Recommendation | Strength | Quality of evidence |
---|---|---|
I Causative bacterial pathogens in sepsis | ||
 Which patients are at risk for sepsis due to third-generation cephalosporin-resistant Enterobacterales or P. aeruginosa in the Netherlands? | ||
  1. We recommend empirical therapy against 3GCR-E in patients with sepsis and prior (1 year) proven infection or colonization with 3GCR-E | Strong | Very low |
  2. We suggest that clinicians take into account the risk of 3GCR-E involvement in sepsis on an individual patient basis to decide if empirical antibacterial therapy against 3GCR-E is appropriate Factors to guide this decision include local prevalence of 3GCR-E, if the infection is hospital-acquired/health-care associated versus community-acquired, prior (2 months) broad-spectrum antibiotic use, concurrent use of SDD, prior (3 months) travel to a highly endemic country (see https://resistancemap.cddep.org/) and prior (2 months) hospitalization abroad | Weak | Very low |
  3. We recommend empirical therapy against P. aeruginosa in patients with sepsis and prior (1 year) infection or colonization with P. aeruginosa | Strong | Very low |
II Empirical antibacterial therapy in sepsis | ||
 What is the importance of appropriate empirical therapy in patients with sepsis? | ||
  4. We recommend empirical broad-spectrum antibacterial therapy for patients presenting with sepsis to cover all pathogenic bacteria that are likely to be involved | Strong | Moderate |
  5. We recommend to take into account prior (1 year) resistance in relevant clinical and screenings cultures in the choice of empirical sepsis therapy | Strong | Very low |
  6. We recommend that empirical antibacterial therapy is guided by the local distribution of pathogens associated with sepsis and their antimicrobial susceptibilities | Strong | Very low |
  7. We suggest empirical antibacterial therapy for patients presenting with sepsis to cover HRMO when these are likely to be involved | Weak | Very low |
  8. We suggest empirical antibacterial therapy covering anaerobic bacteria for patients presenting with sepsis and intra-abdominal infections of the lower intestinal tract or necrotizing soft tissue infections | Weak | Very low |
  9. We generally suggest against routine empirical treatment of anaerobic bacteria in patients presenting with sepsis due to aspiration pneumonia, unless empyema or a lung abscess is suspected | Weak | Very low |
  10. We generally recommend against routine empirical treatment of enterococci in patients presenting with sepsis | Strong | Moderate |
  11. We suggest that anti-enterococcal therapy could be considered in individual patients with sepsis, e.g., those who have a high likelihood of enterococcal involvement based on recent relevant cultures and those with recent complicated intra-abdominal surgery or a suspected CVC infection and substantial exposure to broad spectrum antibiotics | Weak | Very low |
 What is the effect of double active empirical antibacterial therapy compared to monotherapy in patients with sepsis? | ||
  12. We recommend against routine double active empirical antibacterial therapya for patients with sepsis or septic shock | Strong | Moderate |
  13. We suggest that double active therapy is not routinely used as definite therapy for patients with sepsis due to P. aeruginosa infection | Weak | Very low |
  14. We suggest that double active therapy is not routinely used as definite therapy for patients with sepsis due to S. aureus infection not associated to prosthetic material | Weak | Moderate |
 What is the optimal choice of empirical therapy in patients with sepsis in the Netherlands? | ||
  Antibacterial therapy in patients with sepsis in general | ||
   15. In patients with sepsis, we generally recommend using a beta-lactam antibiotic covering the most likely involved pathogens | Strong | Moderate |
   16. In patients with sepsis in general / with no obvious source of infection, we suggest a 3rd generation cephalosporin (3GC). Alternative empirical treatment strategies are listed in Additional file 1: Table S1 | Weak | Low |
   17. In patients with sepsis due to HAP or VAP, we suggest that there are equivalent empirical treatment strategies, listed in Additional file 1: Table S1 | Weak | Low |
