Cefuroxirne in Total Joint Arthroplasty I n t r a v e n o u s or in B o n e C e m e n t
M. M. McQueen,
F R C S (Ed) O r t h , * S. P. F. H u g h e s , M S , F R C S , * P. M a y , FRCS,-[- a n d L. Verity:[:
Abstract: A prospective randomized clinical trial was performed in two centers to compare the effect of systemic cefuroxime and cefuroxime in bone cement in the prophylaxis of infection after total joint arthroplasty. In two comparable groups comprising 200 and 201 patients, there was no statistically significant difference in the incidence of superficial wound infection. The early deep infection rate was 1%, with no difference detected between the group that received antibiotic in bone cement and the group that received systemic antibiotic. There were no late deep infections. It is concluded that cefuroxime given systemically or in bone cement is an effective antibiotic in the prophylaxis of infection after total joint arthroplasty. Key words: cefuroxime, prophylaxis, arthroplasty, infection, cement.
Infection following total hip or knee arthroplasty is a m a j o r clinical problem, often resulting in further operations and prolonging the patient's hospital stay. Prophylaxis against infection by systemic antibiotics is well established in total joint surgery (12) and includes the use of cefuroxime, a broad-spectrum cephalosporin that is effective against both grampositive and gram-negative organisms, including 13 lactamase-producing strains (7). In addition, antibiotics mixed into bone cement have been s h o w n to be effective in reducing the incidence of infection following arthroplasty (1). Cefuroxime a d d e d to CMW b o n e cement (CMW Lab-
oratories) has been shown: (1) to retain antibacterial activity in vitro (6); (2) to have little or no effect on the elasticity, breaking stress, or torsion of b o n e cem e n t at concentrations required for prophylaxis (9); and (3) to remain in vivo as a potential source.of prophylaxis against infection (7). There are no data to indicate w h e t h e r it is preferable to administer antibiotics systemically or to incorporate t h e m into b o n e cement. This study was set up to c o m p a r e the efficacy of cefuroxime given intravenously and ceftiroxime in b o n e cement in the prophylaxis of early and late infections after total joint arthroplasty.
* From the Department of Orthopaedic Surgery, PrincessMargaret Rose Orthopaedic Hospital Fainnilehead, Edinburgh, Scotland. t From the Bath and Wessex Orthopaedic Hospital Combe Park, Bath, England. ¢ From the Glaxo Group Research Lhnited, 891/995 Greenford Road, Greenford, Middlesex, England.
Materials and Methods A controlled prospective, single blind randomized trial was performed in two centers. Patients were r a n d o m l y assigned to a prophylaxis regime as follows:
Reprint requests: bl. _M. McQueen, FRCS Ed (Orth), Department of Orthopaedic Surgery, Princess Margaret Rose Orthopaedic Hospital, Fairmilehead, Edinburgh, EHI0 7ED, Scotland. 169
170
The Journal of Arthroplasty Vol. 5 No. 2 June 1990
Table 1. Patient Data Intravenous Cement No. of operations Male: female ratio Age (years) Mean Range Principal diagnosis: osteoarthritis Hip Knee
201 67:134
204 85:119
67 30-88 173 190 It
67 19-93 170 190 14
1. 1.5 g of cefuroxime was administered intravenously at induction of anaesthesia, followed by two doses of 750 mg intramuscularly at 6 and 12 hours after operation. 2. 1.5 g of cefuroxime p o w d e r was mixed by the surgeon in the operating r o o m with each pack of CMW type 1 cement powder. Barium sulphate was added simultaneously as a marker. The liquid polymer was added and the operation continued in the usual way. Three hundred seventy-eight patients undergoing 405 operations were entered into the trial. Two hundred one operations were performed using the intravenous program and 204 operations were performed using the bone cement program. The mean age of the patients in both groups was 67 years, with Table 2. Classification of Infection Classification
Description
Deep infection
Infection extending deep to the deep fascia, with persistent wound discharge or joint pain, positive or negative cultures from deep tissues and delay in wound healing Infection superficial to the deep fascia with positive or negative bacteriological cultures and no delay in wound healing Superficial or deep wound infection presenting up to 3 months after operation Superficial or deep wound infection presenting after 3 months and up to 2 years after operation Diagnosed by the presence of two or more of the following: Pain in or around joint, at rest or on movement ESR > 30 mm/hr above preoperative level Pathogenic organisms from joint aspirates Radiological evidence of infection, such as pefiosteal reaction or bone resorption A persistent sinus in communication with the joint
Superficial infection
Early infection Late infection
a female to male ratio of 2 : 1. The principal diagnosis in both groups was osteoarthritis. There were 190 patients in each group receiving total hip arthroplastics, with 11 total knees in the intravenous group and 14 in the bone cement group (Table i). Drainage was initiated in all patients. Either the posterior, anterolateral, or lateral approach to the hip joint or a midline incision to the knee joint was used. The w o u n d s were inspected by a research nurse and were classified as superficial or deep infections and as early or late (Table 2). All patients were followed for a period of 2 years after the operation.
