Comparative clinical study of cefcapene pivoxil and cefteram pivoxil in chronic respiratory tract infections by a double-blind method.

In a double-blind study, the efficacy and safety of the novel cephem antibiotic cefcapene pivoxil (CFPN-PI; 450 mg/day) was compared with cefteram pivoxil (CFTM-PI; 600 mg/day) in 171 patients with chronic respiratory tract infections. There was no significant difference between the clinical efficacy of the two drugs (80.2% for CFPN-PI versus 78.9% for CFTM-PI). There was no significant difference in the rate of elimination of the causative bacteria (60.5% for CFPN-PI versus 65.9% for CFTM-PI). Side-effects were observed in 6.0% of patients treated with CFPN-PI compared with 6.4% of patients treated with CFTM-PI. There were no significant differences in incidence of abnormal laboratory findings following treatment with the two drugs (13.9% for each), and none of the side-effects was severe. We conclude that CFPN-PI (450 mg/day) was as effective and as well tolerated as CFTM-PI (600 mg/day) in the treatment of chronic respiratory tract infections.

Clinical analysis of community-acquired pneumonia in the elderly.

OBJECTIVE: To evaluate the clinical features, etiology, and outcome of patients over 65 years old hospitalized for community-acquired pneumonia. PATIENTS: Eighty-four patients (50 males, 34 females) hospitalized for community-acquired pneumonia in Kawasaki Medical School Kawasaki Hospital between April 1998 and March 2000. RESULTS: Most of the patients had respiratory symptoms or signs, but over one-third also had atypical symptoms of pneumonia such as dyspnea, consciousness disturbance, and gastrointestinal symptoms. The causative microorganisms were identified in 48% of these patients. Streptococcus pneumoniae (13%), respiratory viruses (13%), Haemophilus influenzae (8%) and Mycobacterium tuberculosis (8%) were frequently identified, but Mycoplasma pneumoniae was less frequently noted in the elderly. Double infection was recognized in 19 % and a combination of some virus and bacteria in 13%. Treatment consisted of the administration of second or third generation cephalosporin antibiotics intravenously, because antibiotics had already been preadministered in 39%. The prognosis was poor (mortality rate 9%) for the elderly with community-acquired pneumonia despite mechanical ventilation in 8%. CONCLUSIONS: Although the range of microorganisms causing community-acquired pneumonia differed slightly from that in previous reports; namely, lower frequency of Chlamydia pneumoniae and Legionella pneumophila, it is suggested that the initial antibiotic treatment should always cover S. pneumoniae and H. influenzae. In addition, since a prevalence of virus infections related to the increase in community-acquired pneumonia in the elderly was found in this study, the routine use of influenza vaccine and pneumococcal vaccines in the elderly is recommended to reduce the high mortality rate.

[Clinical analysis of community-acquired pneumonia and pulmonary tuberculosis in the elderly and advances in treatment].

We treated 510 elderly case (over 65 years old) among 1,017 patients with community-acquired pneumonia and 60 similar cases among 112 patients with pulmonary tuberculosis in Kawasaki Medical School Kawasaki Hospital during approximately the past 15 years. These were compared with non-elderly cases (below 65 years old). In the elderly cases with community-acquired pneumonia, atypical clinical symptoms or physical signs were frequent and the mortality rate was high because of severe underlying diseases, and poor general and nutritional conditions. Regarding a prospective study of 84 elderly cases with community-acquired pneumonia during the past two years, S. pneumoniae, Respiratory virus, Gram-negative bacilli, H. influenzae, M. Tuberculosis were frequently isolated. In addition, mixed viral and bacterial infections, which were frequently noted during the winter, were significantly related to the increased frequency of community-acquired pneumonia. In treating elderly cases with community-acquired pneumonia, immunization therapy (e.g., influenza vaccine), second cephalosporin and/or macrolide antimicrobial agents for outpatients with mild pneumonia, and carbapenem and/or macrolide antimicrobial agents for hospitalized patients with moderate or severe pneumonia were most effective. The number of elderly cases with pulmonary tuberculosis has recently increased and the recognition of 10 cases was delayed because of a low percentage of positive smears, but no resistance to antituberculosis drugs have been observed. Regarding the treatment of pulmonary tuberculosis, fluoroquinolone and rifamycin derivative antibiotics have been developed as antituberculosis drugs with strong antituberculous activity. However, due to the high percentage of adverse effects in elderly patients, careful treatment with desensitization therapy for antituberculosis drugs is considered important.