   18. In patients with sepsis due to cholangitis, we suggest a 3GC. Alternative empirical treatment strategies are listed in Additional file 1: Table S1 | Weak | Low |
   19. In patients with sepsis due to intra-abdominal infection, we suggest a combination of a 3GC with metronidazole Alternative empirical treatment strategies are listed in Additional file 1: Table S1 | Weak | Low |
   20. In patients with sepsis and a suspected CVC infectionb, we recommend prompt removal of the line | Strong | GPS |
   21. In patients with sepsis and suspected CVC infection, we suggest empirical treatment with a 3GCc with gentamicin or high dose ciprofloxacin Alternative treatment strategies are listed in Additional file 1: Table S1 | Weak | GPS |
   22. For the empirical treatment of sepsis due to UTI, CAP and SSSI’s, we refer to other guidelines [67, 109, 110, 116] |  |  |
  Antibacterial therapy in patients with sepsis and increased risk of involvement of 3GCR-E | ||
   23. In patients with sepsis and high risk of involvement of 3GCR-E based on prior (1 year) infection/colonization, we recommend meropenem or imipenem as empirical antibacterial therapy Alternative strategies are listed in Additional file 1: Table S2 | Strong | Moderate |
   24. In patients with sepsis and increased risk of involvement of 3GCR-E but no prior (1 year) infection/colonization, we suggest that a carbapenem-sparing strategy Additional file 1: Table S2 is acceptable | Weak | Very low |
   25. We cannot provide a recommendation for or against empirical or definite treatment with piperacillin-tazobactam in patients with sepsis due to chromosomal AmpC-producing Enterobacterales (such as Enterobacter, Serratia, Citrobacter, Providencia and Morganella spp) | – | – |
   26. In patients with sepsis due to ESBL-producing Enterobacterales, we recommend against piperacillin-tazobactam as definite antibacterial therapy regardless of the in vitro susceptibility | Strong | Moderate |
Antibacterial therapy in patients with sepsis and increased risk of involvement of Staphylococcus aureus | Â | Â |
   27. There is insufficient evidence to recommend against empirical use of other beta-lactam antibiotics than flucloxacillin or cefazolin in patients with sepsis in which S. aureus is a likely pathogen | - | - |
   28. For definite therapy of patients with sepsis due to S. aureus, we refer to the Dutch guideline on S. aureus bacteraemia [117] |  |  |
What is the optimal empirical antibacterial therapy of sepsis in patients with a penicillin allergy? | Â | Â |
   29. In patients with sepsis and a reported penicillin allergy, we recommend to obtain information (i.e., medical history and skin test results) about the presumed allergy if possible | Strong | GPS |
   30. In patients with sepsis and a reported penicillin allergy but in whom the allergy is very unlikely, we suggest that penicillins can be used if needed (see Table 3) | Weak | Very low |
   31. In patients with sepsis and a reported penicillin allergy that was proven, possible or unspecified, we suggest to avoid penicillins during the primary sepsis treatment and to choose alternative beta-lactams (cephalosporins, carbapenems) | Weak | Very low |
   32. In patients with sepsis and an unspecified or possible immediate type penicillin allergy, we suggest to plan penicillin allergy testing and/or a controlled penicillin challenge when the patient has recovered from sepsis | Weak | Very low |
III Timing and duration of antibacterial therapy in sepsis | ||
 What is the optimal timing of empirical antibacterial therapy in patients with sepsis? | ||
  33. In patients with sepsis or septic shock, we recommend that the administration of antibacterial treatment should be initiated promptly with health care systems working to reduce that time to as short a duration as feasible | Strong | Low |
 What is the optimal duration of antibacterial treatment for sepsis? | ||
  34. For treatment duration of sepsis due to CAP, UTI, SSSI and of sepsis due to S. aureus infection, we refer to other guidelines [67, 109, 110, 116,117,118] |  |  |
