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Limited use of linezolid for treating methicillin-resistant Staphylococcus aureus (MRSA) infection was approved in Japan in 2006. We report here the status of linezolid-resistant MRSAs in Japan. Eleven linezolid-resistant clinical isolates from 11 patients at six hospitals were collected from 2006 through 2008. The minimal inhibitory concentration (MIC) of linezolid in these strains varied from 8 to 64 μg/ml. All strains had at least one G2576T mutation in the chromosomal gene(s) encoding domain V of the 23S ribosomal RNA (rRNA). Chromosomal DNA encoding five copies of the domain V region was analyzed by polymerase chain reaction (PCR). Strains with the linezolid MICs of 64, 32, 16, and 8 μg/ml had the G2576T mutation(s) in four, three (or four), two, and one copy of the 23S rRNA genes, respectively. These results suggest that the level of linezolid resistance seems to be roughly correlated with the number of mutations in the genes encoding 23S rRNA. DNA samples from all 11 strains were subjected to pulsed-field gel electrophoresis and were classified into seven independent clones having >92% identity. Among the 11 patients, five had been treated with linezolid and the remainder, in two hospitals, had no history of prior linezolid use. The results suggested possible nosocomial infections by linezolid-resistant MRSA.

Emphysematous urinary tract infection is a rare, fulminant complication that is characterized by the presence of gas in the pelvicaliceal system, renal parenchyma, perinephric tissues and retroperitoneum. Surgical resection is usually regarded as the treatment of choice, however several studies have shown the safety and efficacy of conservative management under the correct diagnosis and appropriate antibiotic administration. We herein report on two cases of emphysematous urinary tract infection, pyelonephritis and cystitis infected with ESBL-producing Eschrerichia coli, complicated with diabetic mellitus which were successfully treated with conservative treatment.

We report herein on the case of a 71-year-old woman hospitalized for continued postauricular pain of unknown origin with tongue deviation. In view of the severe inflammatory reaction and multiple nodular shadows of the lungs, the existence of infectious disease was indicated. A contrast-enhanced CT scan of the neck revealed a thrombosis of the right internal jugular vein, osteomyelitis of right temporal-occipital bone and upper cervical spine, and cellulitis of the adjacent soft tissue. Multiple nodular shadows of the lungs were suspected to be the result of a metastatic septic embolism. Hence, she was diagnosed with Lemierre syndrome. Following treatment with long course of antimicrobial therapy including beta-lactams and clindamycin, complete recovery in this patient was achieved.

A 35-year-old male patient had a fever, cough, and other symptoms since the end of December 2010. The patient then developed a high fever and decreased SpO2, suggesting possible pneumonia. The patient was admitted to our hospital on the 6th day of illness. Chest computed tomography revealed multiple infiltrative shadows and ground-glass opacities distributed in a patchy pattern in the bilateral lungs. An atypical pneumonia was suspected, and we initiated antibiotic treatment with minocycline. However, the patient developed consciousness disturbance in the afternoon of the 7th day of illness. The high fever persisted, suggesting the patient's poor response to minocycline treatment, which was then replaced with ciprofloxacin and imipenem/cilastatin on the 8th day of illness. Streptococcus pneumoniae was detected in the blood culture bottles submitted at the time of admission. A head magnetic resonance imaging performed on that day showed a high intensity area in the splenium of the corpus callosum, leading to a diagnosis of encephalopathy. Methylprednisolone pulse therapy and gamma globulin treatment were initiated. The patient then recovered consciousness gradually with improvement of inflammatory responses and imaging findings. Subsequently, an influenza virus (H1N1) antibody level was found to have increased from less than 10 times to 640 times. Thus, it was determined that the patient's pneumonia and encephalopathy were attributable to the influenza A (H1N1) pdm09 virus during the flu season and Streptcoccal infection. Combination therapy, such as steroid pulse treatment, appropriate antibiotics and gamma globulin preparation was effective for both the flu-induced mixed pneumonia and encephalopathy in this patient.

A 73-year-old man was admitted to our hospital with a high fever and left paresis. A rapid diagnosis test was positive for influenza A was positive by rapid diagnosis test and diffusion-weighted MRI imaging of the brain showed a high intensity lesion of the right cerebral peduncle. The patient was therefore diagnosed as having influenza A virus infection complicated with lacunar infarction. In spite of initial treatment with oseltamivir and anticoagulant therapy, he lost consciousness eight hours after admission. The high intensity lesion of the cerebral peduncle enlarged and new lesions in the thalamus, hippocampus and calcarine cortex were detected with brain MRI. Additionally, an electroencephalographic study showed an entire slow wave and as the other causative pathogens of central nerve system infection were not detected, the likely diagnosis was influenza-associated encephalitis. We administered a high dose of intravenous immunoglobulin since the low-grade fever and mild unconscious state had continued in spite of the treatment with methylprednisolone pulse therapy. His consciousness was restored and body temperature became normal immediately. We could confirm the efficacy of our treatment by measurement of IL-6 levels in the serum and cerebrospinal fluid during the entire clinical course. In conclusion, a high dose of intravenous immunoglobulin therapy might be one of the effective treatments for influenza-associated encephalitis.

A 78-year-old woman seen in June 2005 for chest abnormal shadows after 3 months of steroid therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies was found in chest computed tomography (CT) revealed bronchiectasis and small nodules in the right middle lobe and left lingula. Sputum cultures were positive for Mycobacterium intracellulare. Based on a diagnosis of pulmonary nontuberculous mycobacteriosis, the woman underwent antimycobacterial therapy with clarithromycin, rifampicin, and ethambutol hydrochloride for 10 months. She was then admitted in June 2009 with right chest pain. Chest CT showed consolidation shadows with bronchiectasis in the right middle lobe and the left lingula and left pleural effusion. Magnetic resonance imaging (MRI) showed that Th7-Th8 vertebral bodies had collapsed. A vertebral body specimen obtained by CT-guided biopsy was positive for M. intracellulare. Based on a diagnosis of vertebral osteomyelitis due to M. intracellulare, she underwent antimycobacterial therapy with clarithromycin (800 mg), rifampicin (450 mg), ethambutol hydrochloride (750 mg), and streptomycin (750 mg). After 4 weeks of antimycobacterial therapy, she underwent radical debridement and decompression surgery with anterior and posterior spinal fusion. Four weeks postoperatively, streptomycin was discontinued. We continued clarithromycin, rifampicin, and ethambutol hydrochloride for 18 months, and no recurrence was detected. Although vertebral osteomyelitis due to nontuberculous mycobacteria is rare, clinicians should consider the combination of nontuberculous mycobacteriosis and vertebral osteomyelitis in cases such at these.

