Development of a score model to predict long-term prognosis after community-onset pneumonia in older patients.

BACKGROUND AND OBJECTIVE: The identification of factors associated with long-term prognosis after community-onset pneumonia in elderly patients should be considered when initiating advance care planning (ACP). We aimed to identify these factors and develop a prediction score model. METHODS: Patients aged 65 years and older, who were hospitalized for pneumonia at nine collaborating institutions, were included. The prognosis of patients 180 days after the completion of antimicrobial treatment for pneumonia was prospectively collected. RESULTS: The total number of analysable cases was 399, excluding 7 outliers and 42 cases with missing data or unknown prognosis. These cases were randomly divided in an 8:2 ratio for score development and testing. The median age was 82 years, and there were 68 (17%) deaths. A multivariate analysis showed that significant factors were performance status (PS) ≥2 (Odds ratio [OR], 11.78), hypoalbuminemia ≤2.5 g/dL (OR, 5.28) and dementia (OR, 3.15), while age and detection of antimicrobial-resistant bacteria were not associated with prognosis. A scoring model was then developed with PS ≥2, Alb ≤2.5, and dementia providing scores of 2, 1 and 1 each, respectively, for a total of 4. The area under the curve was 0.8504, and the sensitivity and specificity were 94.6% and 61.7% at the cutoff of 2, respectively. In the test cases, the sensitivity and specificity were 91.7% and 63.1%, respectively, at a cutoff value of 2. CONCLUSION: Patients meeting this score should be considered near the end of life, and the initiation of ACP practices should be considered.

The efficacy and safety of sitafloxacin and garenoxacin for the treatment of pneumonia in elderly patients: A randomized, multicenter, open-label trial.

Oral treatment for elderly outpatients with pneumonia is becoming increasingly important in this super-aged society from the perspective of cost-effectiveness and limited hospital capacities. We evaluated the efficacy and safety of two oral respiratory quinolones, sitafloxacin and garenoxacin, in elderly patients with pneumonia. This randomized, multicenter, open-label trial was conducted among patients aged ≥65 years with clinically and radiographically confirmed pneumonia in Japan. Patients were randomly assigned (1:1) to receive either sitafloxacin (100 mg/day) or garenoxacin (400 mg/day) for 3-10 days. The primary efficacy endpoint was the clinical cure rate at 5-10 days after the end of treatment. From December 2013 to November 2017, we enrolled 120 patients at 11 hospitals and randomly assigned 59 patients to the sitafloxacin group (1 patient withdrew) and 61 patients to the garenoxacin group. These included 30 patients with nursing and healthcare-associated pneumonia (NHCAP) (18 receiving sitafloxacin, 12 receiving garenoxacin) and 37 patients with aspiration pneumonia (16 receiving sitafloxacin, 21 receiving garenoxacin). The clinical cure rates in the sitafloxacin and garenoxacin groups were 88.5% (95% confidence interval: 76.6-95.6) and 88.9% (95% confidence interval: 77.4-95.8), respectively. No significant differences were observed in the incidence rates of drug-related adverse events between the sitafloxacin (20.7%; 12/58 patients) and garenoxacin (27.9%; 17/61 patients) groups. The most common adverse event was hepatic dysfunction, which occurred in seven patients in each group. We conclude that sitafloxacin and garenoxacin are comparably effective and safe for the treatment of pneumonia, including NHCAP and aspiration pneumonia, in elderly patients.

Utility of a Sputum Antigen Detection Test in Pneumococcal Pneumonia and Lower Respiratory Infectious Disease in Adults.

