276 SA MEDIE E TYDSKRIF 26 Februarie 1977 Bone Cement and Anti biotics E. GER, D. DALL, T. MILES, A. FORDER SUMMARY 4. Which antibiotics in an active form will leach out of the cement, and for how long? Antibiotics of various kinds were added to the powdered Our inve tigation proceeded along two lines - mechani- polymer of methylmethacrylate in a concentration of 1 g cal and bacteriological. antibiotic/40 g cement, prior to the addition of the liquid As acrylic cements are used principally to support com- monomer. pressive loads." the mechanical tests were designed to pro- Specimens were subjected to mechanical testing by vide comparative data on the compressive properties of the loading them in direct compression on a 20-ton Instron mixtures. The bacteriological tests were designed to ascer- Universal Testing Machine, and load deflection curves tain the antibacterial properties of the mixtures. were recorded. It was found that the addition of anti- biotics does have an effect on the mechanical strength of MATERIALS AND METHODS the cement - the loss was small, less than 10% for both the compressive strength and the elastic modulus, pro- Mechanical Study vided the antibiotic was in powder form. Liquid antibiotics resulted in a greater loss of the compressive strength of The main purpose III the design of the experiment wa the mixtures, but specimens tended to be less porous. to obtain uniformity in the preparation of specimens and In vitro studies of the antibiotic properties of the mix- in test procedures rather than specialized methods to pro- tures demonstrated potent antibacterial activity in all the vide accurate quantitative data. Cylindrical specimens antibiotics tes~ed, except chloramphenicol. were the simplest for both the moulding and machining Possible clinical applications are discussed. Further of test specimens and they were also best suited for testing in vivo studies are needed before widespread clinical compression. The cement batches were mixed, 1 g anti- use can be advocated. biotic to 40 g cement, the antibiotics being added before the liquid monomer. The cement mixtures were moulded S. A fr. med. J., 5], 276 (1977). in glass test tubes and machined to a uniform size after complete polymerization. Only the portions of the cement Infection in total joint replacement surgery ean be a cylinders free of any gross voids were used for test speci- disastrou3 complication which usually dooms the prosthe- mens. The cement mixture made with the antibiotic in tic joint. liquid form (lincomycin) was less prone to gross porosity The prevention of bacterial contamination during sur- than the other mixtures. Table I includes the number of gery is the most potent prophylactic measure and Cham- specimens from each batch that were obtainable for testing. ley"s work in this regard has provided the greatest Since each batch of cement was made from the same contribution to the problem. It is well recognized that quantity of cement and mixed and moulded in a similar procedures to correct failed surgery carry a higher risk manner, the variation in the number of specimens obtain- of infection,'" and we were of opinion that it was reason- able from each batch is indicative of the susceptibility of able to use locally acting antibacterial cement-antibiotic the various cement mixtures to gross porosity. mixtures for such cases. The cylindrical test specimens were 12 - 13 mm in dia- The feasibility of cement-antibiotic mixtures has been meter and were machined to give a length to diameter well establishd by studies on gentamicin mixed with ratio of unity. One of the undesirable features of simple Palaco .'" evertheless, the use of CMW and Simplex compression tests is that the friction between the platens cement-antibiotic mixtures has not been established, and of the loading machine and the faces of the specimen we were of opinion that the following questions needed tends to barrel the cylindrical specimens under load. This answering: means that the specimen's cross-sectional area is not con- I. Can CMW and Simplex cements be mixed with stant and affects the quantitative accuracy of the result . antibiotics without interfering with polymerization? Tn addition, owing to the specimen barrelling, any variation 2. Will antibiotics in powder or liquid form have any in the length to diameter ratio of the test specimens will effect on the mechanical strength of the cement? give inconsistent results for the same materiaL" 3. Which antibiotics will retain antibacterial activity after However, provided this ratio is maintained for all test their exposure to the heat of polymerization? specimens, the comparative analysis of the results should not be affected. The test specimens were loaded in direct compression Departments of Orthopaedic Surgery, Mechanical Engineering, and Bacteriology, University of Cape Town on a 20-ton Instron Universal Testing Machine and load E. GER, F.R.C.S. deflection curves for each test were recorded. A low D. DALL, I\LCH. (ORTH.), F.R.C.S. strain rate was used to plot an expanded load deflection T. MILES. ~1.SC. (El\"G.) to enable accurate evaluation of the results. A. FORDER. 