[Management of immune reconstitution inflammatory syndrome].

While antiretroviral therapy(ART) in HIV-infected patients results in dramatic reductions in HIV viral load and subsequent improvements in CD4 cell count, part of patients experience clinical deterioration as a direct consequence of rapid and dysregulated restoration of antigen-specific immune responses. This is termed "immune reconstitution inflammatory syndrome (IRIS)." Because there is no single agreed upon definition for IRIS, the diagnosis of IRIS is clinical. Several studies have demonstrated that lower CD4 cell count and higher viral load at the initiation of ART increase the risk of developing IRIS. Management of IRIS consists of appropriate treatment for the diseases of IRIS, control of the excessive inflammation (NSAIDs or corticosteroids), and interrupting ART.

[A case of acute renal failure involving high amounts of tenofovir after HAART start].

A 58-year-old man admitted for fever, nausea, vomiting, and anuria after the start of HAART, including tenofovir, had a viral load of 1.1 x 10(5) copies/mL, a CD4-positive lymphocyte count of 81/microL, and serum creatinine of 0.8 mg/dL before HAART. He underwent renal biopsy and temporary dialysis. We concluded that the patient had acute tubular necrosis because of potentially impaired renal function and the high amount of medication, and judging from the renal biopsy specimen and clinical course. When implementing HAART, physicians should be aware of and monitor potential patient misunderstanding of instructions on dosage and administration and for possible complications in medicinal combinations and potential side effects. TDF taken together with lopinavir may increase the plasma concentration of TDF or other medications that could worsen renal function. It should also be noted that renal dysfunction is a potential complication in the elderly.

[Case of Scedosporium apiospermum cutaneous soft tissue infection treated with voriconazole].

A 69-year-old man treated with corticosteroids and immunosuppressive agents for acutely exacerbated interstitial pneumonia was found to have an ingrown nail in the left big toe and that suppurated despite treatment by dermatologists. Culture of the pus expressed from the toe yielded Scedosporium apiospermum. The patient suffered liver dysfunction a few days later when treated with intravenous voriconazole (VRCZ), which was discontinued due to the high plasma VRCZ concentration. Discrete erythema and subcutaneous nodules developed in left leg 2 or 3 weeks later. Ultrasonography showed tubular structures with substantial echoes that were not connected to veins in the subcutaneous tissue of the left leg. These findings suggested a nodular lymphangitic pattern of spreading of S. apiospermum soft tissue infection. Oral VRCZ at 100 mg/day was started, and increased to 200 mg/day after the plasma VRCZ concentration was measured. VRCZ was stopped after about 2 months, by which time the man had fully recovered. Because VRCZ-induced liver dysfunction was reported significantly associated with plasma level, we treated this case safely by administering VRCZ while measuring the plasma concentration.

[A case of pulmonary Mycobacterium gordonae infection progressed for no therapy].

A 68-year-old woman, who had been healthy until this event, presented with a complaint of productive cough since 2000. She went to a neighboring hospital because of bloody sputum in October 2001. Although chest radiograph showed abnormal findings then, she received only an expectorant and cough remedy. She consulted us complaining of dyspnea on exertion in April 2005. Chest radiograph revealed cavity formation, bronchiectasis and a nodular shadow, and her condition had deteriorated. Microbiologically, acid-fast bacilli were detected three times in the culture of sputum, and Mycobacterium gordonae was identified by the biochemical method. However, this Mycobacterium gordonae could not be identified by the DNA-DNA hybridization method. Our case also probably was considered to be a primary type pulmonary nontuberculous infection because of her clinical course. In addition, we recognized that pulmonary M. gordonae infection also worsens without the therapy.

Fatal cytomegalovirus-associated adrenal insufficiency in an AIDS patient receiving corticosteroid therapy.

