Therapeutic effects of a combination treatment with flomoxef and tobramycin against infections complicated with hematological disorders]

The efficacy and safety of a combination regimen using flomoxef (FMOX) and tobramycin (TOB) were evaluated in the treatment of infections complicated with hematological disorders. The primary diseases in 40 patients included acute leukemia, malignant lymphoma and others. Complicated infections included 35 cases with suspected septicemia, 4 cases with septicemia and 1 case with pleuritis. Clinical responses were excellent in 10 (25.0%), good in 14 (35.0%), fair in 2 (5.0%) and poor in 14 (35.0%). The efficacy rate was 73.1% in patients with neutrophil counts higher than 501/microliters after administration, but it was 35.7% in patients with counts less than 501/microliters; the difference was statistically significant. No side effects were observed in any of the 40 patients. Abnormal laboratory data in liver functions were identified in 1 patient (2.5%). Degree of this abnormality was very slight, and the continuation of treatment was not disturbed. In conclusion, this combination therapy of FMOX and TOB thus appears to be useful and safe in therapies for infections complicated with hematological disorders.     

Clinical evaluation of a combination treatment with cefminox and fosfomycin for infections complicated in patients with hematological disorders]

We evaluated clinical effects and toxicities of a combination treatment with cefminox (CMNX) and fosfomycin (FOM) for infections complicated with hematological disorders in 56 patients. Among those, 52 patients including 22 with malignant lymphoma, 19 with acute leukemia, and 11 with other hematological disorders were evaluable. Excellent and good responses were obtained in 33 (63.5%) of the 52 patients. This treatment was also effective in 5 of 9 cases in which granulocyte counts were less than 500/mm3 through the course of administration. Side effects were observed in only one patient. Mild nausea occurred but was not serious. These results indicate that the combination of CMNX and FOM is an effective and safe regimen for the treatment of infections complicated in patients with hematological disorders.     

Clinical experience of chemotherapy with cefmetazole for severe infections accompanying malignant hematological disorders

We made an attempt to treat with cefmetazole (CMZ) 25 patients who developed severe infectious diseases while suffering with granulocytopenia associated with the treatment of malignant hematological disorders. 1. Determination of bacteriological efficacy While 20 strains were isolated and identified from 15 patients, no significant bacteria were detected in 9 patients. Isolates obtained were: 5 strains of Enterococcus faecalis, 3 strains of Haemophilus influenzae, 2 strains of Staphylococcus epidermidis, 2 strains of Klebsiella oxytoca, 2 strains of Staphylococcus aureus, and 1 strain each of Neisseria sp., Pseudomonas maltophilia, Enterobacter sp., alpha-Streptococcus, beta-Streptococcus and Gram-positive cocci. Causative organisms were eradicated or markedly in 7 of the 15 patients from whom bacteria were isolated. Clinical findings, including fever, revealed that none of the patients, in whom bacteriological efficacy was determined to be poor, exhibited sufficient clinical response. E. faecalis was isolated from 4 of 6 patients bacteriologically determined to have no response. 2. As for 23 patients, who were found to be evaluable among the 25 patients, 8 (34.8%), 4 (17.4%), 4 (17.4%), and 7 (30.4%) demonstrated excellent, good, fair and poor responses, respectively, showing a 69.6% efficacy rate which indicates a sum of percentages of patients with excellent, good and fair responses. 3. While an efficacy rate of 100% was obtained for 3 patients with number of peripheral neutrophils less than 500/mm3 before the beginning of CMZ administration, only an efficacy rate of 66.7% was obtained for 15 patients with neutrophils more than 500/mm3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical evaluation of a combination treatment with cefbuperazone and amikacin in infections complicating with hematological disorders

The efficacy and the safety of a combination regimen using cefbuperazone (CBPZ) and amikacin (AMK) were evaluated in severe infections in patients with hematological diseases. Twenty two patients were subjected to this combination therapy; among these, 18 patients were evaluable for the effectiveness. They included 9 cases of leukemia, 5 cases of malignant lymphoma, 2 cases of aplastic anemia, and 2 cases of angio-immunoblastic lymphadenopathy with dysproteinemia. Excellent responses were obtained in 5 patients and good responses in 5 patients, with a total effectiveness of 55.6%. Efficacy rates for individual types of infections were; 2/2 in sepsis, 6/14, or 42.9% in suspected sepsis, 1/1 in urinary tract infection, and and 1/1 in upper respiratory infection. The combination treatment was also effective in 4 of 6 cases in which neutrophil counts were less than 500/mm3 prior to therapy. Side effects were observed in only one patient. Mild proteinuria occurred in a 80-year-old male in 6 days after the regimen was started, but was not serious. These results indicate that a combination of CBPZ and AMK is safe and effective for the treatment of infections even in patients with compromised immunodefenses.     

