IDIS Index Record 651317
IS DOUBLE COVERAGE OF GRAM-NEGATIVE ORGANISMS NECESSARY?
JOHNSON S J; ERNST E J; MOORES K G
AM J HEALTH-SYST PHARM, vol 68, iss 2, p 119-124, yr 2011
ANTIBIOTICS 8120000; ANTIBIOTICS-AMINOGLYCOSIDES 8120200; ANTIBIOTICS-QUINOLONES 8122000; ANTIBIOTICS-PENICILLINS 8121600; ANTIBIOTICS-CEPHALOSPORINS 8120600; TAZOBACTAM 44100065
INFECTION, PSEUDOMONAS 041.7; INFECTION, KLEBSIELLA 041.3; INFECTION, ESCHERICHIA 041.4; INFECTION, BACTERIAL NEC 041.; SEPTICEMIA, GRAM-NEG NEC 038.4; SEPTICEMIA, ESCHERICHIA COLI 038.42; CARE, INTENSIVE V66.71
REVIEW ADULT 6; DRUG COMBINATION 16; ECON DRUG ECONOMICS 129; DRUG RESISTANCE 148; SIDE EF ADVERSE REACTION 46
Purpose. The appropriateness of combination therapy for infections caused by gram-negative organisms is examined.
Summary. Mortality from Pseudomonas aeruginosa infection is particularly high; therefore, empirical regimens are often selected to ensure coverage for this organism. The initial use of combination antimicrobial therapy for gram-negative infections is usually justified by one of three reasons: the potential for synergistic activity between two classes of antimicrobial agents, the broad empirical coverage provided by two antimicrobial agents with differing spectra of activity and resistance patterns, or the prevention of resistance development during antimicrobial therapy. Disadvantages of using combination therapy are increased drug toxicity, increased costs, and increased risk of superinfection with more-resistant bacteria or fungi. There are no clinical data that suggest that the combination of a beta-lactam plus a fluoroquinolone results in improved patient outcomes compared with a beta-lactam alone or a beta-lactam plus an aminoglycoside. Results from studies that evaluate combination therapy versus monotherapy for gram-negative bacilli conflict with the common practice of use of double coverage. Strong evidence to support the administration of antimicrobials for double coverage of gram-negative organisms is lacking. Antimicrobial overuse may lead to antibiotic resistance, unnecessary adverse effects, and increased costs.
Conclusion. The available clinical evidence does not support the routine use of combination antimicrobial therapy for treatment of gram-negative infections. Patients with shock or neutropenia may benefit from combination therapy that includes an aminoglycoside.