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Pyogenic infections in orthopaedic surgery
Pyogenic
Infections
in Orthopaedic
Surgery*
COMBINED ANTIBIOTIC AND CLOSED WOUND TREATMENT FLOYD JERGESEN, M.D.AND ERNEST JAWETZ,M.D.,SanFrancisco,
From tbe Department of Ortbopaedic Surgery and tbe
remova of necrotic tissue, obIiteration of cavities, avoidance of further bacteria1 contamination, and subsequent wound closure. Chemotherapy is the principa1 adjunctive treatment. Modification of concepts of principIes and variations of technic can Iead to improved results of treatment of some types of infections. The purpose of this preliminary report is to emphasize the appIication of the concepts of cIosed wound management and combined antibiotic action in the treatment of certain pyogenic infections invoIving the
Department of Microbiology, University of California School of Medicine, and tbe Veterans Administration Hospital, San Francisco, California.
NSPITE of
newer concepts, refinements of surgica1 technic and recent deveIopments in chemotherapy, the seIection of optima1 treatment of some pyogenic infections of the muscuIoskeIeta1 system can be a chaIIenge to the surgeon. RationaI treatment of these infections continues to rest on established surgica1 principIes of adequate drainage of exudates,
I
FIG. I. Method of percutaneous * Presented American
at the AnnuaI
Journal of Surgery,
Meeting
Volume
of the
106. August
1963
California
introduction
of drainage tube into knee joint.
Pacific Coast Surgical February 3-6, 1963.
152
Association
at
Palm
Springs,
CaIifornia,
Pyogenic Infections
is attached
FIG. 2. The colIecting system for closed wound treatment. cock by a modified hypodermic needle hub.
The smaII viny1 catheter
muscuIoskeIeta1 system in ad&s. It is based in part upon the resuhs of a review of our experience gained during the past five years.
pIished with IocaI anesthesia. (Fig. I.) It is preferred to introduce the drainage tube through the skin in an obiique direction at a distance from any surgica1 incision. This minimizes pressure necrosis of the skin edges around the tube and can avoid kinking of the tubing. When the tube is subcutaneous or crosses bony prominences, pressure from dressings must be avoided to prevent necrosis of overlying skin. Various types of fenestrations have been used, but no type has routineIy prevented pIugging of the tube. A ten-gauge trocar permits percutaneous introduction of a tube with an outside diameter of approximateIy 3.0 mm., and a seven-gauge trocar accepts tubing with an outside diameter of approximateIy 4.0 mm. The externa1 end of the rigid-waI1 tubing can be attached to a three-way cock by a hypodermic needIe modified by removing the shaft and
CLOSED
WOUND
TREATMENT
CIosed wound treatment of IocaI infections with suction drainage under certain circumstances can fuIfN the principIe of drainage of exudates which are conducive to microbiai growth. Appropriate chemotherapeutic agents can be introduced intermittentIy into the closed system to bring high concentrations into contact with infected wound surfaces [I]. When open operation is necessary for removal of necrotic tissue or foreign bodies, drainage tubes can be introduced under direct vision. When open drainage of an abscess or an infected joint is not desirabIe, percutaneous introduction of the drainage tube can be accom‘53
to the three-way
Jergesen and Jawetz
FIG. 3. Method of creation of closed cavity with segment of rubber gIove where skin overIying the bone Iesion has been lost.
provides intermittent suction at go or 120 mm. of mercury has been used with satisfaction. OccasionaIIy, it has been advantagenous to create a cIosed system in which overlying soft tissues were destroyed by infection or injury. A reasonabIy effective system has been devised for short periods of use by employing the thumb segment of a surgica1 gIove for covering. The suction tube was introduced through the thumb cot and the free edge of the gIove segment was attached to the surrounding skin by an appropriate adhesive compound such as “Ace Adherant.” (Fig. 3.) GeneraIIy, the topica agent was instiIIed at twetve hourIy intervaIs and suction was discontinued For the folIowing three hours. During
threading the hub so it can be screwed on to the tubing. (Fig. 2.) The three-way cock permits both periodic instiIIation of chemotherapeutic agents into the infected area and reguIation of outflow. Trap bottIes or test tubes of varying size can be introduced into the system between the three-way cock and the suction apparatus for purposes of colIection of wound secretions. Depending upon the rate of drainage, the size of the coIIecting container is seIected to permit accurate and periodic measurement of the voIume of exudates. SpeciaI containers such as test tubes can be inserted in the system for colIection of exudates for bacteriologic study and antibiotic assay. The Gomco Suction Pump@ which ‘54
Pyogenic
FIG. 4. Chronic
osteomyehtis
Infections
of femur. Sinogram showing progressive
the remaining nine hours between instiIIations, suction drainage was effected. Change in the size of soft tissue cavities could be estimated with fair accuracy by the varying volumes of fluid accepted. However, periodic x-ray studies with the cavity distended with an aqueous radiopaque solution provided a graphic record of progress of treatment, and on occasion indicated foci of persistent infection. (Fig. 4.) COMBINED
ANTIBIOTIC
obliteration
of soft tissue abscess cavity.
the rate and compIeteness of killing. For optima1 resuIts of treatment of serious infection, the concentration of antibiotics both in the bIood and IocaIIy, in tissues and exudates, ideaIIy shouId be bactericida1. The selection of effective chemotherapeutic agents and their respective dosage to assure bactericida1 action in a specific infection, requires critica clinica judgment and reIiabIe Iaboratory studies. How can an effective concentration of drug be deIivered to the site of infection? High concentrations of some antibiotics in joints cannot be achieved by systemic administration aIone [r]. The synovia1 membrane of joints or the waIIs of abscess cavities may deIay the passage of drugs from the bIood stream but microorganisms within such spaces can be attacked by direct instiIIation. Therefore, combined systemic and IocaI administration may be more effective than either route aIone. The antimicrobia1 effect of certain singIe notabIy peniciIIin, can be poantibiotics, tentiated by increased dosage [6]. Some antibiotics (such as bacitracin) can be used topicaIIy in high concentrations with less Iike-
ACTION
AIthough the systemic use of a singIe chemotherapeutic agent often suffices for successfu1 treatment of many pyogenic infections of the musculoskeletal system, regrettabIy others do not respond optimaIIy. With the hope of improving the results of treatment of some severe infections, concepts of combined antibiotic action [2-q] were appIied. Bacteriostatic or inhibitory activity of chemotherapeutic agents in vitro is manifest by the reduction of the norma growth of organisms in a suitabIe environment without regard to kiIIing. BactericidaI action reffects 15s
Jergesen and Jawetz Iihood of untoward side effects than when a simiIar IeveI is attained IocaIIy by systemic administration. MuItipIe drugs may give a greater antimicrobia1 effect than that provided by a singIe agent. Combinations of antibiotics can act on bacteria in a synergistic, antagonistic or indifferent fashion [2,3].A reason for combined use is the synergistic antimicrobia1 effect that might not be obtained from a singIe agent. It may be necessary to use muItipIe drugs both IocaIIy and systemicaIIy to eradicate complex microffora of mixed infections in which singIe or dua1 agents would not act effectiveIy on a11 components. The additive action of two drugs can reduce the reIative necessary dosage of thereby minimizing the each component, possibiIity of toxic side effects which might resuIt from higher dosage of a singIe agent. The rapid emergence of strains of bacteria resistant to a singIe antibiotic (such as erythromycin) may be avoided by combined treatment [2]. Antagonistic action of antibiotic combinations can be demonstrated readiIy in vitro [3]. Jones and Finland [7] found the effectiveness of pIasma of norma subjects containing peniciIIin and tetracycline, in various combinations of dosages, was Iess than that containing one or the other antibiotic in which the test organisms were streptococci or pneumococci. Proof of antibiotic antagonism is diffIcuIt to estabIish under cIinica1 conditions of combined drug treatment of estabIished infection, chiefIy because antagonism is readiIy overcome by an excess of either drug in a part. The determination of synergistic or additive effects ilz vitro of antimicrobia1 combinations must be made for the individua1 strain of bacteria. It is a matter of “taiIoring,” because arbitrarily seIected combinations may be ineffective or even antagonistic. Depending on the strain of staphyIococcus tested, peniciIIintetracycIine or peniciIIin-chIoramphenico1 combinations have been demonstrated to have either synergistic, indifferent, additive or antagonistic effect [8]. In the present study, a modified tube diIution technic was used in preference to the disk method for determining bactericida1 or bacteriostatic activities of antibiotic combinations [9,10]. The principIe of seIection of combinations is based upon the idea of using poorIy absorbed, toxic agents (such as neomycin, poIymyxin, or bacitracin) IocaIIy and we11 absorbed drugs 156
