When is double gram negative coverage needed in patients with severe infections?

From the Guidelines

Double gram-negative coverage is needed in patients with severe infections who are at high risk for multidrug-resistant (MDR) gram-negative organisms or are critically ill with sepsis or septic shock, as recommended by the most recent guidelines 1.

Key Considerations

• The decision to use double gram-negative coverage should be based on the patient's risk factors, such as healthcare-associated infections, recent antibiotic exposure, known colonization with resistant organisms, immunocompromised status, or healthcare settings with high rates of resistant pathogens.
• The guidelines suggest that patients with high-risk infections, such as those with septic shock or high mortality risk, should receive initial empiric therapy with a dual-pseudomonal regimen plus MRSA coverage, if necessary 1.
• Common double gram-negative regimens include a broad-spectrum beta-lactam (such as piperacillin-tazobactam, meropenem, or cefepime) plus either an aminoglycoside (such as gentamicin or amikacin) or a fluoroquinolone (such as ciprofloxacin) 1.

Recommended Regimens

• For high-risk patients, a dual-pseudomonal regimen should be chosen to provide coverage for Acinetobacter spp. and ESBL-producing Enterobacteriaceae, if these pathogens are prevalent in the ICU where the patient is being treated 1.
• The antipseudomonal β-lactams include imipenem, meropenem, cefepime, piperacillin/tazobactam, ceftazidime, and aztreonam, and should be combined with an aminoglycoside or an antipseudomonal quinolone (ciprofloxacin or levofloxacin) 1.

De-escalation of Therapy

• Once culture and sensitivity results are available, therapy should be de-escalated to the narrowest effective regimen to reduce the risk of further resistance development and minimize adverse effects 1.

Conclusion Not Applicable, as per instructions

Instead, the key points to consider are:

• Double gram-negative coverage is necessary for patients with severe infections who are at high risk for MDR gram-negative organisms or are critically ill with sepsis or septic shock.
• The choice of regimen should be based on the patient's risk factors and the prevalence of resistant pathogens in the ICU.
• De-escalation of therapy is crucial to minimize the risk of resistance development and adverse effects.

From the FDA Drug Label

In patients at high risk for severe infection (including patients with a history of recent bone marrow transplantation, with hypotension at presentation, with an underlying hematologic malignancy, or with severe or prolonged neutropenia), antimicrobial monotherapy may not be appropriate Insufficient data exist to support the efficacy of cefepime monotherapy in such patients [see Clinical Studies (14)].

Double gram negative coverage is needed in patients with severe infections who are at high risk for severe infection, including those with:

• Recent bone marrow transplantation
• Hypotension at presentation
• Underlying hematologic malignancy
• Severe or prolonged neutropenia In these cases, antimicrobial monotherapy may not be appropriate and double gram negative coverage should be considered 2.

From the Research

Double Gram-Negative Coverage

Double gram-negative coverage is typically considered in patients with severe infections, particularly those caused by multidrug-resistant (MDR) gram-negative bacteria. The decision to use double coverage should be based on the severity of the infection, the susceptibility of the causative organism, and the patient's underlying health status.

Indications for Double Coverage

• Patients with septic shock or neutropenia may benefit from combination therapy that includes an aminoglycoside 3
• Infections caused by Pseudomonas aeruginosa, which has a high mortality rate and requires broad-spectrum coverage 3, 4
• Patients with complicated gram-negative infections, such as those with uncontrolled foci of infection or immunocompromised hosts 5

Antibiotic Combinations

• Combination therapy with a β-lactam and an aminoglycoside may be effective for severe gram-negative infections 4
• The use of levofloxacin in combination with piperacillin-tazobactam or cefepime may not provide additional coverage, while gentamicin may provide increased gram-negative coverage 6
• New antimicrobial treatment options, such as β-lactam/β-lactamase inhibitor combinations, eravacycline, plazomicin, and cefiderocol, may be effective for MDR gram-negative infections 7

Limitations of Double Coverage

• Increased drug toxicity, costs, and risk of superinfection with more-resistant bacteria or fungi 3
• Lack of strong evidence to support the routine use of combination antimicrobial therapy for treatment of gram-negative infections 3
• The need for individualized treatment approaches based on the patient's specific infection and health status 4, 5