Objectives: To determine whether the prophylactic administration of antibiotics in patients undergoing surgical management of hip or other long bone fractures reduces the incidence of wound and other hospital acquired infections.The principles of prophylaxis against post-surgical infection were established in the laboratory in the early 1960s (Burke 1961). The administration of antibiotic prior to surgery is now widely accepted. The period of administration of prophylaxis has been steadily reduced but the optimal duration remains uncertain. During the operative management of closed fractures, antibiotic prophylaxis has been claimed to reduce infection rates from around 5% to less than 1% (Bodoky 1993). As the pathogenesis of post-surgical infection is similar after osteosynthesis of any closed fracture, it has been suggested that combining data from similar prophylactic regimens used during different surgical procedures is quite appropriate (Platt 1991).Search strategy: No language restriction was applied.
Databases searched: Cochrane library, MEDLINE, EMBASE, Current Contents, Dissertation Abstracts, and Index to UK Theses to the end of 1997.
Handsearching of bibliographies of identified articles.Selection criteria: Participants: Any patients with a hip or other closed long bone fracture undergoing surgery for internal fixation or replacement arthroplasty.
Interventions: Any regimen of systemic antibiotic prophylaxis administered at the time of surgery.
Outcome measures: Wound infection (deep and superficial), urinary tract infection, respiratory tract infection, adverse effects of prophylaxis, economic evaluations.Data collection and analysis: Searching, a decision on inclusion or exclusion, methodological assessment, and data extraction were carried out according to a predetermined protocol included in the body of the review. Analysis using Review Manager 3.1.1 allowed pooling of data and calculation of Peto odds ratios and of absolute risk reductions, each with 95% confidence intervals.
Main results: Antibiotic prophylaxis reduces wound, urinary and respiratory tract infections in patients undergoing surgery for closed fracture fixation. Economic modelling has indicated that this is a cost-effective intervention. There are limited data for the incidence of adverse effects, but as expected they appear to be more common in those receiving antibiotics.
Conclusions: Antibiotic prophylaxis should be offered to those undergoing surgery for closed fracture fixation.
On ethical grounds, further placebo controlled randomised trials of the effectiveness of antibiotic prophylaxis in closed fracture surgery are unlikely to be justified. Trials addressing the cost-effectiveness of different effective antibiotic regimens would need to be very large and may not be feasible.
Closed hip fractures in the elderly are common, and surgical management is normal in the developed world. The majority of studies of the efficacy of antibiotic prophylaxis in fracture fixation have focused on this group of patients. Early randomised trials completed in the 1970s suggested a small but definite prophylactic effect. These trials were individually small, and some used prolonged courses of antibiotic. Many further trials have been reported over the following twenty-five years. These have addressed a range of issues: duration of administration, route of administration, and antimicrobial spectrum.
A number of descriptive reviews of antibiotic prophylaxis in orthopaedic surgery have been published (Doyon 1989; Norden 1991), in which some attempt has been made to assess methodological quality and include this in the interpretation of results. However, there is sufficient persisting uncertainty about the efficacy, optimal duration, and cost-effectiveness of antibiotic prophylaxis during the surgical treatment of hip and other long bone fractures to justify a systematic review of the evidence from randomised trials.
The following hypotheses are tested:
1. Antibiotic prophylaxis does not lead to a reduction in the proportion of patients developing a wound infection, either deep or superficial, compared with those given a placebo or no prophylaxis.
2. Single dose antibiotic prophylaxis does not lead to a significant reduction in the proportion of patients developing a wound infection compared with those given longer duration prophylaxis.
3. There is no significant reduction in the proportion of patients with a post-operative wound infection who receive prophylaxis using broad-spectrum antibiotics when compared with those who receive narrow spectrum agents.
4. Antibiotic prophylaxis does not lead to a significant reduction in the proportion of patients developing septicaemia, respiratory or urinary tract infection, compared with those given a placebo or no prophylaxis.
5. Single dose antibiotic prophylaxis does not lead to a significant reduction in the proportion of patients developing septicaemia, respiratory, or urinary tract infection after surgical management of a hip or other long bone fracture compared with those given three or more doses.
6. Oral administration of a prophylactic regimen does not lead to a significant reduction in the proportion of participants experiencing a wound infection, respiratory or urinary tract infection, or adverse drug effect, compared with those receiving parenteral prophylaxis.
7. There is no significant increase in the proportion of patients with conditions such as gastro-intestinal symptoms or skin reactions in those allocated antibiotic prophylaxis when compared with those receiving placebo or no prophylaxis.
Deep wound infection
A surgical wound infection which occurs within 1 year, if an implant is in place and infection involves tissues or spaces at or beneath the fascial layer.
Superficial wound infection
A surgical wound infection which occurs at the incision site within 30 days after surgery and involves the skin subcutaneous tissue, or muscle located above the fascial layer.
In the assessment of methodological quality, more weight was given to studies in which wound infection had been confirmed by microbiological analyses.
2. Urinary tract infection
3. Respiratory tract infection
4. Adverse reaction to antibiotic (gastro-intestinal symptoms, skin reactions)
5. Cost-effectiveness outcomes - length of hospital stay
- reoperation due to infection.
See: Collaborative Review Group search strategy
No language restriction was applied.Trials were identified by searches up to the end of 1997:
i. MEDLINE. The first 2 sections of the optimal Medline search strategy (Dickersin et al 1994) were applied with the following specific search terms:
1 Explode HIP-FRACTURES/complication or fractur* near fem?r*
2 Explode SURGERY, OPERATIVE, ORTHOPEDICS /all subheadings
3 Explode JOINT-PROSTHESIS/all subheadings
4 Prophyla*
5 Explode PROTECTIVE DEVICES/all subheadings
6 Explode ENVIRONMENTAL CONTROLLED/all subheadings
7 Explode SURGICAL WOUND INFECTION/all subheadings
8 (1 or 2 or 3) and (4 or 5 or 6 or 7)
ii. EMBASE.
The search strategy was
1 EX ORTHOPAEDIC-SURGERY OR EX ORTHOPEDIC SURGERY OR EX FRACTURE
2 EX PROPHYLAXIS OR INFECTION-CONTROL OR ANTIBIOTIC-THERAPY
3 EX ANTIBIOTIC-AGENT
4 EX ASEPSIS OR EX ENVIRONMENTAL-PARAMETERS
5 EX COMPLICATION OR EX ABSCESS OR EX BACTERIAL-INFECTION OR EX BONE-AND-JOINT-INFECTIONS
6 CATHETER-INFECTION OR AIRBORNE-INFECTION OR CROSS-INFECTION OR HOSPITAL-INFECTION
7 PERSISTENT-INFECTION OR RECURRENT-INFECTION OR SOFT-TISSUE-INFECTION OR SURGICAL-WOUND-INFECTION OR PUS.DE.
8 EX INFLAMMATION
9 EX RISK OR EX AIR-AND-AIR-RELATED-PHENOMENA
10 OPERATING-ROOM OR SURGICAL-WARD
11 1 AND (2 OR 3)
12 1 AND (4 OR 9 OR 10)
13 1 AND (5 OR 6 OR 7 OR 8 )
14 11 OR 12 OR 13
iii. The Cochrane Library
iv. Current Contents, Dissertation Abstracts, and Index to UK Theses .
v. The bibliographies of identified literature reviews, original articles, and relevant chapters of published books were examined for undetected articles.
vi. Contacts were made in person or by mail with identified trialists and other experts in the field.
