[Acute exacerbations due to Streptococcus pneumoniae in chronic lower respiratory tract infections during long-term macrolide therapy].

In Japan, long-term 14-membered macrolide administration is chosen as a first line therapy against chronic lower respiratory tract infections (CLRTIs) such as diffuse panbronchiolitis, bronchiectasis and chronic bronchitis. However, sometimes acute exacerbations occur in these cases, even if therapy is effective. We investigated 18 episodes of CLRTIs exacerbations that were caused by Streptococcus pneumoniae during long-term macrolides therapy from 1991 to 1999 to clarify the clinical features and prevalence of antimicrobial resistance in S. pneumoniae. Exacerbations did not occur only in winter season, but also in other seasons. Among 18 episodes of exacerbation, only 7 episodes (39%) revealed infiltration in chest roentogenogram and few episodes revealed marked elevations of inflammation markers in laboratory data. Intermediate resistance or resistance rates of S. pneumoniae isolated from sputum or transtracheal aspiration were 100% to erythromycin, 67% to clindamycin or minocycline, 11% to ampicillin, and 0% to cephazoline or imipenem. Coresistance to erythromycin, clindamycin and minocycline was seen in a half of the episodes. Resistance was not correlated with the duration of macrolides administration. All episodes were mainly treated with beta-lactam agents or fluoroquinolones and cured successfully. These findings suggest that acute exacerbations in CLRTIs caused by S. pneumoniae during long-term macrolides therapy do not reveal severe clinical aspects and can be treated successfully at present, but attention should be paid to the trend of antibiotic susceptibility in S. pneumoniae.

A novel missense mutation in human lactate dehydrogenase B-subunit gene.

Reduced activity of serum lactate dehydrogenase (LDH; EC 1.1.1.27) was found in a male medical student during practical examinations of his own blood. Serum LDH isoenzyme pattern showed reductions in activities of the isoenzymes with lower subunit A/B ratios such as LDH1 and LDH2. These findings were indicative of a partial LDH-B subunit deficiency, which was confirmed in erythrocyte hemolysates by Western blotting. Polymerase chain reaction (PCR)-based DNA sequence analysis of the LDH-B subunit gene revealed a heterozygous nucleotide change: a guanine to adenine substitution in codon 69 (GGG --> GAG) at the third exon of the LDH-B subunit gene that resulted in a glycine to glutamic acid substitution (G69E). The mutation was confirmed by PCR-restriction fragment length polymorphism (RFLP) analysis using a mismatched primer to introduce a new NcoI restriction site. The same heterozygous mutation was found in his mother but not in other family members. This mutation involves a residue belonging to alphaC helix in LDH-B subunit protein molecule that functions as an interface for other subunits.

[Pathogenetic study on bronchopulmonary infections in 1,416 patients by transtracheal aspiration method].

We have performed transtracheal aspiration (TTA) in 1,416 patients, who were suspected to have bronchopulmonary infection, in order to collect non-contaminated specimens directly from the lower airway. The overall isolation rates in 1,416 TTA were 68.7% for any microorganisms. Aerobes had a high incidence but many kinds of microorganisms were associated with bronchopulmonary infections. Haemophilus influenzae was the major pathogen in patients with acute bronchitis. Streptococcus pneumoniae was the most important pathogen and mycoplasma was often isolated in patients with community-acquired pneumonia. Major pathogens of nosocomial pneumonia consisted of alpha-streptococcus spp., anaerobes and Pseudomonas aeruginosa. Anaerobes were isolated from transtracheal aspirates in 20 of 33 episodes of lung abscesses. H. influenzae and P. aeruginosa were the main persistent pathogens and H. influenzae, S. pneumoniae and anaerobes were important exacerbated pathogens in patients with chronic lower respiratory tract infection. S. pneumoniae was isolated more from TTA than expectorated sputa. Oropharyngeal flora bacteria were easily isolated in the culture of expectorated sputa. We assessed the final diagnosis or causative factor in 443 patients whom no microorganism was isolated from transtracheal aspirates. The final diagnosis was infectious diseases in 52 patients (11.7%) and non-infectious diseases in 80 patients (18.1%), respectively. The causative factor was unsuited TTA sample in 81 patients (18.3%), preceding antimicrobial chemotherapy in 95 patients (21.4%) and unknown in 135 patients (30.5%), respectively. The pathogenesis of bronchopulmonary infections is complex and various microorganisms are associated with pathogens of bronchopulmonary infections. Therefore, we should accurately diagnose the pathogens in patients with bronchopulmonary infections. TTA is one of the useful methods that we can accurately detect the respiratory pathogens.