[Clinical analysis of patients with community-acquired pneumonia caused by a mixed infection of polymicrobial agents--including a comparative study of an infectious group with monomicrobial agents and an infectious group with unknown agents].

We clinically analyzed 83 patients with community-acquired pneumonia caused by a mixed infection of polymicrobial agents who we have treated during the past 15 years. A comparative study among three groups; an infectious group with polymicrobial agents (83 cases), an infectious group with monomicrobial agents (335 cases), and an infectious group with unknown agents (599 cases) was performed. The results were as follows; (1) The highest percentage of patients were elderly and bedridden. (2) Striking atypical pneumonic symptoms, including dyspnea, consciousness disturbance, gastrointestinal symptoms and hypotension (shock) were present. (3) Laboratory findings of poor nutritional conditions, including decreases in serum protein, albumin, and cholineesterase, and hypoxia remarkably increased. (4) The prognosis was poor because the mortality rate (15.7%) was higher. (5) There were two polymicrobial agents for 75 patients and three agents for 8 patients. The coupling of polymicrobial agents was most frequent in five patients with Haemophilus influenzae + MSSA and five with H. influenzae + respiratory virus. These results suggest that the patients with community-acquired pneumonia caused by a mixed infection of polymicrobial agents had clinical features and causative microorganisms resembling those of elderly patients with community-acquired pneumonia. We recommended that treatment with antibiotics for them was adequate if the treatment resemble that of elderly patients.

[Clinical analysis of patients with community-acquired pneumonia requiring hospitalization classified by age group].

We classified 1017 patients with community-acquired pneumonia requiring hospitalization experienced in Kawasaki Medical School Kawasaki Hospital during the past 15 years into five age groups (< or = 54 years old, 55-64 years old, 65-74 years old, 75-84 years old, > or = 85 years old). With particular emphasis on the elderly patients, we then compared the clinical and microbiological findings in the five groups. The results were as follows; (1) Half of patients in the over 85 years old group were bed-ridden. (2) The proportion receiving antibiotics before hospitalization decreased with age. (3) There were striking atypical pneumonic symptoms, such as dyspnea and consciousness disturbance in the two age groups over 75 years old. (4) Hypotension (shock) increased with age. (5) Markers of nutritional conditions, such as serum protein, albumin, cholinesterase, and hypoxia remarkably increased in the two age groups over 75 years old. (6) There were no significant differences in the isolation rate of etiological microorganisms. (7) The number of polymicrobial agents in the < or = 54 years old group was lower than that in the other age groups. (8) Mycoplasma pneumoniae was most significantly higher in < or = 54 years old group, Haemophilus influenzae in patients 55-64 years old, and Streptococcus pneumoniae in both 65-74 and 75-84 years old groups. (9) The isolation rate of MSSA, gram-negative bacilli such as Klebsiella pneumoniae, Pseudomonas aeruginosa, respiratory viruses increased with age. (10) The amount of sepsis increased with age. (11) The prognosis was poor in the two groups over 75 years old because the mortality rate (over 10%) was higher that for the other age groups.

[Comparison of community-acquired pneumonia in relation to influenza A and RS virus infections].

We experienced 142 cases with community-acquired pneumonia between April 1998 and March 2000. By measuring the titers of respiratory viruses for these cases, we were able to identify acute phase infections of influenza A virus in 10 cases and RS virus in 6 cases and determined that there was an increase in community-acquired pneumonia during both winter seasons. Thereafter we compared the clinical features of community-acquired pneumonia with regard to these two types of virus infection by dividing the patients into two groups, both of which frequently included in the elderly. In the influenza virus group, such general symptoms as high fever, headache and general fatigue were dominant. Common bacteria were isolated in nine cases with mixed infection; four of them with Streptococcus pneumoniae. In the RS virus group, there were fewer general symptoms and common bacteria were isolated in four cases with mixed infection; three with Haemophilus influenzae. The severity of the illness was greater in the Influenza virus group; i.e.) three cases required mechanical ventilation and two of these three cases died. In the RS virus group, on the other hand, the prognosis was good because no mechanical ventilation was required and there were no deaths. Influenza vaccination is especially important for the elderly, because the epidemiology of the influenza virus groups showed none had a history of influenza vaccination in this study.