OBJECTIVE: To compare the utility of Gram staining, a urinary antigen detection kit and a sputum antigen detection kit were examined for the rapid and early detection of pneumococcal pneumonia and lower respiratory infectious diseases. METHODS: A newly developed sputum pneumococcal antigen detection kit (RAPIRUN), Gram staining, and urinary antigen detection kit (BinaxNOW) were comparatively evaluated for their ability to detect Streptococcus pneumoniae in patients with pneumonia or lower respiratory tract infection. Sputum culture results were used as a standard for comparison. Furthermore, the pneumococcus-positive rates in culture and rapid tests were compared using polymerase chain reaction (PCR) as a reference. RESULTS: Of the 169 patients studied, 54 (32.0%) tested positive for S. pneumoniae in culture. S. pneumoniae detection sensitivities for Gram staining, RAPIRUN, and BinaxNOW were 75.9%, 90.7%, and 53.7%, respectively; thus, RAPIRUN had a significantly higher sensitivity than BinaxNOW (p<0.001). For patients with ≥10(5) copies/µg of pneumococcal surface protein A DNA PCR analysis, the detection rates of culture, Gram staining, and RAPIRUN were 85.2%, 72.1%, and 82.0%, respectively, however, the detection rate of BinaxNOW was only 47.5%. Comparisons among 45 patients with culture-positive pneumococcal pneumonia revealed that RAPIRUN had a significantly higher detection rate than BinaxNOW in the mild cases (p<0.006), regardless of the number of days from onset (p<0.03). CONCLUSION: RAPIRUN is a rapid testing kit that detects S. pneumoniae in sputum with a high sensitivity and specificity. It is a particularly more useful detection kit than BinaxNOW for early and mild community-acquired pneumonia in pre-treatment patients whose sputum specimens can be obtained.

Epidemiology and clinical features of pulmonary nontuberculous mycobacteriosis in Nagasaki, Japan.

BACKGROUND AND OBJECTIVES: Recent reports indicate that the incidence of nontuberculous mycobacterial-lung disease (NTM-LD) is increasing. This study aimed to investigate the epidemiology and clinical features of NTM-LD patients in Nagasaki prefecture, Japan to identify the negative prognostic factors for NTM-LD in Japan. METHODS: The medical records of patients newly diagnosed with NTM-LD in eleven hospitals in Nagasaki prefecture between January 2001 and February 2010 were reviewed. Data regarding the annual population of each region and the incidence of all forms of tuberculosis were collected to assess geographic variations in NTM-LD incidence, isolates, and radiological features. RESULTS: A total 975 patients were diagnosed with NTM-LD. The incidence increased over the study period and reached 11.0 and 10.1 per 100,000 population in 2008 and 2009, respectively. M. intracellulare was the most common pathogen in the southern region, and M. avium most common in other regions. The most common radiographic pattern was the nodular-bronchiectatic pattern. Age >60 years, body mass index <18.5 kg/m2, underlying lung disease, and cavitary pattern were the negative prognostic factors at the 1-year follow-up. CONCLUSIONS: The incidence of NTM-LD has been increasing in Nagasaki prefecture. The isolates and radiographic features of patients vary markedly by region.

Two patients who developed leptospirosis-associated acute renal failure within the same season.

In the autumn two patients with general malaise were consecutively admitted to the department of internal medicine of our hospital in the northern region of Nagasaki Prefecture. Since both patients were engaged in rice farm work and showed conjunctival suffusion and pain of the gastrocnemius muscle, leptospirosis was suspected. The first patient required temporary hemodialysis for renal dysfunction, whereas liver dysfunction developed in the second patient. The disease was remitted by antimicrobial agents. A diagnosis of leptospirosis was made serologically in both patients. Leptospirosis should be considered as a differential diagnosis when a patient engaged in farm work in the autumn has typical symptoms, and an early initiation of treatment after onset is important.

Evaluation of a rapid immunochromatographic ODK0501 assay for detecting Streptococcus pneumoniae antigen in sputum samples from patients with lower respiratory tract infection.