Deep-seated mycosis usually occurred in severe immunocompromised patients and is sometimes fatal. Hence, chronic fungal infection occurred in the patients with mild to moderate immunocompromised status and persists for longer period. Biofilm formation is one of the factors related to persisting infection of Candida spp. Biofilm formation resists to the antifungals in catheter-related Candida infection and selection of appropriate antifungals will be an important key to achieve good outcome. Although azoles possessed excellent antifungal activity against planktonic Candida spp., they show lower activity against biofilm-formed Candida spp. Overexpression of efflux pump of Candida spp. is reported to be involved in lowered activity of azoles. Amphotericin B, liposomal amphotericin B, and micafungin however, are expected to have high antifungal activity against biofilm-formed Candida spp. Recently, Aspergillus is also reported to possess potential of forming biofilm. Biofilm formation of Aspergillus is considered to be related to pathogenesis of chronic pulmonary aspergillosis. General antifungals are not highly active to biofilm-formed Aspergillus as same as Candida, and only amphotericin B and its liposomal formulation are expected to be effective in vitro.

Corynebacterium pseudodiphtheriticum, one cause of respiratory tract infection, is rarely considered as a pathogen because it is among normal bacterial flora colonizing the oral cavity. We report two cases of C. pseudodiphtheriticum causing respiratory tract infection--an exacerbation of chronic obstructive pulmonary disease and pneumonia--, both in the presence of underlying respiratory disease. Both required antibiotics after first-line chemotherapy failed. Isolates were susceptible to beta-lactams. Gram-staining of respiratory tract specimens is important in diagnosing this infection and determining appropriate antimicrobial use.

Since plasmid-mediated metallo-beta-lactamase (MBL)-producing Pseudimonas aeruginosa was reported in Japan, MBL-producing Gram-negative rods (GNRs) have emerged worldwide. We developed a way to detect MBL-producing GNRs in routine examination using broth microdilution with the MBL inhibitor sodium mercaptoacetate (SMA) in frozen plates. Between 1996 and 2005, we evaluated this and other methods, including broth microdilution with another MBL inhibitor dipicolinic acid (DPA) in dry plates, conventional PCR, and a combined simple DNA preparation and enzymatic PCR product detection. The combined method is suitable for detecting IMP-type MBL-producing GNRs from numerous isolates. Broth microdilution with SMA at a concentration of 400 microg/mL had high performance and detected most PCR-positive MBL-producing GNRs in routine antimicrobial susceptibility testing. DPA in dry plates at 400 microg/mL yielded false positive results in 11.4% of isolates but worked satisfactorily at 175 microg/mL and 400 microg/mL of SMA in frozen plates. Until 1996, MBL had been detected from only 6 bacterial species, i.e., Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas stutzeri, Achromobacter xylosoxidans, Serratia marcescens, and Citrobacter freundii, MBL-producing GNRs were later found in other glucose nonfermenting GNRs such as Acinetobacter baumanii, Acinetobacter lwoffii, and Burkholderia cepacia complex and Enterobacteriaceae. Most MBL-producing bacteria were multidrug resistant and no antimicrobial agents exist that are active against such isolates in monotherapy, making their rapid detection very important in controlling infection control.

A 37-year-old woman admitted elsewhere for a high fever, dry cough, stridor, and dyspnea was found in chest radiography and computed tomography on admission to have a thickened bronchial wall with centrilobular nodules in both lower lobes and skipped consolidations in the lower and middle lobe of the right lung. She had been diagnosed with mycoplasmal pneumonia because of high Mycoplasma pneumoniae antibody titer, so clarithromycin (CAM) was administrated. She was referred to us due to hypoxia with obstructive impairment in the pulmonary function test. Ventilation/perfusion radioisotope in the lung scan indicated heterogeneous distribution without mismatch, suggesting bronchiolitis obliterans due to M. pneumoniae pneumonia, so steroids were started. Five weeks of steroid administration ameliorated clinical symptoms, hypoxia, and abnormal shadows, but obstructive impairment diod not disappear completely. Early administration of steroid with antibiotics is required for bronchiolitis obliterans caused by M. pneumoniae. We review cases of mycoplasmal bronchiolitis reported in Japan.

We studied 316 adults with community-and hospital-acquired bacterial pneumonia admitted from January 1998 to July 2003. Of these, 66 (20.9%) died. Classified by age, none under 70 died, but mortality increased to 22.6% in the 70-79 age group, 31.6% in the 80-89 age group and 24.2% in the group over 90. Mortality was 3.4% (6/177) for mild pneumonia, 32.0% (24/75) for moderate pneumonia, and 56.3% (36/64) for severe pneumonia. Mortality in hospital-acquired pneumonia (69.1%) was significantly higher than that in community-acquired pneumonia (10.7%). This may result from the higher percentage of moderate by and severe by ill patients who contracted hospital-acquired pneumonia, since 80% of those with hospital-acquired pneumonia were in the moderate and severe group compared to 36.4% of those with community-acquired pneumonia. For antibiotic regimens, mortality was 18.2% to 36.4% for patients who underwent Penicillins-Cephems therapy compared with 51.6% to 66.7% for Carbapenems-Quinolones therapy. The reasons for these differences remain unclear. Our study indicates that severity of illness, age, and antibiotic therapy were factors correlated with death from pneumonia. Underlying diseases such as respiratory failure, chronic heart failure, cerebrovascular disease, renal failure, malignancy, and senile dementia may also be associated with mortality.

