Cefozopran (CZOP) was used as an initial antibacterial therapy for infections in patients with hematological malignancies.CZOP was given at a daily dose of 4g by drip intravenously to patients who were febrile over 38° and were suspected as having bacterial infections.As underlying diseases, 8patients had acute lymphoblastic leukemia (ALL), 9 acute myeloblastic leukemia (AML), 2 aplastic anemia (AA), 2 adult T cell leukemia/lymphoma (ATLL), 28non Hodgkin lymphoma (NHL), and 2 multiple myeloma (MM).Bacterial infections diagnosed were sepsis in 7 patients, suspected sepsis in 32, bronchitis in6, pneumonia in5and acute peritonitis in 1.
Clinical responses among 51 evaluable cases were exelent in14, good in15, fair in3, poor in19and the overall response rate was57%.The overall response rates for AML, ALL, AA, ATLL, NHL and MM were56%, 63%, 100%, 50%, 50%, and100%, respectively.Those for sepsis, suspected sepsis, bronchitis, pneumonia and acute peritonitis were14%, 63%, 100%, 40%, and0%, respectively.This therapy was effective in 53% (9/17) of patients whose granulocyte count remained below 500/μl throughout the course of CZOP therapy.Six bacterial and one fungal strains were isolated from blood and sputum of six patients including five sepsis cases;two bacteria were eradicated and bacterial change was observed in one case.As side adverse effects, 10patients had liver dysfunction, 1 anemia, 2 proteinemia, 1indirect bilirubinemia, 2thrombocytopenia, and1eosinophilia.
We tried to establish a scoring system for the severities of patients with their infections, underlying diseases, treatments for the underlying disease, and granulocyte counts in order to evaluate the efficacy of CZOP more precisely.This scoring system was consisted of three grades;severe, moderate, and mild.CZOP was effective on mild and moderate grades.Theses results indicate that the initial antibacterial therapy by CZOP is useful for the treatment of mild and moderade grade infections complicated with hematological malignancies.

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Thirty three patients with severe infections associated with hematological disorders were treated with panipenem/betamipron as a second line chemotherapy.Of these, 30 patients were evaluated for effectiveness.An excellent response was obtained in 14 patients (46.7%) and a good response in 5 (16.7%), and the overall efficacy rate was 63.3%.Efficacy rates were3/6in patients with sepsis, 68.4% (13/19) in patients with fever of undetermined origin, 2/4in patients with pneumonia.In patients whose peripheral granulocyte count was below100/μl at the start of chemotherapy, the efficacy rate was 3/7.Side effects were observed in 5 of 33 patients (15.2%).
These results show that PAPM/BP is useful as a second line chemotherapy for the treatment of severe infections in patients with hematological disorders.

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We have developed a new method of detecting clinical S.aureus strains possessing heterogeneous resistance to vancomycin (hetero-VRSA).The method exploits characteristic antagonism between vancomycin and β-lactam antibiotics against the strain Mu3, a representative hetero-VRSA.The method comprises of the following procedures: 1) overnight culture of bacteria is streaked on brain heart infusion agar containing 4μg/ml of vancomycin, 2) paper discs impregnated with any one of β-lactam antibiotics are placed onto the plate, and 3) the plate is incubated at 37° and the cell growth was observed after 24h and 48h of incubation.The Mu3 cells were grown only around the β-lactam discs due to the antagonism between vancomycin and β-lactam against Mu3 cells.A total of 321 MRSA clinical strains isolated in1995and1996from12medical facilities in Japan were tested with this method.A total of 39 strains (12.1%;24h) and 67 strains (20.96%;48h) grew around the β-lactam discs.All the 10 strains (representing 10 facilities), tested with the analysis of resistant subpopulations to vancomycin, showed similar heterogeneous patterns as observed with Mu3.The method was considered as a convenient and rapid substitute for the population analysis, the authentic method for the detection of hetero-VRSA strains.

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