A novel, rapid, and noninvasive test (ODK0501) to detect Streptococcus pneumoniae antigen was evaluated in a Japanese multicenter study. ODK0501 uses polyclonal antibodies to detect C polysaccharide of S. pneumoniae from sputum samples by an immunochromatographic assay. The utility of ODK0501 was evaluated for 161 adult patients with lower respiratory tract infection between March 2006 and March 2007. Bacterial culture and identification, real-time PCR, and ODK0501 assays were performed on sputum samples, and the Binax Now Streptococcus pneumoniae antigen test was performed using urine samples obtained from the same patients. The performances of all tests were compared based on the results of bacterial culture and identification. The sensitivity and specificity of ODK0501 were 89.1% (49/55 samples) and 95.3% (101/106 samples), respectively. We then compared the Binax Now Streptococcus pneumoniae antigen test with ODK0501 using samples from 142 patients. The sensitivities of ODK0501 and the Binax Now S. pneumoniae antigen test were 90.0% (45/50 samples) and 62.0% (31/50 samples), respectively (P = 0.002). The relative quantity of S. pneumoniae in expectorated sputum was calculated using real-time PCR and indicated that the possibility of false-positive results for ODK0501 due to indigenous S. pneumoniae was low. The positive and negative concordance rates of ODK0501 and Binax Now were 96.8% (30/31 samples) and 21.1% (4/19 samples), respectively. Binax Now was less capable of detecting S. pneumoniae antigen among patients with underlying chronic obstructive pulmonary disease. In conclusion, ODK0501 is noninvasive, rapid, and an accurate tool for diagnosing respiratory infection caused by S. pneumoniae.

A clinical comparative study of piperacillin and sulbactam/ampicillin in patients with community-acquired bacterial pneumonia.

OBJECTIVE: To evaluate the clinical usefulness of piperacillin (4 g/day) therapy for community-acquired pneumonia compared to sulbactam/ampicillin (6 g/day). METHODS: A randomized prospective clinical study was conducted in patients with mild to severe community-acquired bacterial pneumonia. RESULTS: The overall clinical efficiency of piperacillin therapy (4 g/day) in these patients (41/53=77.4%) was comparable to that of sulbactam/ampicillin therapy (6 g/day: efficiency rate: 33/49=67.3%), when each therapy was administered intravenously for 3-7 days. With regards to clinical efficiency based on disease severity, bacteriological efficiency, improvement in chest X-ray findings and adverse reactions, the two therapies were comparable, even though we found more efficiency for patients who had underlying diseases and there were also cost benefits in piperacillin therapy, compared with sulbactam/ampicillin therapy CONCLUSION: The results suggested that piperacillin therapy has good efficiency and tolerability and that it may be highly effective, even in cases of pneumonia with underlying diseases. This regimen may thus serve as a first line treatment of community-acquired pneumonia.

The roles of the quorum-sensing system in the release of extracellular DNA, lipopolysaccharide, and membrane vesicles from Pseudomonas aeruginosa.

Biofilms play an important role in the establishment of chronic infection caused by Pseudomonas aeruginosa. It has been suggested that membrane vesicles (MVs) are released into the surrounding medium during normal growth and might supply the bacterial extracellular DNA that is required for early biofilm formation, as MVs released from the bacterial outer membrane are suspected to be the source of extracellular DNA. MVs possess lipopolysaccharide (LPS), extracellular DNA, and several hydrolytic enzymes. It is well known that the quorum-sensing (QS) system is important in controlling virulence factors in P. aeruginosa and biofilm formation. In the current study, we investigated extracellular LPS and DNA in the supernatants of culture solutions from PAO1, the wild-type P. aeruginosa, and those of QS mutants. As compared to that of las QS mutants, the amount of LPS and DNA released was significantly higher in PAO1 and in las QS mutants complemented with N-(3-oxododecanoyl) homoserine lactone. Our study indicated that the QS is among the regulators involved in the release of extracellular DNA and LPS. It is possible that these extracellular components are supplied from MVs. Investigation of the mechanism of biofilm formation is of particular interest, as it may be useful for designing treatments for severe P. aeruginosa infection.

[Nontuberculous mycobacterial infections involving solitary pulmonary nodules].