A 76-year-old man admitted for general malaise with fever was found in clinical examination on admission to have eosinophilic pleural effusion, peripheral eosinophilia, and a slightly elevated inflammatory reaction. Immunological examination, including microplate ELISA, showed a high titer of specific antibody against Toxocara canis in both the serum and pleural effusion. We started treatment using albendazole, and found inflammatory findings and serum IgE were ameliorated. Parasitic disease is an important consideration in the differential diagnosis of eosinophilic pleural effusion, and serology is useful in screening for this.

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 studies of sixteen cases with pulmonary cryptococcosis, during the past six years between 1998 and 2004, were peformed mainly with respect to serum cryptococcal antigen titer. Serum cryptococcal antigen was positive in twelve of 16 cases, the other three cases were diagnosed by VATS, the other one by positive culture of cryptococcus in BALF. In these twelve cases, the serum cryptococcal antigen titer was continuously tested after treatment. The serum cryptococcal antigen titer decreased from half to 6 months after treatment. And the cryptococcal Ag changed to negative in six of the 12 cases by antifungal agents from 5 to 19 months. But four cases whose pneumonia was severe tended to have a high titer level of cryptococcal antigen and were positive for a long period. In the Chest CT of four pulmonary cryptococcosis case with negative cryptococcal antigen, all of the maximum nodule size was less than or equal to 15mm in diameter.

Measurement of blood (1-->3)-beta-D-glucan is useful for early diagnosis and follow-up of the therapeutic process of deep seated mycoses. The Fungitec G test MK (Seikagaku Corp., Tokyo) kit using alkaline-pretreatment followed by chromogenic kinetic assay has been widely used in Japan because of its high sensitivity and easy handling of a large number of samples. Discrepancy in the levels of (1-->3)-beta-D-glucan and/or in the quantitative judgement, however, has been pointed out between this kit and other commercial kits. One of the reasons for this discrepancy has been reported to be non-specific reactions caused by substances other than beta-glucan. In this study, we have improved the alkaline pretreatment reagent by changing the concentration of KOH and salts, resulting in a marked reduction of the non-specific reaction. Recovery of standard beta-glucan added to plasma or serum after the improved pretreatment was 80 to 120%, and no amidolytic activity was detected either in plasma or in serum. By the improved pretreatment, the incidence of non-specific reactions, i.e., those that exceed the quantitation limit (3.9 pg/mL), were markedly decreased from 139 to 16 out of 200 plasma samples and from 106 to 22 out of 170 serum samples. The incidence of strong non-specific reactions, i.e., those that exceed the cut-off level (20 pg/mL), were also decreased from seven to one with plasma and seven to zero with serum samples. Correlation between corrected beta-glucan measurements by the current pretreatment and non-corrected ones by the improved pretreatment was quite good. The improved method is thus expected to decrease the frequency of non-specific false-positive reactions, with the high sensitivity of Fungitec G test MK.

A 78-year-old Japanese female was admitted to our hospital because of headache. Trismus, opisthotonus and convulsion appeared in the early morning on the second hospital day. She was diagnosed as tetanus based on these symptoms and the history of trauma on her left hand 6 days ago. A piece of bamboo was extracted from her left hand. However, Clostridium tetani was not identified. Thiamylal and mechanical ventilation were initiated combined with Pancronium, Diazepam and tetanus immune globulin. Gabexate Mesilate was also added for disseminated intravascular coagulation syndrome probably associated with rhabdomyolysis. By these treatments, she was healed leaving only a disuse syndrome of her limbs.

A 53-year-old male was admitted to our hospital with a high fever and pain in the right arm. He was diagnosed as toxic shock-like syndrome by Streptococcus pyogenes. His arm was amputated because of necrotizing myositis and his renal damage was severe, he was treated in the intensive care unit with continuous hemodiafiltration. Bacteria were isolated from blood, ascites, pleural effusion, skin, and muscle. He was treated with a large amount of ampicillin, clindamycin, and gammaglobulin. However, his general status became worse. His illness improved after linezolid was administered. The reason for the success in treatment with linezolid, which was the inhibitory effect on bacterial toxin and its excellent penetration into the tissue.

We have reported two orthopedic patients with Methicillin-resistant Staphylococcus aureus (MRSA) infections successfully treated with linezolid. The first case was a 64-years-old man with bacteremia, spondylitis and psoas abscesses caused by MRSA. He was treated with arbekacin (ABK) and vancomycin (VCM), and then became afebrile. However he complained of a recurrence of fever and oliguria, we administered linezolid for two weeks intravenously because of fluctuating renal dysfunction. Thereafter his clinical conditions improved. The second case was a 26-years-old man with MRSA infection of the pelvis after a trauma. He was treated with teicoplanin (TEIC) for two weeks. However the minimum inhibiratory concentrations (MICs) of TEIC and VCM against MRSA, isolated from the wounds, were 4 micrograms/ml each, we administered linezolid intravenously and the patient was successfully treated in four weeks. Linezolid has been proven to have high efficacy against MRSA by some trials abroad. But the agent has the indication only for VRE by the Medical Insurance in Japan. These cases also suggest that linezolid is useful for MRSA infections in these cases.

