dibekacin and Pneumonia--Bacterial

We performed a clinical trial to investigate the efficacy and safety of arbekacin (ABK), a unique aminoglycoside with activity against methicillin-resistant Staphylococcus aureus (MRSA), in patients with hematological malignancies complicated by high-risk infections. ABK was administered intravenously at a dose of approximately 5 mg/kg with various broad-spectrum β-lactams, followed by therapeutic drug monitoring (TDM). A total of 54 febrile or infectious episodes were registered, and TDM was performed in 44 (81%) cases. The absolute neutrophil count was below 500/μl in 49 (91%) cases, and cytotoxic chemotherapy was being administered in 47 (87%) cases. Before initiation of ABK, 52 (96%) patients had received fluoroquinolones (n = 37) and/or broad-spectrum β-lactams (n = 34). There were 10 cases of documented infections including one of MRSA pneumonia, and 44 cases of febrile neutropenia. The efficacy at the end of treatment was 80% for all patients, and efficacy was significantly higher in patients attaining maximum concentrations ≥ 16 µg/ml or receiving TDM-guided dose-adjustment of ABK (n = 19, 95 vs. 71%, P = 0.039). Renal toxicity was observed in six cases (11%) but was generally acceptable. This study demonstrated that TDM-guided ABK administration may be applicable under limited conditions for patients with hematological malignancies.

Topics: Adult; Aged; Anti-Infective Agents; beta-Lactams; Dibekacin; Drug Monitoring; Drug Therapy, Combination; Febrile Neutropenia; Female; Fluoroquinolones; Hematologic Neoplasms; Humans; Infusions, Intravenous; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pneumonia, Bacterial; Staphylococcal Infections; Treatment Outcome

It was reported that some methicillin-resistant Staphylococcus aureus (MRSA) show resistance to vancomycin (VCM) and beta-lactam antibiotics; thus, they are termed beta-lactam antibiotic-induced VCM-resistant MRSA (BIVR). The VCM resistance of MRSA is induced by the administration of beta-lactam antibiotics, but this phenomenon can be difficult to detect in the clinical laboratory. We detected the BIVR strain in a 64-year-old man who had had a ventilator tube inserted directly into the windpipe during long-term VCM therapy. The patient was diagnosed with MRSA pneumonia and septicemia on July 5, 2007, and sulbactam/ampicillin (SBT/ABPC) was administered for 5 days. However, the fever recurred, and administration of VCM was resumed for 7 days from July 19. Fever developed again, and VCM was administered again for 14 days from September 30. BIVR and VCM-low-sensitive MRSA were isolated from blood on October 18 and 22, although the VCM trough concentration was 10.2 microg/ml. On October 27, we changed to a combination of fosfomycin (FOM) and arbekacin (ABK), and thereafter the fever quickly decreased and the clinical symptoms abated. We isolated five MRSA strains from the blood of the patient, three strains of VCM-sensitive MRSA, one strain of BIVR, and one strain of a VCM-low-sensitive MRSA. The DNA band patterns determined by pulsed-field gel electrophoresis were completely identical except for the VCM-low-sensitive MRSA, which was missing one band. Furthermore, the VCM-low-sensitive MRSA became sensitive to beta-lactam antibiotics. Our results indicate the possibility that long-term VCM therapy is one of the factors that allow BIVR or VCM-low-sensitive MRSA to emerge, and this allows VCM therapy for MRSA to fail.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactams; Dibekacin; Drug Therapy, Combination; Fosfomycin; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Staphylococcal Infections; Time Factors; Vancomycin; Vancomycin Resistance

We experienced successful treatment of postoperative severe pneumonia of Methicillin-resistant Staphylococcus aureus (MRSA) with combination therapy of Arbekacin (ABK) and Fosfomycin (FOM) in three lung cancer patients. Case 1 was a advanced age of seventy-nine man who had had right upper lobectomy. Case 2 was a 61-year-old man who had had left lower lobectomy and extended bilateral mediastinal lymph-node dissection through the median sternotomy. And case 3 was a 59-year-old man who had suffered from pulmonary embolism after right pneumonectomy and partial resection of left atrium and superior vena cava. All cases were immuno-compromised patients and super-infected with Gram-negative rods, and Pseudomonas aeruginosa in case 1 and case 3. Clinical symptoms were improved after the start of administration of ABK and FOM inspite of ineffectiveness of prior treatment with other antibiotics. We added staggered chemotherapy of Sulbactam/Cefoperazone (SBT/CPZ) and Ceftazidime (CAZ) for case 1 and case 3 respectively. Thus, the combination therapy of ABK and FOM might be useful for severe pneumonia of MRSA in the immunocompromised patients, and the combined staggered chemotherapy of beta-lactum agents and above would be the first choice in the treatment for the case involving Pseudomonas aeruginosa.

Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Therapy, Combination; Fosfomycin; Humans; Immunocompromised Host; Lactams; Lung Neoplasms; Male; Methicillin Resistance; Middle Aged; Pneumonia, Bacterial; Postoperative Complications; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus