What is good empiric therapy for sepsis due to negative Gram (Gram-negative) bacteria?

From the Guidelines

For sepsis with suspected gram-negative infection, empiric therapy should include a broad-spectrum beta-lactam antibiotic such as piperacillin-tazobactam (4.5g IV every 6 hours), cefepime (2g IV every 8 hours), or meropenem (1g IV every 8 hours) 1. In critically ill patients or those with risk factors for resistant organisms, consider adding an aminoglycoside like gentamicin (5-7mg/kg IV once daily) or amikakin (15-20mg/kg IV once daily), or a fluoroquinolone such as ciprofloxacin (400mg IV every 8-12 hours) 1. Duration typically ranges from 7-10 days, guided by clinical response and culture results 1. Adjust dosing for renal impairment 1. Source control is essential, so identify and address any infectious focus (drain abscesses, remove infected devices) 1. Monitor renal function when using aminoglycosides 1. These regimens provide coverage against common gram-negative pathogens including Pseudomonas, Klebsiella, and E. coli, while the beta-lactams also offer some gram-positive coverage 1. Once culture results return, narrow therapy to the most appropriate agent to reduce resistance development and minimize adverse effects 1.

Some key points to consider:

• The choice of empiric antibiotic regimens in patients with sepsis should be based on the clinical condition of the patients, the individual risk for infection by resistant pathogens, and the local resistance epidemiology 1.
• In patients with healthcare-associated infections, antibiotic regimens with broader spectra of activity are preferred 1.
• The use of carbapenems should be limited to preserve activity of this class of antibiotics due to the concern of emerging carbapenem-resistance 1.
• New antibiotics such as ceftolozane/tazobactam and ceftazidime/avibactam have been approved for treatment of complicated intra-abdominal infections, including infection by ESBL-producing Enterobacteriaceae and P. aeruginosa 1.

Overall, the management of sepsis with suspected gram-negative infection requires a comprehensive approach that includes prompt empiric antibiotic therapy, source control, and adjustment of therapy based on culture and susceptibility results.

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 Bacterial Septicemia caused by Pseudomonas aeruginosa, Klebsiella spp., Haemophilus influenzae, Escherichia coli, Serratia spp., Streptococcus pneumoniae, and Staphylococcus aureus (methicillin-susceptible strains).

Good empiric therapy for sepsis caused by negative gram bacteria includes Ceftazidime.

• Key points:
  • Ceftazidime can be used alone in cases of confirmed or suspected sepsis.
  • It has been used successfully in clinical trials as empiric therapy.
  • It is effective against various negative gram bacteria, including Pseudomonas aeruginosa, Klebsiella spp., Haemophilus influenzae, and Escherichia coli. 2

From the Research

Empiric Therapy for Sepsis due to Gram-Negative Bacteria

• The initial antimicrobial management of sepsis should include broad-spectrum therapy to cover both gram-positive and gram-negative causative micro-organisms 3, 4.
• For patients with sepsis due to gram-negative bacteria, empiric combination antibiotic therapy may be associated with improved outcomes compared to monotherapy 5.
• The choice of empiric antimicrobials should take into account patient factors, common local pathogens, hospital antibiograms, and resistance patterns, as well as the suspected source of infection 4.

Specific Antibiotic Options

• Meropenem and imipenem/cilastatin are beta-lactam antibiotics with broad-spectrum activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa 6.
• Newer antibiotic combinations, such as ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam, and meropenem/vaborbactam, have shown potent activity against Pseudomonas aeruginosa isolates, including those with multidrug resistance 7.
• These newer combinations may be useful options for empiric therapy in patients with sepsis due to gram-negative bacteria, particularly in cases where resistance is a concern 7.

Key Considerations

• Early administration of broad-spectrum antimicrobial drugs is crucial in the treatment of sepsis and septic shock 4.
• Antimicrobial agent therapy should be de-escalated as soon as possible to minimize the risk of resistance and adverse effects 3, 4.
• Biomarkers, such as procalcitonin, may be useful in guiding antibiotic use and duration of therapy 3.