Comparison of Three Methods of Antibiotic Prophylaxis in Knee Arthroplasty J. Field, BSc, FRCS, J. Webb, MB, ChB, G. C. Bannister, MCh Orth, FRCS Ed Orth, FRCS, A. M. Lovering, BSc, PhD, and D. S. Reeves, MD, FRCPath
Abstract" Prophylactic intravenous cefamandole nafate was administered by the systemic, systemic with probenecid (causing renal tubular blockade of antibiotic excretion), and intravenous regional routes. Bone antibiotic levels were assayed 15 minutes and 12 hours after administration, and hematoma concentrations after 8 hours. Bone concentrations after intravenous regional administration were significantly greater than systemic after 15 minutes, but were not detectable after 12 hours. Probenecid produced inhibitory concentrations in bone after 12 hours and also increased hematoma antibiotic concentrations to three times those achieved by systemic administration. Adequate prophylaxis may be possible with two rather than three doses of cefamandole if probenecid is used. K e y words" antibiotic prophylaxis, tourniquet, hematoma, beta-lactam, probenecid.
the hematoma contributes to preventing infection (4). There appeared a need to explore the possibility of enhancing local antibiotic concentration so that (1) fewer doses of antibiotic might be required, and (2) superior hematoma levels obtained. Prevention of excretion by renal tubular blockade with probenecid or intravenous regional administration (3) merited consideration.
Infection following knee arthroplasty often results in removal of the prosthesis. Antibiotic prophylaxis is the most accessible and effective measure for reducing infection in joint replacement (5, 7). Unidirectional ultraclean air enclosures may not be advantageous in total knee arthroplasty (13). The spectrum of organisms causing infection is covered best by second-generation cephalosporins, of which cefamandole is an example. Prophylaxis for infection accounts for one in three courses of antibiotics (6). Second-generation cephalosporins are expensive, costing five times as much as isoxazolyl penicillins. Costs cannot be reduced by single-dose prophylaxis, as this does not reduce the incidence of deep infection (6, 11 ), and three or more doses covering a 24-hour period seem ~o be necessary (12). Experimentally the level of antibiotic in
Materials and Methods One gram of cefamandole nafate was administered to five groups of five patients undergoing joint replacement. The first group received the antibiotic intravenously at induction of anesthesia. The second group underwent renal tubular blockade with probenecid 500 mg orally 12 hours before intravenous antibiotic administration. The third group had their lower limb isolated from the systemic circulation by exsanguination and application of a tourniquet, and cefamandole in 100 ml saline was perfused region-
From the Departments of Orthopaedics and Microbiology, Southmead Hospital, Bristol, United Kingdom. Reprint requests: G. C. Bannister, Department of Orthopaedic Surgery, Medical School Block, Southmead Hospital, Westbury on Trym, Bristol BSIO 5NB, United Kingdom.
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The Journal of Arthroplasty Vol. 7 No. 1 March 1992 T a b l e 1. Comparison of Three Methods of Antibiotic Prophylaxis in Knee Arthroplasty
Bone levels at 15 r a i n Bone levels after 12 hr Hematoma levels after 8 hr
Route of Administration
No. of Patients
Intravenous regional Systemic Systemic and probenecid Intravenous regional Systemic Intravenous regional Systemic and probenecid
5 5 5 5 5 6 5
Level (mg/l) Mean SD
38.36 26.6 1.45 0 3.4 6.88 10.3
8.1 8.2 0.54 0 1.4 4.1 5.4
ally via a foot vein. Cancellous bone samples were taken from all three groups at operation after 15 minutes and h e m a t o m a from suction drains 8 hours after antibiotic administration. The fourth group received antibiotic systemically with probenecid 12 hours before bone sampling. The fifth group received intravenous regional antibiotic for 15 minutes I2 hours before bone sampling. Samples were assayed for the presence of cefamandole either by bioassay (10) or by high-performance liquid chromatography (8).
ceiving intravenous regional antibiotic were exposed for the duration of tourniquet time, and it is possible that higher and more prolonged levels of cefamandole pertained in practice. Of the two methods of enhancing local cefamandole administration, renal tubular blockade seems more effective, as it not only increases h e m a t o m a concentrations but offers the prospect of effective 24hour prophylaxis using two doses of antibiotic.
Statistical Analysis
References
Data were analyzed using Student's t-test..
Results The results are summarized in Table 1. Bone levels of cefamandole 15 minutes after intravenous regional infusion were higher than concentrations after systemic administration reported previously (2) (P < .05). Bone Ievels 12 hours after intravenous regional infusion were not detectable in any of the five patients. However, after renal tubular blockade, cefamandole bone levels exceeded the m i n i m u m inhibitory concentration for Staphylococcus aureus. The h e m a t o m a levels after 8 hours were higher after renal tubular blockade than after systemic administration (P < .001), as were those following the regional intravenous route.