Clinical effects of combination therapy with cefozopran and amikacin for infections in patients with hematological disorders

Cefozopran (CZOP) and amikacin (AMK) were used concomitantly to treat infections complicated by hematological diseases. A total of 103 subjects were evaluated, and the all over efficacy rate was 69.9%. Acute leukemia was found in the largest number of patient, 57, followed by 29 cases of malignant lymphoma and 7 cases of myelodysplastic syndrome. By type of infection, patients having unknown origin were the largest in number, being 66, and the efficacy rate was 71.2%. The efficacy rates for sepsis, pneumonia and upper respiratory infection were 42.9% (7 cases), 71.4% (14 cases) and 90% (10 cases) respectively. The efficacy rates by neutrophil counts before administration of CZOP and AMK and at 1 week after administration were both 53.3% in the group of less than 100/microliter, both 60% in the group of less than 500/microliter. The efficacy rate by neutrophil counts at 1 week after administration was 58.6% in the group of less than 100/microliter. The efficacy rate was 75.4% in the group of granulocyte colony stimulating factor (G-CSF) concomitant usage, and 61.9% in the group of non-concomitant usage group. The efficacy rates by serum albumin levels before administration of CZOP and AMK and at 1 week after administration were both 92.9% in the group of over than 4 g/dl, both 50% in the group of less than 3 g/dl. Concomitant treatment with CZOP and AMK exhibited a high level of safety and efficacy rates in infections complicated by hematological diseases.     

Clinical evaluation of cefbuperazone in severe infections complicated with hematological disorders

The efficacy and the safety of an antibiotic in cephamycin group, cefbuperazone (CBPZ), were investigated in 93 patients with severe infections complicated with hematological disorders. The efficacy evaluation was made in 85 cases with underlying hematological disorders including 49 cases (57.6%) of leukemia and 18 cases (21.2%) of malignant lymphoma. The overall efficacy rate was 50.6% of the 85 evaluable cases. The clinical efficacy rate for sepsis and suspected sepsis was 53.4%. The most frequently used group of antibiotics for combination therapy was aminoglycosides in 37 cases, in which an efficacy rate of 62.2%, a higher rate than the efficacy rate of 48.5% for all the combination therapy cases, was obtained. In 16 cases in which penicillins were used as combination drug, the efficacy rate obtained was low, 31.3%. Efficacy rates obtained for cases with different neutrophil counts at the start of therapies were as follows: 52.2% in 23 cases with neutrophil counts below 100/mm3, 46.2% in 13 cases with neutrophil counts between 100 and 499/mm3 and 51.3% in 39 cases with neutrophil counts equal to or above 500/mm3, thus no significant differences in efficacy rates were observed for patients with different neutrophil counts. These results appear to suggest that CBPZ, alone or in combination with other antibiotic such as aminoglycosides, may be quite useful in the treatment of severe infections in patients with hematological disorders.     

Clinical evaluation of imipenem/cilastatin sodium against severe infections complicated with hematological disorders and solid tumors

Imipenem/cilastatin sodium (IMP/CS) was administered to patients with severe infections complicated by hematological disorders and solid tumors to assess its efficacy and safety. Primary diseases in this series of 76 cases included 37 cases of hematological disorders (acute leukemia in 25 cases, malignant lymphoma in 7 cases, aplastic anemia in 3 cases and 2 other diseases) and 38 cases of solid tumors (lung cancer in 7 cases, gastric cancer in 11 cases, esophageal cancer in 6 cases, pancreatic cancer in 3 cases, bile duct cancer in 4 cases, hepatocellular cancer in 3 cases, and 4 other diseases). Following results were obtained. 1. Types of infection in hematological diseases were sepsis in 5 cases, suspected sepsis in 24 cases, pneumonia in 5 cases and 3 others. The efficacy rates were 100% in sepsis, 62.5% in suspected sepsis, 80% in pneumonia and 73% in all cases. 2. Types of infection in solid tumors were sepsis in 2 cases, suspected sepsis in 13 cases, pneumonia in 10 cases, cholecystitis in 2 cases, cholangitis in 5 cases, liver abscess in 2 cases, and 4 others. The efficacy rates were 50% in sepsis, 69.2% in suspected sepsis, 80% in pneumonia, and 71.1% in all cases. 3. IPM/CS was administered in single use in 66 cases and in combination with other antibiotics in 9 cases. The efficacy rate in the single use was 72.7% and that in the combination use was 66.7%. 4. The efficacy rate in 35 cases of first use was 71.4% and that in 40 cases of second use was 72.5%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical evaluation of ceftazidime monotherapy for infections complicated with hematological disorders]