[Transitional pattern of the clinical features of patients with pulmonary tuberculosis in a community hospital].

To determine changes in the clinical features of recent patients with pulmonary tuberculosis in a community hospital without restricted tuberculosis wards, the clinical findings of 112 patients with pulmonary tuberculosis (containing miliary tuberculosis) during the past 15 years were compared by dividing the patients into three groups, each encompassing a five-year period. Recently, the number of patients with pulmonary tuberculosis was found to be increasing in a community hospital. In particular, the percentages of elderly patients and smear positive patients have increased. However, because of the improving awareness on tuberculosis, we have diagnosed TB cases correctly on admission and tended to perform the appropriate treatment. The comparative study between pulmonary tuberculosis patients diagnosed at the outpatients department and diagnosed after admission indicated that the patients diagnosed after admission showed pneumonia-like infiltrative shadows without cavity formation and lower smear positivity for tubercle. Fortunately, resistance to antituberculous drugs of isolated tubercle bacilli in our community hospital has not yet increased and the prognosis of the cases proved to be good when the appropriate treatment was performed at an early stage.

[Clinical analysis of nursing home-acquired pneumonia in a community hospital].

To clarify the characteristic features of nursing home-acquired pneumonia in our community hospital, we performed a clinical analysis of 86 patients with nursing home-acquired pneumonia. The patients were divided into young and elderly groups. In the young group cerebral palsy was the underlying disease. In the elderly group, it was cerebrovascular attack. Although there were no differences in ADL, the nutritional condition of the young group was comparatively good, the isolated microorganism consisted of mostly Mycoplasma pneumoniae and the prognosis was good. The elderly group where the nutritional condition was poor, the patients were detected by non-respiratory symptoms and risk factors such as obvious episodes of aspiration led us to be concerned about the risk factors for nursing home-acquired pneumonia. The microorganism isolated from the sputum of the elderly group was frequently a multi-drug resistant microorganism such as Methicillin-resistant Staphylococcus aureus (MRSA) and polymicrobial infection. Their prognosis was poor despite treatment with multiple antibiotics. In the comparative study between survivors and non-survivors in the elderly group, risk factors such as hypotension, consciousness disturbance, the extension of infiltration shadows, respiratory failure, multiple organ failure and metabolic acidosis were influenced for the prognosis, but the isolated microorganisms and the antimicrobial agents were not concerned.

[A case with infectious mononucleosis-like syndrome caused by human herpes virus-6 infection].

A 26-year-old female was admitted because of multiple fractures in lower extremities. While in the hospital, she developed a high fever and generalized skin eruption. Physical examination revealed bilateral cervical lymphadenopathy and mild hepatosplenomegaly. The white cell count was 11,200 with 11% atypical lymphocytes. Serum GOT, GPT, LDH were markedly elevated. Infectious mononucleosis was suspected, but the serological test for EB virus did not show evidence of acute EB virus infection. Anti-HSV, CMV, hepatitis A virus antibody titers also did not show significant change during the coarse. The serological test for HHV-6 only showed increased titer of IgM and IgG antibodies. Rapidly elevated IgG antibody titer was indicative of reactivation of HHV-6. So, she was diagnosed as mononucleosis-like syndrome caused by HHV-6, probably reactivated infection. Her symptoms gradually disappeared during a month.

[Clinical analysis of community-acquired pneumonia requiring hospitalization in a community hospital--comparison of elderly and non-elderly patients].

A comparative study of 890 patients with community-acquired pneumonia requiring hospitalization in a community hospital was performed. The patients were divided into an elderly patient group and a non-elderly patient group. The elderly patients with community-acquired pneumonia exhibited frequent atypical symptoms such as dyspnea, consciousness disturbance and complication of shock, and also were frequently in a poor nutritional condition. The causative microorganism was isolated in 40.8% of the elderly patients and in 44.0% of the non-elderly patients. Polymicrobial agents were detected frequently in the elderly patients. Streptococcus pneumoniae (19.4%), MSSA (16.8%), Klebsiella pneumoniae (15.1%) and Haemophilus influenzae (15.0%) were frequently isolated from the sputum of the elderly patients, while Mycoplasma pneumoniae (25.2%), H. influenzae (15.0%), S. pneumoniae (12.2%) and MSSA (10.2%) were frequently isolated from that of the non-elderly patients. Regarding treatment with antibiotics, therapy with a single antibiotic therapy, such as cephem or carbapenem was carried out for the elderly patients, while new quinolone or tetracycline was administered to the non-elderly patients. Although the treatment with antibiotics was adequate according to the guidelines of the American Thoracic Society, the prognosis was poor; i.e.) in the elderly patients an efficacy rate of 74.3% and a mortality rate of 9.5%. In the non-elderly patients, the prognosis was good; i.e.) an efficacy rate of 88.0% and a mortality rate of 1.7%. These results suggest that the most important factors affecting the prognosis were the general condition of elderly patients and delay in an adequate diagnosis and treatment because of atypical clinical findings.

[Viral infection related to the appearance of acute bacterial respiratory tract infections].

To investigate what viruses are related to acute bacterial respiratory tract infections, we prospectively evaluated 113 cases with respiratory tract infections (always accompanying by purulent sputum) experienced between July 1998 and March 2000. Acute viral infections were detected in 25 cases (22%); 10 cases of influenza A virus and 6 cases of respiratory syncytial (RS) virus. The epidemiology of the influenza A virus and RS virus was mainly identified as from December to February in both winter seasons. A bacteriological examination of sputum cultures isolated 12 cases of Streptococcus pneumoniae and 10 cases of Haemophilus influenzae during the same periods and mixed infections of both viruses and bacteria were recognised in 16 cases (14%). These results suggest a significantly high percentage of mixed infections of both viruses and bacteria. However, it was unknown whether the patients with acute bacterial respiratory infections had been infected with viruses prior to the bacterial infections. The frequency of appearance of respiratory tract infections tended to increase with the seasonale epidemiology of viral infections.

[Clinical analysis of pulmonary tuberculosis in association with corticosteroid therapy].

In the last five years, five patients (three males and two females) among a total of 162 patients (3.1%) ranging from 63 to 79 years old developed pulmonary tuberculosis during the long-term corticosteroid therapy. The underlying diseases of these cases were pulmonary fibrosis in two, polyarteritis nodosa in one, RPGN + pulmonary bleeding in one, and mycosis fungoides in one. The total corticosteroid dose used until the clinical diagnosis of pulmonary tuberculosis was 1.16 g to 5.60 g and the term of administration was two to nine and a half months. Other immunosuppressive drugs were administered to two patients. Though chemoprophylaxis with INH was done in two patients for three months, it was impossible to prevent the development of pulmonary tuberculosis. Since almost all patients except one complained no symptoms at the onset, the follow-up with chest roentgenograms seemed to be most important during corticosteroid therapy, and in fact, four patients were detected by the follow-up. Antituberculous chemotherapy was effective in four patients but was not carried out for one patient due to the delay in the diagnosis. Careful clinical observation, such as by chest roentgenograms, seems to be appropriate for the early diagnosis and treatment of pulmonary tuberculosis in patients on corticosteroid therapy.

[Evaluation of the usefulness of a serodiagnosis kit, the determiner TBGL antibody for tuberculosis: setting reference value].

The determiner TBGL antibody developed by Kyowa-Medex co., ltd. is a new serodiagnostic kit for tuberculosis. To set cut-off point suitable for the kit, TBGL antibody titer of serum from healthy subjects were analyzed in relation to age, sex, previous and family history on tuberculosis. Based on results of healthy subjects, cut-off point was set by using several analytical methods. We propose 2U/ml as a cut-off point for screening of patients with tuberculosis considering the diagnostic efficiency by receiver operating characteristics (ROC) curve analysis and 4U/ml for diagnosis of tuberculosis, which was determined by parametric method considering its specificity.