systemicaIIy. The foIIowing drugs and concentrations have been empIoyed frequentIy for topica use: neomycin I per cent, poIymyxin 0.1 per cent, bacitracjn 1,000 units per m1. Greater concentrations have been used occasionaIIy to dea1 with particuIarIy resistant microorganisms. Assay for antibacteria activity in sera and wound exudates have proved to be a vaIuabIe guide to the dosage of antimicrobia1 drugs. This test is an important adjunct to clinica evaluation and bacterioIogic studies [I I]. Periodic cuItures of wound exudates are necessary for the critica assessment of the success of treatment. CoIIection of reIiabIe specimens of exudate for cuIture requires interruption of IocaI therapy for tweIve hours or more to prevent false negative determinations caused by persistentIy high concentrations of IocaIIy instiIIed drug. ExcessiveIy frequent interruption of treatment for purposes of cuItures may be undesirabIe. cLINIcAL MATERIAL The cIinica1 materia1 seIected as the background of this report was derived from a review of records of sixty-eight patients treated during the past five years. This proved to be a varied group of infections of the motor-skeIeta1 system in aduIts. Closed wound management and combined antibiotic therapy was reserved for the more severe and extensive infections. Minor infections were usuaIIy treated by commonly empIoyed methods and were not incIuded in this study. Hematogenous Osteomyelitis. OnIy three patients with acute hematogenous osteomyeIitis were encountered. AI1 invoIved the spine, and the etioIogic organism identified in each was a staphyIococcus. In addition to genera1 principIes of treatment which incIuded bed rest and externa1 immobiIization 1121,cIosed wound management and combined antibiotic therapy by IocaI and systemic routes proved to be effective in cIinica1 contro1 of the infections of aI1. ScherbeI and Gardner [r3] have suggested that intervertebra disc space infections might be treated by IocaI instiIIation of an effective antibiotic agent through a catheter Ieft for that purpose at the time of operation. There were six patients with acute exacerbations of chronic hematogenous osteomyeIitis. Treatment of soft tissue abscesses without open operation by percutaneous introduction
Pyogenic of the drainage catheter was accompIished in three and was foIlowed by control of the acute recurrence. Treatment in the remaining three patients incIuded extensive sequestrectomy and saucerization. Skin grafting of the exposed bone surface of one patient resulted in arrest of the infection. Persistent drainage in a second patient required a second sequestrectomy; the third patient remains under active treatment. Acute Postoperative Infections. In two patients septic arthritis of the shouIder joint deveIoped, one was biIatera1, foIIowing injections of steroids for treatment of periarthritis. The causative organism was Pseudomonas aeruginosa in both. Local instiIIation of poIymyxin with appropriate systemic antibiotics resuIted in prompt arrest of the infection in both [14]. Four postoperative infections of the knee joint were encountered. AI1 were caused by staphyIococci and folIowing arrest of the infection, function was recovered in three. AIthough the acute infection was controIIed in the fourth patient, supracondylar amputation became necessary subsequentIy because of gangrene secondary to obIiterative vascuIar disease. Culture studies of synovia and cartiIage taken from the knee joint of the specimen faiIed to demonstrate any bacteria1 growth. A singIe postoperative infection in an ankIe joint responded favorabIy. Eight postoperative infections foIIowed repIacement arthropIasty. Six invoIved the hip joint and one each the shouIder and elbow joints. Of the six hip joint infections, five responded favorabIy and the foIIowing case history serves to iIIustrate successfu1 management. CASE
Infections addition to erythromycin, tetracycIine was incIuded for systemic use. Since serum assay showed onIy inhibitory action in a one to five diIution on ApriI 23, 1962, novobiocin was added as a systemic drug. On April 30, 1962, the serum assay demonstrated bactericida1 activity at one to eighty diIution. The drainage catheter was removed on May 15, 1962, but systemic therapy was continued unti1 June 29, 1962. Because of a rash, oxaciIIin was substituted for novobiocin and tetracycIine on May 31, 1962. The clinica response to treatment was favorable; eight months after contro1 of infection there had been no evidence of recurrence.
Comment: The suction drainage tube inserted at the time of operation for removal of bIood and wound exudates [15,16] was removed on the third postoperative day. During the next ten days the patient’s postoperative course was uneventful, aIthough some drainage persisted from the catheter exit. A minor rise in temperature was noted on the thirteenth day after operation; this continued for the next four days. GraduaI rise in fever was apparent unti1 the twenty-first postoperative day when the temperature reached 3g’c. Increase of pain in the hip region then was noted. In retrospect, the diagnosis shouId have been established at Ieast forty-eight hours earIier. Another deIay of forty-eight hours folIowed initia1 aspiration whiIe awaiting cuIture studies and disk sensitivity determinations. Thus, four days elapsed before chemotherapy was started. AIthough the patient’s cIinica1 response to treatment, as judged by Ioss of pain and decreasing febriIe reaction, was favorabIe; cuIture studies were not negative unti1 the twenty-fifth day after institution of antibiotic treatment. Treatment of infection was unsuccessfu1 foIIowing repIacement arthropIasty of the shouIder for fracture-disIocation of the head of the humerus. In this patient, cuItures demonstrated a mixture of staphyIococcus and pseudomonas. AIthough the infection was apparent on the ninth postoperative day, combined therapy was not instituted unti1 two weeks Iater. At that time a sinus tract had deveIoped and it was impossibIe to estabIish a cIosed system. A singIe exampIe of faiIure of treatment foIIowing repIacement arthropIasty of the hip was encountered in which a staphyIococcus was isoIated. The infection was discovered on the
REPORT
In a thirty-seven year oId man (C. C.), acute pain deveIoped in the region of the hip twenty-one days after reconstructive arthropIasty with an intrameduIIary prosthesis. (Figs. 5 and 6.) InitiaIIy, disk sensitivity studies had suggested that erythromycin wouId be effective against the staphyIococcus isolated from the hip joint exudates, and it was given systematicaIIy. SubsequentIy, however, tube dilution studies did not confirm that impression. They demonstrated that the organism was rapidIy kiIIed in vitro by methiciIIin 3 pg. per mI., neomycin 5pg. per m1. pIus tetracycIine I0 pg. per mI., as we11 as by novobiocin 4 pg. per m1. pIus kanamycin IO pg. per m1. A 3 mm. viny1 catheter was introduced percutaneousIy into the hip joint for instiIIation of 1 per cent neomycin IocaIIy. In
I57
Jergesen
and Jawetz
FIG. 5. A, BiIateraI degenerative arthritis of hip secondary to Legg-Perthes disease of childhood. Radiograph two weeks after reconstru‘ctive arthropIasty of right hip with intramedulIary prosthesis. Acetabular reinforcement with corticaI bone pegs. FIG. 5. B, Radiograph six months after operation, and five months after controI of septic arthritis. Absence of radiologic evidence of persistent joint infection.
