How do you monitor response to antibiotics for Sepsis (Systemic Inflammatory Response Syndrome)?

From the Guidelines

Monitoring response to antibiotics for Sepsis (Systemic Inflammatory Response Syndrome) should be done daily, with consideration of de-escalation of antimicrobial therapy and measurement of procalcitonin levels to support shortening the duration of antimicrobial therapy.

Key Considerations

• Daily assessment for de-escalation of antimicrobial therapy is recommended in patients with sepsis and septic shock 1.
• Procalcitonin levels can be used to support shortening the duration of antimicrobial therapy in sepsis patients, with levels less than 0.5 µg/L or a decrease of greater than or equal to 80% from peak levels guiding antibiotic discontinuation once patients stabilize 1.
• Antimicrobial treatment duration of 7 to 10 days is adequate for most serious infections associated with sepsis and septic shock, but longer courses may be necessary in patients with slow clinical response, undrainable foci of infection, or immunologic deficiencies 1.
• Combination therapy should not be administered for more than 3 to 5 days, and de-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known 1.

Biomarkers

• Procalcitonin (PCT) and C-reactive protein (CRP) can provide supportive and complementary information to clinical assessment, but decisions on initiating, altering, or discontinuing antimicrobial therapy should not be made solely based on changes in PCT or CRP levels 1.
• PCT has a higher diagnostic accuracy and specificity than CRP for diagnosis of sepsis in adult patients, but further studies are needed to define the optimal cutoff points for PCT and CRP 1.

From the Research

Monitoring Response to Antibiotics for Sepsis

To monitor the response to antibiotics for sepsis, also known as Systemic Inflammatory Response Syndrome, several strategies can be employed:

• Clinical signs and biomarkers: Diagnosis of sepsis should be based on clinical signs, and clinicians should use biomarkers that are not only sensitive and specific but also cost-effective 2.
• Biomarker measurement: Biomarkers like white cell blood count, C-reactive protein (CRP), or procalcitonin (PCT) can be useful in sepsis recognition, but their accuracy may be limited in post-surgical patients 2.
• Therapeutic drug monitoring: Extended or continuous infusion of beta-lactams and therapeutic drug monitoring can help achieve therapeutic levels of antimicrobials 3, 4.
• Regular treatment review: Duration and adequacy of treatment must be reviewed at regular intervals to allow effective de-escalation and administration of short courses of antimicrobials for most patients 3, 4.
• Antimicrobial stewardship: Antimicrobial stewardship frameworks, leadership, and focus on the optimal duration of treatments, de-escalation, and novel diagnostic stewardship approaches can help improve patients' quality of care 3, 4.

Adjusting Antibiotic Treatment

Adjusting antibiotic treatment based on patient response and pathogen patterns of resistance is crucial:

• Individualized dosing: The principle of individualized dosing should replace the principle of standard dosing, taking into account pharmacokinetics/pharmacodynamics and the presence of renal or liver dysfunction 3, 4.
• Loading dose: A loading dose, an initial higher dose of antimicrobials, should be administered to all patients, regardless of the presence of organ dysfunction 3, 4.
• De-escalation: De-escalation and shortened courses of antimicrobials should be considered for most patients, except in justified circumstances 3, 4.

Reducing Time-to-Antibiotics

Reducing time-to-antibiotics is essential in sepsis treatment:

• Simulation study: A simulation study found that a 50% reduction in time-to-antibiotics for sepsis was associated with a median of 1 to 180 additional antibiotic-treated patients and zero to seven additional adverse events per death averted from sepsis 5.
• Clinical judgment: Clinicians must use their judgment to balance the benefits of rapid antibiotic administration with the potential risks of unnecessary antibiotic use and adverse events 5.