1\1.1".IED. (PATH.) In most of the tests, loading was terminated once the Dale received: 2 August 1976. peak load had been reached. Although gross deformation 26 February 1977 A MEDICAL JOUR AL 277 TABLE I. RESULTS OF COMPRESSION TESTS ON ORTHOPAEDIC CEMENTS WITH AND WITHOUT ANTIBIOTICS Cross head Compressive Elastic Number speed strength so modulus Specimen type tested (mm/min) (MPa) (%) (GPa) CMW Control 6 0,508 86,68 3,7 1,99 4,9 Control- 2 0,508 83,50 Gentamicin 5 0,508 78,82 9,0 1,87 7,0 Cephalothin 7 0,508 81,54 4,0 1,86 8,0 Lincomycin 12 0,508 58,89 3,6 1,59 2,5 Lincomycin + cephalothin 11 0,508 61,33 2,7 1,59 2,9 Fusidic acid 7 0,508 83,49 4,2 1,93 2,9 Simplex Control 2 0,508 90,65 2,12 Control- 2 0,508 86,47 Cephalothin 4 0,508 81,48 4,6 2,01 5,9 Lincomycin 7 0,508 57,99 5,1 1,63 4,6 Lincomycin + cephalothin 8 0,508 70,29 4,1 1,86 2,5 lI" Plane strain compression test. of the specimens occurred when loading was continued, RESULTS there was no evidence of any large-scale fracture in the cement. In a few cases, a small localized fracture was Mechanical Study seen near the voids near the surfaces of the specimen. Generally, however, the specimens tended to flatten plasti- The results of the tests conducted are recorded in caily. Table J. The elastic modulus was determined from the As a check on the quantitative accuracy of the simple initial slope of the load deflection curve. The cement did not exhibit a clearly defined yield point, the change from compression tests, a batch of each of the control cements elastic to plastic deformation being smooth and gradual. was cast as a flat plate and tested in a plane strain com- This behaviour is typical of plastics of this kind. In view pression rig, similar to that described by Ford! The plane of this, any attempt to evaluate the yield stress of the strain compression test yields more accurate quantitative cement would be susceptible to large errors and accord- data than the simple compression tests, since the barrelling ingly only the ultimate compressive strength, which is a effect. usual in the latter, is prevented. measure of the maximal load the cement can carry, ha been calculated. To compensate to some degree for the Bacteriological Study barrelling effect of the specimen, the compressive strength is based on the mean cross-sectional area of the specimen CMW and Simplex bone cement was weighed into 4-g at the time of peak load. quantities under sterile conditions. Quantities of 100 mg Table I also includes the percentage of the standard of antibiotic powder were weighed under the same condi- deviation of the test data for each cement batch te ted. tions and mixed with dry cement. Thus, the concentration Whereas the standard deviation based on such a small of antibiotic was I g/40 g cement. Controls without anti- sample might be erroneous, the low values obtained are biotics were also prepared. encouraging in that they reflect consistency of the mecha- The antibiotics used were: tetracycline, ampicillin, cepha- nical properties. lothin, chloramphenicol, cloxacillin, fusidic acid, genta- Fig. I is a bar chart showing the compressive strength micin (powder and liquid forms), kanamycin, lincomycin and elastic modulus of the cement batches mixed with liquid, lincomycin/cephalothin mixture, and neomycin. antibiotics, as a percentage of the values obtained for the Small pellets of the cement in a doughy state, measur- controls. From this it is evident that the addition of anti- ing approximately 10 x 5 x 2 mm, were made and placed biotics does have an effect on the mechanical strength of on nutrient agar plates seeded with Oxford Staphylococcus. the cement, although, with the exception of the batche The zones of inhibition were noted. containing lincomycin, the loss of strength i small - les Pellets of antibiotic-cement mixtures were then added than 10°\, for both the compressive strength and elastic to tubes of normal saline and incubated at 37"C for 18 modulus. hours. Thereafter the pellets were removed, washed in In the case of cement mixed with lincomycin, the los fresh normal