Results In the intravenous group one patient died leaving 200 patients for study. In the bone cement group two patients died and one patient was lost to follow-up, leaving 201 patients for study. There were eight early superficial infections in the systemic group (4%) and 18 superficial infections in the cement group (9%). This difference was not statistically significant. The organisms encountered were predominantly Staphylococctts attreus or coagulase-negafive staphylococci. A detailed report of the postoperative superficial infections of patients treated intravenously and patients treated with cement is s h o w n in Tables 3 and 4, respectively. None of the patients with superficial infection went on to develop deep infection within the 2-year follow-up period. There was an overall deep infection rate of 1%. Two patients in the intravenous group and two patients in the cement group developed early deep infections (Table 5). There were no ]ate deep infections. We analyzed the use of drainage, the type of approach to the hip joint, the type of prosthesis, and
Table 3. Details of Postoperative Superficial Wound Infections in Patients Treated Intravenously Joint
Time after Operation (days)
Hip
6
Hip Hip Hip Hip Hip Hip Hip
6 8 8 9 7 4 7
Organism Staphylococcus anaerobes Staphylococcus Staphylococcus Staphylococcus Staphylococcus Staphylococcus Enterococci Staphylococcus
epidermidis aureus aureus aureus epidermidis epidermidis aureus
Cefuroxime in Total Joint Arthroplasty
Table 4. Details of Postoperative Superficial Wound Infections in Patients Receiving Cefuroxime Cement Joint
Time after Operation (days)
Hip
14
Hip Hip
4 8
Knee Knee Hip Hip Knee Hip
7 10 3 7 6 9
Knee Hip Hip Hip Hip Hip Hip Hip Hip
9 4 13 2 4 8 12 >28 >28
Organism Staphylococcus epidennidis, later Staphylococcus aureus Staphylococcus epidermidis Staphylococcus epidennidis Micrococcus sp Escherichia coil Escherichia coli
No growth Staphylococcus aureus
No growth Streptococcus faecalis
No growth Escherichia coli, later Staphylococcus epidennidis
No growth No growth No growth Diptheroides + coliforms Staphylococcus epidermidis Staphylococcus aureus
No growth No growth No growth
the length of the operation, but no difference in infection rates was found. A n u m b e r of patients in each group suffered from associated infections, such as postoperative chest infections, and urinary tract infections. Indeed, urinary tract infections were found in a n u m b e r of patients before operation, but n o n e of these patients subsequently developed superficial or deep w o u n d infections or had their hospital stay prolonged by infection.
•
McQueen et al.
