What is a good empiric therapy for sepsis caused by a negative Gram bacillus, such as Piperacillin-Tazobactam (Pip-Tazo) with Ciprofloxacin (Cipro)?

From the Guidelines

For sepsis due to gram-negative bacilli, piperacillin-tazobactam (Pip-tazo) plus ciprofloxacin is an acceptable empiric therapy option, though monotherapy with Pip-tazo alone is often sufficient, as recommended by the Surviving Sepsis Campaign guidelines 1. Pip-tazo is typically dosed at 4.5g IV every 6-8 hours (adjusted for renal function), while ciprofloxacin is given at 400mg IV every 8-12 hours. The combination provides broad coverage against most gram-negative pathogens, including Pseudomonas aeruginosa. However, adding ciprofloxacin to Pip-tazo is generally reserved for patients with severe sepsis, suspected resistant organisms, or immunocompromised status. Some key points to consider when selecting empiric therapy for sepsis due to gram-negative bacilli include:

• The anatomic site of infection and local pathogen prevalence
• The presence of underlying diseases, chronic organ failures, and immunosuppression
• Recent antimicrobial use and potential for multidrug-resistant pathogens
• The need for broad-spectrum coverage and potential for de-escalation of therapy once culture and sensitivity results are available Alternative regimens include carbapenems (meropenem 1g IV q8h) or cefepime (2g IV q8h) with or without an aminoglycoside. Once culture and sensitivity results are available (usually within 48-72 hours), therapy should be narrowed to the most appropriate agent, as recommended by the guidelines 1. The duration of therapy typically ranges from 7-14 days depending on the source, clinical response, and pathogen, with longer courses potentially needed for patients with slow clinical response, undrainable foci of infection, or immunologic deficiencies 1. This approach balances the need for adequate empiric coverage while minimizing the risk of promoting antimicrobial resistance. Optimizing antimicrobial dosing strategies is also crucial, with considerations including the use of loading doses, extended infusions, and therapeutic drug monitoring to ensure adequate plasma concentrations and minimize toxicity 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 CLINICAL STUDIES EMPIRICAL THERAPY IN ADULT FEBRILE NEUTROPENIC PATIENTS The safety and efficacy of ciprofloxacin, 400 mg I.V. q 8h, in combination with piperacillin sodium, 50 mg/kg I.V. q 4h, for the empirical therapy of febrile neutropenic patients were studied in one large pivotal multicenter, randomized trial

Empiric Therapy for Sepsis:

• Pip-tazo with cipro is not directly mentioned in the provided drug labels as a recommended combination for empiric therapy in sepsis due to negative gram bacillus.
• However, ceftazidime is indicated for the treatment of bacterial septicemia caused by various organisms, including Pseudomonas aeruginosa, Klebsiella spp., Haemophilus influenzae, Escherichia coli, Serratia spp., Streptococcus pneumoniae, and Staphylococcus aureus (methicillin-susceptible strains) 2.
• Ciprofloxacin has been studied in combination with piperacillin sodium for the empirical therapy of febrile neutropenic patients, but its use in sepsis due to negative gram bacillus is not explicitly stated in the provided label 3. It is essential to consider local epidemiology and susceptibility patterns when selecting empiric therapy, and to use antibacterial drugs only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.

From the Research

Empiric Therapy for Sepsis due to Gram-Negative Bacteria

• The use of piperacillin-tazobactam (pip-tazo) in combination with ciprofloxacin (cipro) as empiric therapy for sepsis due to gram-negative bacteria has been studied in various research papers 4, 5, 6.
• According to a study published in the American Journal of Infection Control, piperacillin-tazobactam was effective against 84% of gram-negative organisms, and the addition of gentamicin provided an additional 13% increase in coverage 4.
• Another study published in Antimicrobial Agents and Chemotherapy found that the use of combination antibiotic therapy, including a beta-lactam and an aminoglycoside or fluoroquinolone, was associated with improved outcomes in patients with severe sepsis and septic shock due to gram-negative bacteria 5.
• However, the use of ciprofloxacin as part of the empiric therapy regimen may not be the best choice, as studies have shown that gram-negative organisms are increasingly resistant to levofloxacin, a fluoroquinolone similar to ciprofloxacin 4, 6.
• A study published in Clinical Infectious Diseases found that prior antibiotic use, nursing home residence, and transfer from an outside hospital were associated with resistance to piperacillin-tazobactam, cefepime, and meropenem, and that clinical decision trees can be used to distinguish patients at low, intermediate, or high risk of resistance to these antibiotics 6.

Alternative Empiric Therapy Options

• The use of gentamicin in combination with piperacillin-tazobactam may be a more effective empiric therapy option for sepsis due to gram-negative bacteria, as it provides broader coverage and is associated with improved outcomes 4, 5.
• Other studies have suggested that the use of meropenem, a carbapenem antibiotic, may also be effective as part of an empiric therapy regimen for sepsis due to gram-negative bacteria 5, 6.
• The choice of empiric therapy should be guided by the patient's individual risk factors for resistance, as well as the local epidemiology of antibiotic resistance 7, 8, 6.