Over the course of 11 years (1993-2003) we encountered 5 cases of pulmonary nontuberculous mycobacterium (NTM) involving a solitary pulmonary nodule. In this report we analyze the chest computed tomography (CT) of these patients, the utility of bronchoscope and transthoracic fine-needle aspiration techniques, the mycobacterium species involved, and treatment results. Four of the 5 NTM cases were due to infection with M. avium and one was due to infection with M. intracellulare. The characteristic findings of the chest CTs were as follows: A solitary nodule was present just under the pleura. No definite distribution pattern was evident. Some cases had agglutinated nodules or fine calcifications. Although fiberoptic bronchoscopy was not used as a diagnostic tool in all 5 NTM cases and histological samples did not contain granulomas, we determined the presence of NTM and we also verified that no cancer cells were present in any of the 5 NTM patients, using transthoracic fine-needle aspiration. Four out of the 5 NTM patients were treated only with drug therapy and they displayed clinical improvement. We resected a solitary nodule in one of the 5 NTM patients because of slow response to drug therapy. We conclude that the solitary pulmonary nodule of NTM is often due to M. avium and that transthoracic fine-needle aspiration is an easy and effective method of detecting NTM.

In vitro and in vivo activities of novel fluoroquinolones alone and in combination with clarithromycin against clinically isolated Mycobacterium avium complex strains in Japan.

The recommended treatments for Mycobacterium avium complex (MAC) infectious disease are combination regimens of clarithromycin (CLR) or azithromycin with ethambutol and rifamycin. However, these chemotherapy regimens are sometimes unsuccessful. Recently developed antimicrobial agents, such as newer fluoroquinolones (FQs) containing C-8 methoxy quinolone (moxifloxacin [MXF] and gatifloxacin [GAT]), are expected to be novel antimycobacterial agents. Here, we evaluated the in vitro and in vivo antimycobacterial activities of three FQs (MXF, GAT, and levofloxacin) and CLR against clinically isolated MAC strains. Subsequently, the in vitro and in vivo synergic activities of FQ-CLR combinations against MAC strains were investigated. CLR and the individual FQs alone showed promising activity against MAC strains in vitro, and the bacterial counts in organs (lungs, liver, and spleen) of MAC-infected mice treated with single agents were significantly reduced compared to control mice. CLR showed the best anti-MAC effect in vivo. When the three FQs were individually combined with CLR in vitro, mild antagonism was observed for 53 to 57% of the tested isolates. Moreover, mice were infected with MAC strains showing mild antagonism for FQ-CLR combinations in vitro, and the anti-MAC effects of the FQ-CLR combinations were evaluated by counting the viable bacteria in their organs and by histopathological examination after 28 days of treatment. Several FQ-CLR combinations exhibited bacterial counts in organs significantly higher than those in mice treated with CLR alone. Our results indicate that the activity of CLR is occasionally attenuated by combination with an FQ both in vitro and in vivo and that this effect seems to be MAC strain dependent. Careful combination chemotherapy using these agents against MAC infectious disease may be required.

Disease severity in patients with simultaneous influenza and bacterial pneumonia.

OBJECTIVE: To determine the differences in the clinical features of bacterial pneumonia patients between patients co-infected with influenza virus or not co-infected. METHODS: Fifteen adult patients with bacterial pneumonia (7 men and 8 women) who also tested positive for influenza virus antigen were compared with those with bacterial pneumonia alone (n=28). RESULTS: Complications with chronic lung diseases were more frequently found in bacterial pneumonia patients with influenza virus infection, compared with those who had bacteria pneumonia alone. Statistical differences were also found in body temperature, and heart rates between the two groups. CRP levels, chest X-ray infiltrates and the severity of pneumonia, as determined using the criteria of the Japan Respiratory Society (JRS) and/or the Infectious Diseases Society of America (IDSA), were also significantly worse in patients of bacterial pneumonia infected with influenza virus, than in those who had bacterial pneumonia alone. CONCLUSIONS: The severity of pneumonia in patients co-infected with influenza virus and bacteria was significantly higher than in those infected with bacteria alone. These data suggested that the influenza virus infection enhanced the bacterial pneumonia. Further study of the pathogenesis of the synergic interaction between influenza virus and bacteria is warranted.