Fifty patients with infections associated with hematological disorders were treated with ceftazidime (CAZ). Among them 44 cases were evaluable, including 21 with acute leukemia, 17 with malignant lymphoma, and 6 with other hematological disorders. Excellent responses were observed in 15 patients (34.1%) and good responses in 15 (34.1%), with an overall efficacy rate of 68.2%. The efficacy rate among sepsis and suspected sepsis cases was 67.6%. This treatment was also effective in 7 of 10 cases in which neutrophil counts were less than 500/mm3 through the course of administration. Laboratory abnormalities included mild eosinophilia in 1 case, slight elevation of GOT in 1 case and slight elevation of GPT in 1 case. These results suggest that CAZ is an effective and safe antibiotics for the treatment of infections in patients with hematological disorders.     

Therapeutic effects of SM-4300 and antibiotics combination against severe bacterial infections

A newly developed human immunoglobulin preparation for intravenous administration (SM-4300) was applied to the severe bacterial infections in the field of internal medicine. Nine cases of severe infections were treated with SM-4300 and antibiotics combination. Clinical effects of SM-4300 were excellent in 1 case, good in 5, poor in 1 and unknown in 2. The efficacy rate was summarized as 86%, and no side effects were observed.     

The use of SM-4300 against severe infections complicated with hematological diseases

The intravenous human gamma-globulin (SM-4300) was used with antibiotics for 9 patients who had severe bacterial infections resisted to the antibiotics. All of these patients had underlying hematological diseases, acute leukemia, aplastic anemia, malignant lymphoma and pure red cell aplasia. In many of the cases the leukocyte counts were extremely decreased. In 11 episodes of the infections, 4 cases were successfully treated by SM-4300 and 4 cases were not. No adverse reaction was found. It seems that the use of SM-4300 is effective for the treatment of these severe infections.     

Clinical investigation of cefotiam in combination with aminoglycoside or (and) penicillin against complicated infections with hematopoietic disorders

Clinical investigation of combination use of cefotiam (CTM), aminoglycoside, or (and) penicillin against complicated infections with hematopoietic disorders was performed, and the results were as follows. Fifty-one patients were administered CTM in combination with aminoglycoside or (and) penicillin. The clinical response was excellent 19.6%, good 27.4%, fair 21.6%, and poor 31.4% showing efficacy rate of 47.1%. The combined therapy of CTM and aminoglycoside was clinical effective in 70% of 10 patients with complicated sepsis. Therefore, combination use of CTM and aminoglycoside is considered to be the first choice for the treatment of complicated sepsis with hematopoietic disorders. The clinical effectiveness of CTM was not influenced by the number of mature neutrophil at the first phase of CTM treatment, but was influenced at the end phase of CTM treatment. Gram-negative bacilli were dominantly isolated from the patients. Pseudomonas sp. was isolated from 70% of the patients with sepsis. No remarkable side effects were observed in this investigation.     

Comparison of netilmicin with ceftriaxone for the treatment of severe or complicated urinary tract infections

A randomised trial was undertaken to compare the efficacy of netilmicin and ceftriaxone for the treatment of severe or complicated urinary tract infections. Forty-seven patients completed the study. Twenty-three of 24 patients treated with netilmicin and 21 of 23 treated with ceftriaxone were cured. One patient treated with netilmicin had a mild, reversible disturbance of renal function. Six patients developed diarrhoea after ceftriaxone treatment.     

Clinical evaluation of combination therapy with aspoxicillin and ceftazidime for severe infections complicating hematological disorders

Clinical effects of a combination therapy using aspoxicillin (ASPC) and ceftazidime (CAZ) were investigated in 88 patients with severe infections which were complicating hematological disorders. ASPC and CAZ were administered intravenously at daily doses of 8 g and 4 to 6 g, respectively, in 2 to 4 divided doses for at least 3 days. The treatment was markedly effective in 20 cases; effective in 31; fairly effective in 4; and ineffective in 33 cases. Seventy-seven patients with whom detailed data were obtained showed an efficacy rate of 63.6%. Bacteria were detected in 9 patients, from whom 10 strains were isolated. The results of bacteriological effects were: 3 strains disappeared, 1 decreased, 3 unchanged, and 3 unclear. The bacteriological eradication rate was 42.9%. Of the detected 10 strains, 3 were identified as Pseudomonas aeruginosa, with 2 of the 3 strains eradicated and 1 decreased. An evaluation of the relationship between clinical efficacies and neutrophil counts before and after the ASPC-CAZ combination therapy showed that the patients with 500/mm3 or higher neutrophil counts before the therapy or those with increased neutrophils after the therapy tended to be more responsive to the therapy. Side effects were observed in 4 patients, but all of them disappeared upon discontinuation of the therapy. The combination therapy with ASPC and CAZ appears to be useful for the treatment of severe infections complicating hematological disorders.     