All identified studies were read. We included all randomised or quasi-randomised controlled trials reporting the results of antibiotic prophylaxis in patients undergoing hip or other long bone fracture surgery with wound infection as one of the primary outcome measures. Reports in which participants were not allocated at enrolment in a randomised or quasi-randomised fashion into treatment or control groups were excluded.
Quality Assessment:
Methodological assessment was undertaken by two raters, using the criteria described below, supplemented by a pre-designed coding manual. Disagreement was resolved by discussion between raters.
A. Was the assigned treatment adequately concealed prior to allocation?
1=states random, but no description, or quasi-randomisation (Category C)
2=small but real chance of disclosure of assignment (Category B)
3=method did not allow disclosure of assignment (Category A)
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. Comparability of treatment and control groups 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. Method of assessment of wound infection.
0=not stated
1=non-specific criteria; clinical decision
2=definite criteria which might include a microbiological diagnosis
3=microbiological diagnosis
H. Duration of surveillance for wound infection
0=not stated
1=less than one month
2=all at least one month but minimum less than one year
3=all at least one year
Data Extraction:
Data were independently extracted by two reviewers and adjudicated by a third using a data extraction tool which had undergone prior testing. We approached two groups of trialists for clarification of data relevant to the review.
Methods to synthesize data:
Using Review manager 3.1.1, for each study, Peto odds ratios and 95% confidence limits were calculated for dichotomous outcomes. For comparable groups of trials pooled odds ratios with 95% confidence intervals were derived, and where appropriate absolute risk reduction was calculated.
Results in each comparison category are shown in the Metaview summary analysis. We accepted that there was variation between studies in the reported definition of the main outcome measures, but considered that these definitions were clinically sufficiently consistent to permit pooling. Also, although the regimens of antibiotic prophylaxis within each category also varied in respect of the agent and the details of timing, we found that all reported trials employed agents likely to be widely effective at the time of the study against Staphylococcus aureus, the principal organism implicated in post-operative wound infection.
1. A pre-operative dose and two or more post-operative doses of parenteral (injected) antibiotic compared with a placebo or with no treatment.
Data were pooled from 10 trials. Regimens in this category significantly reduced the incidence of deep wound infection (Peto odds ratio 0.34, 95%CI 0.19, 0.59), and of superficial wound infection (Peto odds ratio 0.46, 95%CI 0.27, 0.78), and reduced the incidence of infection of the urinary tract (Peto odds rato 0.61, 95%CI 0.37, 1.00). There was no significant reduction in the rate of respiratory infection (Peto odds ratio 0.80, 95%CI 0.38, 1.68). Adverse effects were rarely reported but appeared more common in participants given antibiotics (Peto odds ratio 2.05, 95%CI 1.02, 4.13). The absolute risk of deep wound infection in the control patients was 4.3%, and the absolute risk reduction 2.9%(95% CI 1.3%, 4.4%).
2. A single preoperative dose of parenteral antibiotic compared with a placebo or no treatment.
Data were pooled from six trials, including one large multi-centre trial of good quality (Boxma 1996). Regimens in this category reduced the incidence of deep wound infection (Peto odds ratio 0.42, 95%CI 0.26, 0.68), superficial wound infection (Peto odds ratio 0.67, 95%CI 0.47, 0.94), urinary tract infection (Peto odds ratio 0.51, 95%CI 0.39, 0.66), and respiratory infection (Peto odds ratio 0.42, 95%CI 0.29, 0.61). The absolute risk of deep wound infection in the control patients was 3.0%, and the absolute risk reduction 1.8%(95%CI 0.8%, 2.8%).
3. A single dose of short-acting parenteral antibiotic compared with multiple doses of the same agent.
Data were pooled from two trials, one of which (Gatell 1987) dominates the analysis by virtue of its size and effect size. This trial is of moderate quality. The analysis indicates that a single dose, in the circumstances described in Gatell 1987 was significantly less effective in preventing deep wound infection (Peto odds ratio 4.45, 95%CI 1.28, 15.55), superficial wound infection (Peto odds ratio 3.60, 95%CI 1.20, 10.80) and urinary tract infection (Peto odds ratio 1.83, 95%CI 1.03, 3.28) after surgery for closed fracture than a multiple dose regimen (see discussion).
4. A single dose of parenteral antibiotic using an agent with a long half-life, compared with multiple doses of other agents with shorter half life.
Data were pooled from three trials in this category. One of these (Garcia 1991) was a large trial of moderate quality, but despite its size, analysis of the pooled data failed to show a significant difference between the two types of regimen for the outcomes of deep wound infection (Peto odds ratio 0.56, 95%CI 0.21, 1.50), superficial wound infection (Peto odds ratio 1.01, 95%CI 0.34, 3.00), urinary tract infection (Peto odds ratio 0.70, 95%CI 0.38,1.30), or respiratory infection (Peto odds ratio 0.41, 95%CI 0.09, 1.81).
5. Multiple doses of parenteral antibiotic administered over 24 hours or less, compared with a longer period of administration.
Data were pooled from the two small trials in this category. There was no evidence of difference between the two types of regimen for the outcomes of deep (Peto odds ratio 1.15, 95%CI 0.19, 6.91) or superficial wound infection (Peto odds ratio 0.55, 95%CI 0.15, 2.01).
5. Oral administration of antibiotic compared with parenteral administration.
Only one small trial (Nungu 1995) has evaluated this comparison for the outcomes of deep and superficial wound infection, and urinary infection. No significant difference between the routes was demonstrated. (Deep infection: Peto odds ratio 0.12, 95%CI 0.00, 5.91; superficial infection: Peto odds ratio 0.22, 95%CI 0.04, 1.12; urinary infection: Peto odds ratio 1.11, 95%CI 0.59, 2.08)
Antibiotic prophylaxis has been widely used in fracture surgery since the 1970s. The 21 trials reported span almost quarter of a century. In the early studies, penicillins effective against gram positive cocci were used. As resistant organisms appeared, subsequent generations of penicillins, and then cephalosporins have been trialed in prophylaxis, both against placebo or no treatment, and against other agents.Over time, shorter durations of prophylaxis have been used. For effective prophylaxis, the minimum inhibitory concentration (MIC) of the antibiotic in the tissues must be exceeded for at least the period from incision to wound closure (Burke 1961). In practice until the last decade this has meant using regimens with several consecutive doses, and the pooled data support their effectiveness. The availability of agents with a long elimination half life has allowed single dose prophylaxis reliably to meet Burke s prerequisite. Amongst published trials the large multi-centre Netherlands trial (Boxma 1996), which used an antibiotic which provided concentrations exceeding MIC for 12-24 hours, dominates the analysis in this category. This trial supported the hypothesis that single dose intravenous prophylaxis is effective in reducing the incidence of deep wound infection, superficial wound infection, and urinary and respiratory tract infections. The effect sizes are similar to those of from multi-dose prophylaxis.
Despite the lack of power in most of the individual studies, pooling of the accumulated evidence supports the hypothesis of effectiveness of antibiotic prophylaxis. Boxma 1996 included an economic evaluation based on the effectiveness data which indicates a cost saving of a little under 500US dollars per patient given prophylaxis. This may be conservative as the evaluation does not appear to take into account the costs of urinary and respiratory infections prevented. Albers and colleagues (Albers et al 1994) have calculated that antibiotic prophylaxis for closed fracture surgery is cost effective if the absolute risk reduction is 0.25% or more; the pooled estimates for absolute risk reduction for single dose or multiple dose prophylaxis in this review exceed that. Therefore, without taking into account the effects of wide adoption of prophylactic regimens on the development of antibiotic resistance, antibiotic prophylaxis appears cost-effective.