The tuberculin skin test (TST) was conducted in 1,087 employees of Nagasaki University Hospital. The size of erythema (T1) was 27.3 +/- 17.0 mm, and 8.6% of all participants showed < = 9 mm, 49.9% showed 10-29 mm, 41.5% showed > = 30 mm. Laboratory technologists showed significantly larger reactions than other groups. Doctors and nurses working on the tuberculosis ward showed larger reactions than those working on the non-tuberculosis wards. Reactions tended to be larger with aging, and the younger employees in their 20s showed significantly smaller reactions than those in their 40s. The second TST was carried out in 253 employees whose T1 was below 30 mm. The size of erythema enlarged from 16.1 +/- 6.6 mm (T1) to 26.4 +/- 15.4 mm (T2), with the difference (booster phenomenon) of 10.2 +/- 14.4 mm. T2 and T2-T1 were larger in nurses working on the tuberculosis ward than those on the non-tuberculosis wards. It was suggested that laboratory technologists, nurses and doctors especially working on the tuberculosis ward are at risk of tuberculosis infection, and the two-step TST was an essential means to know the baseline reactivity, and to determine recent tuberculosis infection.

A 65-year-old male patient with a history of alcoholism visited our outpatient clinic complaining of nausea and diarrhea followed by dizziness. Erythema and swelling with partial exfoliation on the right forearm to hand and right thigh were noticed. Vibrio vulnificus was isolated from the purulent discharge of the skin. Due to urgent and intensive treatment of bacterial shock and antimicrobial drugs, the patient fully recovered three months later. We believe that the patient survived from this fatal infection because; 1) the isolates were highly sensitive to a wide variety of antibiotics, 2) the antibiotic therapy was started immediately, with an alternative usage of different antibiotics, and 3) the liver dysfunction of the patient had not been severely damaged by alcohol before the infection.

The case was a 47-year-old Nigerian male who was thought to have contracted malaria in Nigeria and then manifested fever with chill, arthralgia and diarrhea in Japan. The blood test at International Medical Center of Japan revealed thrombocytopenia and anemia. Ring forms of 0.03% of his RBCs and ICT Malaria P.f/P.v test was also positive for Plasmodium falciparum. We prescribed mefloquine to him, but the number of the paresites in his peripheral blood did not decrease, and, in fact, they came to increase (maximum 6.66%) 20 hours after the drug treatment. As clinical condition of malaria were liable to change seriously, intravenous Artesunate (a qinghaosu derivative) was decided to be given additionally to the patient. Consequently the parasites disappeared in 20 hours from his blood but a low grade fever still continued possibly because of cholecystitis. At the same time of Artesunate treatment, hemoglobinuria started and anemia worsened partly because of his G-6-PD deficiency. All pending problems were improved by the time he left Japan and those parasites were finally found to be susceptible for mefloquine by the in vitro susceptibility test. This is the first reported case of falciparum malaria successfully treated with intravenous Artesunate in Japan.

We experienced a hospital outbreak of salmonella food poisoning after ingestion of omelet which was the hospital evening meal on August 8, 1999. Total number of patients was sixty-two (Male 25: female 37) and the mean age was 52.1 years old. Salmonella Enteritidis was isolated from the stool in 59 cases. Twenty-one of them were associated with the immunosuppression (12 with malignancy, 6 with DM, one with nephrotic syndrome, one with chronic nephritis and one with allergic purpura). Clinical symptoms of the patients were composed of watery diarrhea (100%), fever (88.7%), abdominal pain (82.3%), nausea (45.2%) and vomiting (25.8%). The laboratory data revealed leukocytosis (15/47 = 31.9%), increased CRP (44/46 = 95.7%), elevated creatinin (1/37 = 2.7%) and hypokalemia (5/42 = 11.9%). MICs of 20 strains isolated in our laboratory almost coincided with each other indicating that the source of bacteria was probably the same. In vitro, S. Enteritidis were sensitive to OFLX, TFLX, FOM, most of PCs, CEPs, AGs but resistant to MPIPC, CAM, CLDM, VCM. Therefore we administered LVFX to 59 cases (alone in 45cases, combination with FOM in 6 cases), NFLX to two children and FMOX to one pregnant woman. Lactobacillus was administered to 28 cases (45.2%) and antidiarrhetics were given to 6 cases (9.7%). Finally all patients improved within two weeks. We suspect that the salmonella food poisoning was due to infected egg. The partially cooked omelet would permit the growth of a sufficient inoculum to cause disease. To prevent food poisoning, we have to be consistent in cooking the food well (at 75 degrees C, for more than 1 minute) and should not have omelets during the hot summer season.

We have experienced an outbreak of dysentery in Nagasaki. Shigella sonnei were positively cultured from 467 patients out of suspected 821 cases, and 346 patients were admitted. 121 patients were treated with oral antimicrobials in the outpatient clinic. Five patients were diagnosed as secondary infection. We treated a total of 96 patients in Nagasaki Municipal Medical Center, and studied the clinical and bacterial features in these 96 patients. Chief complaints included fever, abdominal pain and diarrhea. Most diarrheal patients showed waterly diarrhea and only a few were bloody (3 of 47). Treatment of levofloxacine 300 mg a day for 5 days successfully eliminated S. sonnei from all culture positive patients. An environmental surveillance revealed that water in a well at the university to which many patients were using was the origin of the infection with positive cultures of S. sonnei. No difference between the clinical and environmental isolates was observed in results on biochemical, serological and enzymatic tests. All isolates were susceptible to levofloxacin and to ofloxacin, but three isolates showed resistance of fosfomycin with MIC above 64 micrograms/ml. In analysis of pulsed-field gel electrophoresis, both clinical and environmental isolates were considered to be closely related.

Coccidioides immitis is a causative agent of coccidioidomycosis, which is one of the most dreadful mycosis because of its infectious and pathogenic nature. The endemic areas are in the southwestern parts of the United States and other semi-arid regions throughout the Western Hemisphere. During the early 1990s, the incidence of coccidioidomycosis in California increased dramatically, resulting in recognition for this mycosis as a reemerging infectious disease in the United States. The patients included a large number of non-informed visitors from non-endemic countries. Our report is on an imported case of primary pulmonary coccidioidomycosis. A 35-year-old Japanese male, after living in the United States for nine months, suffered from a combination of headache and fever. He was given a serological examination, and a chest radiograph in Phoenix, Arizona in the United States and was diagnosed as coccidioidomycosis. A daily dosage of 400 mg of fluconazole was administered and he returned to Japan. His headache and skin rash persisted and he was admitted to our hospital to evaluate the severity of his disease. There were no fungi cultured from neither bronchoalveolar nor cerebrospinal fluid and he was discharged. The patient had been treated with fluconazole and his symptoms, high-resolution CT and serological antibody titer were monitored. After 18 months, his clinical and radiological evolution was favorable and his serological IgM titer was below its sensitivity medication was stopped and there were no relapses.