171
fection rates b e t w e e n the two methods. The overall deep infection rate of 1% is comparable to other reported results (I, 7, 8). Cefuroxime is therefore an effective antibiotic in the prevention of infection after total joint arthroplasty and its m o d e of administration does not cause a n y important differences in the prevention of w o u n d infection. This is at variance with the results ofJosefsson et al. (9), which revealed a clear statistical benefit in administering gentamicin in bone cement c o m p a r e d with a n u m b e r of different systemically administered antibiotics given over a variable period of time. Our study, however, compares two routes of administration of the same antibiotic with the same dose, and the results are presumably m o r e reliable. The release of antibiotics following systemic injection is well established, being relatively rapid and depending on the efficiency of the vascular system and the available fluid space (11). In contrast, h o w ever, Law et al. (10) demonstrated that the release of antibiotic from bone cement after initial dispersion is extremely slow and m a y take several years, with m i n u t e quantities being released at any one time. Our clinical results imply that neither the speed of the antibiotic n o r the length of time that the antibiotic is present locally are important in the prevention of deep infection. No resistance emerged in our study although the a p p e a r a n c e of coagulase-negarive staphylococci recently reported by Hope et al (4) is worrisome. In conclusion, cefuroxime given either intravenously or in bone cement is an adequate method of preventing deep infection in total joint arthroplasty. Our current practice is to administer cefuroxime intravenously in three doses as described in this study, as this is most convenient.
Discussion Acknowledgment This is a report of a prospective trial conducted by two separate hospitals in order to evaluate the role of systemic and locally applied antibiotic. The antibiotic dose was the same w h e t h e r given systemically or locally, and we found no difference in deep in-
The authors t h a n k Glaxo Group Research Ltd. for supplying the antibiotic and the Consultants at Princess Margaret Rose Orthopaedic Hospital and Bath and Wessex Orthopaedic Hospital for allowing their patients to take part in this study.
Table 5. Details of Deep Wound Infections Study Group Joint Bone cement Bone cement Intravenous Intravenous
Hip Hip Knee Hip
Bacteriology
References
Staphylococcus aureus and coliforms
No growth No growth Staphylococcus attreus
Bucholz ttW, Engelbrecht ti: Uber die deportwirkung einiger antibiotica bie vermischung mit dem kunstharz palacos. Chirurg 41:511, 1970
172
The Journal of Arthroplasty Vol. 5 No. 2 June 1990
2. Coventry MB, Beckenbau~h RD, Molan DR, llstrup DM: 2012 Total hip arthroplasties: a study of the postoperative course and early complications. J Bone Joint Surg 56A:808, 1974 3. Fitzgerald RH, Nolan DR, llstrup DM et al: Deep wound sepsis following total hip arthroplasw. J Bone Joint Surg 59A:847, 1977 4. ttope PG, Kirstinsson KG, Norman P, Elson R: Deep infection of cemented total hip arthroplasties caused by coagulase-negative staphylococci. J Bone Joint Surg 70B:681, 198:8 5. Hughes SPF, Want S, Darrell JH et al: Prophylactic cefuroxime in total joint replacement. Int Orthop 6:155, 1982 6. Hughes SPF, Field CA, Kennedy MRK, Dash C H : Cephalosporins in bone cement. J Bone Joint Surg 61B:96, 1979 7. Innes A, Hughes SOF, Robertson S, Dash CH: Cefu-
8.
9. 10.
11.
