### Alternate Systematic Review Scenario

You are attending morning rounds in the medical-surgical ICU with junior housestaff. They present a 77 year old gentleman who was admitted from the emergency department with progressive SOB and respiratory failure requiring intubation and mechanical ventilation. The housestaff present convincing evidence that this is due to an exacerbation of his underlying heart failure, likely a result of medication non-compliance. After outlining an appropriate plan for the day, one of the clinical fellows suggests prophylactic antibiotics to prevent a respiratory tract infection and points out that an infection would be poorly tolerated in this patient. You acknowledge the concern and ask the group: “In critically ill patients requiring mechanical ventilation, do prophylactic antibiotics reduce the risk of respiratory tract infection?”

You search Medline using the terms “Critical care”, “Antibiotics”, “Respiratory tract infections” and find an interesting systematic review. The abstract looks helpful so you download the article in full text.
BMJ 1998;316:1275-85

Read the article and decide:

• Is the evidence from this systematic review valid?
• Is this valid evidence from this systematic review important?
• Can you apply this valid and important evidence from this systematic review in caring for your patient?

### Completed Systematic Reviews Worksheet for Critical Care Medicine

#### Citation

Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials. BMJ 1998;316:1275-85.

#### Are the results of this systematic review of therapy valid?

Is it a systematic review of randomised trials of the treatment you’re interested in?
Yes it included trials with random allocation and quasi-random allocation
Does it include a methods section that describes finding and including all the relevant trials?
Yes
Does it include a methods section that describes assessing their individual validity?
Yes but did not use this data in the analysis and most studies had small sample size.
Were the results consistent from study to study?
Yes. There was homogeneity when studies of similar treatment route were compared.

#### Are the valid results of this systematic review important?

Translating odds ratios to NNTs. The numbers in the body of the table are the NNTs for the corresponding odds ratios at that particular patient’s expected event rate (PEER).
Odds Ratios
0.9 0.85 0.8 0.75 0.7 0.65 0.6 0.55 0.5
Patient’s Expected Event Rate (PEER) 0.05 2091 139 104 83 69 59 52 46 412
0.10 110 73 54 43 36 31 27 24 21
0.20 61 40 30 24 20 17 14 13 11
0.30 46 30 22 18 14 12 10 9 8
0.40 40 26 19 15 12 10 9 8 7
0.503 38 25 18 14 11 9 8 7 6
0.70 44 28 20 16 13 10 9 7 6
0.90 1014 64 46 34 27 22 18 15 125

#### Can you apply this valid, important evidence from a systematic review in caring for your patient?

##### Do these results apply to your patient?
Is your patient so different from those in the overview that its results can’t help you?
No
##### How great would the potential benefit of therapy actually be for your individual patient?
Method I: In the table on page 1, find the intersection of the closest odds ratio from the overview and the CER that is closest to your patient’s expected event rate if they received the control treatment (PEER):
EER and CER provided in Best Evidence.
Method II: To calculate the NNT for any OR and PEER:
$$text{NNT} = frac{1-(text{PEER}times(1-text{OR})]}{(1-text{PEER})timestext{PEER}times(1-text{OR})}$$
With systemic and topical antibiotic:
NNT for respiratory tract infection is 5, NNT for mortality is 23.
With topical antibiotic the NNT for respiratory tract infection is 9.
##### Are your patient’s values and preferences satisfied by the regimen and its consequences?
Do your patient and you have a clear assessment of their values and preferences?
Would need to assess in individual patients
Are they met by this regimen and its consequences?
Would need to assess in individual patients
##### Should you believe apparent qualitative differences in the efficacy of therapy in some subgroups of patients?

Only if you can say “yes” to all of the following:

• Do they really make biologic and clinical sense?
• Is the qualitative difference both clinically (beneficial for some but useless or harmful for others) and statistically significant?
• Was this difference hypothesised before the study began (rather than the product of dredging the data), and has it been confirmed in other, independent studies?
• Was this one of just a few subgroup analyses carried out in this study?

### Mechanical ventilation: Antibiotic prophylaxis decreases respiratory tract infection and mortality in critically ill patients

#### Clinical Bottom Line

• Antibiotic prophylaxis decreases the incidence of respiratory tract infection and mortality in critically ill patients requiring mechanical ventilation.
• Prophylaxis with topical antibiotics alone decreases the incidence of respiratory tract infection in critically ill patients requiring mechanical ventilation, but does not decrease mortality.

#### Citation

Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials.
BMJ 1998;316:1275-85.

#### Clinical Question

In critically ill patients requiring mechanical ventilation, does prophylactic antibiotics reduce the risk of respiratory tract infection?

#### Search Terms

“Critical care”, “Antibiotics”, “Respiratory tract infections” in Medline

#### The Study

Systematic review of RCTs that studied topical plus systemic antibiotics versus no treatment and topical preparations with or without systemic antibiotics versus a systemic agent or placebo in unselected critically ill adult patients with outcomes of respiratory tract infections or death.

#### The Evidence

16 trials (3361 patients) of topical plus systemic antibiotics; 17 trials (2366 patients) of only topical antibiotics.
Intervention Outcome CER (weighted) EER (weighted) RRR ARR (weighted) [95% CI] NNT [95% CI]
Systemic and Topical Antibiotic Respiratory Tract Infection .36 .16 .56 .20 [.20 – .25] 5 [4 – 5]
Mortality .30 .24 .20 .06 [.01 – .07] 23 [14 – 68]
Topical Antibiotic Respiratory Tract Infection .28 .18 .36 .10 [.08 – .14] 9 [7 – 13]
Mortality .26 .26 0 0 N/A

• The treatment effect is consistent across type of patient (medical, surgical, or trauma and APACHE II stratification.
• No significant difference in pooled data from individual patients v. aggregate data.
• Review does not allow a unique antibiotic regimen to be chosen.

Created by Berenholtz S, Pronovost P

#### References

1. The relative risk reduction (RRR) here is 10%
2. The RRR here is 49%
3. For any OR, NNT is lowest when PEER = .50
4. The RRR here is 1%
5. The RRR here is 9%