A 35-year-old homosexual man, who had already received sulfamethoxazole/trimethoprim and steroid therapy because of human immunodeficiency virus (HIV)-related Pneumocystis jiroveci pneumonia, was referred to our hospital. He was also diagnosed as having cytomegalovirus (CMV) co-infection, and started receiving intravenous gancyclovir for CMV infection on the 2nd day of admission into our hospital. He had to continue the steroid therapy because his respiratory condition did not improve. On the 10th hospitalization day, when 40 mg of prednisolone was administered, cardiopulmonary arrest suddenly occurred, and his laboratory data showed hyponatremia and hyperpotassemia. In spite of resuscitation, he died two days later. The postmortem examination revealed that he died of adrenal failure due to CMV infection. In general, CMV is thought to cause adrenalitis, but rarely leads to manifestations of adrenal insufficiency during the clinical course. It is important to be aware that grave adrenal failure due to CMV infection can develop even under steroid therapy.

Amphotericin B-induced nephrogenic diabetes insipidus in a case of cryptococcemia.

A 66-year-old woman with malignant lymphoma became neutropenic during chemotherapy and developed cryptococcemia. After amphotericin B had been commenced, she developed significant hypokalemia and polyuria, though her renal function remained stable. The laboratory findings showed no evidence of renal tubular acidosis. With vigorous water and potassium replacement, amphotericin B had been continued until the cumulative dose reached 2.5 g. After the cessation of amphotericin B, the hypokalemia and polyuria resolved promptly. Based on theses findings, she was diagnosed as nephrogenic diabetes insipidus with hypokalemia and without renal tubular acidosis due to amphotericin B. This complication is usually reversible, and vigorous water and potassium replacement may allow completion of treatment by amphotericin B, though careful monitoring of body water balance and renal function is of importance.

Clonal dissemination of macrolide-resistant and penicillin-susceptible serotype 3 and penicillin-resistant Taiwan 19F-14 and 23F-15 Streptococcus pneumoniae isolates in Japan: a pilot surveillance study.

Large-scale surveillance studies using molecular techniques such as pulsed-field gel electrophoresis (PFGE) have revealed that the spread of antibiotic-resistant pneumococci is due to clonal spread. However, in Japan, surveillance studies using such molecular techniques have never been done. Therefore, we conducted a pilot surveillance study to elucidate the present situation in Japan. Among the 145 isolates examined, the most prevalent serotype was type 19F (20%), for which most isolates were not susceptible to penicillin (86.2%) but were positive for the mef(A)/mef(E) gene (89.7%). The secondmost prevalent was serotype 3 (16.6%), for which most isolates were susceptible to penicillin (87.5%) and positive for the erm(B) gene (91.7%). PFGE analysis showed that both serotypes consisted mainly of clonally identical or related isolates and, in particular, 38% of the type 19F isolates were indistinguishable from or closely related to the Taiwan 19F-14 clone. In addition, some of the Japanese type 23F isolates with the erm(B) gene were indistinguishable from or related to the Taiwan 23F-15 clone as analyzed by PFGE. Based on the results of our pilot study performed in a single institution, it is likely that international antibiotic-resistant clones have already spread in Japan; therefore, a nationwide surveillance study should be urgently conducted.

Macrolide resistance of Streptococcus pneumoniae isolated during long-term macrolide therapy: difference between erythromycin and clarithromycin.

Longterm macrolide therapy (LTMT) has been employed as an effective therapy both for diffuse panbronchiolitis in Japan and for cystic fibrosis in European countries. However, effects on antibiotic susceptibility profiles of microorganisms, associated with such long-term administration of antibiotics, are of concern. We retrospectively identified 57 pneumococcal isolates, recovered from the same number of patients receiving either LTMT with 400 mg of clarithromycin daily (CAM group; n = 31) or 600 mg of erythromycin daily (EM group; n = 26) by reviewing the patients' records at Nara Medical University. On analysis, we found that all isolates recovered from the CAM group and 25 of the 26 recovered from the EM group were resistant to EM, showing either an MLSB: or an M phenotype. Interestingly, isolates exhibiting the M phenotype were much less frequent in the CAM group (2 of 31; 6.5%) than in the EM group (15 of 26; 57.7%). No increase in the rate of penicillin resistance was observed in either group. The macrolide resistance profiles of microorganisms may be influenced differently according to differences in the kind of macrolide antibiotics used.