saline, transferred to fresh tubes of normal of compressive strength varies from 30% to 35%, and aline and re-incubated at 37"C for 18 hours. in the elastic modulus from 20% to 25%. The linco- Fluid from both sets of tubes was tested for antibiotic mycin was added as a liquid, whereas the other anti- activity by transferring a drop from each tube either to biotics were powders. Recent mechanical tests on clinda- the surface of, or to a well in, a nutrient agar plate seeded mycin in powder form have indicated that the loss of with Oxford STaphylococcus. The zones of inhibition were mechanical strength is con i tent with our finding on again noted. other antibiotic in powder form. In earlier test • it was --~------ 278 s MEDIESE TVDSKRIF 26 Februarie 1977 Bacteriological Study Table 11 pre ent the results obtained with dry pellets or saline supernatant from both ets of tubes. All the antibiotic·cement mixtures gave zones of inhibition, with the excepTion of chloramphenicol. The controls gave no zones of inhibition. Zones of inhibition for 'antibiotic supernatants' placed directly on the surface of the seeded plates and in 'wells' in seeded plates. were virtually of the same size. Zones of inhibition obtained from the second set of tubes (i.e. after washing) were slightly smaller than the zones obtained from the first set. = f t.. IU , ... After approximately 6 months of dry storage, the antibiotic· bone cement mixtures still showed good anti· Fig. I. Comparative mechanic-al properties of l'arious bacterial activity which was maintained after 18 hours' cement-antibiotic mixtures. incubation in saline, washing, and a further 18 hours' incubation in saline. observed that there was a marked difference of mechanical DISCUSSION strength between cements mixed with gentamicin in liquid form and in powder form. the former having a much more adverse effect upon the mechanical strength. Mechanical Study Although the majority of the tests were conducted with The results of the comparative tests indicate that the CMW cement, it seems reasonable to predict that the loss of mechanical strength of CMW and Simplex cements effects of the various antibiotics on the mechanical mixed with antibiotics in powder form is small and strength of Simplex would be similar to those on CMW. should not adversely affect their fixation efficiency. In the This is certainly borne out in the tests on Simplex mixed case of mixtures with liquid antibiotics the loss of mecha· with cephalothin and lincomycin separately, which how nical streng'h is important, but without data on the actual property changes similar to those observed with CMW. stresses in fixation it is difficult to draw conclusions about In the case of Simplex mixed with both cephalothin and the effects of this upon efficient fixation. lincomycin, the results do not permit direct correlation In spite, however, of the poorer mechanical perform· wi h tho:;::: for CMW, since only half the amount of linco· ance of cements mixed with liquid antibiotics, the lower mycin was used in the mixture. because lincomycin was in susceptibility to gross porosity is beneficial. short supply at the time. The cancellous bone which is the bed for the cement The compressive strengths determined in the plane strain has been reported as having an ultimate compressive compression test were slightly lower, about 5%, than strength of 4,3 MPa,' which is considerably lower than the I hose in the direct compression tests, which indicates value determined for cements mixed with liquid Iinco· that the results of the latter tend to be rather high. mycin. 11 would appear that the cancellous bone would be crushed long before the cement. TABLE Ill. BACTERIOLOGICAL RESULTS The long-term effects of antibiotics on the mechanical properties of cement should be studied to determine how Antibiotic Time tested after mixing (wks) the fixation with cement is affected once the antibiotics have leached out of the cement vehicle. 