Direct comparisons of multiple and single dose prophylaxis have also been conducted by Gatell 1987 and Buckley 1990. Buckley 1990 was underpowered to distinguish between the two regimens tested. Gatell 1987, a large single centre study, concluded that single dose prophylaxis was inferior (although use of the Peto Odds ratio rather than relative risk may exaggerate the security of the conclusion (Peto odds ratio 4.45, 95%CI 1.28, 15.5; relative risk 7.89 (95%CI 1.01, 61.98). Also, the tissue MIC may not have been exceeded throughout the procedure in Gatell 1987, in which an agent (cefamandole 2g) with a short half life, was administered 30 minutes prior to the onset of surgery.
References to studies included in this review
Bergman 1982 (published data only) Bodoky 1993 (published data only) Bodoky A, Neff U, Heberer M, Harder F. Antibiotic prophylaxis with two doses of cephalosporin in patients managed with internal fixation for a fracture of the hip. J Bone Joint Surg (Am) 1993; 75A: 61-65. Bodoky A, Neff U, Heberer M, Harder F. (Preoperative assessment of at-risk patients in traumatology). Helv Chir Acta 1989; 56: 91-5. Boxma 1996 (published data only) Boxma H, Broekhuizen T, Patka P, Oosting H. Randomised controlled trial of single dose antibiotic prophylaxis in surgical treatment of closed fractures. Lancet 1996; 347: 1133-1137. Boyd 1973 (published data only) Boyd RJ, Burke JF, Colton T. A double-blind clinical trial of prophylactic antibiotics in hip fractures. J Bone Joint Surg (Am) 1973; 55A: 1251-1258. Buckley 1990 (published data only) Buckley R, Hughes GNF, Snodgrass T, Huchcroft SA. Perioperative cefazolin prophylaxis in hip fracture surgery. Can J Surg 1990; 33: 122-125. Buckley RE, Hughes GNF. Perioperative cefazolin prophylaxis in hip fracture surgery. J Bone Joint Surg(Br) 1989; 71B: 343-. Burnett 1980 (published data only) Burnett JW, Gustilo RB, Williams DN, Kind AC. Prophylactic antibiotics in hip fracture. A double-blind, prospective study. J Bone Joint Surg (Am) 1980; 62: 457-462. Ericson 1973 (published data only) Ericson C, Lidgren L, Lindberg L. Cloxacillin in the prophylaxis of post-operative infections of the hip. J Bone Joint Surg (Am) 1973; 55A: 808-813, 843. Garcia 1991 (published data only) Garcia S, Lozana ML, Gatell JM, Soriana E, Ramon R, Sanmiguel JG. Prophylaxis against infection. Single-dose cefonicid compared with multiple dose cefamandole. J Bone Joint Surg (Am) 1991; 73A: 1044-1048. Gatell 1984 (published data only) Gatell JM, Riba J, Lozana ML, Mana A, Ramon R, SanMiguel JG. Prophylactic cefamandole in orthopaedic surgery. J Bone Joint Surg (Am) 1984; 66A: 1219-1224. Gatell 1987 (published data only) Gatell JM, Garcia S, Lozano L, Soriano E, Ramon R,. SanMiguel JG. Perioperative cefamandole prophylaxis against infections. J Bone Joint Surg (Am) 1987; 69A: 1189-1193. Hedstrom 1987 (published data only) Hedstrom SA, Lidgren L, Sernbo I, Torholm C, Onnerfalt R. Cefuroxime prophylaxis in trochanteric hip fracture operations. Acta Orthop Scand 1987; 58: 361-364. Hjortrup 1990 (published data only) Hjortrup A, Sorensen C, Mejdahl S, Horsneas M, Kjersgaard P. Antibiotic prophylaxis in surgery for hip fractures. Acta Orth Scand 1990; 61: 152-153. Kjersgaard P, Hjortrup A, Moesgaard F, Horsnaes M. Profylaktiske antibiotika ved operation for hoftefraktur. Ugeskr Laeger 1987; 149: 713-714. Hughes 1991 (published data only) Hughes SP, Miles RS, Littlejohn M, Brown E. Is antibiotic prophylaxis necessary for internal fixation of low-energy fractures? Injury. 1991; 22: 111-3. Jones 1987 B (published data only) Jones RN, Wojeski W, Bakke J, Porter C, Searles M. Antibiotic prophylaxis of 1036 patients undergoing elective surgical procedures. A prospective randomized comparative trial of cefazolin, cefoxitin and cefotaxime in a prepaid medical practice. Am J Surg 1987; 153: 341-346. Karachalios 1987 (published data only) Karachalios T, Lyritis G, Hatzopoulos E, Sapkas G. Single dose prophylaxis of ceftriaxone versus standard dosage of cefotaxime in the prophylaxis of bacterial complications in orthopaedic surgery. Chemioterapia 1987; 6: 573-575. Karachalios Th, Lyritis GP, Hatzopoulos E. Antibiotic prophylaxix in the surgical treatment of trochanteric fractures: a comparative trial between two cephalosporins. Chemotherapy 1990; 36: 448-453. Kaukonen 1995 (published data only) Kaukonen JP, Kemppainen E, Makijarvi J, Touminen T. One dose cefuroxime prophylaxis in hip fracture surgery. Ann Chir Gynaecol 1995; 84: 417-419. McQueen 1990 (unpublished data sought but not used) McQueen MM, Littlejohn MA, Miles RS, Hughes SPF. Antibiotic prophylaxis in proximal femoral fracture. Injury 1990; 21: 104-106. Nelson 1983 (published data only) Nelson CL, Green TG, Porter RA, Warren RD. One day versus seven days of preventive antibiotic therapy in orthopaedic surgery. Clin Orth 1983; 176: 258-263. Heydemann JS, Nelson CL. Short-term preventive antibiotics. Clin Orthop 1986; 205: 184-187. Nungu 1995 (published data only) Nungu KS, Olereud C, Rehnberg L, Larsson S, Nordell P, Alvin I, Bengtsson S, Wallinder L, Hedin G. Prophylaxis with oral cephadril versus intravenous cefuroxime in trochanteric fracture surgery. A clinical multicentre study. Arch Orthop Trauma Surg 1995; 114: 303-307. Nungu KS, Larsson S, Wallinder L, Holm S. Bone and wound fluid concentrations of cephalosporins. Oral cefadroxil and parenteral cefuroxime compared in 52 patients with a trochanteric fracture. Acta Orthop Scand 1995; 66: 161-165. Paiement 1994 (published data only) Paiement GD, Renaud E, Dagenais G, Gosselin RA. Double-blind randomized prospective study of the efficacy of antibiotic prophylaxis for open reduction and internal fixation of closed ankle fractures. J Orthop Trauma 1994; 8: 64-6. Tengve 1978 (published data only) Tengve B, Kjellander J. Antibiotic prophylaxis in operations on trochanteric femoral fractures. J Bone Joint Surg (Am) 1978; 60A: 97-99. * indicates the major publication for the study References to studies excluded from this review Benson 1983 Benson DR, Riggins RS, Lawrence RM, Hoeprich PD, Huston AC, Harrison JA. Treatment of open fractures: a prospective study. J Trauma 1983; 23: 25-30. Braun 1987 Braun R, Enzler MA, Rittmann WW. A double blind clinical trial of prophylactic cloxacillin in open fractures. J Orthop Trauma 1987; 1: 