[Enterococcus gallinarum septicemia in a patient with acute myeloid leukemia].

A 62-year-old male was admitted with complaints of fever and body weight loss. The patient was diagnosed as acute myeloid leukemia (M1) and chemotherapy was started. About 80 days after admission, the patient developed diarrhea with high fever. And E. gallinarum was isolated from the blood culture. We carried out PCR using primers for vanA, vanB and vanC in our E. gallinarum, and showed the existence of the vanC1. This organism should be considered as one of the possible pathogenes in the infectious complications of the immuno-compromized patient.

[Clinical evaluation of anaerobic infections in patients with bronchopulmonary infections diagnosed by transtracheal aspiration].

We evaluated the clinical and bacteriologic features in the patients with bronchopulmonary infections isolated anaerobes from transtracheal aspirates between April 1990 and March 1998. Some anaerobe was isolated in 42 (10.9%) in 387 patients whom we performed transtracheal aspiration (TTA), in 42 (15.7%) of 268 in whom some organism was isolated from TTA, or in 42 (16.3%) of 257 patients in whom some bacterium excluding acid-fast bacteria, fungi or mycoplasma from TTA. The isolation rate of anaerobic bacteria was 93.3% in the patients with lung abscess, 22.7% in the patients with nosocomial pneumonia, 19.4% in the patients with community-acquired pneumonia, 26.7% in the patients with acute exacerbation of chronic lower respiratory tract infection (CLRTI), 1.6% in the patients with persistent infection of CLRTI, and 3.0% in the patients with acute bronchitis, respectively. The major anaerobes, isolated from TTA, were Peptostreptococcus micros and Prevotella melaninogenica. The aerobic bacteria were isolated with anaerobic bacteria in 32 of 42 patients at the same time. The quantitive grade of colonial growth of anaerobes was equal to or more than aerobes in the patients with lung abscess and pneumonia. We mostly administrated 3rd generation cephems or carbapenems with or without clindamycin for the treatment of anaerobic infections. Forty-one of 42 patients were cured only by the therapy of antimicrobial agents, but pneumonia patient with lung cancer died in spite of adequate antimicrobial therapy. These results suggest that the anaerobic infections are important in the bronchopulmonary infections.

[Two cases of Achromobacter xylosoxidans sepsis].

Achromobacter xylosoxidans is a gram-negative bacterium whose natural habitat has not been clearly defined. It has been isolated from ear discharge and the large intestine of humans and from various hospital or environmental water sources. Infection with A. xylosoxidans in humans has been documented, and resulting illnesses include meningitis, pneumonia, cholecystitis, peritonitis and urinary tract infection. Bacteremia due to A. xylosoxidans is rare, and little information on treatment is available. Two cases of bacteremia due to A. xylosoxidans in patients with hemapoietic malignancies are reported herein. Case 1 involved a 70-yr. male whose clinical diagnosis was IgA lambda-type plasmacytoma. Case 2 involved 72-yr. male whose clinical diagnosis was acute lymphatic leukemia (L2). Both patients had been catheterized. Neutropenia was noted and the white blood cell counts were 20/microliter in case 1 and 35/microliter in case 2 when A. xylosoxidans was isolated from the blood culture. We suggest that bacteremia due to A. xylosoxidans may have been related to the presence of the catheter and neutropenia.

[Clinical analysis of patients with sepsis--comparison between underlying diseases].