12,
roxime in CMW bone cement: A clinical study. Int Orthop 9:265, 1986 Josefsson G, Lindberg L, Wiklander B: Systemic antibiotics and gentamicin-containing bone cement in the prophylaxis of postoperative infections in total hip arthroplasw. Clin Orthop 159:194, 1981 Law HT: Biomechanics ofbone cement. Semin Orthop 1:23, 1986 Law HT, Fleming RH, Gilmore M e t al: In vitro measurement and computer'modelling of the diffusion of antibiotic in bone cement. J Biomed Eng 8:149, 1986 Pinto M, Fleming RH, Hughes SPF et al: The volume of distribution of ceftazidime and albumin in normal, immature and infected bone. J Antimicrob Chemother 18:381, 1986 Pollard JP, Hughes SPF, Scott J E e t ah Antibiotic prophylaxis in total hip replacement. Br Med J t:707, 1979
M. M. McQueen,
F R C S (Ed) O r t h , * S. P. F. H u g h e s , M S , F R C S , * P. M a y , FRCS,-[- a n d L. Verity:[:
Abstract: A prospective randomized clinical trial was performed in two centers to compare the effect of systemic cefuroxime and cefuroxime in bone cement in the prophylaxis of infection after total joint arthroplasty. In two comparable groups comprising 200 and 201 patients, there was no statistically significant difference in the incidence of superficial wound infection. The early deep infection rate was 1%, with no difference detected between the group that received antibiotic in bone cement and the group that received systemic antibiotic. There were no late deep infections. It is concluded that cefuroxime given systemically or in bone cement is an effective antibiotic in the prophylaxis of infection after total joint arthroplasty. Key words: cefuroxime, prophylaxis, arthroplasty, infection, cement.
Infection following total hip or knee arthroplasty is a m a j o r clinical problem, often resulting in further operations and prolonging the patient's hospital stay. Prophylaxis against infection by systemic antibiotics is well established in total joint surgery (12) and includes the use of cefuroxime, a broad-spectrum cephalosporin that is effective against both grampositive and gram-negative organisms, including 13 lactamase-producing strains (7). In addition, antibiotics mixed into bone cement have been s h o w n to be effective in reducing the incidence of infection following arthroplasty (1). Cefuroxime a d d e d to CMW b o n e cement (CMW Lab-
oratories) has been shown: (1) to retain antibacterial activity in vitro (6); (2) to have little or no effect on the elasticity, breaking stress, or torsion of b o n e cem e n t at concentrations required for prophylaxis (9); and (3) to remain in vivo as a potential source.of prophylaxis against infection (7). There are no data to indicate w h e t h e r it is preferable to administer antibiotics systemically or to incorporate t h e m into b o n e cement. This study was set up to c o m p a r e the efficacy of cefuroxime given intravenously and ceftiroxime in b o n e cement in the prophylaxis of early and late infections after total joint arthroplasty.
* From the Department of Orthopaedic Surgery, PrincessMargaret Rose Orthopaedic Hospital Fainnilehead, Edinburgh, Scotland. t From the Bath and Wessex Orthopaedic Hospital Combe Park, Bath, England. ¢ From the Glaxo Group Research Lhnited, 891/995 Greenford Road, Greenford, Middlesex, England.
Materials and Methods A controlled prospective, single blind randomized trial was performed in two centers. Patients were r a n d o m l y assigned to a prophylaxis regime as follows:
Reprint requests: bl. _M. McQueen, FRCS Ed (Orth), Department of Orthopaedic Surgery, Princess Margaret Rose Orthopaedic Hospital, Fairmilehead, Edinburgh, EHI0 7ED, Scotland. 169
170
The Journal of Arthroplasty Vol. 5 No. 2 June 1990
Table 1. Patient Data Intravenous Cement No. of operations Male: female ratio Age (years) Mean Range Principal diagnosis: osteoarthritis Hip Knee
201 67:134
204 85:119
67 30-88 173 190 It
67 19-93 170 190 14
1. 1.5 g of cefuroxime was administered intravenously at induction of anaesthesia, followed by two doses of 750 mg intramuscularly at 6 and 12 hours after operation. 2. 1.5 g of cefuroxime p o w d e r was mixed by the surgeon in the operating r o o m with each pack of CMW type 1 cement powder. Barium sulphate was added simultaneously as a marker. The liquid polymer was added and the operation continued in the usual way. Three hundred seventy-eight patients undergoing 405 operations were entered into the trial. Two hundred one operations were performed using the intravenous program and 204 operations were performed using the bone cement program. The mean age of the patients in both groups was 67 years, with Table 2. Classification of Infection Classification
Description
Deep infection
Infection extending deep to the deep fascia, with persistent wound discharge or joint pain, positive or negative cultures from deep tissues and delay in wound healing Infection superficial to the deep fascia with positive or negative bacteriological cultures and no delay in wound healing Superficial or deep wound infection presenting up to 3 months after operation Superficial or deep wound infection presenting after 3 months and up to 2 years after operation Diagnosed by the presence of two or more of the following: Pain in or around joint, at rest or on movement ESR > 30 mm/hr above preoperative level Pathogenic organisms from joint aspirates Radiological evidence of infection, such as pefiosteal reaction or bone resorption A persistent sinus in communication with the joint
Superficial infection
Early infection Late infection
a female to male ratio of 2 : 1. The principal diagnosis in both groups was osteoarthritis. There were 190 patients in each group receiving total hip arthroplastics, with 11 total knees in the intravenous group and 14 in the bone cement group (Table i). Drainage was initiated in all patients. Either the posterior, anterolateral, or lateral approach to the hip joint or a midline incision to the knee joint was used. The w o u n d s were inspected by a research nurse and were classified as superficial or deep infections and as early or late (Table 2). All patients were followed for a period of 2 years after the operation.
