns in both temperate and tropical regions. Using surveillance data, collected over 7 years in the subtropical region of Japan, this study aims to characterize the epidemic patterns of influenza B infection and its association with ambient temperature and relative humidity, in a parallel comparison with influenza A. METHODS: From January 2007 until March 2014, two individual influenza surveillance datasets were collected from external sources. The first dataset, included weekly rapid antigen test (RAT) results from four representative general hospitals, located in the capital city of Okinawa. A nation-wide surveillance of influenza, diagnosed by RAT results and/or influenza-like illness symptoms, included the age distribution of affected patients and was used as the second dataset. To analyze the association between infection and local climate conditions, ambient temperature and relative humidity during the study period were retrieved from the Japanese Meteorological Agency website. RESULTS: Although influenza A maintained high number of infections from December through March, epidemics of influenza B infection were observed annually from March through July. The only observed exception was 2010, when the pandemic strain of 2009 dominated. During influenza B outbreaks, influenza patients aged 5 to 9 years old and 10 to 14 years old more frequently visited sentinel sites. Although both ambient temperature and relative humidity are inversely associated with influenza A infection, influenza B infection was found to be directly associated with high relative humidity. CONCLUSION: Further studies are needed to elucidate the complex epidemiology of influenza B and its relationship with influenza A. In the subtropical setting of Okinawa, epidemics of influenza B infection occur from March to July following the influenza A epidemic, and primarily affect school-age children. These findings help to define unknown aspects of influenza B and can inform healthcare decisions for patients located outside temperate regions.

Long-term Treatment of Teicoplanin for Methicillin-resistant Staphylococcus aureus Sternal Osteomyelitis with Renal Impairment: A Case of High Teicoplanin Trough Levels Maintained by Therapeutic Drug Monitoring.

Teicoplanin, a glycopeptide antibiotic for methicillin-resistant Staphylococcus aureus, is recommended for therapeutic drug monitoring during treatment. Maintaining a high trough range of teicoplanin is also recommended for severe infectious disease. However, the optimal dose and interval of treatment for severe renal impairment is unknown. We report a 79-year-old man who received long-term teicoplanin treatment for methicillin-resistant Staphylococcus aureus bacteremia due to postoperative sternal osteomyelitis with renal impairment. Plasma teicoplanin trough levels were maintained at a high range (20-30 µg/mL). Although the patient required long-term teicoplanin treatment, a further decline in renal function was not observed, and blood culture remained negative after the start of treatment. Teicoplanin treatment that is maintained at a high trough level by therapeutic drug monitoring might be beneficial for severe methicillin-resistant Staphylococcus aureus infection accompanied by renal impairment.