We evaluated the clinical data in 83 patients with sepsis, which was diagnosed by both Bone's definition of sepsis and positive isolates from blood culture, according to their underlying diseases. This study enrolled a total of 117 septic episodes in 83 patients (57 males and 26 females, mean age: 52.0 years). We classified 3 groups, including hematological malignancies (46 patients, 72 episodes), solid malignant tumors (23 patients, 25 episodes) and non-malignancies (14 patients, 20 episodes), by the underlying diseases. Of the total number of isolates from blood culture, 53.0% were single gram-positive bacteria, 33.3% were single gram-negative bacteria, 7.7% were single fungus and 6.0% were polymicrobial organisms. In addition, coagulase negative staphylococci was isolated most often in patients with hematological malignancies. Sepsis was often caused by infectious focuses of hemorrhoid, stomatitis or intravenous catheter in patients with hematological malignancies, by pneumonia in patients with solid malignant tumors and by urinary tract infection in patients with non-malignancies. Mortality of sepsis in patients with solid malignant tumors (48%) was highest in 3 groups. Septic patients, who were complicated with shock and/or DIC, has poor prognosis in all groups. Serum albumin level was significantly lower in dead patients than patients who survived. These results suggest that clinical features may be different according to the underlying diseases of patients with sepsis.

[An epidemiological investigation for MRSA and PRSP in Kinki area. Kinki Infection Working Group].

Recent trends in the development of resistance of the Staphylococcus aureus and Streptococcus pneumoniae to antibiotics were investigated, using a questionnaire delivered to participants at a meeting of the Kinki District Society of Infections. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 55.4% of all isolated S. aureus, and more than 80% of MRSA was detected within hospitals. In outpatients, MRSA was often detected in pus, while in hospitalized patients, MRSA was often detected in sputum. Further, MRSA was accompanied by some other organisms (most frequently Pseudomonas aeruginosa) in 64.7% of MRSA positive patients. The sensitivity of MRSA to vancomycin (VCM) was 100%, to sulfamethoxazole-trimethoprim (ST) 99.2%, and to arbekacin, 98.6%. In contrast, Penicillin-resistant Streptococcus pneumoniae (PRSP) accounted for 42.4% of all isolates of Streptococcus pneumoniae. About 50% of PRSP was detected in out-patients. For both hospitalized patients and outpatients, PRSP was most frequently detected in sputum. PRSP was accompanied by some other organisms (most frequently Haemophilus influenzae) in 49.3% of PRSP positive patients, PRSP had high sensitivity to cephems, carbapenems and VCM.

[Bacillus cereus septicemia in a patient with severe aplastic anemia].

A 78-year-old female was admitted with complaints of malaise and fatigue in the legs. The patient was diagnosed as severe aplastic anemia and treatment was started with metenolone and steroid pulse therapy. Administration of antibiotics and granulocyte-colony stimulating factor which led to a resolution of the high fever. About four months after admission, the patient developed vomiting and abdominal pain with a spiking fever. The next day after suddenly losing consciousness, she died. B. cereus was isolated from blood cultures. Autopsy specimens of the liver, cardiac muscle and lung showed changes due to B. cereus. This pathogen is widely distributed in nature. We should not overlook B. cereus as a contamination, but rather should consider it a potential pathogen in immunocompromised hosts, when it is isolated from blood cultures.

[A clinical study of respiratory infection isolating non-pathogenic Neisseria by transtracheal aspiration].

