What are the empiric antibiotics for a blood culture positive for Gram-negative bacilli?

From the Guidelines

For blood cultures showing gram-negative bacilli, I recommend starting empiric therapy with a broad-spectrum antibiotic such as piperacillin-tazobactam 4.5g IV every 6 hours, cefepime 2g IV every 8 hours, or meropenem 1g IV every 8 hours, as these regimens have been shown to be effective against a wide range of gram-negative bacilli, including Pseudomonas aeruginosa 1.

Key Considerations

• The choice of empiric antibiotic therapy should be based on the local epidemiology of resistant organisms and the patient's individual risk factors, such as recent antibiotic use or hospitalization 1.
• In critically ill patients or those with risk factors for resistant organisms, consider adding an aminoglycoside like gentamicin 5-7mg/kg IV daily or amikacin 15-20mg/kg IV daily to the initial empiric regimen, as this may provide synergistic effects against some gram-negative bacilli 1.
• For suspected Pseudomonas infections, combination therapy may be beneficial initially, but the use of aminoglycosides should be carefully considered due to the potential for nephrotoxicity and ototoxicity 1.

Adjusting Therapy

• Adjust dosing for patients with renal impairment, as this can significantly impact the efficacy and safety of the antibiotic regimen 1.
• Once susceptibility results are available (typically within 48-72 hours), narrow therapy to the most appropriate agent, as this can help reduce the risk of adverse effects and promote more effective treatment 1.
• Total treatment duration depends on the source of infection, typically 7-14 days, but may need to be extended in cases of complicated infections or immunocompromised patients 1.

From the FDA Drug Label

Gentamicin injection may be considered as initial therapy in suspected or confirmed gram-negative infections, and therapy may be instituted before obtaining results of susceptibility testing Gentamicin Injection, USP is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella-Enterobacter-Serratia species, Citrobacter species Ceftazidime is effective against Gram-negative bacteria, including Pseudomonas aeruginosa, Escherichia coli, Klebsiella species, and Enterobacter species

Empiric Antibiotic Options for Blood Culture with Gram-Negative Bacilli:

• Gentamicin: may be considered as initial therapy in suspected or confirmed gram-negative infections
• Ceftazidime: effective against Gram-negative bacteria, including Pseudomonas aeruginosa, Escherichia coli, Klebsiella species, and Enterobacter species Key Considerations:
• Therapy should be instituted before obtaining results of susceptibility testing
• Gentamicin and ceftazidime have different spectrums of activity and resistance patterns
• The decision to continue therapy with these drugs should be based on the results of susceptibility tests, the severity of the infection, and important additional concepts contained in the BOXED WARNINGS 2, 3

From the Research

Empiric Antibiotics for Blood Culture with Gram-Negative Bacilli

• The choice of empiric antibiotics for blood culture with gram-negative bacilli depends on various factors, including the patient's risk factors, clinical presentation, and local antimicrobial resistance patterns 4, 5.
• Novel antimicrobial agents, such as new β-lactam/β-lactamase inhibitor combinations and cefiderocol, have been introduced for treating multidrug-resistant gram-negative bloodstream infections 4.
• The use of these new antibiotics is associated with improved outcomes in critically ill patients with multidrug-resistant gram-negative bloodstream infections, although further randomized clinical trials are necessary to determine the most effective antimicrobial therapies 4.
• Empirical therapy with novel agents should be considered in patients with risk factors for difficult-to-treat gram-negative infections and severe clinical presentation of acute infection 5.
• The choice of empiric antibiotics can be guided by clinical decision trees that take into account factors such as prior antibiotic use, nursing home residence, and transfer from an outside hospital 6.

Antibiotic Options

• Cefepime has been shown to have in vitro activity against a wide range of gram-negative bacilli, including those with extended-spectrum beta-lactamase (ESBL) production 7.
• Piperacillin-tazobactam, cefepime, and meropenem are commonly used antibiotics for treating gram-negative bloodstream infections, although resistance rates vary depending on the local epidemiology 6, 7.
• Combinations of beta-lactam antibiotics may be synergistic, but also have the potential for antagonism, and should be evaluated closely before clinical use 8.

Treatment Duration and De-escalation

• Empirical treatment with novel agents should preferably be continued only for a few hours, until de-escalation, modification, or confirmation is made possible by the results of rapid diagnostic tests 5.
• Prompt diagnosis and identification of resistance patterns are crucial for initiating effective antibiotic therapy and minimizing the risk of antimicrobial resistance 4, 5.