IDSA Guidelines for Double Gram-Negative Coverage

Specific Indications for Double Gram-Negative Coverage

The Infectious Diseases Society of America (IDSA) recommends double gram-negative coverage primarily for patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) who have risk factors for multidrug-resistant pathogens, particularly Pseudomonas aeruginosa, or who are at high risk for mortality 1
For patients with HAP who have factors increasing the likelihood for Pseudomonas or other gram-negative infection or a high risk for mortality, double coverage with two different classes of antibiotics with activity against P. aeruginosa is recommended 1
For VAP with risk of multidrug-resistant pathogens, treatment should include one β-lactam-based agent with antipseudomonal activity plus one non-β-lactam agent with antipseudomonal activity 2

Prior intravenous antibiotic use within 90 days is a risk factor for requiring double coverage 1, 2
Septic shock at time of VAP is a risk factor for requiring double coverage 2
Acute respiratory distress syndrome (ARDS) preceding VAP is a risk factor for requiring double coverage 2
Five or more days of hospitalization prior to pneumonia onset is a risk factor for requiring double coverage 2
Acute renal replacement therapy prior to VAP onset is a risk factor for requiring double coverage 2

The IDSA recommends antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, meropenem) plus either ciprofloxacin or levofloxacin (750-mg dose) for double coverage 3
Antipseudomonal β-lactam plus an aminoglycoside and azithromycin is another recommended combination for double coverage 3
Antipseudomonal β-lactam plus an aminoglycoside and an antipneumococcal fluoroquinolone is also recommended for double coverage 3

For ICU patients with community-acquired pneumonia (CAP), combination therapy is recommended with a β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin or a fluoroquinolone 3
For patients with suspected Pseudomonas infection, an antipneumococcal, antipseudomonal β-lactam plus either ciprofloxacin/levofloxacin or an aminoglycoside plus azithromycin is recommended 3
Double gram-negative coverage is generally not recommended for community-acquired intra-abdominal infections of mild-to-moderate severity 4, 5
For health care-associated intra-abdominal infections, multidrug regimens that include agents with expanded spectra of activity against gram-negative aerobic and facultative bacilli may be needed 5

Aminoglycosides should not be used as the sole antipseudomonal agent due to lower clinical response rates 1, 2
Empiric therapy should be tailored when culture and susceptibility reports become available to reduce the number and spectra of administered agents 5
The decision to use double coverage should consider local resistance patterns, with the 10% threshold for deciding whether to prescribe one antipseudomonal agent or two 2