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Antibiotics for preventing infection in open limb fractures

  1. Richard A Gosselin1,*,
  2. Ian Roberts2,
  3. William J Gillespie3

Editorial Group: Cochrane Bone, Joint and Muscle Trauma Group

Published Online: 26 JAN 2004

Assessed as up-to-date: 27 JUL 2009

DOI: 10.1002/14651858.CD003764.pub2


How to Cite

Gosselin RA, Roberts I, Gillespie WJ. Antibiotics for preventing infection in open limb fractures. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD003764. DOI: 10.1002/14651858.CD003764.pub2.

Author Information

  1. 1

    University of Manchester, c/o Cochrane Bone, Joint and Muscle Trauma Group, Manchester, UK

  2. 2

    London School of Hygiene & Tropical Medicine, Cochrane Injuries Group, London, UK

  3. 3

    University of Hull, Hull York Medical School, Hull, UK

*Richard A Gosselin, c/o Cochrane Bone, Joint and Muscle Trauma Group, University of Manchester, School of Translational Medicine, 2nd Floor Stopford Building, Oxford Road, Manchester, M13 9PT, UK. froggydoc@comcast.net.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 26 JAN 2004

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Characteristics of included studies [ordered by study ID]
Bergman 1982

MethodsRCT
Double-blinded
Placebo
Cultures for diagnosis


ParticipantsSweden
90 adults with open extremity fractures, excluding hand and finger fractures, recruited over 30 months
60 cases treated with dicloxacillin or benzyl penicillin
30 controls treated with placebo


Interventions1. Intervention: 2 g dicloxacillin: first dose given pre-operatively with infusions repeated every six hours for two days.
2. Intervention: 3 million units benzyl penicillin: first dose given pre-operatively with infusions repeated every six hours for two days.
3. Control: 100 ml saline: in the same dosing regimen as for the intervention groups.


OutcomesEarly wound infection: a wound was considered infected when signs of inflammation were present, i.e. supra-fascial drainage and a positive bacterial culture.
Deep infection was defined as a subfascial process going down to the bone or osteosynthesis material.
Superficial thrombophlebitis was defined as a palpable fibrotic vessel or visible inflammation along the course of the vessel.


NotesF/U until wound healed or drainage


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Unclear"The patients were randomly allocated to treatment"

Allocation concealment?Yes"The drugs were packed in coded boxes according to random number, each box containing divided doses for a treatment period for one patient"

Blinding?
All outcomes
YesDouble blind. "The patients were treated with either dicloxacillin,
benzyl penicillin or saline (placebo)".

Braun 1987

MethodsRCT
Double-blinded
Placebo
Cultures for diagnosis


ParticipantsSwitzerland
100 consecutive adults with open extremity fractures 13 excluded (hand fractures, skull fractures, colon injury, previous use of antibiotics)
87 participants:
43 cases treated with cloxacillin
44 controls treated with placebo


Interventions1. Intervention: During the first four days, four 1 g doses of cloxacillin were administered intravenously. Thereafter, four 1.5 g doses of cloxacillin were given orally for six days.
2. Control: Indistinguishable placebo given in the same dosing regimen as for the intervention group.


OutcomesEarly wound infection: (up to 6 weeks). Wound swabs were taken at weekly intervals from the base of the wound and the surrounding skin.


NotesF/U up to 10 months
Cloxacillin group:
- 2 urticaria
- 3 Gastro-intestinal symptoms
- 1 phlebitis
Placebo group:
- 7 phlebitis


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearUnclear; no description given

Allocation concealment?UnclearPlacebo controlled

Blinding?
All outcomes
YesDouble blind

Dickey 1989

MethodsCCT quasi-randomised (alternate days)
No blinding
No placebo
No cultures


ParticipantsUSA
96 adults with open extremity fractures, excluding hand and finger fractures, recruited over 20 months:
46 cases with treatment
50 controls without treatment
Results reported on 32 cases treated with cefazolin, 35 without treatment

Hand injuries excluded.


Interventions1. Intervention: One day of intravenous cefazolin, three 1 g doses given eight hourly.
2. Control: No antibiotics


OutcomesEarly wound infection: any wound complication including prolonged drainage, erythema, or any physical findings such as cellulitis, localised fluctuance or drainage.


NotesF/U until bony union
30% loss to F/U
low-velocity gunshot wounds only
case-definition?