12-17. Centulio 1988 Centulio F, Conticello A. (Antimicrobial chemoprophylaxis with ceftriaxone in surgical implantation of a non-cemented hip prosthesis: comparison of 2 dosage schemes). Chir Organi Mov 1988; 73(4): 357-61. De Benedictis 1984 De Benedictis KJ, Rowan NM, Boyer BL. A double-blind study comparing cefonicid with cefazolin as prophylaxis in patients undergoing total hip or knee replacement. Rev Infect Dis 1984; 6: S901-S904. Dellinger 1988 Dellinger EP, Caplan ES, Weaver LD, Wertz MJ, Droppert BM, Hoyt N, Brumback R, Burgess A, Poka A, Benirschke SK, Lennard ES, Lou MA. Duration of preventive antibiotic administration for open fractures. Arch Surg 1988; 123: 333-339. Evrard 1988 Evrard J, Doyon F, Acar JF, Salord JC, Mazas F, Flamant R. Two day cefeamandole versus five-day cephazolin prophylaxis in 965 total hip replacements. Report of a multicentre double blind randomised trial. Int Orthop 1988; 12: 69-73. Gunst 1984 Gunst JP, Deletang S, Rogez JM, Blanloeil Y, Baron D, Dixneuf B. Antibiotherapie prophylactique par le cefamandole dans la chirurgie de la prosthese totale de hanche sous tente de Charnley. Etude randomisee. Path Biol (Paris) 1984; 32: 567-569. Henley 1986 Henley MB, Jones RE, Wyatt RWB, Hofmann A, Cohen RL. Prophylaxis with cefamandole nafate in elective orthopaedic surgery. Clin Orthop 1986; 209: 249-254. Hill 1981 Hill C, Flamant R, Mazas F, Evrard J. Prophylactic cefazolin versus placebo in total hip replacement. Report of a multicentre double-blind randomised trial. Lancet 1981; 1: 795-797. Johnson 1988 Johnson KD, Bone LB, Scheinberg R. Severe open tibial fractures: a study protocol. J Orthop Trauma 1988; 2: 175-80. Jones 1985 Jones S, DiPiro JT, Nix DE, Bhatti NA. Cephalosporins for prophylaxis in operative repair of femoral fractures. levels in serum, muscle, and hematoma. J Bone Joint Surg (Am) 1985; 67A: 921-924. Jones 1987 A Jones RN, Wojeski WV. Single dose cephalosporin prophylaxis of 929 surgical procedures in a prepaid group practice: a prospective randomized comparison of cefoperazone and cefotaxime. Diagn Microbiol Infect Dis 1987; 6: 323-334. Knapp 1996 Knapp TP, Patzakis MJ, Lee J, Seipel PR, Abdollahi K, Reisch RB. Comparison of intravenous and oral antibiotic therapy in the treatment of fractures caused by low-velocity gunshots. A prospective, randomized study of infection rates. J Bone Joint Surg (AM) 1996; 78: 1167-71. Lidwell 1984 Lidwell OM, Lowbury EJL, Whyte W, Blowers R, Stanley SJ, Lowe D. Infection and sepsis after operations for total hip of knee joint replacement: influence of ultraclean air, prophylactic antibiotics and other factors. J Hyg Camb 1984; 93: 505-529. Mauerhan 1994 Mauerhan DR, Nelson CL, Smith DL, Fitzgerald RH, Slama TG, Petty RW, Jones RE, Evans RP. Prophylaxis against infection in total joint arthroplasty. One day of cefuroxime compared with three days of cefazolin. J Bone Joint Surg (Am) 1994; 76A: 39-45. Mollan 1994 Mollan RAB, Haddock M, Webb CH. Teicoplanin vs cephamandole for antimicrobial prophylaxis in prosthetic joint implant surgery; preliminary results. Eur J Surg 1992; (Suppl 567): 19-21. Patzakis 1977 Patzakis MJ, Ivler D. Antibiotic and bacteriologic considerations in open fractures. Southern Medical Journal 1977; 70 Suppl 1:46-8: 46-8. Pavel 1974 Pavel A, Smith RL, Ballard A, Larson IJ. Prophylactic antibiotics in elective orthopaedic surgery: a prospective study of 1,591 cases. S Med J 1977; 70 (Suppl.1): 50-5. Pavel A, Smith RL, Larsen IJ. Prophylactic antibiotics in clean orthopaedic surgery. J Bone Joint Surg 1974; 56A: 777-782. Periti 1989 Periti P, Jacchia E. Ceftriaxone as short-term antimicrobial chemoprophylaxis in orthopedic surgery: a 1-year multicenter follow-up. Eur J Surg Res 1989; 21: 25-32. Periti 1992 Periti P, Stringa G, Donati L, Mazzei T, Mini E,Novelli A. Teicoplanin- its role in systemic therapy of burns infections and as prophylaxis for orthopaedic surgery. Eur J Surg 1992; (Suppl 567): 3-8. Pollard 1979 Pollard JP, Hughes SP, Scott JE, Evans MJ, Benson MK. Antibiotic prophylaxis in total hip replacement. Br Med J 1979; 1: 707-709. Schulitz 1980 Sculitz KP, Winkellman W, Schoening B. The prophylactic use of antibiotics in alloartroplasty of the hip joint for coxarthrosis. A randomized study. Arch Orthop Trauma Surg 1980; 96: 79-82. Vainionpaa 1988 Vainionpaa S, Wilppula E, Lalla M, Renkonen OV, Rokkanen P. Cefamandole and isoxazolyl penicillins in antibiotic prophylaxis of patients undergoing total hip or knee-joint arthroplasty. Arch Orthop Trauma Surg 1988; 107: 228-230. Van Meirhaeghe 1989 Van Meirhaeghe J, Verdonk R, Vershraegen G, Myny P, Paeme G, Claessens H. Flucloxacillin compared with cefazolin in short-term prophylaxis for clean orthopaedic surgery. Arch Orthop Trauma Surg 1989; 108: 308-313. Visuri 1976 Visuri T, Antila P, Laurent LE. A comparison of dicloxacillin and ampicillin in the antibiotic prophylaxis of total hip replacement. Ann Chirurg Gynaecol 1976; 65: 58-61. Wymenga 1992 Wymenga A, van Horn J, Theeuwes A, Muytjens H, Slooff T. Cefuroxime for prevention of post-operative coxitis. One versus three doses tested in a randomized multi-center study of 2651 arthroplasties. Acta Orthop Scand 1992; 63: 19-24. References to studies awaiting assessment Chiu 1993 Chiu KY, Ng KH, Fung B, Lau SK, Chow SP. A prospective randomized study on four regimes of antibiotic prophylaxis for hip fracture operations. (Abstract) J Bone Joint Surg (Br) 1993; 75B (Suppl III): 230-. Additional references Albers et al 1994 Albers BA, Patka P, Haarman HJTM, Kostense PJ. Kosteneffektivat einer Antibiotikaprophylaxe bei Senkung des Infectionsrisikos um 0,25%. (Cost effectiveness of antibiotic prophylaxis for closed fractures). Unfallchirurg 1994; 97: 625-628. Burke 1961 Burke JF. The effective period of preventive antibiotic action in experimental incision and dermal lesions. Surgery 1961; 50: 161-168. Dickersin et al 1992 Dickersin K, Berlin JA. Meta-analysis: state-of-the-science. Epidemiol Rev 1992; 14: 154-76. Doyon et al 1989 Doyon F, Evrard J, Mazas F. Evaluation des essais therapeutiques publies sur l antibioprophylaxie en chirugie orthopedique. Rev Chir Orth 1989; 75: 72-76. Norden 1991 Norden CW. Antibiotic prophylaxis in orthopaedic surgery. Rev Infect Dis 1991; 13(Suppl.10): S842-6. Platt 1991 Platt R. Methodological aspects of clinical studies of perioperative antibiotic prophylaxis. Rev Infect Dis 1991; 13(Suppl.10): S810-4. Extramural sources of support to the review Intramural sources of support to the review Fig 03 SINGLE DOSE SHORT-ACTING VERSUS MULTIPLE DOSE- SAME AGENT Fig 04 SINGLE DOSE LONG ACTING VERSUS ANY MULTIPLE DOSE REGIMEN Fig 05 OPERATIVE DAY ONLY VERSUS LONGER PROPHYLAXIS Fig 06 ORAL VERSUS PARENTERAL ADMINISTRATION OF ANTIBIOTIC AGENT Bergman BR. Antibiotic prophylaxis in open and closed fractures: a controlled clinical trial. Acta Orthop Scand 1982: 53: 57-62