恶性血液病患儿继发侵袭性肺部真菌感染4例的诊断和治疗

目的提高临床医师对儿童恶性血液病、肿瘤疾病患儿合并侵袭性肺部真菌感染(IPFI)尤其是侵袭性肺曲霉菌感染(IPA)的认识,早期及时地诊断及治疗提高患儿生存率。方法对本院在2007年1月至2008年6月收治的4例血液病患儿合并IPA的临床诊治过程及预后进行回顾性分析。结果 4例患儿均符合IPFI的诊断标准,1例为临床诊断,另3例为拟诊;4例患儿存在化疗后中性粒细胞减少>10 d,造血干细胞移植后移植物抗宿主病,长期应用激素等宿主因素,典型肺CT空洞改变;1例痰培养示咽曲霉菌生长的诊断依据,同时应用伏立康唑、米卡芬净等抗真菌药物治疗。4例患儿均死亡。结论儿童恶性血液病、恶性肿瘤合并IPA进展快、病原学诊断困难、预后差,早期诊断及治疗对挽救患儿生命至关重要。     

Penetration of cefmetazole and netilmicin into the cerebrospinal fluid

1. Cefmetazole (CMZ) and netilmicin (NTL) were administered by one-shot intravenous and intramuscular injection, respectively, and measurements were made on their concentrations in the serum as well in the cerebrospinal fluid (CSF) which was collected using a drainage tube inserted into the cisterna basalis after the operation of ruptured cerebral aneurysm. 2. Concentrations of CMZ and NTL in the CSF changed nearly in parallel to those in the serum. 3. A one-shot intravenous injection of these drugs seemed to achieve their high concentrations in the CSF, though high concentrations may not last very long.     

Therapeutic effects of micronomicin against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group

Micronomicin (MCR) at a daily dose of 120 to 360 mg was administered to patients with severe infections who had hematopoietic disorders as underlying diseases. Efficacy and safety of the drug were evaluated. The underlying diseases in the 56 patients included in the evaluation of efficacy were acute myelocytic leukemia (24 cases), acute lymphocytic leukemia (8), acute promyelocytic leukemia (6), acute monomyelocytic leukemia (4), acute monocytic leukemia (1), erythroleukemia (1), chronic myelocytic leukemia-blastic crisis (4), malignant lymphoma (3), aplastic anemia (2), and others (3). The infections were septicemia in 9 patients, suspected septicemia in 48, respiratory tract infection in 7, and perianal abscess in 2. The clinical efficacy of MCR was 'excellent' in 12 patients, 'good' in 17, 'fair' in 7, 'poor' in 30 for an efficacy rate of 43.9%. The efficacy rate classified according to infections was 22.2% in septicemia, 56.3% in suspected septicemia. The organisms isolated from the patients with septicemia were Escherichia coli in 2, Klebsiella pneumoniae in 2, Pseudomonas aeruginosa in 1, alpha-Streptococcus in 1, Serratia marcescens in 1, and Acinetobacter sp. in 1. The efficacy rate was 15.4% in the 13 patients whose causative organisms were identified. The efficacy rate for patients who had failed to respond to prior antibiotic therapy was 43.9%. The efficacy rate in patients (34 cases) with an initial neutrophil count less than 100/microliter was 44.1%. Side effect which might have been caused by MCR was skin eruption in only one episode among 83 episodes those were evaluated for safety.     