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?NoInadequate. Alternate days

Allocation concealment?NoInadequate. Alternate days.

Blinding?
All outcomes
NoNot blinded

Patzakis 1974

MethodsRCT
No blinding
No placebo
Cultures for diagnosis


ParticipantsUSA
310 consecutive patients with open extremity fractures, including hand and finger fractures, recruited over 12 months
212 cases treated with penicillin and streptomycin, or cephalotin
98 controls without treatment


Interventions1. Intervention: Adults received 10 million units benzyl penicillin per day in a continuous infusion and 0.5 g streptomycin intramuscularly every 12 hours. Children received 100,000 units of penicillin per kilogram of body weight per day in a continuous infusion and 7.5 mg of streptomycin per kilogram of body weight every 12 hours intramuscularly.
2. Intervention: Both adults and children received cephalothin, 100 mg per kilogram of body weight per day in divided dosage intravenously every six hours.
3. Control: No antibiotics.


OutcomesEarly wound infection: clinical signs and symptoms of wound infection present such as fever, erythema, tenderness, and wound drainage with either a positive gram stain or a positive culture. Either of the latter two had to be present before the wound was classified as infected.


NotesLength of F/U not specified.
If gunshot wounds excluded (none got an infection) infections in cases: 11 in 176
Infections in controls: 11 in 79


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearConsecutive patients "randomly assigned to one of three study groups: Group I, no antibiotics; Group II, penicillin and streptomycin; and Group III, cephalothin (Keflin)".

Allocation concealment?UnclearConsecutive patients "randomly assigned to one of three study groups: Group I, no antibiotics; Group II, penicillin and streptomycin; and Group III, cephalothin (Keflin)".

Blinding?
All outcomes
NoNo placebo

Rojczyk 1983

MethodsCCT quasi-randomised (alternate days)
No blinding
No placebo
Cultures for diagnosis


ParticipantsGermany
199 participants of all ages with open extremity fractures, excluding hand and finger fractures, recruited over 30 months:
111 cases treated with cefazolin
88 controls without treatment


Interventions1. Intervention: Cefazolin 1 g intravenously every six hours for five days.
2. Control: no antibiotics


OutcomesEarly wound infection


NotesHand and feet open fractures excluded.
80% F/U at 1 year


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?NoInadequate. Alternate days

Allocation concealment?NoInadequate. Alternate days

Blinding?
All outcomes
NoNot blinded

Sloan 1987

MethodsRCT
No blinding
Placebo controlled
Cultures for diagnosis


ParticipantsUK
40 adults with open finger fractures

85 planned, but stopped after 40 because of 30% infection rate in placebo group
Study continued with remaining three antibiotics groups - time?

30 cases treated with one of three regimens of cephradine
10 controls treated with placebo


Interventions1. Intervention: Cephradine 500 mg orally every six hours for five days
2. Intervention: Cephradine 1 g intravenously followed by 500 mg orally every six hours for five days
3. Intervention: Cephradine 1 g intravenously followed by one dose of 1 g orally
4. Control: Placebo


OutcomesEarly wound infection: Swabs were taken if there was any evidence of infection (erythema, pus or exudate).


NotesOnly fingers
F/U 5 days
8 lost to F/U


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearInsufficient information

Allocation concealment?UnclearInsufficient information

Blinding?
All outcomes
UnclearPlacebo controlled but insufficient information on early stop.

Stevenson 2003

MethodsRCT
Placebo controlled
Double blind
Cultures for diagnosis (infection was defined on clinical grounds)


ParticipantsUK
200 randomised. 7 did not meet criteria on review, or were lost. 193 analysed.
98 treated with flucloxacillin
93 controls treated with placebo

Inclusion criteria: recent fracture of a distal phalanx in a finger with an overlying wound, including fractures associated with subungual hematoma bleeding externally or trephined as part of the treatment process.

Exclusion criteria: less than 16 years of age, wound was more than 12 hours old, history of diabetes or symptomatic peripheral vascular disease, taking oral steroids, fracture caused by a bite, already coincidentally taking an antibiotic or had a known allergy to penicillin.


Interventions1. Flucloxacillin 250 mg capsule
2. Lactose placebo


OutcomesInfection, defined using clinical parameters of erythema, pain, swelling, wound discharge, presence of pus or cellulitis.


