Lactam + Aminoglycoside Combo Gives Lowest Dual-Resistance

SAN FRANCISCO, CA—Resistance patterns for antibiotics used against Gram-negative bacteria over the past 12 years have shown significant associations relevant to the selection of initial double-coverage of suspected Gram-negative species, a study reported at IDWeek 2013.

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Initial treatment for patients with suspected sepsis from Gram-negative organisms is often a two antibiotic regimen to decrease the chance of missing a resistant isolate; however, “rates of resistance may differ based on geography and time,” Dooshanveer Nuckchady, MD, from the department of infectious diseases, Mount Auburn Hospital, Cambridge, MA, noted.

Dr. Nuckchady and Robert Colgrove, MD, conducted a retrospective, single-center, cohort study to analyze all antibiotic sensitivity data from blood cultures growing Gram-negative organisms from 2000–2012 at their hospital. They examined rates of dual-resistance for all pair wise combinations to determine which pairs showed the lowest rates of dual-resistance. Also, they sought to determine which second antibiotic gave the largest decrease in dual resistance when added to a given antibiotic.

A total of 1607 blood culture specimens were analyzed and 527 antibiotic combinations checked.

Results showed that antibiotic resistance is not independent. For example, piperacillin-tazobactam + gentamicin had an expected resistance of 2%; however, dual resistance was 6% (P<0.05). Similar results were found for piperacillin-tazobactam + ciprofloxacin (expected 1%, dual 3%), ceftriaxone + gentamicin (expected 4%, dual 20%), and ceftriaxone + ciprofloxacin (expected 9%, dual, 29%; all P<0.05).

Adding an aminoglycoside to a lactam antibiotic gave the lowest dual-resistance and the greatest added benefit, proving superior to the fluoroquinolones in most combinations: both ceftriaxone + gentamicin and ceftriaxone + gentamicin showed about a 20% reduction in resistance compared with <5% for piperacillin-tazobactam + levofloxacin and meropenem + ciprofloxacin.

For Pseudomonas aeruginosa isolates, aztreonam + amikacin and imipenem + amikacin demonstrated a greater reduction in resistance (both >20%) compared with ceftazidime + ciprofloxacin, ceftazidime + ciprofloxacin, and piperacillin-tazobactam + ciprofloxacin (all <5%).

“Aminoglycoside-containing combinations most often gave the greatest additional benefit as the second drug,” Dr. Nuckchady concluded. “Such data may influence risk-benefit decisions in the choice of initial therapy, where the toxicities of the drugs must be balanced against minimizing the chance of ineffective initial therapy. Similar hospital-based analysis may help tune optimal therapy to current local resistance patterns.”

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