Neisseria species other than N. meningitidis and N. gonorrhoeae are generally regarded as commensal bacterial flora of the oropharynx, and little is known regarding cases of these non-pathogenic Neisseria species in the lower respiratory tract. We clinically examined respiratory tract infections from which non-pathogenic Neisseria species were isolated by transtracheal aspiration (TTA). The incidence of non-pathogenic Neisseria isolated was 54 (15.7%) out of 344 episodes of respiratory tract infections with isolated microorganisms from TTA, and was 17.6%, 15.8%, 14.3% for pneumonia, acute bronchitis, and chronic lower respiratory tract infection, respectively. All 54 episodes were isolated with other microorganisms such as alpha-Streptococcus spp. (75.9%), Haemophilus influenzae (25.9%) and anaerobics (22.2%). The isolation ratio according to the age group increased at 45 years of age or more, but did not increase with the advance of age. Predisposing factors were identified such as overt aspiration, iatrogenic procedure and heavy smoking. Cases without overt aspiration that had fevers of 38 degrees C or more or hypoxemia of less than PaO2 70 torr when detecting non-pathogenic Neisseria were observed more frequently in the aged than the non-aged. The findings suggest the detection of non-pathogenic Neisseria by TTA is influenced by the host state that the fall of microorganisms from the upper to lower respiratory tract cannot be defended or excluded by mucociliary transportation disorder due to underlying disease and smoking, or deterioration of physical status other than overt or silent aspiration.

[Clinical evaluation of lung abscess diagnosed by transtracheal aspiration].

We have diagnosed lung abscess according to findings of infiltration with cavity formation on chest X-ray and/or CT-scan and pathogens isolated from transtracheal aspirates. We evaluated the clinical features of 20 patients with lung abscess (18 males and 2 females, mean age; 54.3 years). Diabetus mellitus and periodontal diseases were prominent underlying diseases in patients with lung abscess. Cough was complained in 13 patients, chest or back pain in 9, purulent sputum in 8 and hemosputum in 5 when the patients admitted to our hospital. A temperature higher than 38 degrees C was present in 12 patients but temperature les than 37 degrees C in 2. Multiple microorganisms were cultured from TTA in 15 patients. A mean of 2.7 bacterial species per patient was isolated, aerobes alone being isolated in 2 patients, anaerobes alone in 3, and mixed aerobic and anaerobic isolates in 10. Seventeen strains of aerobes and 35 of anaerobes were isolated. Major pathogens were Streptococcus pneumoniae, Streptococcus intermedius and other in aerobes, and Peptostreptococcus micros, Fusobacterium necrophorum, Prevotella melaninogenica and others in anaerobes. Abnormality of chest X-ray was located on the right upper lobe in 6 patients, the right lower lobe in 6, the left upper lobe in 6, the left lower lobe in 4 and the right middle lobe in 1. All patients were cured only by treatment of antimicrobial agents, but cavity formation on chest X-ray remained in 4 patients after the treatment.

[Campylobacter jejuni enteritis in three patients with HIV infection].

Gatrointestinal symptoms, which include diarrhea, are as common as respiratory symptoms in patients with HIV infection. Gastrointestinal symptoms may result from infections, neoplasma, HIV enteropathy or drug toxicity. Three HIV-infected patients admitted to our hospital complaining of diarrhea and fever. We confirmed their diagnosis as Campylobacter jejuni enteritis by bacteriological examination of their feces. All of them had eaten inadequately cooked meat in restaurants before the onset of their enteritis. Their symptoms immediately improved after the administration of antimicrobial agents. One strain of C. jejuni isolated in our cases, however, was resistant to ofloxacin. This case report suggests that we must counsel HIV-infected patients to avoid inadequately cooked food and observe resistant patterns of C. jejuni to antimicrobial agents in Japan in the future.

[A case of multiple muscular abscesses of the lower limbs by Staphylococcus aureus after chemotherapy for lung cancer].

A 67-year-old male was admitted to our hospital because of lung cancer and interstitial pneumonia. Cisplatin, vindesie and mitomycin C were administered for treatment of lung cancer. The leucocyte-counts declined to 1700/microliter on the eighth day after the chemotherapy. Though granulocyte colony-stimulating factor was administered, pain in the right thigh and high grade fever developed. Because Staphylococcus aureus was isolated from the blood specimen, piperacillin was administered. But the high grade fever continued and the pain was expanded to the right hip, left hip, thigh and leg. Because a computed tomograph of the lower limbs showed low density areas in bilateral gluteus maximus muscle right adductor magnus muscle, left biceps femoris muscle and left soleus muscle and the culture of an aspirate from abscess of right leg detected S. aureus, multiple muscular abscesses of the lower limbs was confirmed. We changed the antibiotics from PIPC to imipenem/cilastatin and minocycline on nineteenth day after the chemotherapy. His symptoms improved after the change of antibacterial agents. But he died of acute exacerbation of interstitial pneumonia, after about two months of the chemotherapy. Muscular abscesses of the limbs are very rare in Japan. Only four cases with muscular abscess of the limbs were reported in Japan, since 1988. This case suggests that a muscular abscess must be considered in the differential diagnosis of fever in patients with neutropenia.