Longterm azithromycin therapy for three patients with chronic lower respiratory tract infections.

Longterm macrolide therapy has been reported to be effective in treating chronic lower respiratory tract infections (CLRTIs). In this context, erythromycin and clarithromycin are usually used for this purpose. However, refractory cases are occasionally encountered, thereby indicating a major problem pending. In the present study, we administered azithromycin to three patients with CLRTIs whose clinical course had been unsatisfactory with longterm therapy of either erythromycin or clarithromycin. Following longterm therapy with azithromycin, both the incidence of acute exacerbations and the sputum volume were decreased. A significant change in the sputum flora was observed, without obvious side effects; however, no improvement was evidenced in the findings on flow volume curve tests and arterial blood gas analysis. In advanced disease, longterm azithromycin therapy may be as effective as that with erythromycin or clarithromycin; in our view, however, its efficacy may be limited, and large-scale clinical trials are required to determine the most suitable macrolide for the treatment of CLRTIs.

Translocation model of Candida albicans in DBA-2/J mice with protein calorie malnutrition mimics hematogenous candidiasis in humans.

To elucidate the mechanism of translocation of Candida albicans from the intestine to the bloodstream, we attempted to establish a murine model for hematogenous translocation of C. albicans using DBA-2/J mice with protein calorie malnutrition (PCM). PCM severely affected the development of the intestinal epithelia; thereby, the keratin and mucinous layers became very thin. Oral inoculation with C. albicans resulted in long-term colonization in the intestine of the PCM mice but not the well-nourished animals. Chemotherapy with a combination of cyclophosphamide and methotrexate, which started four days after oral inoculation of C. albicans, resulted in the systemic dissemination of C. albicans from the intestine in the PCM mice. Among systemic organs, C. albicans was first isolated from the liver, in which focal necrosis, containing fungal balls of yeast-like forms and/or hyphae, was formed. Subsequently, C. albicans was first recovered from the blood of the infected PCM mice at one day after the isolation from the liver, and thereafter, candidemia continued to increase its intensity until death. Histological study indicated that C. albicans gained entry into the systemic organs from the epithelia of the esophago-cardiac junction as well as the Ileo-cecal portions of the infected mice. The results of our present study therefore suggest that this PCM mouse model may be useful for better understanding of the chemotherapy-induced translocation by C. albicans from the gut to the systemic organs in compromised humans.

Aerosolized pentamidine prophylaxis against AIDS-related Pneumocystis carinii pneumonia and its short- and long-term effects on pulmonary function in the Japanese.

We evaluated the incidence of prophylaxis failure with aerosolized pentamidine (AP) for Pneumocystis carinii pneumonia (PCP) in Japanese patients with human immunodeficiency virus (HIV) infection, and we examined the short- and long-term effects of AP on pulmonary function. The patients inhaled 300 mg of pentamidine by ultrasonic nebulizer, after the inhalation of procaterol (80 micrograms), every 4 weeks. PCP developed in 2 of 16 patients receiving primary prophylaxis with AP, and in 4 of 13 patients with secondary prophylaxis. The CD4(+) T-lymphocyte count was very low in the patients with prophylaxis failure. The chest radiographic presentations were atypical in 4 of the 6 patients with prophylaxis failure. There were no significant changes in the vital capacity (VC), VC/predictive VC (%VC), forced expiratory volume in 1 s (FEV(1.0)), FEV(1.0)/forced vital capacity (FEV(1.0)%), and maximum expiratory flow rate at 25% of vital capacity (MEF(25))/height comparing values before and after initial AP treatment. However, a reduction of oxygen saturation (SpO(2)) of over 3% was noted in 4 patients during the initial AP administration. In 9 patients receiving AP prophylaxis for more than 36 months, we compared the pulmonary function parameters between the baseline and final observations (mean, 52.7 months). There were no changes in VC, %VC, FEV(1.0,) FEV(1.0)%, and SpO(2), but there was a statistically significant decline in MEF(25)/height after long-term AP treatment. We concluded that the incidence of prophylaxis failure with AP for PCP in Japanese patients was similar to that in Western patients, and that long-term AP treatment affected MEF(25)/height in spite of the safe pulmonary effects in short-term AP inhalation.

AIDS-related Pneumocystis carinii pneumonia with disappearance of cystic lesions after treatment.

A 21-year-old hemophiliac with human immunodeficiency virus (HIV) infection was admitted to our hospital because of bilateral pneumothoraces associated with Pneumocysis carinii pneumonia (PCP). He underwent chest tube drainages and intravenous pentamidine therapy, resulting in clinical improvement. Two months after treatment for PCP, cystic lesions that had existed before treatment disappeared on chest computed tomography. We concluded that Pneumocystis carinii infection might be associated with lung destruction and cyst formation, and that inflammatory exudates in the small bronchioles might act as a ball-valve with subsequent spontaneous pneumothoraces.

[Non-steroid therapy for sarcoidosis].

Sarcoidosis is a systemic granulomatous disease that the epidemiology remains unknown. The appropriate therapy for sarcoidosis also has not been well defined. Systemic therapy is clearly indicated for cardiac disease, neurologic disease, eye disease without response to topical therapy, hypercalcemia, and progressive symptomatic disease. Corticosteroid are very commonly used as systemic therapy for sarcoidosis. However, there are some patients who can not be controlled with corticosteroid alone and/or have adverse reactions to corticosteroid. Several cytotoxic agents, including methotrexate, azathioprine, cyclophosphamide, chlorambucil and cyclosporine A, have been used to treat sarcoidosis. There are no studies that have clearly concluded when these agents should be used for treatment. On the basis of safety and efficacy, methotrexate and azathioprine are the preferred drugs. The antimalarial agents, including chloroquine and hydroxychloroquine, most often used to treat sarcoidosis.

[An elderly case with Listeria monocytogenes sepsis and pulmonary non-tuberculous mycobacterial infection].

A 88-year-old woman, who had lived in a nursing home, was admitted to our hospital because of the suspicion of pulmonary tuberculosis. She had a cough, fever and diarrhea on admission. She suffered from sepsis because Listeria monocytogenes was isolated from only the blood culture twice. We immediately administered imipenem/cilastatin to her on admission. She simultaneously had pulmonary non-tuberculous mycobacterial infection because the chest roentgenogram showed a cavity in the right upper lung field and Mycobacterium intracellulare was isolated from the sputum many times. She was treated with isoniazid, rifampicin and clarithromycin for the pulmonary non-tuberculous mycobacterial infection. Her condition improved soon after the administration of IPM/CS but a low grade fever and cough persisted. L. monocytogenes and M. intracellulare are important pathogens in the elderly because cell-mediated immunity mainly works as host defenses against both organisms.

[A case of AIDS-associated Haemophilus influenzae pneumonia with diffuse reticulonodular shadows].

A 32-year-old male was admitted to our hospital complaining of fever and dyspnea on effort. Laboratory data on admission indicated leukocytosis and elevation of C-reactive protein. A chest radiograph showed diffuse reticulonodular shadows in both lower lung fields, and a chest computed tomography showed centrilobular reticulonodular opacity. Bronchoscopic findings revealed a large amount of slightly yellowish secretion in all bronchi. Cells found in the bronchoalveolar lavage fluid (BALF) included 61% neutrophils. Haemophilus influenzae was isolated from cultures of the BALF and sputum. Transtracheal lung biopsy specimens showed focal infiltration of neutrophils in the alveoli, and the pathological findings in the lung were compatible with bronchiolopneumonia. Since the CD4/CD8 ratio was 0.09 and a positive reaction was obtained for anti-human immunodeficiency virus (HIV) antibody, HIV-associated pneumonia due to H. influenzae was diagnosed. Seven days' administration of cefozopran improved the patient's condition. It is interesting that radiological findings are often unusual in HIV-infected patients with H. influenzae pneumonia.