Results In the intravenous group one patient died leaving 200 patients for study. In the bone cement group two patients died and one patient was lost to follow-up, leaving 201 patients for study. There were eight early superficial infections in the systemic group (4%) and 18 superficial infections in the cement group (9%). This difference was not statistically significant. The organisms encountered were predominantly Staphylococctts attreus or coagulase-negafive staphylococci. A detailed report of the postoperative superficial infections of patients treated intravenously and patients treated with cement is s h o w n in Tables 3 and 4, respectively. None of the patients with superficial infection went on to develop deep infection within the 2-year follow-up period. There was an overall deep infection rate of 1%. Two patients in the intravenous group and two patients in the cement group developed early deep infections (Table 5). There were no ]ate deep infections. We analyzed the use of drainage, the type of approach to the hip joint, the type of prosthesis, and
Table 3. Details of Postoperative Superficial Wound Infections in Patients Treated Intravenously Joint
Time after Operation (days)
Hip
6
Hip Hip Hip Hip Hip Hip Hip
6 8 8 9 7 4 7
Organism Staphylococcus anaerobes Staphylococcus Staphylococcus Staphylococcus Staphylococcus Staphylococcus Enterococci Staphylococcus
epidermidis aureus aureus aureus epidermidis epidermidis aureus
Cefuroxime in Total Joint Arthroplasty
Table 4. Details of Postoperative Superficial Wound Infections in Patients Receiving Cefuroxime Cement Joint
Time after Operation (days)
Hip
14
Hip Hip
4 8
Knee Knee Hip Hip Knee Hip
7 10 3 7 6 9
Knee Hip Hip Hip Hip Hip Hip Hip Hip
9 4 13 2 4 8 12 >28 >28
Organism Staphylococcus epidennidis, later Staphylococcus aureus Staphylococcus epidermidis Staphylococcus epidennidis Micrococcus sp Escherichia coil Escherichia coli
No growth Staphylococcus aureus
No growth Streptococcus faecalis
No growth Escherichia coli, later Staphylococcus epidennidis
No growth No growth No growth Diptheroides + coliforms Staphylococcus epidermidis Staphylococcus aureus
No growth No growth No growth
the length of the operation, but no difference in infection rates was found. A n u m b e r of patients in each group suffered from associated infections, such as postoperative chest infections, and urinary tract infections. Indeed, urinary tract infections were found in a n u m b e r of patients before operation, but n o n e of these patients subsequently developed superficial or deep w o u n d infections or had their hospital stay prolonged by infection.
•
McQueen et al.
