Nobu Akiyama

Necrotizing Bacillus cereus infection of the meninges without inflammatory reaction in a patient with acute myelogenous leukemia: a case report.

Abstract A 64-year-old man in a severely immunocompromised state due to acute myelogenous leukemia died, respirator-unaided, about 10 h after the abrupt onset of coma. An earlier blood culture had yielded Bacillus cereus. The autopsy, performed 2 h after death, demonstrated diffuse subarachnoid hemorrhage without berry aneurysms, and the formalin-fixed brain was tinged with gray-brownish discoloration. The sections of the brain presented a whitish tint of the surface layer of all portion of the cerebral cortices, even those in the sulci. Histological examination of the brain revealed leptomeningeal B. cereus dissemination, and widespread necrosis of the leptomeninges and arachnoid vessels without inflammatory cell reaction. The grossly recognizable whitish surface layer of the cerebral cortex showed overt hyperchromatism, and contained neurons more degenerative than those located in the deeper cortical layer. The total absence of inflammatory reaction may be explained by a combination of the immunocompromised state of the patient and the character of B. cereus infection, which in itself induces little inflammatory reaction. The prominent lesions were confined to the cerebral surface layer and leptomeningeal tissue including the arachnoid vessels, which were all bathed in the cerebrospinal fluid, suggesting that some necrotizing toxins had been secreted into the fluid by the B. cereus. The necrosis of arachnoid vessels is thought to have in turn caused diffuse subarachnoid hemorrhage and marked disturbance of the cerebral blood flow, resulting in the terminal coma.

Cefozopran, meropenem, or imipenem–cilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients: A multicenter prospective randomized trial

We conducted an open-label, randomized study to evaluate the clinical efficacy of cefozopran, meropenem or imipenem-cilastatin using cefepime as a control in febrile neutropenia (FN) patients. Three hundred and seventy-six patients received cefepime, cefozopran, meropenem or imipenem-cilastatinas initial therapy for FN. The primary endpoint was the non-inferiority of response rates including modification at day 7 in cefozopran, meropenem or imipenem-cilastatin patients compared with cefepime in the per-protocol population (delta = 10%). The response rates for cefozopran, meropenem and imipenem-cilastatin were not significantly different compared with cefepime (cefozopran: 54/90 (60%), meropenem: 60/92 (65%), and IPM/CS: 63/88 (72%) versus cefepime: 56/85 (66%) (p = 0.44, 1.0 and 0.51, respectively)), and the differences in treatment success for cefozopran, meropenem and imipenem-cilastatin compared with cefepime were -5.9% (95% confidence interval (CI): -20.1-8.4), -0.7% (95% CI: -14.6-13.3), and 5.7% (95% CI: -8.1-19.4), respectively. The same tendency was seen in the modified intention-to-treat population. Based on the evaluation of initial drug efficacy performed on days 3-5, there was no significant difference between the four drugs. In the subgroup with an absolute neutrophil count ≤ 100 × 10(6)/L for longer than seven days, there was significantly better efficacy in the carbapenem arm compared to 4th generation beta-lactams (52% versus 27% at days 3-5, p = 0.006, and 76% versus 48% at day 7, p = 0.002). Our results suggest that the effects of these four drugs as empiric therapy were virtually the same for adult FN patients, although non-inferiority was shown only in imipenem-cilastatin compared with cefepime (clinical trial number: UMIN000000462).

Management of infection in patients with acute leukemia during chemotherapy in Japan: questionnaire analysis by the Japan Adult Leukemia Study Group

Guidelines for the management of febrile neutropenia (FN), deep fungal infection or use of granulocyte colony-stimulating factor (G-CSF) published in the US and Europe cannot be directly applied in other countries. In this study, we undertook a questionnaire survey of member institutions of the Japan Adult Leukemia Study Group to investigate the status of, and problems with, the management of infectious complications in patients with acute leukemia. The questionnaire consisted of 52 multiple-choice questions covering therapeutic environment, antibacterial, and antifungal prophylaxis, empirical therapy (ET) for FN, and use of G-CSF. The results were compared to a previous survey performed in 2001. Usable responses were received from 134 of 184 (71.7%) institutions. With regard to antibacterial prophylaxis, fluoroquinolones and sulfamethoxazole-trimethoprim were most commonly used. Regarding antifungal prophylaxis, the most frequently used agent was fluconazole, followed by itraconazole. In ET for FN, monotherapy with cephems or carbapenems accounted for almost all of the responses. Most respondents indicated that they used micafungin (MCFG) in ET. Prophylactic use of G-CSF during remission induction therapy in acute myeloid leukemia was reported by only 4% of respondents. Strategies for antibacterial and antifungal prophylaxis or treatment of FN should be reviewed and updated as needed.