cefoxitin and Neutropenia

The optimal therapeutic regimen and duration of treatment for Mycobacterium abscessus lung disease is not well established.. To assess the efficacy of a standardized combination antibiotic therapy for the treatment of M. abscessus lung disease.. Sixty-five patients (11 males, 55 females, median age 55 yr) with M. abscessus lung disease were treated with clarithromycin, ciprofloxacin, and doxycycline, together with an initial regimen of amikacin and cefoxitin for the first 4 weeks of hospitalization.. Treatment response rates were 83% for symptoms and 74% for high-resolution computed tomography. Sputum conversion and maintenance of negative sputum cultures for more than 12 months was achieved in 38 (58%) patients. These rates were significantly lower in patients whose isolates were resistant to clarithromycin (17%, 2/12) compared with those whose isolates were susceptible or intermediate to clarithromycin (64%, 21/33; P = 0.007). Neutropenia and thrombocytopenia associated with cefoxitin developed in 33 (51%) and 4 (6%) patients, respectively. Drug-induced hepatotoxicity occurred in 10 (15%) patients. Because of these adverse reactions, cefoxitin was discontinued in 39 (60%) patients after treatment for a median of 22 days.. Standardized combination antibiotic therapy was moderately effective in treating M. abscessus lung disease. However, frequent adverse reactions and the potential for long-duration hospitalization are important problems that remain to be solved.

Topics: Adult; Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Cefoxitin; Chemical and Drug Induced Liver Injury; Ciprofloxacin; Clarithromycin; Doxycycline; Drug Therapy, Combination; Female; Humans; Liver; Lung; Lung Diseases; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Neutropenia; Nontuberculous Mycobacteria; Retrospective Studies; Sputum; Thrombocytopenia; Tomography, X-Ray Computed; Treatment Outcome

The efficacy of beta-lactam antibiotics and amikacin alone and in various combinations against Pseudomonas aeruginosa was studied in a rabbit model simulating a closed-space infection in a locally neutropenic site. Six strains of P. aeruginosa were studied in semipermeable chambers placed subcutaneously in rabbits. Therapy was begun 4 h after inoculation of 5 X 10(4) CFU of bacteria per ml of pooled rabbit serum into the chambers. Antibiotics were administered intramuscularly every 6 h for 16 doses. Quantitative bacteriology was measured at the start of therapy and at 20, 44, and 92 h thereafter. Antibiotic concentrations were measured in blood and chamber fluid. Results were compared with in vitro tests of susceptibility and synergy. No single-agent therapy eradicated any of the six test organisms. Azlocillin (100 mg/kg per dose) plus amikacin (20 mg/kg per dose) eliminated five of six organisms by 92 h, and ceftizoxime (100 mg/kg per dose) plus amikacin (20 mg/kg per dose) eliminated three of six test strains. Azlocillin plus ceftizoxime (each 100 mg/kg per dose) failed to eliminate any of the six strains. To eliminate P. aeruginosa in this model, two drugs were required, with one being an aminoglycoside. In vitro susceptibility tests of synergy were predictive of successful therapy whenever the antibiotic concentrations (free and total) at the infection site exceeded the MBC for both the aminoglycoside alone and the beta-lactam when tested in combination with amikacin.

Topics: Agranulocytosis; Amikacin; Animals; Anti-Bacterial Agents; Azlocillin; Cefotaxime; Cefoxitin; Ceftizoxime; Disease Models, Animal; Drug Combinations; Female; Hydrogen-Ion Concentration; Kanamycin; Microbial Sensitivity Tests; Neutropenia; Penicillins; Protein Binding; Pseudomonas Infections; Rabbits

Disseminated disease due to rapidly growing mycobacteria is manifested by positive blood cultures and multiple skin and subcutaneous abscesses. A patient had T-cell lymphoma and disseminated disease; he also had neutropenia intermittently. Single-agent therapy with amikacin sulfate or cefoxitin sodium was not adequate during periods of neutropenia, and combination therapy was necessary to control the infection. Clinical response correlated with detectable serum inhibitory levels of the antimicrobial agents. Surprisingly, the organism was not killed by either amikacin or cefoxitin, a finding that correlated with the absence of serum bactericidal levels. This case suggests that granulocytes may play a role in the host's response to this organism, and determination of serum inhibitory and possible bactericidal levels may be useful in monitoring therapy.

Topics: Adult; Amikacin; Cefoxitin; Drug Resistance, Microbial; Granulocytes; Humans; Kanamycin; Lymphoma; Male; Mycobacterium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Neutropenia; Nontuberculous Mycobacteria; Skin Diseases, Infectious