Dissections OBSERVATIONAL

14 August 2009
Evidence-based Medicine for Surgeons

Timing of antimicrobial prophylaxis and the risk of surgical site infections

Authors: Steinberg JP, Braun BI, Hellinger WC, et al
Journal: Annals of Surgery 2009; 250: 10–16
Centre: [Multicentre] Trial to Reduce Antimicrobial Prophylaxis Errors (TRAPE), USA
Antimicrobial prophylaxis (AMP) can reduce the risk of surgical site infection (SSI) after many
operations. Studies conducted over the past 3 decades suggest that antimicrobials should be
BACKGROUND given prior to the incision and that efficacy diminishes or disappears if the antibiotic is given
either too early or much after incision. However, there are still some unanswered questions about
the timing of the first dose.

RESEARCH QUESTION IN SUMMARY

Population Time of administration of AMP and SSI
A posthoc, randomly selected, Infection risk Relative risk (95% CI) 'p'
subgroup analysis of patients
enrolled in the Trial to Reduce Number 4472
Antimicrobial Prophylaxis Errors
Timing of first dose of AMP and SSI incidence
(TRAPE)
Not given or more than 120 4.7% (4/96) 2.54 (0.89, 7.21) 0.07
Indicator variable mts before incision
Timing, duration, and 61 - 120 mts before incision 2.4% (12/489) 1.49 (0.74, 3.00) 0.26
intraoperative redosing of surgical
antimicrobial prophylaxis (AMP) 31 - 60 mts before incision 2.4% (38/1558) 1.48 (0.88, 2.50) 0.13
0 - 30 mts before incision 1.6% (22/1339) Reference group
Outcome variable
1 - 30 mts after incision 4.0% (4/100) 2.44 (0.86, 6.93) 0.09
Primary: Surgical site infection
(SSI) > 31 mts after incision 6.8% (5/74) 4.12 (1.60, 10.53) 0.002
3405 of 4472 patients received only cephalosporin prophylaxis
Comparison
Authors' claim(s): “...a consistent relationship between the timing of AMP
- [antimicrobial prophylaxis] and SSI risk with a trend toward lower risk
occurring when AMP with cephalosporins and other antibiotics with short
infusion times were given within 30 minutes prior to incision.”

THE TISSUE REPORT

MSSA
As always, any unplanned, posthoc 6%
16% MRSA
analyses of randomized clinical 29%
Gm -v e
trials, should be interpreted with Other
caution. This study corroborates No
what, by now, is a standard of care 16% growth
58%
of prophylaxis of SSI, emphasizing
48%
the critical nature of the timing of 13%
the first dose of antibiotic.
14%
Super- Deep Organ
f icial space

Location of SSI Culture results

EBM-O-METER
Evidence level Overall rating Bias levels
Double blind RCT Sampling
Randomized controlled trial (RCT) Comparison
Trash Swiss Safe News-
Prospective cohort study - not randomized cheese worthy Measurement
Life's too Holds water
short for this Full of holes “Just do it”
Case controlled study
Interestingl | Novel l | Feasible l
Case series - retrospective  Ethical l | Resource saving l

The devil is in the details (more on the paper) ... 

© Dr Arjun Rajagopalan
 SAMPLING
Sample type Inclusion criteria Exclusion criteria Final score card
Simple random No evidence of Not stated AMP and SSI
infection preop 
Stratified random Target ?
Surgical start time
Cluster documented  Accessible ?
Prophylaxis timing
Consecutive documented if AMP Intended ?
Convenience given  Drop outs ?
Judgmental Study 4472

 = Reasonable | ? = Arguable |  = Questionable

Of 44 hospitals in the parent TRAPE study, 29 volunteered to participate in the SSI ancillary study.
100 randomly selected surgical cases in two 6 month periods from June to November 2003 (baseline) and February to
July 2005 (remeasurement) were used for the analysis.

Sampling bias: The study is a post hoc (secondary) analysis of prospectively collected data. It is a convenience
sample of randomly selected patients from the database and not an all inclusive study. A third of the hospitals that
took part in the primary study dropped out of this secondary analysis.

COMPARISON
Randomized Case-control Non-random Historical None

Controls - details
Allocation details All TRAPE participating hospitals measured antibiotic prophylaxis performance in 100 randomly
selected surgical cases in two 6 month periods from June to November 2003 (baseline) and
February to July 2005 (remeasurement). Hospitals used a customized data entry system to
collect data on the AMP process on randomly selected cases. Collected data on day and time
of surgical incision, surgical close and the timing, drug, route and dose of all antibiotics given
before surgery and after surgery up to 8 total doses.

When a preoperative antibiotic was given more than 3 hours before incision and a
postoperative dose was given within an hour of incision, the postoperative dose was taken to
be the prophylactic dose.
Comparability There were no significant differences in the hospitals taking part in the study.
Disparity -

Comparison bias: -

MEASUREMENT
Measurement error
Device used Device error Observer error
Gold std.
Repetition

Protocols

Device suited to task

Training

Scoring

Blinding

Y ? N

1.Surgical site infection (SSI) Y N Y Y Y N N

The SSI surveillance was conducted at each participating hospital as part of their routine infection control practices. All
participating hospitals used NNIS (National Nosocomial Infections Surveillance) definitions and risk stratification. When
an infected case was identified, a standardized, de-identified case report form was completed.

Measurement bias: The outcome measured is a well documented event with established guidelines for detection
and reporting.

© Dr Arjun Rajagopalan