A 46-year-old male patient with alcoholic cirrhosis of the liver was carried to our out-patient clinic as he had developed shock while under routine follow-up, and died on the way to the hospital. He had been admitted several times since the diagnosis eight years ago, and was finally discharged from the hospital six weeks ago with improved physical condition and laboratory findings. A vesicle and bulla formation with phlegmon on the skin of right leg and sole of foot was noticed. Vibrio vulnificus was detected from the purulent discharge of the skin on culture. We conclude that the patient developed V. vulnificus-septicemia which resulted in sudden death. Since V. vulnificus infection may frequently take a fulminant course in patients with liver cirrhosis, adequate measures should be taken for early diagnosis and treatment to prevent the fatal outcome.

A study was made to clarify to what degree the booster phenomenon was present when the employees in a community hospital in Japan received two-step tuberculin testing (PPD). Of the seventy-five employees, most of all BCG-vaccinated subjects, twenty-three showed strongly positive of more than 30 mm of induration at the first test (PPD/T1), and the remaining fifty-two subjects received a second (PPD/T2) after 2 weeks. The second PPD showed a marked increase in reactivity, sixteen subjects newly became strongly positive and six of eight who were initially PPD negative (< 10 mm) were converted positive, and the mean reaction size changed from 14.7 +/- 5.6 mm (PPD/T1) to 31.5 +/- 15.5 mm (PPD/T2). The degree of boosting, measured by the change in millimeters induration size between PPD/T1 and PPD/T2 (PPD/T2-PPD/T1), was correlated with neither the size of PPD/T1 nor the age of the study participants, and was not associated with the difference of the position in the hospital. Thus, we could not explain the factor why such a marked boosting was observed in this study. However, these results indicated that the two-step tuberculin testing is an essential means of distinguishing new tuberculous infection from booster phenomenon. We agree with the current recommendation for routine two-step testing of new employees in the hospital.

A 63-year old female was admitted because of an abnormal shadow on chest X-ray film. Chest CT showed a nodular shadow in the right S6 and a patchy shadow in the right S10. Right lower lobectomy was performed under a diagnosis of lung cancer made by TBLB in the right S6. Pathological examination of the resected lung revealed papillary adenocarcinoma in the right S6 and numerous cryptococci in the right S10. No cryptococcal infection was found in the resected lymph nodes.

A 73-year-old male was admitted to our hospital because of productive cough and infiltrate on the chest roentogenogram. The underlying diseases was found to be multiple myeloma. He received a physical examination in June, 1996. The chest X-ray and CT scan on admission showed an infiltrative shadow with multiple bulla in the left upper lung field. Internal use of antibiotics and drip infusion of IPM/CS were ineffective. The chest X-ray showed air-fluid level in left upper peripheral bullous lesion and a percutaneus needle aspiration of the lung was performed. The specimen was pus with blood and microscopical examination of smears revealed no acid-fast bacilli, but Mycobacterium szulgai was isolated and identified by DNA-DNA hybridization method. The patient was treated with isoniazid and rifampicin, and improved in a few months. There are a few case reports of pulmonary infection due to M. szulgai associated with emphysematous bulla of the lung in Japan. M. szulgai infection of the lung is similar to M. kansasii infection in respect to clinical features (improvement of chest abnormal shadow, efficacy of drug).

The genus Clinostomum is a cause of parasitic laryngo-pharyngitis. We report the 15th case of Clinostomum sp. infection in Japan. A 29-year-old female visited our hospital because of throat discomfort and expectoration of a worm by sneezing on November 17, 1997. The pharyngitis was caused by the worm. The worm was morphologically identified as the adult of the genus Clinostomum.

In this study, we compared the types of methicillin-resistant Staphylococcus aureus (MRSA) isolated from several foci of the same patient to find the incidence of multiple strain infection of MRSA in bacteremia cases. We will also evaluate the utility of the typing methods of phenotyping and genotyping for the above mentioned objective and judge the dissimilarity of clinical characteristics between the single strain infection and multiple strains infection. We studied 21 cases of MRSA bacteremia who were culture-positive both from blood and other foci in the same patient at Nagasaki University Hospital during 1990-1994. Clinical data were retrospectively collected from the patients' records. Phenotyping of all 113 MRSA isolates were done by coagulase typing (I-VIII), production of enterotoxins (SEA-SED) and toxic shock syndrome toxin-1 (TSST-1), hemolysis typing and antibiogram (MIC). In addition, typing of the same isolates were done by Pulsed-Field Gel Electrophoresis (PFGE), using Gene Navigator System as the genotyping. Several types of MRSA were found from different foci in the same patient in 8 of 21 cases (38%) by phenotyping. The same typing results were obtained in 7 of 8 the multiple strains isolated cases by PFGE. Two types were obtained from another case by phenotyping, but by PFGF, 3 types were obtained. We consider that phenotyping method is convenient and reliable for judgment of the difference in types isolated from different foci in the same patient, but PFGE possibly provide us more detailed epidemiological information. The epidemiological investigation must be done very carefully, especially in immunocompromised hosts as MRSA bacteremia cases, because the chance of multiple strains infection is relatively high among these cases.