Clinical characteristics of pneumonia caused by beta-lactamase negative ampicillin resistant Haemophilus influenzae (BLNAR).

We wished to assess the clinical differences between beta-lactamase-negative, ampicillin-sensitive and beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae pneumonia. The medical records of 118 patients with H. influenzae pneumonia admitted between March 1998 and March 2003 to Nagasaki University Hospital and affiliated institutions were reviewed. In line with CLSI (Clinical and Laboratory Standards Institute) criteria, we classified H. influenzae according to sensitivity to ampicillin as follows: S (sensitive), minimum inhibitory concentration (MIC) =1; I (intermediate sensitivity), MIC =2; R (resistant), MIC =4. We defined the R strains as the BLNAR group and the S and I strains as the non-BLNAR group. We measured the patient's background, Pneumonia Severity Index (PSI), drug sensitivity of H. influenzae, and evaluation of antibiotic choices. There were no significant clinical differences between the beta-lactamase-negative, ampicillin-susceptible and the beta-lactamase-negative, ampicillin-resistant groups. However, BLNAR pneumonia was more prominent in the younger than the older patients. This study should provide useful information for understanding the clinical characteristics of BLNAR pneumonia.

[A case of multiple nodular pulmonary amyloidosis complicated with primary Sjogren syndrome].

A 79-year-old woman was admitted to the Department of Orthopedics Surgery for treatment of osteoarthritis in her knee. Multiple pulmonary nodular lesions were found on preoperative chest x-ray film screening. Metastatic lung tumor was suspected, but no tumorous lesions were detected in other organs. CT guided lung biopsy was performed. Histopathological examination revealed amyloid consisting of homogenous eosinophilic materials. No amyloid deposits were detected in other organs, so we diagnosed localized nodular pulmonary amyloidosis. She was subsequently given a diagnosis of primary Sjögren syndrome. We believe that such a case of multiple nodular pulmonary amyloidosis with Sjögren syndrome is rare, and the case showed interesting radiological findings, such as mimicking metastatic lung tumor.

Telithromycin inhibits the number of viable bacteria but not lymphocyte accumulation in a murine model of chronic respiratory infection.

The 14-membered macrolides, such as clarithromycin (CAM) and erythromycin (EM), are effective against diffuse panbronchiolitis. However, there have been no studies on the effects of telithromycin (TEL) on chronic respiratory infection in vivo. In this study, we determined the effect of TEL on an experimental murine model of chronic respiratory infection caused by Pseudomonas aeruginosa with biofilm formation. TEL significantly reduced the number of viable bacteria but had no effect on the proliferation of lymphocytes. In contrast, CAM decreased the number of lymphocytes but had no effect on the number of viable bacteria in the lung. These results suggest that TEL and CAM have different effects on chronic respiratory infection caused by P. aeruginosa.

Severe Japanese spotted fever successfully treated with fluoroquinolone.

A 77 years old woman who had a bite with eschar on her left arm, was admitted to emergency ward in our hospital, because of high fever, severe malaise, skin eruption, and consciousness disturbance beginning 5 days previously. She was diagnosed as Japanese spotted fever by seropositive of Rickettsia japonica (R. japonica) antibody, and successfully treated with fluoroquinolone, after minocycline hydrochloride had been proven ineffective. R. japonica-specific DNA was detected by PCR from the tick: Haemaphysalis hystricis larvae collected from a mountainous location in Fukuoka, Japan where the patient had been bitten.

[Case report of disseminated nocardiosis complicated in an elderly person with pneumoconiosis].

