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Table 3 Results Delphi procedure: first questionnaire, consensus meeting and second questionnaire

From: Development of quality indicators for antimicrobial treatment in adults with sepsis

Quality indicators

Level of supporting evidence (see Table2)

First questionnaire

Consensus meeting

Second questionnaire

  

Median score

% in highest tertile

Conclusion

 

Nr of experts prioritizing the QI

Total score

Conclusion

1. Start antimicrobial therapy intravenously in adult patients with sepsis

4

9

92

Accepteda

Accepted

7

26

Accepted

2. Start antimicrobial therapy as soon as possible, preferably within the first hour in adult patients with severe sepsis and septic shock

2

9

100

Accepted

Accepted

12

50

Accepted

3. Before starting antimicrobial therapy, at least two sets of blood cultures, and specimens for culture from suspected sites of infection should be taken.

4

9

100

Accepted

Accepted

9

36

Accepted

4. For community-acquired sepsis without neutropenia and without an obvious site of infection, start a second or third generation cephalosporin, or amoxicillin and clavulanic acid + an aminoglycoside. Duration of therapy: 7–10 days.

*

8

92

Accepted

Mergedd into number 43/44

   

5. For nosocomial sepsis without neutropenia and with no obvious site of infection, start piperacillin with tazobactam, or a second or third generation cephalosporin (except ceftazidime) in combination with either an aminoglycoside or an anti-pseudomonal fluoroquinolone. Duration of therapy: 7–10 days.

*

7

75

Discussionb

Merged into number 43/44

   

6. For community-acquired or nosocomial sepsis with neutropenia and without an obvious site of infection, start piperacillin and tazobactam +/− an aminoglycoside or a carbapenem with anti-pseudomonal activity (imipenem/meropenem) as empirical antibacterial regimen. Duration of therapy: 7–10 days.

*

7

75

Discussion

Merged into number 43/44

   

7. The addition of an aminoglycoside to a beta-lactam agent in adult patients with sepsis is not recommended, unless based on local resistance data and epidemiology (e.g. risk factors for ESBL) a broad spectrum of empirical therapy against Gram-negative pathogens is needed.

*

8

75

Accepted

Accepted

3

6

Rejected

8. Glycopeptides should generally not be part of the empirical antibacterial regimen in adults with sepsis (with or without neutropenia), unless patients are known to be colonised with MRSA, or in patients with severe sepsis and neutropenia who received penicillin or cephalosporin prophylaxis.

*

8

83

Accepted

Accepted

0

0

Rejected

9. For community-acquired and nosocomial sepsis and prior use of cephalosporins or quinolones within 30 days before presentation, an aminoglycoside should be added or a carbapenem with antipseudomonal activity should be started. This also accounts for adults colonised with ESBL-producing micro-organisms and for those admitted to a hospital with high prevalence of ESBL-producing Enterobacteriaceae. If prevalence is unknown, risk factors for ESBL should be used. Risk factors are: a nosocomial infection, prior use of antibiotics and presence of an indwelling urinary catheter.

2

8

92

Accepted

Accepted

2

4

Rejected

10. Empirical antifungal therapy may be considered in selected cases: unexplained sepsis with long-term ICU stay, significant Candida colonisation, and clinical risk factors such as abdominal surgery, anastomosis leakage, the presence of a central venous catheter and the use of broad spectrum antibiotics.

*

8

73

Accepted

Merged into number 43/44

   

11. For sepsis with a hospital-acquired pneumonia or a ventilated-acquired pneumonia, start amoxicillin and clavulanic acid + an aminoglycoside or ciprofloxacin, or the combination of a second/third generation cephalosporin (excluding ceftazidime) with an aminoglycoside or ciprofloxacin or start piperacillin with tazobactam. Duration of therapy: maximum of 8 days.

1

7

67

Rejectedc

    

12. For urosepsis, start a second/third generation cephalosporin or the combination of amoxicillin and gentamicin as empirical antibacterial regimen. Duration of therapy: 10 days.

*

7

92

Discussion

Merged into number 43/44

   

13. For urosepsis and an indwelling urinary catheter, start a second/third generation cephalosporin + an aminoglycoside or quinolone as empirical antibacterial regimen.

