COMPARISON OF EMPIRIC AZTREONAM AND AMINOGLYCOSIDE REGIMENS IN THE TREATMENT OF SERIOUS GRAM-NEGATIVE LOWER RESPIRATORY-INFECTIONS

An open-label, controlled, randomized study was performed to assess the efficacy and safety of combination regimens using either aztreonam or an aminoglycoside control regimen as empiric therapy for suspected aerobic gram-negative bacillary pneumonia or purulent bronchitis. Eighty-four patients, 42 in each arm of the study, were randomly assigned to one of two treatment regimens. The combination aztreonam regimen included aztreonam, 2 gm every 8 hours (q8h), plus either clindamycin, 600 to 900 mg q8h, or nafcillin, 1.5 gm to 2 gm every 6 hours (q6h). The control regimen was one of the following depending on the combination therapy that was designated standard at each of the three study institutions: amikacin, 5 mg/kg q8h, plus cefazolin, 1 gm q8h; amikacin, 500 mg every 12 hours plus mezlocillin, 4 gm q6h; or kinetically dosed tobramycin plus ticarcillin, 3 gm to 4 gm q4h. The two groups were well matched in terms of demographics and clinical characteristics. Among the 84 patients, organisms from the Enterobacteriaceae family accounted for the largest proportion of isolates (44%) including Escherichia coli (13%), Klebsiella species (14%), and Serratia species (9%). Other commonly identified organisms were Pseudomonas aeruginosa (19%), Haemophilus influenzae (15%), Streptococcus pneumoniae (12%), and Staphylococcus aureus (8%). Results of this trial included clinical response rates of 83% in both groups (P=0.951) and a microbiologic cure rate of 75% in the aztreonam group and 63% in the control group (P=0.291). In the 59 patients with documented aerobic gram-negative pneumonia, microbiologic eradication rates were 72% in the aztreonam group versus 57% in the control group (P=0.359). Duration of treatment tended to be shorter in the aztreonam group than in the control group, with a median 10 days of therapy versus 12 days of therapy (P=0.095), respectively. In addition, the percentage of patients requiring nonstudy antimicrobial agents tended to be lower in the aztreonam group than the control group, involving 21% of patients in the aztreonam group compared with 36% of patients in the control group (P=0.086). All regimens were well tolerated, and no patient was withdrawn because of adverse reactions to the study medications. Two patients, both in the control group, required dose reduction, which was necessitated by possible aminoglycoside-induced nephrotoxicity. This trial shows that aztreonam is an effective agent with an excellent safety profile when used in combination regimens for the empiric treatment of pneumonia. A well-controlled trial is needed to verify the trend toward shorter hospital stays and a reduced need for additional antimicrobial agents seen with the aztreonam regimen when compared with those receiving aminoglycoside-combination regimens.