[Prognostic analysis of sepsis in patients with lung cancer].

Sepsis is one of the most serious infections occurring in patients with lung cancer. Thus, we determined what is most predisposing factor in prognosis of sepsis in lung cancer patients; the type of causative bacteria, neutropenia or host nutritional status. A total of 27 lung cancer patients with sepsis, which consisted of 23 males and 4 females (mean age 70.7 +/- 6.6), were included in this study. The study was conducted from 1991 to 1995. All subjects were classified into the survival group and the dead group. Staphylococcus aureus or Esherichia coli most frequently isolated from the blood of the patients in the survival group, while either E. coli alone or multiple organisms were predominant in the dead group. Neutropenia did not affect the outcome of sepsis in lung cancer patients. In contrast nutritional status, as determined by serum albumin levels, was closely related to the mortality in septic lung cancer patients. These results predict that the prognosis of sepsis is dependent on nutritional status of lung cancer patients.

[Analysis of prognosis of bronchopulmonary infectious disease with lung cancer].

Bronchopulmonary infection affects the prognosis of lung cancer patients. Thus, we investigated the relationship between the prognosis of bronchopulmonary infectious diseases and their causative bacteria isolated by transtracheal aspiration (TTA) in lung cancer patients. In the present study, we determined which factor is more predisposing for the outcome of bronchopulmonary infections, the type of causative bacteria or the host nutritional status. A total of 107 lung cancer patients, which consisted of 105 males and 5 females (mean age 67.3 +/- 8.0), were included in this study. The study was conducted from 1981 to 1994. They were classified into the survival group and the deceased group. Causative agents of infection were compared between these 2 groups. S. pneumoniae, alpha-Streptococcus sp., M. catarrhalis, and Neisseria sp. were predominant in organisms isolated from TTA-specimens of lung cancer patients with bronchopulmonary infections, regardless of prognosis. Nutritional status, as determined by serum levels of cholinesterase, albumin, and cholesterol, was poor in the deceased group than in the survival group. These results indicate that the outcome of bronchopulmonary infections in lung cancer patients are affected mainly by the nutritional status of the host.

[A clinical features of acute respiratory infection with Haemophilus influenzae by transtracheal aspiration].

We performed a clinical study of 26 cases (27 episodes) of acute respiratory infection with H. influenzae by trans tracheal aspiration (TTA) from May 1987 to April 1995. 15 episodes (14 cases) were bronchitis and 12 episodes (12 cases) were pneumonia. 8 episodes were monomicrobial infection and 19 episodes were polymicrobial infection. Compared to the group of patients of monomicrobial infection, the number of elderly patients and the levels of WBC and CRP were higher in the group of patients of monomicroibal infection. In bronchitis cases, monomicrobial infections of H. influenzae were 7 episodes and polymicrobial infection containing H. influenzae were 8 episodes. In the latter group, PaO2 level was lower and CRP was higher on average. All patients recovered, but the period for treatment was longer in the latter group. In the pneumonia group, only one episode was monomicrobal infection and 11 episodes were polymicrobial infection. Inspite of treatment, one patient died. It was considered that polymicrobial infection was an important factor of acute respiratory infection with H. influenzae.

[A case of AIDS with intractable cryptococcal meningitis].