158
Pyogenic MARCH
APRIL
1962
CULTURE-STAPHYLOCOCCUS CULTURE-YEAST ERYTH
ROMYClN
TETRACYCLINE NOVOBIOCIN OXACILLI
N -
-
-
Infections MAY
+ --
JUNE
+
3,0gms/da. P.O. 2.Ogms/da.P0. 2.0gms/da P 0 Z.Ogms/da P 0
NEOMYCIN 1% LOCALLY - 15.0 ,I - IO,0
cc BI.0. cc B.I.O. ?
SERUM
ASSAY
-INHIBITORY -BACTERICIDAL
FIG. 6. CASE C. C., aged thirty-seven years. Septic arthritis arthropIasty. Course of infection and rest&s of therapy.
fourteenth day after operation. Treatment was instituted immediately and the response both from the clinica point of view and from cuIture studies seemed favorabIe. However, the infection recurred within four weeks after cessation of treatment. The response was temporariIy favorabIe on the second occasion onIy to be foIIowed by recurrence with progressive evidence of destruction of the hip joint. Drainage did not cease unti1 the metaIIic apparatus had been removed. Acute postoperative infections foIIowing open reduction of cIosed fractures and a variety orthopaedic procedures on of other “cIean” bone composed a heterogenous group of five patients that was diff&uIt to anaIyze because of Iack of uniformity of circumstances. The response to treatment varied from apparent eradication of infection in four patients to temporary suppression folIowed by recurrence in one. The foIIowing exampIe serves to emphasize a favorable response. CASE
of hip joint folIowing reconstructive
coliform organism isoIated from wound secretions suggested sensitivity to chIoramphenico1, kanamycin and polymyxin. Two days later, a nonhemoIytic coagulase negative staphyIococcus was recovered from the fracture site in addition to Eschericbia coli. Disk sensitivity determinations suggested the staphyIococcus wouId respond favorably to a wide variety of chemotherapeutic agents in&ding erythromycin, chIoramphenico1 and neomycin. The drainage tube was introduced percutaneously to the fracture site on July rg, 1962, and IocaI treatment with neomycin I per cent was instituted. Erythromycin and chIoramphenico1 were selected initially for systemic administration. Tube dilution studies subsequently demonstrated that the staphylococcus was rapidIy kiIIed in vitro by erythromycin z pg. per mI. pIus bacitracin I unit per ml. PoIymyxin@ I pg. per m1. pIus chIoramphenico1 20 pg. per m1. was significantly bactericida1 to the Eschericbia coli. Neomycin and polymyxin were seIected then for Iocal instiIIation whiIe erythromycin and chioramphenicoi were used SystemicaIIy. Because of development of Ieucopenia, chIoramphenico1 was discontinued subsequentIy and novobiocin substituted. Afterward, jaundice developed and systemic administration of both novobiocin and erythromycin was stopped. These were suppIanted by oxaciIIin whiIe neomycin and poIymyxin were continued IocaIly. Wound cuItures taken on August I, 1962, demonstrated no growth and the suction tube was removed on August I I, 1962. Systemic treatment
REPORT
In a fifty-three
year oId man (W. S.), fever and acute pain deveIoped in the region of the hip eighteen days after open reduction of a comminuted intertrochanteric fracture of the femur. (Fig. 7.) Initial disk sensitivity studies of the
‘59
Jergesen and Jawetz &GUST
JULY
JUNE 1962
39
TPR (%I
36
CULTURE
-STAPHYLOCOCCUS
CULTURE-
COLI FORM
ERYTHROMYCI
N -
3.0 gm/da. P.O. 2.0 gm/da. P.O.
CHLORAMPHENICOL-3,0gm/da. 1.M 3.0gm/do.P0. 2.0gm/do. P.O. NOVOBIOCIN OXACILLIN
-.
2.0gm/da
P.O.
3.0gm/da
P.O.
NEOMYCIN 1% LOCALLY - 1080 cc B.I.D. POLYMYXI N 001 % LOCALLY-.iO.O
cc B.I.D.
FIG. 7. CASE W. S., aged fifty-three years. Wound infection foIlowing open reduction and internal fixation of cornminuted intertrochanteric fracture. Course of infection and results of therapy.
Chronic Secondary Osteomyelitis. Recurrent or chronic secondary OsteomyeIitis foIIowing open fracture or as a resuIt of postoperative infection was encountered in a major proportion of these patients. GeneraIIy, open operation was necessary for remova of sequestra, infected soft tissues, or metal&c foreign bodies. The type of infection varied widely both in character and in microbia1 Aora. Because of lack of uniform clinica materia1, detaiIed anaIysis of the resuIts of treatment was not attempted. Certain significant features are discussed beIow.
was
continued unti1 August 26, 1962. During the succeeding six months the fracture healed; there has been no evidence of recurrent infection.
Comment: The nature and origin of the mixed infection in this patient couId not be determined. The isolation of a staphylococcus two days after recovery of the colon bacilIus might have represented a superinfection caused by contamination in the course of Iocal treatment. Inadequate sampling or deficient Iaboratory isoIation technics suggest other reasons for failing to demonstra’te both organisms in the initial culture. This example emphasizes the importance of periodic cuIture studies not onIy for the determination of efficacy of treatment, but aIso for the earIy recognition of any change in wound flora. Chronic Septic Arthritis. Five patients with chronic pyogenic infections of joints were treated. IncompIete function was restored to two knee joints foIIowing arrest of infection. Infection was arrested in two hip joints after debridement of one, and remova of a prosthesis and debridement of the other. Infection in the hip joint of the fifth patient recurred and required further treatment.
COMMENTS
Combined antibiotic action and cIosed wound management as adjuncts to estabIished surgica1 principIes of treatment of pyogenic infections of the motor-skeletal system had some disadvantages as we11 as advantages. Suction drainage provided adequate egress for wound exudates and bits of free tissue. However, bone sequestra, Iarge masses of necrotic soft tissue and infected granuIation tissue required remova by open operation. A significant cause of treatment faiIure was inadequate 160
Pyogenic remova of necrotic tissue which provided both pabuIum and haven for microbia1 propagation. In other instances, sclerotic bone and extensive soft tissue scar seemed to provide foci for recurrence of infection. Inadequate operative treatment was not overcome by antibiotic treatment. Frequent checking of the suction system was necessary to insure its proper function; this required attention of medica personnel. In spite of scrupuIous aseptic technic, repeated instiIIation of antibiotic agents and the presence of the irrigation system provided a potentia1 source of contamination. CIosed wound treatment required infrequent dressings which saved time and spared the patient pain. The comparative possibiIity of secondary contamination appeared to be Iess with cIosed treatment than in open wounds that were dressed frequentIy. RemovaI of exudates by a closed system minimized soiIing of the patient, and contamination of bed cIothing and per$onneI with dissemination of the organisms in the hospita1 environment. EarIy cIosure of the wound was thought to decrease scarring tha% commonIy foIIowed proIonged open treatment. Tube diIution tests for the determination of bacteria1 susceptibiIity to combinations of antibiotics and assays of antibacteria activity in sera and wound exudates were timeconsuming and required a we11 equipped Iaboratory with trained personne1. ObviousIy, these costIy tests were reserved for serious and major infections. The simuhaneous use of muItipIe chemotherapeutic agents increased the Iikelihood of undesirabIe side effects, and at times made difl?cuIt the assignment of a reaction to a specific drug (such as used in patient W. S.). The serious consequences of some drug reactions had to be baIanced against the IikeIy gain from subjecting the patient to such hazards. Continued and widespread use of a singIe antibiotic combination, such as stock mixtures, was avoided among hospital parients since it was thought to increase the possibility of emergence of microfl ora resistant to a11 drug components. Another hazard was that of superinfection which implies the appearance of an infection caused by an organism different from the one for which antimicrobial therapy was instituted [17,18]. Such a possibility was suspected when response to treatment did not