Discussion The clinical efficacy of antibiotic prophylaxis by both systemic (5, 7) and bone cement routes (9) has been clearly demonstrated. Experimentally, hematoma concentrations w o u l d appear to play a role. While the tourniquet has been s h o w n to exclude antibiotic from the vulnerable site of surgery (i), it can also enhance it provided that the intravenous regional route is employed. At operation, patients re-
1, Bannister GC, Auchincloss JM, Johnson DP, Newman JH: The timing of tourniquet application in relation to antibiotic administration. J Bone Joint Surg 70B:322, 1988 2. Bannister GC, Bitounis B, James T et al: The pharmacodynamics of prophylaxis in joint replacement. Acta Orthop Hell 40:35, 1989 3. Bier A: Weber Einen Leg Local Anaesthetic En Den Gleidmassen Zu Erzeugen. Arch Clin Chir 86:1007, 1908 4. Bowers WH, Wilson FC, Greene WB: Antibiotic prophylaxis in experimental bone infections. J Bone Joint Surg 55A:795, 1973 5. Ericson C, Lidgren L, Lindberg L: Cloxacillin in prophylaxis of postoperative infections of the hip. J Bone Joint Surg 55A:808, 1973 6. Gatell JM, Riba J, Lozanxo ML et al: Prophylactic cefamandole in orthopaedic surgery. J Bone Joint Surg 66A:1219, 1984 7. Hill C, Mazas F, Flamont R, Evard J: Prophylactic cephazolin versus placebo in total hip replacement. Report of a multicentre double blind randomised trial. Lancet 1:795, 1981 8. Hodinott C, Lovering AM, Fernando HC et al: Deterruination of bone and fat concentrations following systemic cefamandole and intravenous regional cefuroxime in patients undergoing knee arthroplasty. J Antimicrob Chemother 26:823-829, 1990 9. Joseffson G, Lindberg L, Wiklander L: Systemic antibiotics and gentamicin-containing bone cement in
Antibiotic Prophylaxis in Knee Arthroplasty the prophylaxis of postoperative infections in total hip arthroplasty. CIin Orthop 159:194, 1981 10. Leigh DA, Marriner J, Nisbet D et al: Bone concentrations of cefuroxime and cefamandole in the femoral head in 96 patients undergoing total hip replacement surgery. J Antimicrob Chemother 9:303, 1982 11. McQueen MM, Littlejohn MA, Miles RS, Hughes SPF: Antibiotics in proximal femoral neck fracture. Injury 21:104, 1990
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Field et al.
19
12. Nelson CL, Green TG, Porter RA, Warren RD: One day versus seven days of preventative antibiotic therapy in orthopaedic surgery. Clin Orthop 176:258, 1973 13. Salvati EA, Robinson RP, Send SM et al: Infection rates after 3175 total hip and knee replacements performed with and without a horizontal unidirectional filtered air flow system. J Bone Joint Surg 64A:525, 1982
Abstract" Prophylactic intravenous cefamandole nafate was administered by the systemic, systemic with probenecid (causing renal tubular blockade of antibiotic excretion), and intravenous regional routes. Bone antibiotic levels were assayed 15 minutes and 12 hours after administration, and hematoma concentrations after 8 hours. Bone concentrations after intravenous regional administration were significantly greater than systemic after 15 minutes, but were not detectable after 12 hours. Probenecid produced inhibitory concentrations in bone after 12 hours and also increased hematoma antibiotic concentrations to three times those achieved by systemic administration. Adequate prophylaxis may be possible with two rather than three doses of cefamandole if probenecid is used. K e y words" antibiotic prophylaxis, tourniquet, hematoma, beta-lactam, probenecid.
the hematoma contributes to preventing infection (4). There appeared a need to explore the possibility of enhancing local antibiotic concentration so that (1) fewer doses of antibiotic might be required, and (2) superior hematoma levels obtained. Prevention of excretion by renal tubular blockade with probenecid or intravenous regional administration (3) merited consideration.
Infection following knee arthroplasty often results in removal of the prosthesis. Antibiotic prophylaxis is the most accessible and effective measure for reducing infection in joint replacement (5, 7). Unidirectional ultraclean air enclosures may not be advantageous in total knee arthroplasty (13). The spectrum of organisms causing infection is covered best by second-generation cephalosporins, of which cefamandole is an example. Prophylaxis for infection accounts for one in three courses of antibiotics (6). Second-generation cephalosporins are expensive, costing five times as much as isoxazolyl penicillins. Costs cannot be reduced by single-dose prophylaxis, as this does not reduce the incidence of deep infection (6, 11 ), and three or more doses covering a 24-hour period seem ~o be necessary (12). Experimentally the level of antibiotic in
Materials and Methods One gram of cefamandole nafate was administered to five groups of five patients undergoing joint replacement. The first group received the antibiotic intravenously at induction of anesthesia. The second group underwent renal tubular blockade with probenecid 500 mg orally 12 hours before intravenous antibiotic administration. The third group had their lower limb isolated from the systemic circulation by exsanguination and application of a tourniquet, and cefamandole in 100 ml saline was perfused region-
From the Departments of Orthopaedics and Microbiology, Southmead Hospital, Bristol, United Kingdom. Reprint requests: G. C. Bannister, Department of Orthopaedic Surgery, Medical School Block, Southmead Hospital, Westbury on Trym, Bristol BSIO 5NB, United Kingdom.
