Antibiotic Selection for Dual Coverage of Pseudomonas aeruginosa and Coryneform Gram-Positive Rods

Rationale for Combination Therapy

The American College of Physicians recommends that ceftazidime has poor activity against gram-positive cocci, including viridans streptococci and coagulase-negative staphylococci, and would be ineffective against coryneform organisms 1
Coryneform gram-positive rods require agents with gram-positive activity such as vancomycin, daptomycin, or linezolid, as suggested by the Infectious Diseases Society of America 2
Combining two beta-lactams provides no mechanistic advantage when synergy is the goal; a beta-lactam plus aminoglycoside should be used instead if dual gram-negative coverage is needed, according to the European Society of Clinical Microbiology and Infectious Diseases 1

The European Society of Clinical Microbiology and Infectious Diseases recommends ceftazidime 2 grams IV every 8 hours PLUS vancomycin (dosed to achieve trough 15-20 mcg/mL for serious infections) 3, 4
Ceftazidime PLUS vancomycin remains appropriate for non-severe infections, with consideration for de-escalation once susceptibility results are available, as suggested by the Clinical Microbiology and Infection society 3, 4

For severe difficult-to-treat CRPA, ceftolozane-tazobactam is suggested if active in vitro (conditional recommendation, very low evidence), according to the Clinical Microbiology and Infection society 3, 4
When treating severe CRPA infections with polymyxins, aminoglycosides, or fosfomycin, use two in vitro active drugs, as recommended by the Clinical Microbiology and Infection society 3, 4

Extended use of cephalosporins including ceftazidime should be discouraged due to selective pressure for ESBL-producing Enterobacteriaceae, as suggested by the World Journal of Emergency Surgery 5
De-escalation to monotherapy should occur within 3-5 days once clinical improvement is evident and culture results are available, according to the Praxis Medical Insights 1