Infections foIIow prediction. Superinfection occurred Iate in the course of treatment of one patient and convalescence was significantIy proIonged. Treatment of acute infections in seriously iII patients was not deIayed unti1 microflora had been isolated and antibiotic sensitivities had been determined. For the critica interva1 between diagnosis of infection and compIetion of preIiminary Iaboratory studies, the empiric seIection of drug combinations for IocaI and systemic use was made on the basis of probabIe effectiveness in deaIing with types of microorganisms that were most frequentIy isolated from acute infections of the motorskeIeta1 system. The common etioIogic organisms of acute infections in these patients were staphyIococci, enterococci and gram-negative baciIIi of the coIiform and pseudomonas groups. The dosages of drugs arbitrarily selected for combined therapy were adjusted so that bactericida1 effects wouId IikeIy be obtained. Because of the high incidence of peniciIIinase-producing staphyIococci, generaIIy penicillin was withheId unti1 its possible eficacy had been demonstrated in vitro. For interim treatment of the average aduIt under such urgent circumstances, sodium coIistimethate 300 mg. and sodium methiciIIin 12 gm. were given systemicaIIy in divided doses each day. When open operation was unnecessary or couId be deferred temporariIy, drainage was provided by a smaI1 viny1 catheter introduced percutaneousIy into the joint or abscess cavity. Otherwise, the tube for IocaI therapy was impIanted at the time of the initia1 open operation. A soIution of I per cent neomycin and 0.1 per cent poIymyxin-a in the amounts of 5 to 15 m1. was instiIIed twice daiIy for local therapy. As soon as causative bacteria were identified and IikeIy sensitivities determined, proper antibiotic combinations were substituted. Recurrent or chronic infections d?d not aIways require immediate chemotherapy, and it was frequentIy delayed unti1 proper Iaboratory studies had been compIeted. The IeveI of predicted drug concentrations in sera was determined in many patients by periodic assays. An attempt was made to maintain a IeveI of antibacteria activity in serum diIuted I : IO or more. FaiIure to make such studies for guidance in treatment may heIp to expIain faiIure to contro1 infection folIowing hip arthroplasty in one patient. The rate and character of wound drainage were indications of eflicacy of treatment. Pro161
Jergesen
and
gressive decrease in voIume and diminishing turbidity were accepted as added evidence of favorabIe response. On occasion, and especiaIIy in articuIar infections, high concentrations of drug appeared to cause irritation and maxima1 clearing of exudates was not observed unti1 IocaI therapy had been discontinued. Additives such as fibrinoIytic agents or soIvents were not used in treatment of these infections [19,20]. SUMMARY
This is a preIiminary report of experiences in the treatment of serious pyogenic infections of the motor-skeIeta1 system in aduIts. EstabIished surgica1 principIes of treatment of infected wounds was observed. Open wound treatment was abandoned in favor of the cIosed technic with intermittent suction and combined antibiotic therapy. Antibiotic combinations were seIected for simuItaneous systemic and IocaI administration in accordance with in vitro determinations of bactericida1 activity. In addition to usua1 cIinica1 criteria of success of treatment, periodic wound cutture studies and assays of sera and wound exudates for antimicrobia1 activity were thought to provide dependabIe guidance. The resuIts of treatment of acute postoperative infections in this smaI1 series was encouraging and have stimuIated further study. Six acute infections foIIowing prosthetic arthropIa.sty were controIIed and subsequentIy remova1 of metaIIic foreign bodies was not necessary because of recurrent infection. AnaIysis of two faiIures of treatment of infection after prosthetic arthropIasty suggested factors that in retrospect might have been significant causes. The most discouraging resuIts were encountered in chronic or recurrent infections of bone wherg necrotic tissue, infected granuIation tissue or extensive scarring of soft tissue were present. Inadequate operative remova of infected or necrotic tissue couId not be compensated by adjunctive chemotherapy. Certain advantages and disadvantages of cIosed wound treatment and combined antibiotic therapy are discussed.
Jawetz 3. JAWETZ, E. and GUNNXSON,J. B. An basis of combined antibiotic action. 150: 693, 1952. 4. LOWBURY, E. L. Cross infection of antibiotic-resistant organisms. Brit.
experimenta J. A. M. A., wounds with M. J., I : 985,
1955. 5. JOCSON, C. T. The diffusion of antibiotics through the synovial membrane. J. Bone @ Joint Surg., 37-A: 107, 1955. 6. ALTMEIER, W. A. and WULSIN, J. H. Antimicrobial therapy in injured patients. J. A. M. A., 173: 527, 1960. 7. JONES, W. F. and FINLAND, M. Antibiotic combinations; antibacteria action of plasma of normaI subjects after ora doses of peniciIIin v, tetracychne hydrochIoride, and a combination of both. New England J. Med., 256: 869, 1957. 8. HINTON, N. A. and ORR,J. H. The effect of combinations of antibiotics on coagulase-positive staphylococci. Canad. M. A. J., 82: 31 I, ;g6o. g. GUNNISON, J. B. and JAWETZ, E. Sensitivity tests with combinations of antibiotics: unsuitabihtv of disk method. J. Lab. ti Clin. Med., 42: 16;, 1953. IO. JAWETZ, E., GUNNISON, M. A., COLEMAN, V. R. and KEMPE, H. C. A Iaboratory test for bacteria1 sensitivity to combinations of antibiotics. Am. J. Clin. Patb., 25: 1016, 1945. I I. JAWETZ, E. Assay of antibacteria activity in serum. Am. J. Dis. Cbild.. IO?: 81. 1062. 12. GARCIA, A., JR. and GRANTHAM, S. A. Hematogenous pyogenic vertebra1 osteomyehtis. J. Bone TVJoint Surg., 42-A: 429, 1960. 13. SCHERBEL, A. L. and GARDNER, W. J. Infections involving the intervertebra disks. J. A. M. A., 174: 370, 1960. 14. JAWETZ. E. Infections with Pseudomonas aeruginosa treated with polymyxin B. Arch. Int. Med., 89: go, 1952. I 5. MCELVENNY, R. T. Mechanical suction of wounds. &rt. Bull. Nortbwestern M. School, 35: 235, 16. WAUGH, T. R. and STINCHFIELD, F. E. Suction drainage of orthopaedic wounds. J. Bone EdJoint Surg., 43-A: 939, rg6r. 17. RANTZ, L. A. Consequences of the widespread use of antibiotics. California Med., 81: I, 1954. 18. WEINSTEIN, L., G~LDFIELD, M. and CHANG, T. Infections occurring during chemotherapy: a study of their frequency, type and predisposing factors. New England J. Med., 25 I : 247, 1954. rg. COMPERE, E. L. Treatment of osteomyeIitis and infected wounds by cIosed irrigation and a detergent-antibiotic solution. Acta ortbop. scandinav., 32: 324, 1962. 20. GRACE, E. J. and BRYSON, V. TopicaI use of concentrated peniciIIin in surface active soIution. Arch. Surg.. 50: 219, 1945.
REFERENCES
DISCUSSION
I. MILLER,
R. H. and SMITH-PETERSEN, M. N. Further report on osteomyelitis at the Massachusetts General HospitaI. New England J. Med., 216: 827, 1937. 2. JAWETZ, E. Combined antibiotic action. 4th Internat. Cong. Biocbem., 5: gr, 1959.