Notes


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Yes"Two hundred identical bottles of study medication were prepared in the hospital pharmacy department. The bottles were randomised into blocks of ten using a random number table and sequentially labelled. Each group of ten bottles consisted of five of placebo and five of flucloxacillin."

Allocation concealment?Yes"Sealed code identifying each bottle was kept in the pharmacy department and not opened until completion"

Blinding?
All outcomes
Yes"Each patient entered in the study was given the next sequential bottle containing the study medication and instructed to take two capsules four times daily for five days."

Suprock 1990

MethodsCCT quasi-randomised (alternate days)
No blinding
No placebo
No cultures


ParticipantsUSA
91 patients with open finger fractures recruited over 25 months
45 cases treated with cephalosporin, dicloxacillin or erythromycin
46 controls without treatment


Interventions1. Intervention: either a first generation cephalosporin, dicloxacillin or erythromycin for three days - dose and route of administration were not reported.
2. Control: no antibiotics.


OutcomesEarly wound infection: clinical signs of infection - full details not reported.


NotesOnly fingers
F/U up to one year
No antibiotic dosage reported.
Cultures done only if clinical suspicion.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?NoInadequate. Alternate days

Allocation concealment?NoInadequate. Alternate days

Blinding?
All outcomes
NoNot blinded

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Almanza 1999CCT. Non randomised comparison.

Altergott 2008RCT. Antibiotic therapy versus no antibiotic for fingertip injuries in children. Only 39% of 146 randomised had fracture. No separate data presented.

Cutler 1944CCT. Non randomised comparison. Fractures are not separated from soft tissue injuries only.

Miller 1986RCT. All participants received an initial dose of antibiotics, then were randomised to more or no more antibiotics.

Peacock 1988RCT. Fractures are not separated from soft tissue injuries only.

 
Comparison 1. Any antibiotic treatment versus control

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Early wound infection81106Risk Ratio (M-H, Fixed, 95% CI)0.43 [0.29, 0.65]

    1.1 Studies with lower risk of bias
3370Risk Ratio (M-H, Fixed, 95% CI)0.32 [0.15, 0.68]

    1.2 Studies with higher risk of bias
5736Risk Ratio (M-H, Fixed, 95% CI)0.50 [0.31, 0.82]

 2 Early wound infection (risk difference)81106Risk Difference (M-H, Fixed, 95% CI)-0.07 [-0.10, -0.03]

    2.1 Studies with lower risk of bias
3370Risk Difference (M-H, Fixed, 95% CI)-0.09 [-0.15, -0.03]

    2.2 Studies with higher risk of bias
5736Risk Difference (M-H, Fixed, 95% CI)-0.05 [-0.10, -0.01]

 3 Early wound infection by location of open injury7839Risk Ratio (M-H, Fixed, 95% CI)0.43 [0.27, 0.69]

    3.1 Open limb fracture excluding finger fractures
4472Risk Ratio (M-H, Fixed, 95% CI)0.37 [0.21, 0.68]

    3.2 Open finger fractures
3367Risk Ratio (M-H, Fixed, 95% CI)0.56 [0.26, 1.23]

 
Table 1. Quality assessment tool

ItemsScores

A. Was the assigned treatment adequately concealed prior to allocation?1 = states random, but no description, or quasi-randomisation
2 = small but real chance of disclosure of assignment
3 = method did not allow disclosure of assignment

B. Were the outcomes of patients who withdrew described and included in the analysis (intention-to-treat)?1 = not mentioned
2 = states numbers and reasons for withdrawal, but analysis unmodified
3 = primary analysis based on all cases as randomised

C. Assessment of outcome. Were assessors of outcome blinded to treatment status?1 = not done or not mentioned
2 = moderate chance of unblinding of assessors
3 = action taken to blind assessors, or outcomes such that bias is unlikely

D. Were treatment and control groups comparable at entry?1 = large potential for confounding or not discussed
2 = confounding small; mentioned but not adjusted for
3 = unconfounded; good comparability of groups or confounding adjusted for

E. Was a placebo treatment assigned as part of the randomisation?1 = no
3 = yes

F. Were exclusion criteria clearly defined?1 = not defined
2 = poorly defined
3 = well defined

G. Was the method of assessment of wound infection stated?1 = not stated
2 = clinical decision, or definite criteria without a microbiological diagnosis
3 = definite criteria including a microbiological diagnosis

H. Was the method and duration of surveillance stated?1 = not stated, or not active
2 = active, but less than three months
3 = active, and at least one year