*

7

67

Rejected

    

14. In adults with urosepsis, glycopeptides should be restricted to those septic patients with previously bacteriologically proven Enterococcus faecium urinary tract infections in which enterococci are suspected to be the causative pathogens.

*

8

83

Accepted

Merged into number 43d

   

15. For community-acquired intra-abdominal sepsis, start a second/third generation cephalosporin + metronidazole +/− an aminoglycoside or amoxicillin and clavulanic acid +/− an aminoglycoside. Duration of therapy: 5–7 days.

2

8

92

Accepted

Merged into number 43/44

   

16. For nosocomial intra-abdominal sepsis, start a second/third generation cephalosporin + metronidazole + an aminoglycoside or amoxicillin and clavulanic acid + an aminoglycoside or piperacillin with tazobactam +/− an aminoglycoside. Duration of therapy: 5–7 days.

2

7

75

Discussion

Merged into number 43/44

   

17. For community-acquired sepsis with cholangitis, start amoxicillin + an aminoglycoside or amoxicillin and clavulanic acid +/− an aminoglycoside. Duration of therapy: up to 3 days following adequate drainage.

*

7

83

Discussion

Merged into number 43/44

   

18. For nosocomial sepsis with cholangitis, start amoxicillin (with or without clavulanic acid) + an aminoglycoside. Duration of therapy: up to 3 days following adequate drainage.

*

7

75

Discussion

Merged into number 43/44

   

19. For uncomplicated skin and skin structure infections (SSSI) with sepsis, start flucloxacillin.

2

8

82

Accepted

Merged into number 43

   

20. For community acquired complicated SSSI with sepsis, start amoxicillin and clavulanic acid. Duration of therapy: 7–10 days.

*

8

67

Discussion

Merged into number 43/44

   

21. For nosocomial complicated SSSI with sepsis, start amoxicillin and clavulanic acid + an aminoglycoside or piperacillin with tazobactam. Duration of therapy: 7–10 days.

*

8

75

Accepted

Merged into number 43/44

   

22. For community-acquired sepsis and necrotising fasciitis, start amoxicillin and clavulanic acid + clindamycin.

*

6

50

Rejected

    

23. For nosocomial sepsis and necrotising fasciitis, start amoxicillin and clavulanic acid + an aminoglycoside + clindamycin or piperacilllin with tazobactam +/− an aminoglycoside + clindamycin.

*

7

67

Rejected

    

24. Cephalosporins (+/−metronidazole) are suitable alternatives in patients with non-IgE mediated penicillin rash.

*

7

67

Rejected

    

25. In type I IgE allergic reactions to penicillins, aztreonam or ciprofloxacin +/− an aminoglycoside in combination with vancomycin should be chosen.

*

6

45

Rejected

    

26. Individualization of dosing using therapeutic drug monitoring should be used whenever possible in adults with sepsis. For aminoglycosides after 3 days and for vancomycin after 5 days.

3

6

50

Rejected

    

27. When starting vancomycin therapy, at least one trough concentration (just before the fourth dose) should be determined and the concentration should be 15-20 mg/l.

3

7

50

Rejected

    

28. Frequent measuring of vancomycin trough concentrations is recommended in patients with an increased risk of toxicity or unstable kidney function and > 5 days of treatment.

3

8

75

Accepted

Rephrased to number 47

   

29. With proven Pseudomonas bacteraemia, combination therapy should not be prescribed. Duration of therapy is 7 – 10 days.

2

7

70

Discussion

Merged into number 44/45

   

30. For sepsis due to methicillin susceptible Staphylococcus aureus, start flucloxacillin.

2

8

100

Accepted

Accepted

1

3

Rejected

31. Micro-organisms with MICs > 1 mg/l such as Pseudomonas aeruginosa or patients with neutropenia should have an intravenous ciprofloxacin dosage of 400 mg tid.

4

8

100

Accepted

Accepted

0

0

Rejected

32. Treatment duration should be 14 days for sepsis and pneumonia due to S. aureus.

4

9

89

Accepted

Merged into number 44

   

33. Treatment duration should be 14–21 days for sepsis and pneumonia due to Legionella pneumophila, Mycoplasma pneumoniae or Chlamydia spp.