F. E. WEST (San Diego, CaIif.): It is a pieasure to have the opportunity to discuss the paper on Pyogenic Infections in Orthopedic Surgery by Doctors Jergesen and Jawetz. For a11 of us surgeons, the treatment of pyogenic infections is a
162
Pyogenic Infections serious task; and certainIy for the orthopedist, infection frequentIy presents itself as a tragedy. The loss of a joint, or the tota failure of a reconstructive procedure is a major calamity. Dr. Jergesen and Dr. Jawetz have presented a prehminary survey of their approach to this most distressing problem. In their paper the age oId axiom that where there is an estabhshed debris and a coIIection of pus, open and adequate drainage is necessary, has been modified. When infection is first seen, that is, earIy in its deveIopment, either postoperative or by spontaneous onset in bone or joint, these authors bebeve, this infection may be handied by cIosed drainage and a strong barrage of antibiotics: (I) The appropriate more toxic and nonabsorbabIe drugs, such as, neomyecin, poIymyxin and bacatracin, may be used in the area of the IocaI infection through cIosed system drainage. (2) ProperIy seIected parentera antibiotics with less toxic effects may be used by oraI or injection routes. (3) They have aIso suggested that the proper method of election of the antibiotic is by the tube diIution method, in contrast to the ordinary disc evahration methods commonly used. In regard to this last assumption, I do not believe that I am qualified to discuss the probIem, but would leave this decision to the bacterioIogists. In the report Dr. Jergesen mentions that sixtyeight cases have been so treated, but actualIy onIy twenty-five cases have been reviewed as to the resuIts of this method of treatment. The remainder of the cases are not reported in detai1. The three cases of acute hematogenous osteomyehtis of the spine, and six of recurrent infection of hematogenous osteomyelitis are of interest, but they are not convincing; I shouId expect that further evidence wiI1 be uItimateIy obtained. Among the ten cases of marked interest are four cases of postoperative infection of the knee which recovered under this form of treatment and six cases of postoperative infection foIIowing prosthetic surgery of the hip. In five of the six patients, the prosthetic device was saIvaged. It is we11 known that in instances of an acute pyogenic infection of a joint, a serviceabIe articuIation may be obtained by an earIy diagnosis, proper parentera antibiotics; and on certain occasions, a thorough cIosed irrigation of the infected joint with norma saIine soIution or an antibiotic, according to the methods previousIy described. However, the same experience has not been mine in the case of an infected postoperative hip prosthesis. The usua1 course in this situation has been the fina removal of the foreign body. In this paper, in five of six patients with such infections, the prosthesis has been saved. I shouId like to know the fina results in regards motion, function and durabiIity of these saIvaged affected joints.
The additiona report of a case of an infected intertrochanteric fracture is, I believe, of double interest. First, the proper seIection of antibiotics for a mixed type of infection; and secondIy, the heaIing of the serious fracture with a foreign body present, in face of infection, is of significant importance to emphasize the advantages of such a course of therapy. There is no question that the problem of treating acute pyogenic infections of bones, joints and postoperative reconstructive procedures is a matter of great concern. Any method which may lead to avoiding Ioss of joint motion or Ioss of operative repair demands our attention. This paper is provocative and chaIIenging. It is my opinion that through such endeavors we will ultimateIy make progress in our seIective therapy of such infections. I trust that Doctors Jergesen and Jawetz wiI1 continue to pioneer in this important heId. DR. FLOYD JERGESEN (cIosing): First of a11 I shouId like to thank Dr. West for his thoughtful and pertinent remarks. He requested a foIIow-up report concerning the outcome of the five patients in whom hip prostheses were saIvaged. I wish he had asked the question Iast week. It couId have been said that a11 five prostheses were in situ. A few days ago, we removed one from a patient with rheumatoid arthritis, not because of the infection, but because of restricted motion. This was in spite of a supplementa operation a year ago, at which time cuItures of Iarge samples of excised capsuIe were steriIe. There had been no recurrence of infection in the two year period foIIowing the first operation. Infections in the other four patients are quiescent, one to five years after operation. They have recovered varying degrees of function. The first patient was treated in 1957; and in retrospect, we were not vigorous in treatment. Recurrence of infection was noted preciseIy one year Iater; again, we treated it in a similar fashion. Two years later, a third recurrence responded favorably to treatment. The infection has been quiescent for the past two and a haIf years. Motion in the involved hip is essentiaIly complete. I shouId emphasize that the infections complicating prosthetic arthropIasty among these eight patients were treated in the acute stage and were treated soon after occurrence. In so far as I could determine, the infection ultimately had IittIe or no effect upon subsequent function when the prosthesis was retained. Dr. Stephens has asked whether or not we used continuous drip. In the Iate forties we did use continuous drip. GeneraIIy, at this time, local instiIIation twice daiIy is preferred. Suction is discontinued for three hours after each IocaI injection.
163
Infections
in Orthopaedic
Surgery*
COMBINED ANTIBIOTIC AND CLOSED WOUND TREATMENT FLOYD JERGESEN, M.D.AND ERNEST JAWETZ,M.D.,SanFrancisco,
From tbe Department of Ortbopaedic Surgery and tbe
remova of necrotic tissue, obIiteration of cavities, avoidance of further bacteria1 contamination, and subsequent wound closure. Chemotherapy is the principa1 adjunctive treatment. Modification of concepts of principIes and variations of technic can Iead to improved results of treatment of some types of infections. The purpose of this preliminary report is to emphasize the appIication of the concepts of cIosed wound management and combined antibiotic action in the treatment of certain pyogenic infections invoIving the
Department of Microbiology, University of California School of Medicine, and tbe Veterans Administration Hospital, San Francisco, California.
NSPITE of
newer concepts, refinements of surgica1 technic and recent deveIopments in chemotherapy, the seIection of optima1 treatment of some pyogenic infections of the muscuIoskeIeta1 system can be a chaIIenge to the surgeon. RationaI treatment of these infections continues to rest on established surgica1 principIes of adequate drainage of exudates,
I
FIG. I. Method of percutaneous * Presented American
at the AnnuaI
Journal of Surgery,
Meeting
Volume
of the
106. August
1963
California
introduction
of drainage tube into knee joint.
Pacific Coast Surgical February 3-6, 1963.
152
Association
at
Palm
Springs,
CaIifornia,
Pyogenic Infections
is attached
FIG. 2. The colIecting system for closed wound treatment. cock by a modified hypodermic needle hub.
The smaII viny1 catheter
muscuIoskeIeta1 system in ad&s. It is based in part upon the resuhs of a review of our experience gained during the past five years.
pIished with IocaI anesthesia. (Fig. I.) It is preferred to introduce the drainage tube through the skin in an obiique direction at a distance from any surgica1 incision. This minimizes pressure necrosis of the skin edges around the tube and can avoid kinking of the tubing. When the tube is subcutaneous or crosses bony prominences, pressure from dressings must be avoided to prevent necrosis of overlying skin. Various types of fenestrations have been used, but no type has routineIy prevented pIugging of the tube. A ten-gauge trocar permits percutaneous introduction of a tube with an outside diameter of approximateIy 3.0 mm., and a seven-gauge trocar accepts tubing with an outside diameter of approximateIy 4.0 mm. The externa1 end of the rigid-waI1 tubing can be attached to a three-way cock by a hypodermic needIe modified by removing the shaft and
CLOSED
WOUND
TREATMENT
CIosed wound treatment of IocaI infections with suction drainage under certain circumstances can fuIfN the principIe of drainage of exudates which are conducive to microbiai growth. Appropriate chemotherapeutic agents can be introduced intermittentIy into the closed system to bring high concentrations into contact with infected wound surfaces [I]. When open operation is necessary for removal of necrotic tissue or foreign bodies, drainage tubes can be introduced under direct vision. When open drainage of an abscess or an infected joint is not desirabIe, percutaneous introduction of the drainage tube can be accom‘53
to the three-way
Jergesen and Jawetz
FIG. 3. Method of creation of closed cavity with segment of rubber gIove where skin overIying the bone Iesion has been lost.