Toxic shock syndrome toxin-1 (TSST-1) and enterotoxins are important virulence factors produced by Staphylococcus aureus. It is reported that these toxins are associated with septic shock and toxic shock syndrome. We investigated the toxin production and coagulase types of 701 MRSA strains isolated in Sasebo City General Hospital between 1994 and 1996 TSST-1 or/and enterotoxins were detected in 67% of all MRSA strains, and those were detected in 88% of MRSA strains isolated from blood samples. 45% of all MRSA strains produced both TSST-1 and enterotoxin C, and 70% of MRSA strains obtained from blood produced those toxins. Frequency of TSST-1 or/and enterotoxin production by MRSA strains isolated from blood samples was significantly higher than that by MRSA strains isolated from urine and pharynx (p < 0.05), and frequency of both TSST-1 and enterotoxin C production by MRSA isolates from blood was significantly higher than that by MRSA strains isolated from pharyngeal sample (p < 0.05). This study indicated that investigation of virulence factors produced by MRSA might give the useful information on prevention and treatment of MRSA infection.

Recently, the therapeutic guideline has been mentioned in opportunistic infection of the compromised host, and many observations regarding complication of infection in these hosts have been reported. However, there were few reports in the relationship between infection and immune function or nutritional status. In this study, we confirmed that the nutritional status influences immune function in patients with lung cancer, hepatoma and renal failure, and that malnutrition markedly reduces their immunity. In patients after operation who where the pre-operative assessment of the nutritional status was performed an attempt to improve the nutritional status has been already made to improve their prognosis. Therefore, we emphasize that the management of the nutritional status even in hosts with many other diseases is thought to be important in protection against infection and prognosis of the disease.

We evaluated the clinical efficacy of LCR MTB, a reagent developed by Abbott in the USA, in the full automatic ligase chain reaction (LCR) for detection of DNA of M. tuberculosis complex using a thermostable ligase. Using 458 samples isolated from patients with tuberculosis, LCR was compared with a smear method and with a culture method, and was also compared with two other methods of gene amplification, MTD and Amplicor, using 340 and 200 of the 458 samples, respectively. The LCR method detected M. tuberculosis in 49.8% (228/458) of the samples, and was superior to the smear method (31.9%, 146/458) and the culture method (39.1%, 179/458) in sensitivity. The LCR method was also superior to the MTD and Amplicor methods; sensitivity were 37.9% (129/340) for MTD vs. 47.6% (162/340) for LCR, and 56.5% (113/200) for Amplicor vs. 59.5% (119/200) for LCR. These favorable results and the convenience of the LCR method, which enables rapid detection of target genes with a high degree of sensitivity, strongly suggest that LCR MTB is useful as a reagent for detection of M. tuberculosis using nucleic acid amplification.

We investigated the effect of erythromycin (EM) in patients with diffuse panbronchiolitis (DPB) who were divided into 2 groups, the short term group with 8 patients who were treated for at least 2 years and the long term group with 7 patients who were treated for more than 3 years. Each mean value of %VC, FEV1.0, FEV1.0% and PaO2 two years after administration to these patients was improved than before administration of EM, with the exception of PaO2 in the long term group. There was no change in %VC, FEV1.0, FEV1.0% or PaO2 in each group between one year after the therapy and thereafter, with the exception of the fact that FEV1.0% in the short term group, except patients restarting EM therapy, 2 years after the therapy was significantly higher than in the long term group. One patient was readministered EM because of recurrence of DPB after cessation of EM therapy, whose %VC, FEV1.0 and PaO2, but not FEV1.0%, one year after the therapy were increased in those before the therapy. The Neutrophil proportion in the bronchoalveolar lavage (BAL) fluid in this patient was still high after the therapy (94.5%), while that in the patients with cessation of the therapy was improved to the level of less than 8%. Neutrophil proportion in BAL fluids in the patients with continuation of the therapy revealed a high or low level after the therapy. These results suggest that the patients, whose %VC, FEB1.0% and PaO2 were improved and whose proportion of neutrophils in BAL fluid reduced to a normal level compared with those before EM therapy, can be allowed to cease therapy after 2 years or more of EM therapy.

Streptococcus agalactiae is a well-recognized cause of neonatal sepsis and meningitis. In adults, infections by S. agalactiae are rare. We report an adult case of lung abscess and pyogenic spondylitis caused by S. agalactiae. A 51-year-old male was admitted to our hospital because of an abnormal shadow in the chest and lumbago on May 25, 1995. He was diagnosed as lung abscess from the chest roentgenogram and CT scan and the subcutaneous pus was aspirated. The pus culture was only positive for S. agalactiae. He was treated with IPM/CS 1 g/day and CLDM 1.2 g/day and the abscess was drained. MRI showed his lumbago was caused by pyogenic spondylitis. The underlying disease of this case was diabetes mellitus. He recovered from the infections with in about 10 weeks of antibiotic treatment.

Efficacy and safety of a newer injectable cephalosporin, cefluprenam (CFLP) on cases with bacterial pneumonia and chronic respiratory tract infections were evaluated at a dose of 1g (potency), d.i.d for 7 days. 1. Of 130 cases in total, 116 cases were enrolled for the clinical efficacy evaluation. The efficacy rate (excellent and good responses) was 94.8% (110/116). The efficacy rate was 93.8% (60/64) for cases with bacterial pneumonia, and 96.2% (50/52) for cases with chronic respiratory tract infections. The recurrence was noted in 1.2% (1/82). The bacteriological response rate was 100.0% (32/32) for gram positive cocci, 93.8% (15/16) for gram negative rods and 97.9% (47/48) in total. 2. Adverse drug reactions were noted in 3.9% (5/129), consisting of 2 cases with skin rash, 1 case with drug fever, 1 case with skin rash and skin itching and 1 case with drug fever and headache. The abnormal laboratory changes were noted in 23.6% (30/127), mainly containing the elevation in GPT and GOT, and eosinophylia. The safety rate (no problem evaluation) was 74.8% (95/127). 3. The usefulness rate (very useful and useful evaluations) was 93.1% (108/116). As suggested by the evaluation on the secondary endpoint in the phase III comparative studies with both bacterial pneumonia and chronic respiratory tract infections, it was confirmed that the 7 day therapy of CFLP was promising for treatment of moderate bacterial pneumonia and chronic respiratory tract infections, because the high clinical efficacy was obtained and also the incidence of allergic reactions with CFLP was almost the same as that of ceftazidime (CAZ) evaluated highly safe. Based on these results, it was concluded that CFLP was useful in the management of moderate respiratory tract infections and also the recommended therapeutic period with CFLP was within 7 days.