Clinical evaluation of a combination therapy using cefmenoxime and cefsulodin on infections complicated by hematological disorders. Tohkai Research Group on Infections in Hematopoietic Disorders

Infected patients with hematological disorders were treated with the combination of cefmenoxime (CMX) and cefsulodin (CFS). This therapy was done on 74 patients, of whom 38 (51%) had acute myelocytic leukemia, 14 (19%) malignant lymphoma, 7 (9%) acute lymphocytic leukemia, 5 aplastic anemia, 4 adult T cell leukemia, 4 chronic myelocytic leukemia, 1 multiple myeloma and 1 histiocytic medullary reticulosis. Complicated infections included 5 cases of septicemia, 41 cases of suspected septicemia, 19 cases of respiratory tract infection, 2 with anal abscess, 1 with urinary tract infection and others. The obtained results were as follows: Clinical effectiveness of the combination therapy was excellent in 17 cases (23.0%), good in 24 (32.4%) and poor in 33 (44.6%). Total clinical efficacy rate was 55.4%. Clinical efficacy rate was 40% against septicemias, 51.2% against suspected septicemias and 57.9% against respiratory tract infections. Causative pathogens were isolated in only 21 cases (28.4%): Gram-positive bacteria in 9 cases, Gram-negative bacteria in 11 and fungus in 1. About half of the Gram-negative bacteria belonged to Pseudomonas sp. The efficacy rate of this combination therapy against Gram-negative bacterial infections was 72.7% but the rate against Gram-positive bacterial infections were only 33.3%. Only in 1 case, this combination therapy was discontinued because of drug eruption. Abnormal laboratory findings were observed in 5 cases: Elevation of BUN in 3, GOT and GPT in 1 and prolongation of activated partial thromboplastin time in 1. In conclusion, this combination therapy of CMX and CFS is useful and safe against infections complicated by hematological disorders.     

Clinical investigation of the therapeutic effects of cefmenoxime in the treatment of infections complicated by hematological diseases

Therapeutic effects on cefmenoxime hemihydrochloride (CMX, Bestcall), a new synthetic cephem antibiotic, were examined in the treatment of various infections complicated with hematological diseases. The number of patients treated with CMX was 37 including 5 cases of sepsis or suspected sepsis, 14 cases of pneumonia or suspected pneumonia, 5 cases of upper respiratory diseases, 2 cases of urinary tract infections and 11 cases of other infections. All of these infections were complicated with hematological diseases: Acute leukemia, 13 cases; chronic myelocytic leukemia, 1 case; adult T cell leukemia, 3 cases; malignant lymphoma, 8 cases; Hodgkin's disease, 2 cases and myeloma, 3 cases. CMX were administered by a single intravenous injection or by a drip infusion. The dose was between 2 and 6 grams per day. Good to excellent clinical results were obtained in 25 out of 37 cases, total effective rate of 67.6%. No clinical side effects or abnormal laboratory findings attributable to CMX were observed except for light diarrhea in 2 cases. By the clinical investigation, it was demonstrated that CMX was one of safe and effective antibiotics for treating infections in the compromised hosts complicated with hematological diseases.     

Therapeutic effects of cefuzonam against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group]

Cefuzonam (CZON) was used to treat severe infections in 151 patients with hematopoietic disorders, and its efficacy and safety were assessed. The drug was given in doses of 2.0 to 6.0 g a day, divided into 2 or 3, intravenously by injection or infusion. The clinical effects were excellent in 34 cases, good in 40 cases, fair in 5 cases, and poor in 57 cases. Therefore, the results were excellent or good in 54.4% of the patients treated. The efficacy rates were 43.8 and 35.9% for groups of patients whose neutrophil counts were 500/microliters or less and 100/microliters or less, respectively. It was excellent or good in 70.6% of patients in whom causative agents were identified, and in 66.7 and 80.0% of patients infected with Gram-negative and -positive bacilli, respectively. The efficacy rate for patients infected with unidentified agents was 52.1%. The rate for patients who had received other antibiotics previously was 41.5%. The rate for patients having received only one antibiotic for the preceding treatment was 50.0%. Six (3.9%) of the treated patients experienced adverse effects including changes in laboratory test results observed in 4.     

Therapeutic effects of cefclidin against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group]

One hundred thirty-eight patients with severe infections associated with hematopoietic disorders were treated with cefclidin (CFCL), and the efficacy and the safety of the drug were evaluated. The results obtained are summarized below. 1. Of the 126 patients in whom the efficacies were evaluable, 22 (17.5%) responded markedly well and 48 (38.1%) moderately, and the overall efficacy rate was 55.6%. 2. Efficacy rates for different infections were: 20.0% in septicemia, 61.2% in suspected septicemia, 46.7% in respiratory tract infection and 25.0% in others. 3. Significantly different efficacy ratings were observed between a group of patients with neutrophil counts of less than 100/mm3 and that with neutrophil counts of higher than 501/mm3. 4. Out of 138 patients in whom the safety was evaluable, side effects were observed in 5 patients (3.6%) and abnormal laboratory test values in 9 (6.5%). None was serious, however.