provides intermittent suction at go or 120 mm. of mercury has been used with satisfaction. OccasionaIIy, it has been advantagenous to create a cIosed system in which overlying soft tissues were destroyed by infection or injury. A reasonabIy effective system has been devised for short periods of use by employing the thumb segment of a surgica1 gIove for covering. The suction tube was introduced through the thumb cot and the free edge of the gIove segment was attached to the surrounding skin by an appropriate adhesive compound such as “Ace Adherant.” (Fig. 3.) GeneraIIy, the topica agent was instiIIed at twetve hourIy intervaIs and suction was discontinued For the folIowing three hours. During
threading the hub so it can be screwed on to the tubing. (Fig. 2.) The three-way cock permits both periodic instiIIation of chemotherapeutic agents into the infected area and reguIation of outflow. Trap bottIes or test tubes of varying size can be introduced into the system between the three-way cock and the suction apparatus for purposes of colIection of wound secretions. Depending upon the rate of drainage, the size of the coIIecting container is seIected to permit accurate and periodic measurement of the voIume of exudates. SpeciaI containers such as test tubes can be inserted in the system for colIection of exudates for bacteriologic study and antibiotic assay. The Gomco Suction Pump@ which ‘54
Pyogenic
FIG. 4. Chronic
osteomyehtis
Infections
of femur. Sinogram showing progressive
the remaining nine hours between instiIIations, suction drainage was effected. Change in the size of soft tissue cavities could be estimated with fair accuracy by the varying volumes of fluid accepted. However, periodic x-ray studies with the cavity distended with an aqueous radiopaque solution provided a graphic record of progress of treatment, and on occasion indicated foci of persistent infection. (Fig. 4.) COMBINED
ANTIBIOTIC
obliteration
of soft tissue abscess cavity.
the rate and compIeteness of killing. For optima1 resuIts of treatment of serious infection, the concentration of antibiotics both in the bIood and IocaIIy, in tissues and exudates, ideaIIy shouId be bactericida1. The selection of effective chemotherapeutic agents and their respective dosage to assure bactericida1 action in a specific infection, requires critica clinica judgment and reIiabIe Iaboratory studies. How can an effective concentration of drug be deIivered to the site of infection? High concentrations of some antibiotics in joints cannot be achieved by systemic administration aIone [r]. The synovia1 membrane of joints or the waIIs of abscess cavities may deIay the passage of drugs from the bIood stream but microorganisms within such spaces can be attacked by direct instiIIation. Therefore, combined systemic and IocaI administration may be more effective than either route aIone. The antimicrobia1 effect of certain singIe notabIy peniciIIin, can be poantibiotics, tentiated by increased dosage [6]. Some antibiotics (such as bacitracin) can be used topicaIIy in high concentrations with less Iike-
ACTION
AIthough the systemic use of a singIe chemotherapeutic agent often suffices for successfu1 treatment of many pyogenic infections of the musculoskeletal system, regrettabIy others do not respond optimaIIy. With the hope of improving the results of treatment of some severe infections, concepts of combined antibiotic action [2-q] were appIied. Bacteriostatic or inhibitory activity of chemotherapeutic agents in vitro is manifest by the reduction of the norma growth of organisms in a suitabIe environment without regard to kiIIing. BactericidaI action reffects 15s
Jergesen and Jawetz Iihood of untoward side effects than when a simiIar IeveI is attained IocaIIy by systemic administration. MuItipIe drugs may give a greater antimicrobia1 effect than that provided by a singIe agent. Combinations of antibiotics can act on bacteria in a synergistic, antagonistic or indifferent fashion [2,3].A reason for combined use is the synergistic antimicrobia1 effect that might not be obtained from a singIe agent. It may be necessary to use muItipIe drugs both IocaIIy and systemicaIIy to eradicate complex microffora of mixed infections in which singIe or dua1 agents would not act effectiveIy on a11 components. The additive action of two drugs can reduce the reIative necessary dosage of thereby minimizing the each component, possibiIity of toxic side effects which might resuIt from higher dosage of a singIe agent. The rapid emergence of strains of bacteria resistant to a singIe antibiotic (such as erythromycin) may be avoided by combined treatment [2]. Antagonistic action of antibiotic combinations can be demonstrated readiIy in vitro [3]. Jones and Finland [7] found the effectiveness of pIasma of norma subjects containing peniciIIin and tetracycline, in various combinations of dosages, was Iess than that containing one or the other antibiotic in which the test organisms were streptococci or pneumococci. Proof of antibiotic antagonism is diffIcuIt to estabIish under cIinica1 conditions of combined drug treatment of estabIished infection, chiefIy because antagonism is readiIy overcome by an excess of either drug in a part. The determination of synergistic or additive effects ilz vitro of antimicrobia1 combinations must be made for the individua1 strain of bacteria. It is a matter of “taiIoring,” because arbitrarily seIected combinations may be ineffective or even antagonistic. Depending on the strain of staphyIococcus tested, peniciIIintetracycIine or peniciIIin-chIoramphenico1 combinations have been demonstrated to have either synergistic, indifferent, additive or antagonistic effect [8]. In the present study, a modified tube diIution technic was used in preference to the disk method for determining bactericida1 or bacteriostatic activities of antibiotic combinations [9,10]. The principIe of seIection of combinations is based upon the idea of using poorIy absorbed, toxic agents (such as neomycin, poIymyxin, or bacitracin) IocaIIy and we11 absorbed drugs 156
systemicaIIy. The foIIowing drugs and concentrations have been empIoyed frequentIy for topica use: neomycin I per cent, poIymyxin 0.1 per cent, bacitracjn 1,000 units per m1. Greater concentrations have been used occasionaIIy to dea1 with particuIarIy resistant microorganisms. Assay for antibacteria activity in sera and wound exudates have proved to be a vaIuabIe guide to the dosage of antimicrobia1 drugs. This test is an important adjunct to clinica evaluation and bacterioIogic studies [I I]. Periodic cuItures of wound exudates are necessary for the critica assessment of the success of treatment. CoIIection of reIiabIe specimens of exudate for cuIture requires interruption of IocaI therapy for tweIve hours or more to prevent false negative determinations caused by persistentIy high concentrations of IocaIIy instiIIed drug. ExcessiveIy frequent interruption of treatment for purposes of cuItures may be undesirabIe. cLINIcAL MATERIAL The cIinica1 materia1 seIected as the background of this report was derived from a review of records of sixty-eight patients treated during the past five years. This proved to be a varied group of infections of the motor-skeIeta1 system in aduIts. Closed wound management and combined antibiotic therapy was reserved for the more severe and extensive infections. Minor infections were usuaIIy treated by commonly empIoyed methods and were not incIuded in this study. Hematogenous Osteomyelitis. OnIy three patients with acute hematogenous osteomyeIitis were encountered. AI1 invoIved the spine, and the etioIogic organism identified in each was a staphyIococcus. In addition to genera1 principIes of treatment which incIuded bed rest and externa1 immobiIization 1121,cIosed wound management and combined antibiotic therapy by IocaI and systemic routes proved to be effective in cIinica1 contro1 of the infections of aI1. ScherbeI and Gardner [r3] have suggested that intervertebra disc space infections might be treated by IocaI instiIIation of an effective antibiotic agent through a catheter Ieft for that purpose at the time of operation. There were six patients with acute exacerbations of chronic hematogenous osteomyeIitis. Treatment of soft tissue abscesses without open operation by percutaneous introduction
Pyogenic of the drainage catheter was accompIished in three and was foIlowed by control of the acute recurrence. Treatment in the remaining three patients incIuded extensive sequestrectomy and saucerization. Skin grafting of the exposed bone surface of one patient resulted in arrest of the infection. Persistent drainage in a second patient required a second sequestrectomy; the third patient remains under active treatment. Acute Postoperative Infections. In two patients septic arthritis of the shouIder joint deveIoped, one was biIatera1, foIIowing injections of steroids for treatment of periarthritis. The causative organism was Pseudomonas aeruginosa in both. Local instiIIation of poIymyxin with appropriate systemic antibiotics resuIted in prompt arrest of the infection in both [14]. Four postoperative infections of the knee joint were encountered. AI1 were caused by staphyIococci and folIowing arrest of the infection, function was recovered in three. AIthough the acute infection was controIIed in the fourth patient, supracondylar amputation became necessary subsequentIy because of gangrene secondary to obIiterative vascuIar disease. Culture studies of synovia and cartiIage taken from the knee joint of the specimen faiIed to demonstrate any bacteria1 growth. A singIe postoperative infection in an ankIe joint responded favorabIy. Eight postoperative infections foIIowed repIacement arthropIasty. Six invoIved the hip joint and one each the shouIder and elbow joints. Of the six hip joint infections, five responded favorabIy and the foIIowing case history serves to iIIustrate successfu1 management. CASE
Infections addition to erythromycin, tetracycIine was incIuded for systemic use. Since serum assay showed onIy inhibitory action in a one to five diIution on ApriI 23, 1962, novobiocin was added as a systemic drug. On April 30, 1962, the serum assay demonstrated bactericida1 activity at one to eighty diIution. The drainage catheter was removed on May 15, 1962, but systemic therapy was continued unti1 June 29, 1962. Because of a rash, oxaciIIin was substituted for novobiocin and tetracycIine on May 31, 1962. The clinica response to treatment was favorable; eight months after contro1 of infection there had been no evidence of recurrence.