4

8

90

Accepted

Merged into number 44

   

34. Treatment duration should be 14 days in an uncomplicated Staphylococcus aureus bacteraemia.

4

9

91

Accepted

Merged into number 44

   

35. With S. aureus bacteraemia it is important to search for complications, this will determine the duration of therapy. Complications are: a secondary infection together with the S. aureus bacteraemia (like an endocarditis, infected prosthesis, arthritis, osteomyelitis, meningitis, fasciitis, spleen abscess)

4

8

67

Discussion

Accepted

1

2

Rejected

36. Persistence of positive blood cultures for more than 72 hours after starting antibiotics should be considered as complicated S. aureus bacteraemia.

4

8

75

Accepted

Accepted

1

1

Rejected

37. With sepsis and Listeriosis, the duration of therapy should be 21 days.

4

7

67

Rejected

    

38. After clinical recovery and when the identity and susceptibility of the causative micro-organism has been determined, a switch to oral agents with high bioavailability should be made.

2

8

91

Accepted

Rephrased to number 48

   

39. Empirical antimicrobial therapy for presumed sepsis should be discontinued in case of clinical improvement and a lack of clinical and microbiological evidence of infection. Maximum duration of therapy is 7 days.

4

8

83

Accepted

Accepted

2

5

Rejected

40. Discontinue broad spectrum antimicrobial therapy after 72 hours of clinical stability in patients with persisting febrile neutropenia that show no clinical or microbiological evidence of infection. Oral antimicrobial prophylaxis against Gram-negative micro-organisms should be continued until resolution of neutropenia.

2

9

91

Accepted

Accepted

2

2

Rejected

QIs added after first questionnaire:

        

41. When starting treatment in adults with sepsis, dose and dosing interval of systemic antimicrobial therapy should be adapted to renal function.

4

  

Addede

Accepted

3

4

Rejected

42. Concerning empirical therapy for adult patients with sepsis, local guidelines should correspond to the national guideline, but should deviate based on local resistance patterns.

4

   

Added

9

27

Accepted and merged with number 43

43. Empirical antimicrobial therapy (only choice of antimicrobial agent) in all adult patients with sepsis should be prescribed according to the national guideline.

*

   

Added

2

7

Accepted and merged with number 42

44. In all adult patients with sepsis starting antimicrobial therapy the duration of therapy should be prescribed according to the national guideline.

4

   

Added

3

4

Rejected

45. Change empirical antimicrobial therapy to pathogen-directed therapy if culture results become available.

3

   

Added

7

15

Accepted

46. Patients with a S. aureus bacteraemia should have a blood culture taken 48 – 72 hours after starting empirical antibiotic therapy.

4

   

Added

0

0

Rejected

47. Therapeutic drug monitoring should be done if vancomycin or aminoglycosides are given > 48 hours, according to the local guideline. The vancomycin trough concentration should be 15-20 mg/l.

    

Result from rephrasing number 28

1

1

Rejected

48. After clinical recovery and when the identity and susceptibility of the causative micro-organism has been determined, a switch to oral agents with high bioavailability should be made. Exceptions are: S. aureus bacteraemia, liver abscess, empyema, endocarditis, meningitis and infected prosthetic material.

    

Result from rephrasing number 38

1

1

Rejected

  1. *Based on available Dutch epidemiology and resistance data. aAccepted: the potential QI was selected for the next round because of an overall median score of 8 or 9, without disagreement. Disagreement was defined as the case in which less than 70% of the scores were in the top tertile (scores 7, 8, or 9). bDiscussion: the QI had a median score of 7 without disagreement or a median score of 8 or 9 with disagreement, and so it was discussed during the consensus meeting. cRejected: disagreement between panel members and the median was also lower than 8; the potential indicator was deselected and not discussed during the consensus meeting. dMerged: multiple indicators were ‘rejected’ and merged into a composite, more generic indicator. eAdded: the indicator was proposed by one of the experts and was added to the initial set of indicators.