17
18
The Journal of Arthroplasty Vol. 7 No. 1 March 1992 T a b l e 1. Comparison of Three Methods of Antibiotic Prophylaxis in Knee Arthroplasty
Bone levels at 15 r a i n Bone levels after 12 hr Hematoma levels after 8 hr
Route of Administration
No. of Patients
Intravenous regional Systemic Systemic and probenecid Intravenous regional Systemic Intravenous regional Systemic and probenecid
5 5 5 5 5 6 5
Level (mg/l) Mean SD
38.36 26.6 1.45 0 3.4 6.88 10.3
8.1 8.2 0.54 0 1.4 4.1 5.4
ally via a foot vein. Cancellous bone samples were taken from all three groups at operation after 15 minutes and h e m a t o m a from suction drains 8 hours after antibiotic administration. The fourth group received antibiotic systemically with probenecid 12 hours before bone sampling. The fifth group received intravenous regional antibiotic for 15 minutes I2 hours before bone sampling. Samples were assayed for the presence of cefamandole either by bioassay (10) or by high-performance liquid chromatography (8).
ceiving intravenous regional antibiotic were exposed for the duration of tourniquet time, and it is possible that higher and more prolonged levels of cefamandole pertained in practice. Of the two methods of enhancing local cefamandole administration, renal tubular blockade seems more effective, as it not only increases h e m a t o m a concentrations but offers the prospect of effective 24hour prophylaxis using two doses of antibiotic.
Statistical Analysis
References
Data were analyzed using Student's t-test..
Results The results are summarized in Table 1. Bone levels of cefamandole 15 minutes after intravenous regional infusion were higher than concentrations after systemic administration reported previously (2) (P < .05). Bone Ievels 12 hours after intravenous regional infusion were not detectable in any of the five patients. However, after renal tubular blockade, cefamandole bone levels exceeded the m i n i m u m inhibitory concentration for Staphylococcus aureus. The h e m a t o m a levels after 8 hours were higher after renal tubular blockade than after systemic administration (P < .001), as were those following the regional intravenous route.
Discussion The clinical efficacy of antibiotic prophylaxis by both systemic (5, 7) and bone cement routes (9) has been clearly demonstrated. Experimentally, hematoma concentrations w o u l d appear to play a role. While the tourniquet has been s h o w n to exclude antibiotic from the vulnerable site of surgery (i), it can also enhance it provided that the intravenous regional route is employed. At operation, patients re-
1, Bannister GC, Auchincloss JM, Johnson DP, Newman JH: The timing of tourniquet application in relation to antibiotic administration. J Bone Joint Surg 70B:322, 1988 2. Bannister GC, Bitounis B, James T et al: The pharmacodynamics of prophylaxis in joint replacement. Acta Orthop Hell 40:35, 1989 3. Bier A: Weber Einen Leg Local Anaesthetic En Den Gleidmassen Zu Erzeugen. Arch Clin Chir 86:1007, 1908 4. Bowers WH, Wilson FC, Greene WB: Antibiotic prophylaxis in experimental bone infections. J Bone Joint Surg 55A:795, 1973 5. Ericson C, Lidgren L, Lindberg L: Cloxacillin in prophylaxis of postoperative infections of the hip. J Bone Joint Surg 55A:808, 1973 6. Gatell JM, Riba J, Lozanxo ML et al: Prophylactic cefamandole in orthopaedic surgery. J Bone Joint Surg 66A:1219, 1984 7. Hill C, Mazas F, Flamont R, Evard J: Prophylactic cephazolin versus placebo in total hip replacement. Report of a multicentre double blind randomised trial. Lancet 1:795, 1981 8. Hodinott C, Lovering AM, Fernando HC et al: Deterruination of bone and fat concentrations following systemic cefamandole and intravenous regional cefuroxime in patients undergoing knee arthroplasty. J Antimicrob Chemother 26:823-829, 1990 9. Joseffson G, Lindberg L, Wiklander L: Systemic antibiotics and gentamicin-containing bone cement in
Antibiotic Prophylaxis in Knee Arthroplasty the prophylaxis of postoperative infections in total hip arthroplasty. CIin Orthop 159:194, 1981 10. Leigh DA, Marriner J, Nisbet D et al: Bone concentrations of cefuroxime and cefamandole in the femoral head in 96 patients undergoing total hip replacement surgery. J Antimicrob Chemother 9:303, 1982 11. McQueen MM, Littlejohn MA, Miles RS, Hughes SPF: Antibiotics in proximal femoral neck fracture. Injury 21:104, 1990
•
Field et al.
19
12. Nelson CL, Green TG, Porter RA, Warren RD: One day versus seven days of preventative antibiotic therapy in orthopaedic surgery. Clin Orthop 176:258, 1973 13. Salvati EA, Robinson RP, Send SM et al: Infection rates after 3175 total hip and knee replacements performed with and without a horizontal unidirectional filtered air flow system. J Bone Joint Surg 64A:525, 1982