Short title Antibiotic prophylaxis for closed fracture surgery Reviewer(s) Gillespie WJ, Walenkamp G Date of most recent amendment 14 August 1998 Date of most recent substantive amendment 04 August 1998 Contact address Prof William Gillespie
Dean
Dunedin School of Medicine
PO Box 913
Dunedin
NEW ZEALAND
Telephone: +64 3 479 7149
Facsimile: +64 3 479 5200
E-mail: bill.gillespie@stonebow.otago.ac.nzEditorial group Cochrane Cochrane Musculoskeletal Injuries Sub-Group Editorial group code HM-MUSKINJ This review should be cited as :
Gillespie WJ, Walenkamp G. Antibiotic prophylaxis in patients undergoing surgery for proximal femoral and other closed long bone fractures (Cochrane Review). In: The Cochrane Library, Issue 4, 1998. Oxford: Update Software.Sources of support
Comment, Reply and Editorial notes
The protocol for this review was published under the short title: Antibiotic prophylaxis: hip fracture. The scope of this review has been expanded to include other closed long bone fractures.Table of comparisons
Fig 01 ANTIBIOTIC AGENT (MULTIPLE DOSE) VERSUS PLACEBO OR NO TREATMENT
Fig 02 ANTIBIOTIC AGENT (SINGLE DOSE) VERSUS PLACEBO OR NO TREATMENT Tables of other data
Tables of other data are not available for this review
g = gramStudy Method Participants Interventions Outcomes Notes Bergman 1982 RCT
Location: University Hospital, Sweden
Recruitment period:1974-1977
Adequacy of concealment of assigned allocation: B
Intention to treat analysis: 3
Blinding of outcome assessors: 2
Comparability of treatment groups at entry: 1
Use of placebo: 3
Blinding of participants: 2
Blinding of treatment providers: 2
Comparability of care programmes: 1
Definition of inclusion and exclusion criteria: 1
Definition of outcome measures: 2
Duration of surveillance: 1
Losses to follow up: None described180 analysed (92 women, 88 men, mean age 47 years)
Inclusion criteria: undergoing surgery for closed ankle fracture
Exclusion criteria: None describeda. Dicloxacillin 2g pre-operatively and 6 hourly for 48 hrs
b. Benzyl penicillin 3 million international units (IU), same regimen
c. Saline placebo, same regimen.1. Deep wound infection
2. Superficial wound infection
3. Adverse reactionsThis report also contains data for use of the same regimen in 90 open fractures. The total number of individuals given antibiotics was 270 (antibiotic 177, placebo 93); the adverse reaction data are reported and analysed using these denominators. Bodoky 1993 RCT.
Location: University Hospital, Switzerland.
Recruitment period: 1984-1987
Adequacy of concealment of assigned allocation: A
Intention to treat analysis: 2
Blinding of outcome assessors: 3
Comparability of treatment groups at entry: 3
Use of placebo: 3
Blinding of participants: 3
Blinding of treatment providers: 3
Comparability of care programmes: 3
Definition of inclusion and exclusion criteria: 3
Definition of outcome measures: 3
Duration of surveillance: 1
Losses to follow up: 45 of 284 (16%)239 analysed (female 184, male 55, mean age 77 years)
Inclusion criteria: Undergoing internal fixation for intracapsular hip fracture.
Exclusion criteria: Preexisting infection, Antibiotic allergy, Antibiotic prophylaxis for other reason eg , valve, Immunosuppression, polytrauma.a. Cefotiam 2g induction; 2g once 12 hours later
b. Placebo induction once; 12 hours later1. ""Major"" wound infection. In the analysis, considered as ""deep""
2. ""Minor"" wound infection In the analysis, considered as ""superficial""
3. Urinary tract infection
4. Pulmonary infection
5. Septicaemia
6. Adverse drug effects
7. Infection related death Boxma 1996 RCT.
Location: Multi-centre study, Netherlands.
Recruitment period: 1989-1991
Adequacy of concealment of assigned allocation: A
Intention to treat analysis: 3
Blinding of outcome assessors: 3
Comparability of treatment groups at entry: 3
Use of placebo: 3
Blinding of participants: 3
Blinding of treatment providers: 3
Comparability of care programmes: 1
Definition of inclusion and exclusion criteria: 3
Definition of outcome measures: 2
Duration of surveillance: 2
Losses to follow up:None described2195 analysed (female 1132 mean age 65, male 1063, mean age 44)
Inclusion criteria: undergoing surgery for closed fracture.
Exclusion criteria: External fiation or percutaneous wire fixation, pregnancy, immunosuppressive treatment, known hypersensitivity to cephalosporins, antimicrobial use or symptoms of infection in the week prior to surgery.a. Ceftriaxone 2g given intravenously at induction of anaesthesia for surgery
b. Placebo by same regimen1. Deep wound infection.
2. Superficial wound infection.
3. Respiratory infection
4. Urinary tract infection. Boyd 1973 RCT.
Location: University Hospital, Boston USA
Recruitment period:1966-1969.
Adequacy of concealment of assigned allocation: A
Intention to treat analysis: 1
Blinding of outcome assessors: 2
Comparability of treatment groups at entry: 3
Use of placebo: 3
Blinding of participants: 3
Blinding of treatment providers: 2
Comparability of care programmes: 2
Definition of inclusion and exclusion criteria: 2
Definition of outcome measures: 2
Duration of surveillance: 3
Losses to follow up: 68/348 (20%)280 analysed (female 203, male 77, age range 40-90+)
Inclusion criteria: undergoing operative treatment for proximal femoral fracture, either fixation or endoprosthesis.
Exclusion criteria: Pre-existing infection, Antibiotic allergy.a. Nafcillin systemically 500mg Theatre call; 500mg 6 hourly im for 48 hours
b. Placebo (glucose in saline ) Theatre call; Same regimen1. Deep infection (All infected haematomas were treated as deep infections in the analysis.)
2. Superficial infection
3. Adverse drug effects
4. Infection related death Buckley 1990 RCT.
Location: University Hospital, Canada.
Recruitment period: 1985-1988.
