A Comparative Analysis of Aztreonam + Clindamycin versus Tobramycin + Clindamycin or Amikacin + Mezlocillin in the Treatment of Gram-Negative Lower Respiratory Tract Infections

Abstract

One hundred ten patients were randomized to receive one of the following antibiotic combinations: aztreonam + clindamycin, tobramycin + clindamycin, or amikacin + mezlocillin for the treatment of lower respiratory tract infections (LRTI) caused by gram-negative bacilli. Of the 68 patients who received aztreonam + clindamycin, 60 were clinically evaluable and 50 were bacteriologically evaluable. Of the 60 clinically evaluable patients, 54 were cured and 5 were treatment failures or died during the study period. Of the 50 bacteriologically evaluable patients, 46 were cured and 3 failed to respond to therapy. Of the 26 clinically evaluable patients in the tobramycin + clindamycin group, 22 were cured and 4 either failed to respond or died during the study period. Of 18 bacteriologically evaluable patients in this group, 16 were cured and 2 failed to respond. In the amikacin + mezlocillin group, 14 of the 15 clinically and bacteriologically evaluable patients were cured, and 1 failed to respond. The most commonly isolated pathogens were Klebsiella pneumoniae, Escherichia coli, and Pseudomo-nasaeruginosa. The very few adverse drug reactions that were seen were transient and comparable in all three groups except for renal function parameters, which deteriorated in 6–8% of patients receiving the aminoglycoside combination. All three antibiotic combinations were similar in effectiveness and safety.

Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group

“…Flaws of these studies have included lack of a double-blind design, exclusion of patients with underlying conditions associated with higher mortality, small sample sizes, and absence of intent-to-treat analyses (15-17, 27, 39-41, 43, 44). Other trials allowed inclusion of patients with a variety of lower respiratory tract infections and therefore did not enroll a clearly defined patient population (15,17,21,23,37,41,43,48,49). In the present study, we sought to avoid these criticisms and, accordingly, enrolled a relatively homogeneous population in which severity of illness measured by objective indices of respiratory dysfunction served as the entry criterion.…”

“…Of the 81 deaths that occurred, 43 were in the ciprofloxacin treatment group and 38 were in the imipenem treatment group (P = 0.619). Eighteen of the 43 deaths in the ciprofloxacin treatment group were attributed to the patients' underlying disease(s), 23 were attributed to bacterial infection, and 2 were considered indeterminate.…”

“…Although numerous clinical studies have compared various antimicrobial regimens for the treatment of pneumonia, the ability to draw meaningful conclusions regarding the relative efficacy or safety of the agents being evaluated has often been compromised by aspects of trial design or the way results were analyzed and reported. Previous trials often excluded critically ill patients, especially those requiring mechanical ventilation or with severe renal or hepatic dysfunction (16,17,43). Most previous trials have employed nonblind study designs (15,16,23,27,48,49), lacked an intent-to-treat analysis (16,27), suffered from small patient sample sizes (39)(40)(41)44), or enrolled patients with other infections in addition to pneumonia (21,23,27,48,49).…”

Treatment of Nosocomial Postoperative Pneumonia in Cancer Patients: A Prospective Randomized Study

“…14,15 In these studies, the clinical response rate to this combination regimen ranged from 87% to 90%; however, the patient population under treatment was a relatively low-risk group without underlying cancer or extensive surgery as in this study. In these referenced studies, 14,15 Cl/Az was compared with Cl/Tobramycin. Data related to the use of P/T in nosocomial pneumonia are limited to either open trials or studies that compared it with ceftazidime without any other effective antimicrobial therapy to cover for Gram-positive or anaerobic organisms.…”

“…In two studies in which the combination of CI and Az was used to treat nosocomial pneumonia, a clinical response of 87% to 90% was reported. 14,15 Piperacillin is an extended-spectrum penicillin that has been used to treat serious infections. It is active against most Gram-negative bacilli and has shown good activity against most anaerobic bacteria.…”