What is a good empiric therapy for sepsis caused by a negative Gram (Gram-negative) bacillus?

From the Guidelines

For sepsis caused by gram-negative bacilli, the recommended empiric therapy is a broad-spectrum beta-lactam antibiotic such as piperacillin-tazobactam (4.5g IV every 6 hours), meropenem (1g IV every 8 hours), or cefepime (2g IV every 8 hours) as suggested by the Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 1.

Key Considerations

• The choice of empiric antimicrobial therapy depends on complex issues related to the patient’s history, clinical status, and local epidemiologic factors, including the anatomic site of infection, prevalent pathogens, and resistance patterns 1.
• In critically ill patients or those with risk factors for resistant organisms, combination therapy with an aminoglycoside like gentamicin (5-7mg/kg IV once daily) or amikacin (15-20mg/kg IV once daily) may be added for the first 48-72 hours 1.
• For patients with beta-lactam allergies, aztreonam (2g IV every 8 hours) plus a fluoroquinolone such as ciprofloxacin (400mg IV every 8-12 hours) can be used 1.

Treatment Duration and Adjustments

• Treatment duration typically ranges from 7-14 days depending on clinical response, source control, and patient factors 1.
• Dosing adjustments are necessary for patients with renal impairment 1.

Rationale

• Early administration of empiric antimicrobial therapy within the first hour of recognizing sepsis is crucial for improving outcomes 1.
• Therapy should be reassessed after 48-72 hours based on culture results to allow for de-escalation to more targeted therapy 1.

From the FDA Drug Label

FORTAZ may be used alone in cases of confirmed or suspected sepsis. Ceftazidime has been used successfully in clinical trials as empiric therapy in cases where various concomitant therapies with other antibacterial drugs have been used Colistimethate for Injection, USP may be used to initiate therapy in serious infections that are suspected to be due to gram-negative organisms and in the treatment of infections due to susceptible gram-negative pathogenic bacilli Gentamicin has been shown to be active against most of the following bacteria, both in vitro and in clinical infections: Gram-Negative Bacteria Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Proteus species, Serratia species, Pseudomonas aeruginosa

Good empiric therapy options for sepsis caused by negative gram bacillus include:

• Ceftazidime 2
• Colistin 3
• Gentamicin 4 These antibiotics have been shown to be effective against various gram-negative bacteria, including those that can cause sepsis. However, it is essential to note that the choice of empiric therapy should be based on local epidemiology and susceptibility patterns, and treatment should be adjusted according to culture and susceptibility results when available.

From the Research

Empiric Therapy for Sepsis due to Gram-Negative Bacteria

• The optimal approach for empirical antibiotic therapy in patients with severe sepsis and septic shock remains controversial 5.
• Empiric combination antibiotic therapy directed against Gram-negative bacteria, such as beta-lactam plus aminoglycoside or fluoroquinolone, is associated with improved outcomes 5.
• The addition of an aminoglycoside to a carbapenem can increase appropriate initial therapy, and aminoglycosides offer broader coverage than fluoroquinolones as combination agents 5.

Antibiotic Combinations for Gram-Negative Coverage

• Combination therapy with piperacillin-tazobactam and gentamicin provides nearly equivalent coverage to meropenem and gentamicin 6.
• Levofloxacin does not increase coverage when used in combination with cefepime and meropenem, but provides an 8% increase in coverage when used in combination with piperacillin-tazobactam 6.
• Gentamicin provides increased gram-negative coverage when compared with levofloxacin 6.

Predicting Resistance to Antibiotics

• Prior antibiotic use, nursing home residence, and transfer from an outside hospital are associated with resistance to piperacillin-tazobactam, cefepime, and meropenem 7.
• Resistance to meropenem is specifically linked with infection attributed to Pseudomonas or Acinetobacter spp. 7.
• Clinical decision trees can be used to distinguish patients at low, intermediate, or high risk of resistance to piperacillin-tazobactam, cefepime, and meropenem 7.

Appropriate Empirical Agents for Sepsis

• Piperacillin-tazobactam is recommended as an empirical therapy for hospital-acquired sepsis of unknown origin in Australia 8.
• There is a paucity of evidence available for piperacillin-tazobactam use in sepsis of unclear origin, and an urgent need for an Australian audit of its use in patients with sepsis of unknown origin 8.