From the Guidelines
For suspected sepsis in a hospital setting, the recommended empiric antibiotic regimen should include broad-spectrum coverage with a combination of vancomycin (15-20 mg/kg IV every 8-12 hours) plus either piperacillin-tazobactam (4.5g IV every 6 hours) or a carbapenem such as meropenem (1g IV every 8 hours), as suggested by the Surviving Sepsis Campaign guidelines 1. This combination provides coverage against gram-positive organisms including MRSA (vancomycin), and gram-negative and anaerobic bacteria (piperacillin-tazobactam or meropenem).
- The selection of an optimal empiric antimicrobial regimen in sepsis and septic shock is one of the central determinants of outcome, and survival may decrease as much as fivefold for septic shock treated with an empiric regimen that fails to cover the offending pathogen 1.
- For patients with beta-lactam allergies, aztreonam (2g IV every 8 hours) can replace the beta-lactam component.
- In cases of suspected pseudomonal infections or in immunocompromised patients, consider adding an aminoglycoside like gentamicin (5-7 mg/kg IV daily).
- Antibiotics should be administered within one hour of sepsis recognition, as each hour of delay increases mortality, as recommended by the guidelines 1.
- Blood cultures should be obtained before starting antibiotics but should not delay treatment.
- The initial regimen should be reassessed after 48-72 hours based on culture results and clinical response, with de-escalation to narrower-spectrum antibiotics when possible, as suggested by the guidelines 1.
- Typical treatment duration is 7-10 days, though this may vary based on source control, clinical improvement, and specific pathogens identified.
- Daily assessment for de-escalation of antimicrobial therapy in patients with sepsis and septic shock is recommended, and measurement of procalcitonin levels can be used to support shortening the duration of antimicrobial therapy in sepsis patients 1.
From the FDA Drug Label
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for injection, USP (I.V.) and other antibacterial drugs, Meropenem for injection, USP (I.V.) should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
The selection of antibiotics for in-hospital suspected sepsis should be based on local epidemiology and susceptibility patterns in the absence of culture and susceptibility information.
- Meropenem can be used to treat infections caused by susceptible bacteria, with a recommended dose of 500 mg every 8 hours for skin and skin structure infections and 1 gram every 8 hours for intra-abdominal infections.
- Piperacillin and Tazobactam can be used to treat infections caused by susceptible bacteria, with a recommended dose of 3.375 g every 6 hours for adult patients with indications other than nosocomial pneumonia. It is essential to consider the renal function of the patient when selecting the dosage of these antibiotics, as dosage adjustments may be necessary for patients with renal impairment 2 3.
From the Research
Antibiotics Selection for In-Hospital Suspected Sepsis
- The selection of antibiotics for in-hospital suspected sepsis is crucial to reduce mortality and prevent antimicrobial resistance 4.
- Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens 4.
- Empiric, broad-spectrum therapy is necessary for patients with severe sepsis and/or shock, but this approach should be accompanied by a commitment to de-escalation and antimicrobial stewardship 4.
Recommended Antibiotics
- Meropenem is a widely prescribed β-lactam antibiotic that exhibits maximum pharmacodynamic efficacy when given by continuous infusion 5, 6.
- Combination therapy with an anti-pseudomonal beta-lactam and a fluoroquinolone or an aminoglycoside is recommended for patients with severe pneumonia or septicemia 7.
- Appropriate beta-lactam antibiotics recommended for the treatment of severe CAP, NP, and septicemia include cefepime, imipenem, meropenem, and piperacillin-tazobactam 7.
Administration Methods
- Continuous administration of meropenem may improve clinical outcomes compared to intermittent administration 5, 6.
- However, a randomized clinical trial found that continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28 5.
- A systematic review and meta-analysis found that continuous meropenem infusion was superior to intermittent infusion in terms of mortality, clinical cure rate, and microbiological eradication 6.