Adequacy of concealment of assigned allocation: A
Intention to treat analysis: 1
Blinding of outcome assessors: 1
Comparability of treatment groups at entry: 2
Use of placebo: 3
Blinding of participants: 2
Blinding of treatment providers: 2
Comparability of care programmes: 3
Definition of inclusion and exclusion criteria: 3
Definition of outcome measures: 2
Duration of surveillance: 2
Losses to follow up: 40/352 (12%)312 analysed (female 225, male 87, mean age 77 years).
Inclusion criteria: undergoing hip fracture surgery.
Exclusion criteria - Cephalosporin allergy, pathologic fracture, previous surgery on fractured hip, antibiotic treatment with other agent, more than 7 days in hospital pre-op.a. Cefazolin 2g iv induction; 1g 6 hourly iv 3 more doses
b. Cefazolin 2g iv induction; placebo (saline) 6 hourly iv 3 doses
c. Placebo (saline) iv induction; placebo (saline) 6 hourly iv 3 doses1. Deep wound infection
2. Superficial wound infectionNumbers of patients allocated to groups a. multiple dose and c. placebo are reversed in some of the text (including the abstract) compared with the tables in the report. We used the numbers which were consistent with the results (percentages etc) given in the report. Burnett 1980 RCT.
Location: County hospital, Minneapolis USA.
Recruitment period: 1973-1977.
Adequacy of concealment of assigned allocation: A
Intention to treat analysis: 2
Blinding of outcome assessors: 3
Comparability of treatment groups at entry: 2
Use of placebo: 3
Blinding of participants: 2
Blinding of treatment providers: 2
Comparability of care programmes: 3
Definition of inclusion and exclusion criteria: 3
Definition of outcome measures: 3
Duration of surveillance: 1
Losses to follow up: 46/307 (15%)261 analysed (161 women, 100 men, mean age 72 years)
Inclusion criteria: undergoing hip fracture surgery.
Exclusion criteria: history of allergy to cephalosporin, active infection requring therapy, history of previous infection about the involved hip.a. Cephalothin 1g iv 4 hourly for 72 hours
b. Placebo iv 4 hourly for 72 hours1. Deep wound infection
2. Urinary tract infection
3. Pulmonary infection
4. Septicaemia
5. Death from infection Ericson 1973 RCT
Location: University and regional hospital, Sweden.
Recruitment period: 1970-1972.
Adequacy of concealment of assigned allocation: B
Intention to treat analysis: 1
Blinding of outcome assessors: 2
Comparability of treatment groups at entry: 1
Use of placebo: 3
Blinding of participants: 2
Blinding of treatment providers: 2
Comparability of care programmes: 3
Definition of inclusion and exclusion criteria: 1
Definition of outcome measures: 2
Duration of surveillance: 2
Losses to follow up: 59/230 (25%) overall; losses for hip fracture sub-group not described. See notes.53 analysed. (39 internal fixation of trochanteric fracture, 14 hemiarthroplasty, mean age 70 years).
Inclusion criteria: undergoing hip arthroplasty for arthritis, or hip fracture surgery.
Exclusion criteria: none described.a. Cloxacillin 1g IM, 1 hour before operation and for three further doses at six hourly intervals. Thereafter 1g orally 6 hourly, with probenecid 1g twice daily until day 14.
b. Placebo to same regimen.1. Wound infection (interpreted as deep infection)
2. Adverse drug reactionsThis report also contains data for use of the same regimen in open fractures. The total number of individuals given antibiotics was 171 (antibiotic 83, placebo 88); the adverse reaction data are reported and analysed using these denominators. Garcia 1991 RCT.
Location: University hospital, Spain.
Recruitment period: 1987-89.
Adequacy of concealment of assigned allocation: A
Intention to treat analysis: 3
Blinding of outcome assessors: 2
Comparability of treatment groups at entry: 3
Use of placebo: 1
Blinding of participants: 1
Blinding of treatment providers: 1
Comparability of care programmes: 2
Definition of inclusion and exclusion criteria: 3
Definition of outcome measures: 3
Duration of surveillance: 3
Losses to follow up: No losses described1489 (976 female, 513 male, mean age 68 years)
Inclusion criteria: undergoing fracture fixation surgery, of which 305 had a Moores arthroplasty inserted, 697 had an Ender nail inserted, and 487 had another device used to fix a closed fracture.
Exclusion criteria: undergoing total joint replacement, known allergy to cephalosporin or penicillin, receiving immunosuppression or antibiotics for other infection, history of infection in the operative field, open fracture.a. Cefonicid 2g iv at induction of anaesthesia
b. Cefamandole 2g iv 3 doses ( 30 minutes pre-op, 2 , 8 hours)
c. Cefamandole 2g iv 5 doses ( 30 minutes pre-op, 2, 8, 14, 20 hours)1. Deep infection
2. Superficial infection
3. Urinary tract infection
4. Respiratory infection
5. Infection related death Gatell 1984 RCT.
Location: University Hospital, Spain.
Recruitment period: not given.
Adequacy of concealment of assigned allocation: B
Intention to treat analysis: 2
Blinding of outcome assessors: 3
Comparability of treatment groups at entry: 1
Use of placebo: 1
Blinding of participants: 3
Blinding of treatment providers: 3
Comparability of care programmes: 1
Definition of inclusion and exclusion criteria: 3
Definition of outcome measures: 2
Duration of surveillance: 3
Losses to follow up: 16 of 300 (6%)284 analysed (169 female, 145 male, mean age 55 years)
Inclusion criteria: undergoing internal fixation of a long bone fracture.
Exclusion criteria: patients having a total joint replacement or a procedure directly involving the hip joint, patients on immunosuppression or with a history of sensitivity to penicillins or cephalosporins.a. Cefamandole 2g by intravenous injection 30 mins before surgery, and at 2, 8,14 and 20 hours after the start of surgery.
b. Placebo using the same regimen as group a.1. Deep wound infection
2. Superficial wound infection Gatell 1987 RCT.
Location: University Hospital, Spain.
Recruitment period: not described.
Adequacy of concealment of assigned allocation: B
Intention to treat analysis: 2
Blinding of outcome assessors: 3
Comparability of treatment groups at entry: 2
Use of placebo: 3
Blinding of participants: 3
Blinding of treatment providers: 3
Comparability of care programmes: 2
Definition of inclusion and exclusion criteria: 3
Definition of outcome measures: 3
Duration of surveillance: 3
Losses to follow up: 33/750 (4%)717 analysed (445 female, 272 male, mean age 65 years).
Inclusion criteria: undergoing closed fracture fixation
Exclusion criteria: Open fractures, previous total joint replacement, known allergy to penicillin or cephalosporin, immunosuppressive treatment, previous infection in the operative field, already on antibiotics.a. Single dose of cefamandole 2g by intravenous injection 30 minutes before start of surgery and four doses of placebo at 2, 8,14, and 20 hours.
b. Cefamandole 2g by intravenous injection 30 minutes before the start of surgery and at 2,8,14, and 20 hours.1. Deep infection
2. Superficial infection
3. Urinary tract infection Hedstrom 1987 RCT.
Location: University Hospitals, Sweden.
Recruitment period: 1982-1984
Adequacy of concealment of assigned allocation: A
Intention to treat analysis: 1
Blinding of outcome assessors: 3
Comparability of treatment groups at entry: 2
Use of placebo: 3
Blinding of participants: 3
Blinding of treatment providers: 3
Comparability of care programmes: 1
Definition of inclusion and exclusion criteria : 2
Definition of outcome measures: 2
Duration of surveillance: 1
Losses to follow up: 26/ 147 (18%)121 analysed (female 87, male 34, mean age 77 years)
Inclusion criteria: undergoing surgery for fixation of trochanteric fracture.