171
fection rates b e t w e e n the two methods. The overall deep infection rate of 1% is comparable to other reported results (I, 7, 8). Cefuroxime is therefore an effective antibiotic in the prevention of infection after total joint arthroplasty and its m o d e of administration does not cause a n y important differences in the prevention of w o u n d infection. This is at variance with the results ofJosefsson et al. (9), which revealed a clear statistical benefit in administering gentamicin in bone cement c o m p a r e d with a n u m b e r of different systemically administered antibiotics given over a variable period of time. Our study, however, compares two routes of administration of the same antibiotic with the same dose, and the results are presumably m o r e reliable. The release of antibiotics following systemic injection is well established, being relatively rapid and depending on the efficiency of the vascular system and the available fluid space (11). In contrast, h o w ever, Law et al. (10) demonstrated that the release of antibiotic from bone cement after initial dispersion is extremely slow and m a y take several years, with m i n u t e quantities being released at any one time. Our clinical results imply that neither the speed of the antibiotic n o r the length of time that the antibiotic is present locally are important in the prevention of deep infection. No resistance emerged in our study although the a p p e a r a n c e of coagulase-negarive staphylococci recently reported by Hope et al (4) is worrisome. In conclusion, cefuroxime given either intravenously or in bone cement is an adequate method of preventing deep infection in total joint arthroplasty. Our current practice is to administer cefuroxime intravenously in three doses as described in this study, as this is most convenient.
Discussion Acknowledgment This is a report of a prospective trial conducted by two separate hospitals in order to evaluate the role of systemic and locally applied antibiotic. The antibiotic dose was the same w h e t h e r given systemically or locally, and we found no difference in deep in-
The authors t h a n k Glaxo Group Research Ltd. for supplying the antibiotic and the Consultants at Princess Margaret Rose Orthopaedic Hospital and Bath and Wessex Orthopaedic Hospital for allowing their patients to take part in this study.
Table 5. Details of Deep Wound Infections Study Group Joint Bone cement Bone cement Intravenous Intravenous
Hip Hip Knee Hip
Bacteriology
References
Staphylococcus aureus and coliforms
No growth No growth Staphylococcus attreus
Bucholz ttW, Engelbrecht ti: Uber die deportwirkung einiger antibiotica bie vermischung mit dem kunstharz palacos. Chirurg 41:511, 1970
172
The Journal of Arthroplasty Vol. 5 No. 2 June 1990
2. Coventry MB, Beckenbau~h RD, Molan DR, llstrup DM: 2012 Total hip arthroplasties: a study of the postoperative course and early complications. J Bone Joint Surg 56A:808, 1974 3. Fitzgerald RH, Nolan DR, llstrup DM et al: Deep wound sepsis following total hip arthroplasw. J Bone Joint Surg 59A:847, 1977 4. ttope PG, Kirstinsson KG, Norman P, Elson R: Deep infection of cemented total hip arthroplasties caused by coagulase-negative staphylococci. J Bone Joint Surg 70B:681, 198:8 5. Hughes SPF, Want S, Darrell JH et al: Prophylactic cefuroxime in total joint replacement. Int Orthop 6:155, 1982 6. Hughes SPF, Field CA, Kennedy MRK, Dash C H : Cephalosporins in bone cement. J Bone Joint Surg 61B:96, 1979 7. Innes A, Hughes SOF, Robertson S, Dash CH: Cefu-
8.
9. 10.
11.
12,
roxime in CMW bone cement: A clinical study. Int Orthop 9:265, 1986 Josefsson G, Lindberg L, Wiklander B: Systemic antibiotics and gentamicin-containing bone cement in the prophylaxis of postoperative infections in total hip arthroplasw. Clin Orthop 159:194, 1981 Law HT: Biomechanics ofbone cement. Semin Orthop 1:23, 1986 Law HT, Fleming RH, Gilmore M e t al: In vitro measurement and computer'modelling of the diffusion of antibiotic in bone cement. J Biomed Eng 8:149, 1986 Pinto M, Fleming RH, Hughes SPF et al: The volume of distribution of ceftazidime and albumin in normal, immature and infected bone. J Antimicrob Chemother 18:381, 1986 Pollard JP, Hughes SPF, Scott J E e t ah Antibiotic prophylaxis in total hip replacement. Br Med J t:707, 1979