3 10 16 26 Control CMW Antibacterial Study Control Simplex Tetracycline HCI + + + + As far as the antibacterial properties of the mixtures are Ampicillin + + + concerned, it is very gratifying to have these in vitro Cephalothin + + + + studies indicate potent antibacterial activity of all anti· Chloramphenicol biotics tested, with the exception of chloramphenicol. Mix· Cloxacillin + + + tures of cephalothin and fusidic acid also show potent Fusidic acid + + + + antibacterial activity and it appears reasonable to assume Gentamicin + + that other compatible mixtures will do the same, Kanamycin + + + + In vivo studies are now being undertaken to ascertain Neomycin + + + how long the antibacterial properties of the mixtures Lincomycin and cephalothin + + + + persist after constant contact with body fluids, It is en· Lincomycin + + + couraging to find that the mixtures exhibited strong anti· Palacos cement with bacterial activity after storage in saline for 36 hours, and gentamicin + + + + washing, + = zone of inhibItion. The clinical application of these findings is still debat- - = no zone of inhibition. able. Clearly, if late infection arises from haematogenou 26 Febmary 1977 A MEDICAL 10 R AL 279 sources, these cement-antibiotic mixtures are unlikely to could become acceptable practice, becau e failure in this be of benefit, since the body fluids would wash out the ituation could result in di a ter, with a further 10 of antibiotic. month or years after insertion.' On the other bone and tissue nece sitating mutilating procedures. Is it hand. if late infection originates in low-grade sepsis which justifiable to take this risk or should we accept pseudo- eventually becomes evident, there may be a place for arthrosis as the alternative? cement-antibiotic mixtures in combating the initial bac- terial infection at the bone-cement interface in the early REFERENCES postoperative period. I. Dall, D. (1974): S. Mr. med. J .. 48, 1979. Hessert and Ruckdeschel'o have shown that as much as 2. Buchholz. H. W. and Siege I. A. (1973): Acta lraumawl., 3, 233. 3. BlIchholz. H. W. and Engelbrecht, H. (1970): Der Chirllrg. 41. 511. 800 mg can be liberated in the first 24 hours after opera- 4. Wahlig. H. and BlIchholz. H. W. (1972): [bid .. 43. 441. 5. Charnley. J. (1970): Acrylic Cement in Orthopaedic .'. "llrgery. p. 93. tion from I g of gentamicin sulphate added to Palacos Edinhurgh: E. & S. Livingstone. cement. 6. Dieler. G. E. (I 61): MecfJallim[ Mecallurg}', pp. 479 - 4 O. New York: 1cGraw-Hill. The use of gentamicin Palacos cement in the treatment 7. Ford, H. (1964 - 6): Proc. Ins!. Mech. Eng., vo!. I, Pt 38. of established infection by total replacement of the Ger, E., Dall, 0 .. Forder, A. and Miles, T. (1975): S. Arr. med. J .. 49. 252. infected prosthesis and cement, has been advocated by 9. Williams. J. F. and Svensson, N. L. (1971): Med. bioI. Eng .. 9. 479. 10. Hessen, G. R. and RlIckdeschel, G. (1970): Arch. onhop. Unrall-Chir.. Buchholz and Siege!.' More work is required before this 68, 249. Sputum Induction by Saline Aerosol E. M. S. GATNER, D. GARTIG, H. H. KLEEBERG SUMMARY obtain a specimen of bronchial secretion. These techniques are too cumbersome infield surveys. There are several A simple technique for inducing sputum production with reports on the successful use of a technique involving the vaporized 15% aqueous NaCI is described. Fifteen in- inhalation of nebulized fluids which are subsequently ex- halations of saline aerosol, followed by a waiting period pelled as sputum.'" In this article we describe a simplified of 15 - 30 minutes, were sufficient to induce a productive saline aerosol inhalation technique, suitable for use in the cough in 93% of the persons tested. The apparatus is field and under hospital conditions - wherever a person portable, cheap, easily maintained and suitable for llse is unable to produce sputum by a spontaneous cough. under field or hospital conditions. MATERIALS A D METHODS S. Air. med. J., 51, 279 (1977). The Apparatus Difficulty in obtaining an adequate sputum specimen from The apparatus consists of a Drager nebulizer M 123 2* some patients is a long-standing problem in the diagnosis which emits droplets in the range 0,5 - 5 Jlm and which is of tuberculosis. If a patient cannot produce a sputum speci- linked by standard rubber tubing to a portable cylinder of men by means of a spontaneous cough. an investigator compressed air. The nebulizer is charged with a 15% olu- may resort to mechanical irritation of the epiglottis, tion of aCI in sterile water. The saline vapour flow rate bronchoscopy, gastric lavage or medication in order to is controlled by manipulation of the air pressure valve on the compre sed air cylinder and is satisfactory when the cylinder output pressure gauge reads between 21 and 28 Tuberculosis Research Institute of the South African Medical kPa. A disposable cardboard cylinder, approximately 8 cm Research Council, Pretoria E. M. S. GAT ER, n.se., PH.D. in length, conducts air laden with droplets from the exit of D. GARTIG, OR :\1 EO. the nebulizer to the vicinity of the recipient's mouth. H. H. KLEEBERG. OR MED. VET. ... Oblainable from Premier Medical and Indu,tri3J Equioment (Pty) Ltd. Dale recei"ed: 8 Seplerr,ber 1976. PO Box 4367, Johannesburg. 2000 R A.