[A case of pulmonary infectious disease due to Mycobacterium szulgai].

A 49-year-old male was admitted to our hospital complaining of cough and general fatigue. There was nothing unusual about his past history, and he has been healthy. On admission, a chest roentogenogram revealed an infiltrative shadow with a cavity in the left middle and lower fields. Because the acid fast staining of a bronchoscopic specimen was positive for mycobacteria, he was transferred to another hospital to be treated as pulmonary tuberculosis. Culture tests of multiple specimens were positive, and were identified as Mycobacterium szulgai, and the case was diagnosed as pulmonary atypical mycobacteriosis caused by M. szulgai. He was treated with isoniazid, rifampicin and ethambutol daily, but because of side effects, such as drug eruptions, all drugs were stopped. However, his clinical symptoms and infiltration shadow improved gradually. We described a rare case of pulmonary disease with Mycobacterium szulgai infection appearing in a healthy male without underlying diseases.

[Clinical analysis of pneumonia in the elderly in a community hospital--comparison of community-acquired pneumonia and nosocomial pneumonia].

We experienced 530 elderly cases with pneumonia among 930 patients with pneumonia in Kawasaki Medical School Kawasaki Hospital between April 1986 and September 1998. Clinical analysis of all these patients and a comparison of one group consisting of 418 patients with community-acquired pneumonia and another group composed of 112 patients with nosocomial pneumonia were performed. In all of the elderly patients with pneumonia, respiratory symptoms and inflammatory findings were less frequent, but were frequent for those in poor general and nutritional condition. The causative microorganism was isolated in 42% of these patients. Streptococcus pneumoniae, MSSA and Klebsiella pneumoniae were frequently isolated from the sputum of the patients with community-acquired pneumonia, while Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Methicillin-sensitive Staphylococcus aureus (MSSA) were frequently isolated from that of nosocomial pneumonia patients. Mycoplasma pneumoniae, Chlamydia pneumoniae and some viruses were less frequent for patients in both groups. Although many intravenous antibiotics, such as cephem or carbapenem were administered to patients in both groups, the prognosis was relatively good for those with community acquired pneumonia but was extremely poor for those with nosocomial pneumonia despite mechanical ventilation or steroid pulse therapy for many patients.

[Clinical analysis of the prognosis of severe pneumonia requiring mechanical ventilation].

To determine which factors are important in predicting the outcome of patients with severe pneumonia requiring mechanical ventilation, we compared 43 surviving pneumonic patients with 37 non-surviving pneumonic patients. The following results were obtained. The following characteristics were noted in the non-surviving patients as compared with surviving patients; 1. a worsening of performance status in the background, 2. presence of physical signs such as hypotension and trachycardia, 3. abnormal laboratory data such as leukocytosis, lymphocytopenia, hypoalbuminemia, hepatorenal dysfunction and metabolic acidosis, 4. presence of massive pulmonary infiltrations on chest roentgenograms, 5. a prevalence of resistant microorganisms for many antibiotics such as MRSA (Methicillin resistant Staphylococcus aureus). These results suggest that the most important factor affecting the prognosis of patients with severe pneumonia requiring mechanical ventilation may by the condition of the host and of the microorganisms rather than antibiotic treatment.

[Three cases of pneumonia due to mixed infection of bacteria and Mycoplasma pneumoniae].

We reported three cases of pneumonia due to mixed infection of bacteria (2 cases: Streptococcus pneumoniae, 1 case: methicilline-sensitive Stapholococcus aureus) and Mycoplasma pneumoniae. Increased serum antibody titers of M. pneumoniae were noted in all cases. They were a 36-year-old-female with bronchial asthma, a 74-year-old-male with old pulmonary tuberculosis and a 82-year-old-male with chronic bronchitis. All cases had fever, productive cough with purulent sputum and coarse crackle by auscultation. Leukocytosis was noted in 2 cases. Chest X-ray films showed dense consolidation in all cases, 2 cases were cured by administration of cephems and 1 case was cured by administration of carbapenems and minocycline.