A 75-year-old female with diabetes mellitus, who was born and lived in West north Kyusyu, was admitted to our hospital, because of unconsciousness and loss of appetite. The physical examination showed neck stiffness and a high fever. The laboratory data showed accentuation of inflammatory reaction and azotemia and positive HTLV-1 antibody. The spinal fluid showed increase of cell count and amount of protein. A stool and sputum smear revealed rhabditis form larvae of the nematode. Antibiotics and ivermectin were administered for the bacterial meningitis and hyperinfection of the strongyloides, respectively. Consequently, meningitis and strongyloidiasis improved. It was considered that the patient was infected with strongyloides from her husband who serve in the army during World-War II, and hyperinfection of strongyloides resulted from the immunosuppressive state of diabetes mellitus. Ivermectin, and anti-strongyloides agent, was effective, and no side effects were seen. However, the therapeutic resistance in this case was associated with the positive HTLV-1 antibody.

We report a rare case of cytomegalovirus (CMV) retinitis in association with systemic lupus erythematosus (SLE). A 36-year-old female was admitted to our hospital because of nephrotic syndrome and renal insufficiency due to lupus nephritis. After steroid and immunosuppressant treatment for lupus nephritis, she began to complain of floaters and visual disturbance. She was diagnosed as having CMV retinitis based upon the depressed immune status and the clinical appearance of fundus. As soon as CMV retinitis was diagnosed, antiviral treatment with intravenous ganciclovir was instituted and maintained for 7 months. She was treated successfully and almost no progression or relapse of CMV retinitis was documented without ganciclovir maintenance treatment during a 2 year follow-up period. It is suggested that CMV retinitis can occur in patients with SLE treated with steroid and immunosuppressant, indicating the importance of early diagnosis and treatment for CMV retinitis.

We evaluated the relationship between rifampicin (RFP)-susceptibility and genetic alterations in rpoB gene of clinically isolated Mycobacterium tuberculosis strains, collected from different geographic locations within Japan. Alterations in rpoB gene were detected by PCR-direct sequencing analysis, and the minimum inhibitory concentrations (MICs) of RFP were determined by broth microdilution method using Middlebrook 7H9 broth. One hundred and sixty six epidemiologically unrelated M. tuberculosis strains were examined. A total of 99 genetic alterations in the 69 bp core region of rpoB gene were detected in 95 out of 166 strains. Among them, 96 out of 166 strains showed RFP-resistant phenotypes with MICs > or = 2 micrograms/ml. Examination of the correlation between the MICs of RFP and amino acid substitutions in 69 bp core region of rpoB gene revealed that 58 out of 59 strains containing amino acid substitution in codon 531 showed highly RFP-resistant phenotypes with MICs > or = 64 micrograms/ml. In contrast, a variable level of RFP-susceptibility was observed among strains containing amino acid substitutions in either codon 516 or 526. On the other hand, the MICs of three strains with a point mutation in either codon 515 or 533 were all < or = 1 microgram/ml. Our results suggest that rpoB gene sequencing is useful for not only the detection of RFP-resistant M. tuberculosis strains, but also the prediction of RFP-susceptibility of the strains.

The prognosis of chronic respiratory tract infection with Pseudomonas aeruginosad considered to be poor. However, low-dose and long-term 14 membered macrolide, such as erythromycin or clarithromycin, treatment has been reported as effective clinically in chronic lower respiratory tract disease. There was no report to investigate the effect of macrolide on chronic biofilm related Pseudomonas aeruginosa respiratory tract infection in vivo. In a newly established murine model of chronic Pseudomonas aeruginosa respiratory infection mimicking diffuse panbronchiolitis (DPB), we investigated the effect of erythromcin inhalation on viable bacteria in the lungs. Infection was produced by placement of a plastic tube in the bronchus with inoculating. Pseudomonas aeruginosa suspended in saline was also inoculated in bronchus after intubation of the tube. Viable bacteria were constantly isolated at 10(4) 10(6) cfu-specimen from the lungs for more than 30 days. Treatment with erythromycin inhalation for four days reduced the number of viable bacteria in the lungs with statistically significant. Our result indicated that our new model of chronic respiratory tract infection is simple and provides a useful tool to study the pathogenic process and treatment of such infection. Our results also suggest that the erythromycin inhalation is effective on chronic Pseudomons aeruginosa respiratory infection.

In order to promote the serological diagnosis of legionellosis in the clinical laboratory, the cutoff values of serum anti-Legionella antibody titers for microplate agglutination (MPAT) test were determined. Antibody levels were tested for 178 serum specimens including 98 healthy persons, 22 ordinally workers having either metabolic or renal failure, definitely diagnosed patients of 17 mycoplasmal and 9 chlamydial pneumonia, 32 patients of other bacterial pneumonia. Heat killed unstained cell suspension of each strain of Legionella pneumophila serogroup (SG) 1a, 1b, SGs 2 to 6, L. bozemanii, L. dumoffii, L. gormanii, and L. micdadei were used as antigens. Strains of L. pneumophila SG 1b were mainly isolated from environmental specimens. However, in some Legionella pneumonia cases, etiologic agents were determined as L. pneumophila SG 1 b. Thus the representative strain of SG 1b was used as an antigen for the determination of the patient's antibody titer. Quantitative agglutination was performed by using a 96-well U-bottom microplate for each antigen. Test sera were diluted from 1:16 to 1:256. Results were read after 20 h at 25 degrees C. Cutoff values for 11 antigens were determined, at this moment, as 4-fold or greater increase in level to > or = 1:128 in paired sera, and > or = 1:256 in single serum. However, final diagnosis should be given by over-all coordination of serological results and clinical symptoms together with other laboratory findings. Two culture-positive Legionella pneumonia cases due to either SG3 or 6 in which significant rise of serum antibody titers against organisms of corresponding SG estimated by MPAT method were discussed.