Exclusion criteria: decreased renal function, severe senility, known or suspected allergy to penicillins or cephalosporins.a. 1 day of prophylaxis (cefuroxime 750 mg thrice daily on the operative day followed by 6 days of placebo tablets)
b. 7 days of prophylaxis(cefuroxime 750 mg thrice daily on the operative day followed by cephalexin 0.5g thrice daily orally for 6 days)1. Deep infection
2. Superficial infection
3. Adverse effects Hjortrup 1990 RCT.
Location: Regional Hospital, Denmark.
Adequacy of concealment of assigned allocation: B
Intention to treat analysis: 2
Blinding of outcome assessors: 1
Comparability of treatment groups at entry: 1
Use of placebo: 1
Blinding of participants: 1
Blinding of treatment providers: 1
Comparability of care programmes: 2
Definition of inclusion and exclusion criteria: 2
Definition of outcome measures: 2
Duration of surveillance: 1
Losses to follow up: 15 / 200 (7.5%)185 analysed (female 142, male 43, mean age 80 years)
Inclusion criteria: Undergoing surgery for hip fracture
Exclusion criteria: history of allergy to penicillin, active infection requiring antibiotic therapy, decreased renal function, patients subjected to arthroplasty.a. Single dose Methicillin 2g intravenously at the start of the operation.
b. No antibiotic prophylaxis1. Deep infection
2. Superficial infection Hughes 1991 RCT.
Location: University Hospital, Scotland.
Adequacy of concealment of assigned allocation: B
Intention to treat analysis: 3
Blinding of outcome assessors: 1
Comparability of treatment groups at entry: 3
Use of placebo: 1
Blinding of participants: 1
Blinding of treatment providers: 1
Comparability of care programmes: 2
Definition of inclusion and exclusion criteria: 1
Definition of outcome measures: 1
Duration of surveillance: 1
Losses to follow up: none described54 analysed (15 female, 39 male, mean age 44)
Inclusion criteria: undergoing surgery for low energy closed fractures
Exclusion criteria: none describeda.Cefuroxime 1.5g at induction of anaesthesia
b. No treatment1. Deep wound infection
2. Superficial wound infection
3. Urinary tract infection
4. Respiratory tract infection Jones 1987 B RCT.
Location: Prepaid medical care program, Oregon, USA.
Recruitment period: 1984-1985
Adequacy of concealment of assigned allocation: B
Intention to treat analysis: 2
Blinding of outcome assessors: 1
Comparability of treatment groups at entry: 1 (see notes)
Use of placebo: 1
Blinding of participants: 3
Blinding of treatment providers: 2
Comparability of care programmes: 1
Definition of inclusion and exclusion criteria: 2
Definition of outcome measures: 2
Duration of surveillance: 1
Losses to follow up: 122 of 1036 (12%).914 in main analysis of which analysed of which a subgroup of 58 underwent fracture surgery. No demographic details for the fracture subgroup.
Inclusion criteria: Main analysis:undergoing elective surgery in a range of specialties. Subgroup- undergoing open reduction and fixation of fracture.
Exclusion criteria: Concurrent antibiotic treatment, history of hypersensitivity to cephalosporins or penicillins, pregnancy, preoperative urinary tract infection, renal or hepatic disease.a. Cefazolin 1g by intravenous injection at onset of anaesthesia, and 8 hourly for 24 hrs.
b. Cefoxitin 2g by intravenous injection at onset of anaesthesia and 6 hourly for 24 hrs.
c. Cefotaxime 1g by intravenous injection at onset of anaesthesia (with second dose if operation time exceeded 2 hours)1. Wound infection. (defined as drainage of purulent material from the wound) within 30 days of operation. Demographic data available only for the whole group, but wound infection data for a fracture fixation subgroup. Karachalios 1987 RCT.
Location: University Hospital, Greece.
Recruitment period: Not described.
Adequacy of concealment of assigned allocation: B
Intention to treat analysis: 3
Blinding of outcome assessors: 1
Comparability of treatment groups at entry: 1
Use of placebo: 1
Blinding of participants: 1
Blinding of treatment providers: 1
Comparability of care programmes: 1
Definition of inclusion and exclusion criteria: 3
Definition of outcome measures: 1
Duration of surveillance: 1
Losses to follow up: None during the 10 day follow up period.200 analysed. Demographic details not provided.
Inclusion criteria: undergoing internal fixation of proximal femoral fracture.
Exclusion criteria: Known or suspected hypersenitivity to cephalosporins , concomitant or recent antibiotic use, or evidence of pre-existing infection at the time of surgery.a. Ceftriaxone 1g at start of surgery
b. Cefotaxime 1g at start of surgery and every 8 hours for 3 days.1. Deep wound infection.
2. Superficial wound infection
3. Adverse effects Kaukonen 1995 CCT. (Quasi-randomised- allocation based on odd or even year of birth)
Location: Regional Hospital, Finland.
Recruitment period: 1990-1991 Follow up of variable quality depending on hospital length of stay.
Adequacy of concealment of assigned allocation: C
Intention to treat analysis: 2
Blinding of outcome assessors: 1
Comparability of treatment groups at entry: 1
Use of placebo: 1
Blinding of participants: 1
Blinding of treatment providers: 1
Comparability of care programmes: 1
Definition of inclusion and exclusion criteria: 2
Definition of outcome measures: 1
Duration of surveillance: 1
Losses to follow up: 13 / 162 (8%).149 analysed (female 112, male 37, mean age 76 years)
Inclusion criteria: undergoing operative treatment of hip fracture.
Exclusion criteria: antibiotic treatment for active infection at the time of admission.a. Single dose prophylaxis with cefuroxime 3g at the start of the operation.
b. No antibiotic prophylaxis.1. Deep wound infection
2. Superficial wound infection. McQueen 1990 RCT.
Location: University Hospital , Scotland.
Recruitment period: 1985-1986
Adequacy of concealment of assigned allocation: B
Intention to treat analysis: 2
Blinding of outcome assessors: 2
Comparability of treatment groups at entry: 1
Use of placebo: 3
Blinding of participants: 2
Blinding of treatment providers: 2
Comparability of care programmes: 2
Definition of inclusion and exclusion criteria: 1
Definition of outcome measures: 3
Duration of surveillance: 1
Losses to follow up: Not described502 analysed (434 female, 68 male, mean age 79 yrs)
Inclusion criteria: undergoing surgical management of hip fracture
Exclusion criteria: none describeda. Cefuroxime 1.5g by intravenous injection at start of operation
b. Placebo by intravenous injection at start of operation1. Deep wound infection
2. Superficial wound infection
3. Urinary tract infection
4. Pulmonary infection Nelson 1983 CCT. (Quasi-randomised by last digit of hospital number: odd or even).
Location: University Hospital, USA.
Recruitment period: Not described.
Adequacy of concealment of assigned allocation: C
Intention to treat analysis: 1
Blinding of outcome assessors: 1
Comparability of treatment groups at entry: 1
Use of placebo: 1
Blinding of participants: 1
Blinding of treatment providers: 1
Comparability of care programmes: 1
Definition of inclusion and exclusion criteria: 1
Definition of outcome measures: 2
Duration of surveillance: 3
Losses to follow up: 6 / 358 (2%). 103 men and women undergoing hip fracture surgery. Subgroup within a larger study which also included a further 255 joint replacement patients. No demographic details provided.