Comment: The suction drainage tube inserted at the time of operation for removal of bIood and wound exudates [15,16] was removed on the third postoperative day. During the next ten days the patient’s postoperative course was uneventful, aIthough some drainage persisted from the catheter exit. A minor rise in temperature was noted on the thirteenth day after operation; this continued for the next four days. GraduaI rise in fever was apparent unti1 the twenty-first postoperative day when the temperature reached 3g’c. Increase of pain in the hip region then was noted. In retrospect, the diagnosis shouId have been established at Ieast forty-eight hours earIier. Another deIay of forty-eight hours folIowed initia1 aspiration whiIe awaiting cuIture studies and disk sensitivity determinations. Thus, four days elapsed before chemotherapy was started. AIthough the patient’s cIinica1 response to treatment, as judged by Ioss of pain and decreasing febriIe reaction, was favorabIe; cuIture studies were not negative unti1 the twenty-fifth day after institution of antibiotic treatment. Treatment of infection was unsuccessfu1 foIIowing repIacement arthropIasty of the shouIder for fracture-disIocation of the head of the humerus. In this patient, cuItures demonstrated a mixture of staphyIococcus and pseudomonas. AIthough the infection was apparent on the ninth postoperative day, combined therapy was not instituted unti1 two weeks Iater. At that time a sinus tract had deveIoped and it was impossibIe to estabIish a cIosed system. A singIe exampIe of faiIure of treatment foIIowing repIacement arthropIasty of the hip was encountered in which a staphyIococcus was isoIated. The infection was discovered on the
REPORT
In a thirty-seven year oId man (C. C.), acute pain deveIoped in the region of the hip twenty-one days after reconstructive arthropIasty with an intrameduIIary prosthesis. (Figs. 5 and 6.) InitiaIIy, disk sensitivity studies had suggested that erythromycin wouId be effective against the staphyIococcus isolated from the hip joint exudates, and it was given systematicaIIy. SubsequentIy, however, tube dilution studies did not confirm that impression. They demonstrated that the organism was rapidIy kiIIed in vitro by methiciIIin 3 pg. per mI., neomycin 5pg. per m1. pIus tetracycIine I0 pg. per mI., as we11 as by novobiocin 4 pg. per m1. pIus kanamycin IO pg. per m1. A 3 mm. viny1 catheter was introduced percutaneousIy into the hip joint for instiIIation of 1 per cent neomycin IocaIIy. In
I57
Jergesen
and Jawetz
FIG. 5. A, BiIateraI degenerative arthritis of hip secondary to Legg-Perthes disease of childhood. Radiograph two weeks after reconstru‘ctive arthropIasty of right hip with intramedulIary prosthesis. Acetabular reinforcement with corticaI bone pegs. FIG. 5. B, Radiograph six months after operation, and five months after controI of septic arthritis. Absence of radiologic evidence of persistent joint infection.
158
Pyogenic MARCH
APRIL
1962
CULTURE-STAPHYLOCOCCUS CULTURE-YEAST ERYTH
ROMYClN
TETRACYCLINE NOVOBIOCIN OXACILLI
N -
-
-
Infections MAY
+ --
JUNE
+
3,0gms/da. P.O. 2.Ogms/da.P0. 2.0gms/da P 0 Z.Ogms/da P 0
NEOMYCIN 1% LOCALLY - 15.0 ,I - IO,0
cc BI.0. cc B.I.O. ?
SERUM
ASSAY
-INHIBITORY -BACTERICIDAL
FIG. 6. CASE C. C., aged thirty-seven years. Septic arthritis arthropIasty. Course of infection and rest&s of therapy.
fourteenth day after operation. Treatment was instituted immediately and the response both from the clinica point of view and from cuIture studies seemed favorabIe. However, the infection recurred within four weeks after cessation of treatment. The response was temporariIy favorabIe on the second occasion onIy to be foIIowed by recurrence with progressive evidence of destruction of the hip joint. Drainage did not cease unti1 the metaIIic apparatus had been removed. Acute postoperative infections foIIowing open reduction of cIosed fractures and a variety orthopaedic procedures on of other “cIean” bone composed a heterogenous group of five patients that was diff&uIt to anaIyze because of Iack of uniformity of circumstances. The response to treatment varied from apparent eradication of infection in four patients to temporary suppression folIowed by recurrence in one. The foIIowing exampIe serves to emphasize a favorable response. CASE
of hip joint folIowing reconstructive
coliform organism isoIated from wound secretions suggested sensitivity to chIoramphenico1, kanamycin and polymyxin. Two days later, a nonhemoIytic coagulase negative staphyIococcus was recovered from the fracture site in addition to Eschericbia coli. Disk sensitivity determinations suggested the staphyIococcus wouId respond favorably to a wide variety of chemotherapeutic agents in&ding erythromycin, chIoramphenico1 and neomycin. The drainage tube was introduced percutaneously to the fracture site on July rg, 1962, and IocaI treatment with neomycin I per cent was instituted. Erythromycin and chIoramphenico1 were selected initially for systemic administration. Tube dilution studies subsequently demonstrated that the staphylococcus was rapidIy kiIIed in vitro by erythromycin z pg. per mI. pIus bacitracin I unit per ml. PoIymyxin@ I pg. per m1. pIus chIoramphenico1 20 pg. per m1. was significantly bactericida1 to the Eschericbia coli. Neomycin and polymyxin were seIected then for Iocal instiIIation whiIe erythromycin and chioramphenicoi were used SystemicaIIy. Because of development of Ieucopenia, chIoramphenico1 was discontinued subsequentIy and novobiocin substituted. Afterward, jaundice developed and systemic administration of both novobiocin and erythromycin was stopped. These were suppIanted by oxaciIIin whiIe neomycin and poIymyxin were continued IocaIly. Wound cuItures taken on August I, 1962, demonstrated no growth and the suction tube was removed on August I I, 1962. Systemic treatment
REPORT
In a fifty-three
year oId man (W. S.), fever and acute pain deveIoped in the region of the hip eighteen days after open reduction of a comminuted intertrochanteric fracture of the femur. (Fig. 7.) Initial disk sensitivity studies of the
‘59
Jergesen and Jawetz &GUST
JULY
JUNE 1962
39
TPR (%I
36
CULTURE
-STAPHYLOCOCCUS
CULTURE-
COLI FORM
ERYTHROMYCI
N -
3.0 gm/da. P.O. 2.0 gm/da. P.O.
CHLORAMPHENICOL-3,0gm/da. 1.M 3.0gm/do.P0. 2.0gm/do. P.O. NOVOBIOCIN OXACILLIN
-.
2.0gm/da
P.O.
3.0gm/da
P.O.
