Antimicrobial therapy:

Intravenous antimicrobials must be initiated as soon as possible after recognition for both sepsis and septic shock. In absence of a definitive diagnosis at presentation, which is common (in the Golden hour), empiric broad-spectrum therapy should be initiated to cover all likely pathogens (including bacterial, potentially fungal or viral coverage).  Selection of an optimal empiric antimicrobial regimen in sepsis and septic shock is one of the central determinants of outcome. Various factors which must be taken into consideration for deciding the choice of empiric antimicrobial therapy are shown in box 2.

Box 2: Factors determining the selection of antimicrobials for sepsis and septic shock
  1. Clinical syndrome/site of infection
  2. Prevalent pathogens and their resistance patterns
  3. Severity of illness
  4. Age and concomitant underlying diseases, chronic organ failures, medications, indwelling devices
  5. Immunosuppression or other form of immunocompromise
  6. Recent infections, intake of antimicrobials within the previous 3 months

Refer to the appropriate sections in this guideline for the empirical antibiotic therapy for a different site of infection. The table below gives empirical therapy for sepsis when the source is unclear.

Antimicrobial choice for disease conditions
Diagnosis Suggested regimens Remarks

 

 Preferred Alternative  
Sepsis or septic shock with focus unclear   Rule out common tropical infections (chapter 1)   Refer to appropriate sections for empirical antibiotic therapy for different sites of infection Imipenem-Cilastatin
+/-
Amikacin

+/-
Vancomycin Teicoplanin +/- doxycycline
+/- Colistin or polymyxin B
*If risk factors for candida add an echinocandin
(Caspofungin or micafungin or anidulafungin)		 Meropenem
or
Cefoperazone –Sulbactam

+/-
Amikacin +/-
Vancomycin or
Teicoplanin
  • Septic shock patient must receive empiric combination therapy with at least two antibiotics of different antimicrobial classes.
  • Add MRSA or CR-GNB coverage or antifungals in patients with appropriate risk factors.
  • Avoid piperacillin-tazobactam in septic shock till bacteremia with cephalosporin resistant organisms is excluded, as mortality increases (MERINO trial)6
  • De-escalation of antimicrobials should be considered daily and at the earliest stage when the clinical situation permits/ once culture susceptibility reports are available**
  • Treatment duration of 7 to 10 days is adequate for most cases. 
  • Longer courses appropriate in slow clinical response, undrainable foci of infection, bacteremia with S. aureus, some fungal and viral infections, or immunologic deficiencies.
  • Measurement of procalcitonin levels can be used to support shortening the duration of antimicrobial therapy.

*Risk factors for invasive Candida infections include immunocompromised status (neutropenia, chemotherapy, transplant, diabetes mellitus, chronic liver failure, chronic renal failure), prolonged invasive vascular devices (hemodialysis catheters, central venous catheters), total parenteral nutrition, necrotizing pancreatitis, recent major surgery (particularly abdominal), prolonged administration of broad-spectrum antibiotics, prolonged hospital/ICU admission, recent fungal infection, and multisite colonization. Triazoles are acceptable in hemodynamically stable, less ill patients who have not had previous triazole exposure and are not known to be colonized with azole-resistant species.

**If the infection is subsequently proven not to exist, then antimicrobials should be discontinued. De-escalation includes discontinuation of combination therapy within the first few days in response to clinical improvement and/or evidence of infection resolution.