Inclusion criteria: undergoing hip fracture surgery
Exclusion criteria: none describeda. Intravenous antibiotics for 24 hours (either nafcillin or cefazolin 500mg 6 hourly, choice being surgeon dependent)
b. Intravenous antibiotics (same agent and dose as in group a) or three days intravenously, and for a subsequent 4 days orally.1. Deep wound infection Nungu 1995 RCT.
Location: Multi-centre recruitment from University and regional Hospitals, Sweden.
Recruitment period: 1991 - 1993.
Adequacy of concealment of assigned allocation: B
Intention to treat analysis: 2
Blinding of outcome assessors: 1
Comparability of treatment groups at entry: 1
Use of placebo: 1
Blinding of participants: 1
Blinding of treatment providers: 1
Comparability of care programmes: 1
Definition of inclusion and exclusion criteria: 2
Definition of outcome measures: 3
Duration of surveillance: 2
Losses to follow up: 107/559 (19%)559 randomised (412 women, 147 men, mean age 81 years). No demographic details for the 452 analysed.
Inclusion criteria: undergoing internal fixation for an extracapsular fracture of the hip.
Exclusion criteria: current antibiotic treatment, known allergy to penicillin or cephalosporin.a.Oral prophylaxis with cefadroxil 1g 2hours before surgery and again at 12 hours.
b. Intravenous prophylaxis with cefuroxime. Regimen was 750 mg at 8 hour intervals in three participating hospitals, and 1.5g as a single dose in one centre.1. Deep wound infection
2. Superficial wound infection Paiement 1994 RCT
Location: Two University Hospitals, USA and Canada
Recruitment period: 1989-1990
Adequacy of concealment of assigned allocation: B
Intention to treat analysis: 2
Blinding of outcome assessors: 1
Comparability of treatment groups at entry: 3
Use of placebo: 3
Blinding of participants: 2
Blinding of treatment providers: 2
Comparability of care programmes: 2
Definition of inclusion and exclusion criteria: 3
Definition of outcome measures: 2
Duration of surveillance: 3
Losses to follow up:3/125 (2%)122 analysed (64 female, 58 male , mean age 43 yrs)
Inclusion criteria: Undergoing surgery for isolated closed fracture
Exclusion criteria: Aged less than 18 years, concomitant infection, surgery delayed over 72 hours, extensive skin blistering, history of allergy to penicillin or cephalosporin, receiving antibiotic or immunosupression.a. Cephalotin 1g at least 7 minutes before application of surgical tourniquet, and 6 hourly for 24 hours.
b. Placebo, same regimen1. Deep infection
2. Superficial infection.
3. Adverse drug reactions (none) Tengve 1978 CCT (Quasi-randomised -allocation by year of birth).
Loaction: Regional Hospital, Sweden.
Recruitment period: 1973-74
Adequacy of concealment of assigned allocation: C
Intention to treat analysis: 1
Blinding of outcome assessors: 1
Comparability of treatment groups at entry: 1
Use of placebo: 1
Blinding of participants: 1
Blinding of treatment providers: 1
Comparability of care programmes:3
Definition of inclusion and exclusion criteria: 2
Definition of outcome measures: 2
Duration of surveillance: 2
Losses to follow up: 13 / 140 (9%).127 analysed (table states 38 women, 89 men, average age 77 years). Female/male ratio is reversed from that expected, and may be an error in the report.
Inclusion criteria: undergoing surgery for trochanteric hip fracture
Exclusion criteria: none described.a.Cephalothin 2g at start of anaesthesia, at two hours, and every six hours until tolerating oral intake; therafter 1g cephalexin orally 6 hourly for total of 48 hours/
b. No prophylaxis.1. Deep infection
2. Superficial infection
iv = intraveneous
im = intra-muscularStudy Reason for exclusion Benson 1983 CCT. Open fracture management. One comparison is of antibiotic management. Braun 1987 RCT. Open extremity fractures only. Comparison: cloxacillin and placebo. Centulio 1988 RCT. Comparison of single dose of ceftriaxone with 3 days of ceftriaxone. Uncemented joint replacement used in hip surgery. 13 hip fracture patients included but no usable data for this subgroup. De Benedictis 1984 RCT. Comparison: cefonicid versus cefazolin. Joint replacement patients only. Dellinger 1988 RCT. Open fracture management. Comparison between one day of antibiotic prophylaxis with a cephalosporin, and five days (2 groups - each a different cephalosporin). Evrard 1988 RCT. Comparison of 5 days of cefazolin versus two days of cefamandole . Hip replacement data only. Gunst 1984 RCT. Comparison: parenteral cefamandole and no antibiotic. Total hip replacement data only. Henley 1986 RCT. Comparison: intravenous cefamandole versus placebo. 130 of 743 participants had fracture surgery, but no usable data for this group are available. Hill 1981 RCT. Comparison: cefazolin by injection over 5 days versus placebo. Total joint replacement patients only. Johnson 1988 RCT. Antibiotic management in open tibial fractures. Jones 1985 RCT. Participants 30 patients undergoing lower limb fracture surgery. Conducted to evaluate levels of three cephalosporins in serum, muscle and haematoma. No usable data on clinical outcomes. Jones 1987 A RCT. Comparison: single dose cefoperazone versus two doses of cefotaxime. Participants included subgroup undergoing joint replacement and other unspecified orthopaedic procedures. No usable data on fracture fixation. Knapp 1996 RCT. Antibiotic management of open fractures caused by gunshot wounds. Lidwell 1984 RCT. Participants: hip and knee replacement. Randomised by clean air or not. Mauerhan 1994 RCT. Comparison one day of cefuroxime compared with three days of cefazolin. Total joint replacement only. Mollan 1994 RCT. Comparison: single dose teicoplanin versus 4 doses of cephamandole over 24 hrs. Total joint replacement patients only. Patzakis 1977 RCT. Comparison of antibiotic regimens in the management of open fractures. Pavel 1974 RCT. Comparison: cephaloridine versus placebo. Participants were udergoing clean orthopaedic surgery, the procedures being unspecified. It is likely that closed fracture patients were amongst these, but there are no usable data. Periti 1989 RCT comparing single dose prophylaxis using ceftriaxone with multi-dose prophylaxis using cefamandole. Only 9 of 883 participants underwent fracture surgery, and no usable data were available. Periti 1992 RCT. Comparison: single dose teicoplanin versus multiple dose cefazolin. All participants underwent total hip or knee replacement. Pollard 1979 RCT. Comparison: 3 doses of cephaloridine versus 14 days of flucloxacillin. Joint replacement patients only. Schulitz 1980 RCT. Joint replacement patients only. Vainionpaa 1988 RCT comparing narrow-spectrum agent (cloxacillin) with a broad spectrum agent (cefamandole). Joint replacement patients only included. Van Meirhaeghe 1989 RCT. Comparison: narrow spectrum antibiotic (flucloxacillin) versus broad spectrum (cefazolin) in clean orthopaedic surgery. A proportion (not described) were fracture fixation but a wide range of other clean orthopaedic operations were included. No usable data for this review. Visuri 1976 CCT (alternation). Narrow spectrum (dicloxacillin) versus broad spectrum (ampicillin) in patients undergoing total joint replacement. Wymenga 1992 RCT. Single dose versus multiple dose of cephalosporin in hip replacement. Some hip fracture patients are included but no data are available for this subgroup.