What are the appropriate antibiotics for treating sepsis (Systemic Inflammatory Response Syndrome)?

From the Guidelines

Empiric antibiotic therapy for sepsis should be initiated within one hour of recognition, using broad-spectrum antibiotics that cover likely pathogens based on the suspected source of infection. For community-acquired sepsis, a reasonable initial regimen includes a combination of piperacillin-tazobactam (4.5g IV every 6 hours) or cefepime (2g IV every 8 hours) plus vancomycin (15-20 mg/kg IV loading dose, then 15-20 mg/kg every 8-12 hours, adjusted for renal function) 1. For healthcare-associated sepsis or if resistant organisms are suspected, consider adding an aminoglycoside like gentamicin (5-7 mg/kg IV daily) or using meropenem (1g IV every 8 hours) instead of piperacillin-tazobactam 1. Some key points to consider when selecting empiric antibiotic therapy for sepsis include:

• The suspected source of infection and likely pathogens involved
• The patient's individual risk factors for resistant organisms, such as recent antibiotic use or hospitalization
• The local epidemiology and resistance patterns of common pathogens
• The severity of the infection and the patient's clinical condition Therapy should be tailored once culture results are available, typically within 48-72 hours 1. The total duration of antibiotics is generally 7-10 days, depending on clinical response, source control, and the specific infection 1. Early administration of appropriate antibiotics is critical as each hour of delay in sepsis increases mortality by approximately 7-8% 1. Reassess therapy daily to de-escalate when possible to reduce antibiotic resistance, toxicity, and cost while maintaining effective treatment 1.

From the FDA Drug Label

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 piperacillin-tazobactam antibiotic is used for the treatment of various infections, including sepsis. However, the exact dosage for sepsis is not explicitly stated in the provided drug labels.

• The usual total daily dosage of piperacillin and tazobactam for adult patients with indications other than nosocomial pneumonia is 3.375 grams every six hours [totaling 13.5 grams (12.0 grams piperacillin and 1.5 grams tazobactam)], to be administered by intravenous infusion over 30 minutes 2.
• The recommended duration of piperacillin and tazobactam treatment is from 7 to 10 days for indications other than nosocomial pneumonia, and 7 to 14 days for nosocomial pneumonia 2. It is essential to consult the latest clinical guidelines and seek advice from a healthcare professional for the appropriate treatment of sepsis with piperacillin-tazobactam.

From the Research

Sepsis Antibiotics

• Sepsis is a medical emergency that requires immediate treatment with broad-spectrum antimicrobials within the first hour of diagnosis 3
• The choice of antibiotic should be based on the likely pathogens involved and the patient's previous risk of multidrug-resistant (MDR) pathogens 3
• Individualized dosing should be used, taking into account pharmacokinetics (PK)/pharmacodynamics (PD) and the presence of renal/liver dysfunction 3
• Extended or continuous infusion of beta-lactams and therapeutic drug monitoring (TDM) can help achieve therapeutic levels of antimicrobials 3

Comparison of Antibiotics

• Meropenem and piperacillin-tazobactam are two commonly used antibiotics for treating sepsis and septic shock 4, 5
• A study comparing meropenem and piperacillin-tazobactam found no significant difference in the duration of stay in ICU, but meropenem had a lower mortality rate on ventilator-free days, vasopressor-free days, and hospital-free days 4
• Another study found that meropenem-vaborbactam was non-inferior to piperacillin-tazobactam in treating complicated urinary tract infections, including acute pyelonephritis 6

Antimicrobial Stewardship

• Antimicrobial stewardship is essential to ensure successful outcomes and reduce adverse antibiotic effects, as well as prevent drug resistance 3, 7
• Biomarkers such as procalcitonin can provide decision support for antibiotic use and guide duration of antibiotic therapy 7
• De-escalation and shortened courses of antimicrobials should be considered for most patients, except in some justified circumstances 3, 7