A 21-year-old male nearly drowned in a reservoir by a traffic accident and he aspirated a large mount of polluted water containing Aspergillus fumigatus. On admission to our hospital, he was alert but cyanotic. Chest rentogenograms showed scatter infiltrative shadows in bilateral lung fields. We administered methylpredonizolon and antimicrobial agents immediately because of respiratory failure which was rapidly progressing. During the following six days, infiltrative shadows diminished but multiple nodular shadows in both lung fields appeared. The diagnosis of pulmonary aspergillosis was confirmed by serological and microbiological studies. Intravenous amphotericin B and oral itraconazol were administrated, and clinical improvement was observed.

We reported two cases of pulmonary dirofilariasis in Nagasaki Prefecture. Each case was admitted to our hospitals for evaluation of an abnormal shadow on chest X-ray film taken for examination. We strongly suspected lung cancer before operation. It was resected in order to confirm the pathological diagnosis. There was a Dirofilaria immitis in the vessels surrounded by the necrotic tissues. The case of pulmonary dirofilariasis tends to increase in Japan, but the positive rate of dogs with Dirofilaria immitis tends to decrease, because of decreasing breeding places of mosquitoes by the spread of the public sewage system in Nagasaki City.

A 51-year-old female was admitted with complaints of fever and general fatigue. Chest X-ray showed diffuse bilateral fine nodular shadows and infiltrates. Complication of hepatic and muscular injury was suspected from increased levels of GOT, GPT and CPK in the serum. Arterial blood gas analysis revealed hypoxemia. Because hypoxemia aggravated despite treatment with intravenous minocycline (200 mg/day), corticosteroids and mechanical ventilation were started, and the administration of minocycline (400 mg/day) and sparfloxacin was added. Consequent, chest X-rays and several laboratory data improved gradually. The final diagnosis was established with a significant rise of both IgG and IgM antibody against Chlamydia psittaci with MIF and identification of Chlamydia with the cell culture method. Chlamydia was successfully isolated from BALF of this patient obtained 5 days after commencement of minocycline treatment. Psittacosis should be considered as a possible cause of severe respiratory failure necessitating emergency care including mechanical ventilation.

We estimated defensins, antimicrobial and cytotoxic peptides localized in azurophil granules of neutrophils, in bronchoalveolar lavage fluid (BALF) in patients with diffuse panbronchiolitis (DPB). BALF from DPB patients contained a higher concentration of defensins than those from patients with idiopathic pulmonary fibrosis and healthy volunteers. A significant correlation was observed between the concentration of defensins and the number of neutrophils, the concentration of interleukin-8 or neutrophil elastase in BALF of DPB patients. An immunohistochemical defensins in neutrophils and mucinous exudates in the airways and in the surface of bronchiolar epithelial cells. After treatment with macrolide antibiotics, significant reductions in the concentrations of defensins, IL-8 and neutrophil numbers in BALF of DPB patients were observed. These findings suggest that the lung injury in DPB could be caused by defensins released by neutrophils accumulated in the airways.

Cryptococcosis is one of the serious deep-seated mycoses in immunocompromised patients, especially those with AIDS. Cryptococcus neoformans ordinarily lives in natural environments such as soil and reproduces in pigeon excreta. It spreads in the air and infects human by inhalation. We isolated C. neoformans from pigeon excreta in hospitals, private houses, parks in Nagasaki from October to December in 1994. C. neoformans was isolated from 4 of 8 samples (50%) of pigeon excreta and the isolation rate increased to 80% (4/5) if they were weathered excreta. Two patients with pulmonary cryptococcosis occurred in the last two years in the area where C. neoformans was isolated during that period. Epidemiological studies of clinical isolates and environmental isolates are important to determine its origin of infection and the route of transmission.

The organic symptoms and results of coagulation tests of disseminated intravascular coagulopathy (DIC) in 17 patients with infection were compared with those in 12 patients with malignancy. The infectious diseases were mainly sepsis and pneumonia, and the malignancy was mainly lung cancer. The mean antithrombin III (AT III) before treatment was 54% in infection and 68% in malignancy, and the AT III values improved after administration of 1500 U of AT III concentrates per day. The mean thrombin-antithrombin complex level decreased from 22 ng/ml to 9 ng/ml after the treatment in infection, but it increased in malignancy. There were no differences in DIC scores between infection and malignancy before treatment; however, the scores were significantly more improved in infection than in malignancy after treatment (p < 0.05). The fibrin/fibrinogen degradation product level, platelet count, and fibronectin level were also significantly more improved in infection than in malignancy. This better response to treatment in infection than in malignancy is probably due to eradication of the causative organisms by antibiotics in infection. These data suggest that therapy against both DIC and the underlying disease is crucial for successful treatment.

Basic and clinical evaluation of lysis centrifugation using Isolator 10 was performed and compared with culture bottle methods. Blood, which was inoculated with C. albicans, C. tropicalis or C. parapsilosis, was cultured using lysis centrifugation or culture bottle method. The culture duration of C. albicans and C. parapsilosis by lysis centrifugation was shorter than that by the culture bottle (BHI release). C. albicans, C. parapsilosis and C. tropicalis became culture-positive within 1 or 2 days after culture by lysis centrifugation. C. albicans and C. parapsilosis became positive 4 days and C. tropicalis 6-8 days after culture by the culture bottle (BHI super). Clinical evaluation of both blood culture method as performed from April 1990 to March 1994. Sixty samples (4.4%) were positive out of 1370 samples. Twenty eight samples (7.2%) were positive out of 389 samples, which were examined by both methods. Twenty two samples were positive by both methods and the rest of the 6 samples was positive only by Lysis centrifugation.