Nocardia is typically regarded as an opportunistic infection, with pulmonary nocardiosis frequently disseminated to organs hematogenous by, and nearly half of these cases resulting in complicated nocardia brain abscess. Disseminated nocardia has a dismal prognosis with high mortality, and should be checked for multiple organs including the brain when nocardiosis is diagnosed. We describe the successful treatment of nocardia brain abscesses in an immunocompetent older people with pneumoconiosis by combining trimethoprim-sulfamethoxazole and ciprofloxacin. Patients had no history of fever, headache, or respiratory symptoms such as cough, or sputum until the acute hemiplegia episode. Nocardia infection is not as rare as generally assumed and should be considered as a possibility in the elderly due to its high mortality.

Clinical comparative study of sulbactam/ampicillin and imipenem/cilastatin in elderly patients with community-acquired pneumonia.

OBJECTIVE: To evaluate the clinical usefulness of sulbactam/ampicillin therapy for community-acquired pneumonia in the elderly. METHODOLOGY: A randomized prospective clinical study was conducted in the elderly patients with moderate-to-severe community-acquired bacterial pneumonia. RESULTS: Overall clinical efficacy of sulbactam/ampicillin therapy (6 g/day) in these patients (efficacy rate: 91.4%) was comparable to that of imipenem/cilastatin therapy (1 g/day; efficacy rate: 87.5%), when each therapy was administered intravenously twice daily for 7-14 days. With regard to clinical efficacy based on disease severity, bacteriological efficacy, improvement of chest X-ray findings and adverse reactions, the two therapies were comparable. CONCLUSION: These results suggest that sulbactam/ampicillin therapy has excellent efficacy and tolerability and that it may be highly effective, even in severe cases of pneumonia. This regimen may thus serve as first-line treatment for the treatment of community-acquired pneumonia in elderly patients.

Potency of DX-619, a novel des-F(6)-quinolone, in haematogenous murine bronchopneumonia caused by methicillin-resistant and vancomycin-intermediate Staphylococcus aureus.

In this study, the potency of DX-619, a novel des-fluoro(6)-quinolone agent, was compared with that of vancomycin (VCM) in a murine model of haematogenous bronchopneumonia infection caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate S. aureus (VISA). The minimum inhibitory concentrations (MICs) of DX-619 and VCM against MRSA were 0.03 microg/mL and 1.0 microg/mL, respectively, whilst the MICs against VISA were 0.125 microg/mL and 8.0 microg/mL, respectively. Treatment with DX-619 resulted in a significant decrease in the number of viable bacteria in the MRSA infection model (mean+/-standard error of the mean for control, VCM and DX-619 groups: 7.97+/-0.32, 7.19+/-0.33 and 2.91+/-0.60 log(10) colony-forming units/lung, respectively). For infection with VISA, mice were pre-treated with cyclophosphamide. The survival rate of mice treated with DX-619 (90% survival) was significantly higher than survival rates in the other two groups (45% both for VCM and control groups; P<0.05). Histopathological examination revealed that inflammatory changes in the DX-619-treated group were less marked than in the other two groups. The parameters in lung tissue for the area under the concentration-time curve/MIC ratio both for MRSA and VISA were higher in the DX-619 group than in the VCM group. Our results emphasise the potency of DX-619 against MRSA and VISA murine haematogenous pulmonary infection.

Quorum sensing system lactones do not increase invasiveness of a MexAB-OprM efflux mutant but do play a partial role in Pseudomonas aeruginosa invasion.

We studied the quorum sensing (QS) system and the related homoserine lactones (HSLs) observing Pseudomonas aeruginosa invasion using the epithelial cell monolayer penetration assay model. Compared to the PAO1 wild-type, the QS mutants, DeltalasI and DeltarhlI, were compromised in their capacity to invade. The decreased invasiveness of DeltarhlI was restored by adding 100 microM exogenous C(4)-HSL. However, the decreased invasiveness of an efflux mutant, DeltamexAB-oprM, was not restored in the presence of exogenous HSLs. The QS system partially plays a role in P. aeruginosa invasion; however, C(4)-HSL and 3-O-C(12)-HSL are not the essential determinants for invasiveness for P. aeruginosa.