  35. We recommend source control interventions when possible to support antibacterial treatment in patients with sepsis | Strong | Low |
  36. We recommend that a 4-day course of antibacterial treatment is appropriate for patients with sepsis due to intra-abdominal infections following effective source control and with favourable clinical response | Strong | Moderate |
  37. We suggest that shorter courses of antibacterial treatment (up to 3 days) are appropriate in patients with sepsis and cholangitis following adequate drainage of the biliary tree | Weak | Very low |
  38. We recommend that an antibacterial treatment duration of 7 days is adequate for most patients with sepsis due to VAP | Strong | Moderate |
  39. We suggest that an antibacterial treatment duration of 7 days is adequate for most patients with sepsis due to HAP | Weak | Very low |
  40. We suggest that an antibacterial treatment duration of 7 days at maximum is adequate for most patients with sepsis due to suspected CVC infection with gram-negative pathogens following removal of the CVC and with favourable clinical response | Weak | Very low |
  41. We suggest that an antibacterial treatment duration of 0 to 7 days is adequate for most patients with sepsis due to suspected CVC infection with CNS or enterococci following removal of the CVC and with favourable clinical response | Weak | GPS |
  42. We suggest that an antibacterial treatment duration of 7 days is adequate for sepsis and septic shock without a clear focus in most patients with favourable clinical response | Weak | Low |
  43. We recommend daily assessment for the need of antibacterial therapy in patients with sepsis and to discontinue therapy when during follow-up there is lack of clinical or microbiological evidence of infection | Strong | GPS |
  44. We suggest that procalcitonin levels are used to support shortening the duration of antibacterial therapy in patients with sepsis if optimal duration of antibiotic therapy is unclear | Weak | Moderate |
  45. We recommend to consider antibiotic de-escalation (resulting in smaller spectrum antibiotics) in all patients on antibiotics for sepsis on a daily basis and based on pathogen identification, sensitivities and risk of adverse events | Strong | Very low |
  46. We recommend to stop empirical aminoglycoside therapy within a maximum of two days | Strong | Low |
  47. We recommend to switch systemic antibiotic therapy from intravenous to oral antibiotic therapy after 48–72 h on the basis of the clinical condition and when oral treatment is feasible | Strong | Very low |
IV Pharmacokinetic and pharmacodynamic considerations in sepsis | ||
 In patients with sepsis, should we recommend pharmacokinetic/pharmacodynamic dosing optimization for empirical antibacterial therapy? | ||
  48. In patients with sepsis, we suggest that dosing strategies of antibacterial therapy be optimized based on accepted pharmacokinetic / pharmacodynamic principles and specific drug properties (Additional file 1: Table S3) | Weak | Low |
  49. In patients with sepsis we recommend prolonged or continuousd infusion of piperacillin-tazobactam and carbapenems | Strong | High |
  50. In patients with sepsis we suggest prolonged or continuousd infusion of other beta-lactam antibiotics than piperacillin-tazobactam and carbapenems | Weak | Low |
  51. In patients with sepsis, we recommend direct therapeutic drug monitoring (including either mid-dosing or both peak and through levels) during aminoglycoside treatment in patients with sepsis and septic shock | Strong | GPS |
  52. In patients with sepsis, we recommend therapeutic drug monitoring during vancomycin treatment in patients with sepsis and septic shock | Strong | GPS |
  53. In patients with sepsis, we suggest therapeutic drug monitoring when there are concerns on target attainment of other antibacterial drugs than aminoglycoside and vancomycin (e.g., extreme body weight, augmented or decreased renal clearance, hypoalbuminemia) | Weak | GPS |
  54. In patients with sepsis, we suggest continuousd infusion of vancomycin | Weak | GPS |
  55. In patients with sepsis in whom ciprofloxacin is indicated, we suggest empirical ciprofloxacin three times daily 400 mg iv | Weak | GPS |