A 38-year-old hemophiliac, who had been infected with HIV by the administration of blood products and had been diagnosed as AIDS by the onset of Pneumocystis carinii pneumonia, was admitted to our hospital with the complaints of headache and vomiting. After he was diagnosed as cryptococcal meningitis using the microscopy, cryptococcal antigen detection and culture of cerebrospinal fluid, treatment with amphotericin-B and fluconazole was started. As there was no clinical improvement, spinal drainage was performed and acetazolamide administered in order to reduce the intracranial pressure. Treatment was changed from AMPH-B and FLCZ to a combined therapy of AMPH-B and itraconazole. As his clinical features showed improvement, he was discharged home on a maintenance dose of ITCZ and acetazolamide after having been hospitalized for three months. This case-report may be of use in the management of cryptococcal meningitis in patients with AIDS.

[Effect of prolonged administration of erythromycin on the drug sensitivity and the biological properties of Streptococcus pneumoniae].

From April 1990 to February 1992 two hundred and ten strains of Streptococcus pneumoniae were isolated in the laboratory of Nara Medical University Hospital. Frequency of erythromycin resistant Streptococcus pneumoniae, prescription mode of macrolide antibiotics and biological properties were investigated. 1. Erythromycin resistant Streptococcus pneumoniae was predominantly isolated from the wards of the respiratory unit of Inter- nal Medicine and Pediatrics. 2. Patients with erythromycin resistant Streptococcis pneumoniae were treated with macrolide antibiotics frequently in the respiratory unit of Internal Medicine and Pediatrics. 3. MIC90 of EM, CLDM, MINO and ABPC for Streptococcus pneumoniae was 8.0, 8.0, 8.0 and 1.0 micrograms/ml, respectively, indicating moderate resistance to penicillin derivatives and high resistance to macrolides, particularly EM; some strains showed high levels of MIC over 400 micrograms/ml. 4. Investigations on biological properties using VITEK GPI cards revealed that some erythromycin resistant strains showed less responsiveness to DEX, LAC, PUL and MEL. 5. The survival rate of mice infected with erythromycin resistant strains was longer than that with erythromycin sensitive strains. These findings suggested that the prolonged administration of erythromycin causes a virulence reduction of the organism.

[A case of sepsis due to Escherichia coli isolated from blood, transtracheal aspiration and urine].

We reported a 53-year-old female who was admitted due to partial loss of consciousness. She had been diagnosed as old pulmonary tuberculosis and diabetes mellitus. She was diagnosed as diabetic keto-acidosis on admission. We isolated Escherichia coli in the blood, transtracheal aspiration (TTA) and from the urine. We have experienced 6 cases where the same bacteria was isolated from the blood and TTA at the same time. In all 6 cases, we have found single bacteria in the blood and a few other bacteria in TTA. Blood culture is the most certain method to detect the origin of infectious diseases. But the compromised host, as in this case, has multifocal infections in many cases. In order to understand the pathological aspects of the infection, we must obtain many kinds of samples and as many as possible.

[Clinical study of anaerobic respiratory infection].

This clinical study involved 35 cases, anaerobic bacteria were detected by TTA (transtracheal aspiration) or percutaneous lung aspiration, or pleural puncture. These cases were treated over the last 8 years in our department. There were 9 empyema, 9 pneumonitis, 5 lung abscess, 1 necrotizing pneumonia and 11 chronic lower airway infection. In 13 cases (37%), anaerobic bacteria alone were detected, whereas both anaerobic and aerobic bacteria were observed in the other 22 cases (63%). Of all bacteria detected. Bacteroids and Peptostreptococcus were the most common. With respect to host factors involved in the pathogenesis of pleural and parenchymal infection, aspiration was though to be a major trigger in only 11 out of the 24 cases (46%). The other 13 cases (54%) showed no evidence of aspiration, indicating that some other triggers was responsible. In further study, these 13 cases were found either to be heavy smokers with Brinkman index of more than 600, or to show sign of chronic lower airway infection. Both conditions were characterized by an inhibition of the mucociliary transport in the lower airway. Therefore, this study suggested that in the case without apparent aspiration the failure of local defense mechanisms in the airway, as a result of heavy smoking and/or chronic lower airway infection are involved in the pathogenesis of anaerobic respiratory infection.