NEOMYCIN 1% LOCALLY - 1080 cc B.I.D. POLYMYXI N 001 % LOCALLY-.iO.O
cc B.I.D.
FIG. 7. CASE W. S., aged fifty-three years. Wound infection foIlowing open reduction and internal fixation of cornminuted intertrochanteric fracture. Course of infection and results of therapy.
Chronic Secondary Osteomyelitis. Recurrent or chronic secondary OsteomyeIitis foIIowing open fracture or as a resuIt of postoperative infection was encountered in a major proportion of these patients. GeneraIIy, open operation was necessary for remova of sequestra, infected soft tissues, or metal&c foreign bodies. The type of infection varied widely both in character and in microbia1 Aora. Because of lack of uniform clinica materia1, detaiIed anaIysis of the resuIts of treatment was not attempted. Certain significant features are discussed beIow.
was
continued unti1 August 26, 1962. During the succeeding six months the fracture healed; there has been no evidence of recurrent infection.
Comment: The nature and origin of the mixed infection in this patient couId not be determined. The isolation of a staphylococcus two days after recovery of the colon bacilIus might have represented a superinfection caused by contamination in the course of Iocal treatment. Inadequate sampling or deficient Iaboratory isoIation technics suggest other reasons for failing to demonstra’te both organisms in the initial culture. This example emphasizes the importance of periodic cuIture studies not onIy for the determination of efficacy of treatment, but aIso for the earIy recognition of any change in wound flora. Chronic Septic Arthritis. Five patients with chronic pyogenic infections of joints were treated. IncompIete function was restored to two knee joints foIIowing arrest of infection. Infection was arrested in two hip joints after debridement of one, and remova of a prosthesis and debridement of the other. Infection in the hip joint of the fifth patient recurred and required further treatment.
COMMENTS
Combined antibiotic action and cIosed wound management as adjuncts to estabIished surgica1 principIes of treatment of pyogenic infections of the motor-skeletal system had some disadvantages as we11 as advantages. Suction drainage provided adequate egress for wound exudates and bits of free tissue. However, bone sequestra, Iarge masses of necrotic soft tissue and infected granuIation tissue required remova by open operation. A significant cause of treatment faiIure was inadequate 160
Pyogenic remova of necrotic tissue which provided both pabuIum and haven for microbia1 propagation. In other instances, sclerotic bone and extensive soft tissue scar seemed to provide foci for recurrence of infection. Inadequate operative treatment was not overcome by antibiotic treatment. Frequent checking of the suction system was necessary to insure its proper function; this required attention of medica personnel. In spite of scrupuIous aseptic technic, repeated instiIIation of antibiotic agents and the presence of the irrigation system provided a potentia1 source of contamination. CIosed wound treatment required infrequent dressings which saved time and spared the patient pain. The comparative possibiIity of secondary contamination appeared to be Iess with cIosed treatment than in open wounds that were dressed frequentIy. RemovaI of exudates by a closed system minimized soiIing of the patient, and contamination of bed cIothing and per$onneI with dissemination of the organisms in the hospita1 environment. EarIy cIosure of the wound was thought to decrease scarring tha% commonIy foIIowed proIonged open treatment. Tube diIution tests for the determination of bacteria1 susceptibiIity to combinations of antibiotics and assays of antibacteria activity in sera and wound exudates were timeconsuming and required a we11 equipped Iaboratory with trained personne1. ObviousIy, these costIy tests were reserved for serious and major infections. The simuhaneous use of muItipIe chemotherapeutic agents increased the Iikelihood of undesirabIe side effects, and at times made difl?cuIt the assignment of a reaction to a specific drug (such as used in patient W. S.). The serious consequences of some drug reactions had to be baIanced against the IikeIy gain from subjecting the patient to such hazards. Continued and widespread use of a singIe antibiotic combination, such as stock mixtures, was avoided among hospital parients since it was thought to increase the possibility of emergence of microfl ora resistant to a11 drug components. Another hazard was that of superinfection which implies the appearance of an infection caused by an organism different from the one for which antimicrobial therapy was instituted [17,18]. Such a possibility was suspected when response to treatment did not
Infections foIIow prediction. Superinfection occurred Iate in the course of treatment of one patient and convalescence was significantIy proIonged. Treatment of acute infections in seriously iII patients was not deIayed unti1 microflora had been isolated and antibiotic sensitivities had been determined. For the critica interva1 between diagnosis of infection and compIetion of preIiminary Iaboratory studies, the empiric seIection of drug combinations for IocaI and systemic use was made on the basis of probabIe effectiveness in deaIing with types of microorganisms that were most frequentIy isolated from acute infections of the motorskeIeta1 system. The common etioIogic organisms of acute infections in these patients were staphyIococci, enterococci and gram-negative baciIIi of the coIiform and pseudomonas groups. The dosages of drugs arbitrarily selected for combined therapy were adjusted so that bactericida1 effects wouId IikeIy be obtained. Because of the high incidence of peniciIIinase-producing staphyIococci, generaIIy penicillin was withheId unti1 its possible eficacy had been demonstrated in vitro. For interim treatment of the average aduIt under such urgent circumstances, sodium coIistimethate 300 mg. and sodium methiciIIin 12 gm. were given systemicaIIy in divided doses each day. When open operation was unnecessary or couId be deferred temporariIy, drainage was provided by a smaI1 viny1 catheter introduced percutaneousIy into the joint or abscess cavity. Otherwise, the tube for IocaI therapy was impIanted at the time of the initia1 open operation. A soIution of I per cent neomycin and 0.1 per cent poIymyxin-a in the amounts of 5 to 15 m1. was instiIIed twice daiIy for local therapy. As soon as causative bacteria were identified and IikeIy sensitivities determined, proper antibiotic combinations were substituted. Recurrent or chronic infections d?d not aIways require immediate chemotherapy, and it was frequentIy delayed unti1 proper Iaboratory studies had been compIeted. The IeveI of predicted drug concentrations in sera was determined in many patients by periodic assays. An attempt was made to maintain a IeveI of antibacteria activity in serum diIuted I : IO or more. FaiIure to make such studies for guidance in treatment may heIp to expIain faiIure to contro1 infection folIowing hip arthroplasty in one patient. The rate and character of wound drainage were indications of eflicacy of treatment. Pro161
Jergesen
and
gressive decrease in voIume and diminishing turbidity were accepted as added evidence of favorabIe response. On occasion, and especiaIIy in articuIar infections, high concentrations of drug appeared to cause irritation and maxima1 clearing of exudates was not observed unti1 IocaI therapy had been discontinued. Additives such as fibrinoIytic agents or soIvents were not used in treatment of these infections [19,20]. SUMMARY
This is a preIiminary report of experiences in the treatment of serious pyogenic infections of the motor-skeIeta1 system in aduIts. EstabIished surgica1 principIes of treatment of infected wounds was observed. Open wound treatment was abandoned in favor of the cIosed technic with intermittent suction and combined antibiotic therapy. Antibiotic combinations were seIected for simuItaneous systemic and IocaI administration in accordance with in vitro determinations of bactericida1 activity. In addition to usua1 cIinica1 criteria of success of treatment, periodic wound cutture studies and assays of sera and wound exudates for antimicrobia1 activity were thought to provide dependabIe guidance. The resuIts of treatment of acute postoperative infections in this smaI1 series was encouraging and have stimuIated further study. Six acute infections foIIowing prosthetic arthropIa.sty were controIIed and subsequentIy remova1 of metaIIic foreign bodies was not necessary because of recurrent infection. AnaIysis of two faiIures of treatment of infection after prosthetic arthropIasty suggested factors that in retrospect might have been significant causes. The most discouraging resuIts were encountered in chronic or recurrent infections of bone wherg necrotic tissue, infected granuIation tissue or extensive scarring of soft tissue were present. Inadequate operative remova of infected or necrotic tissue couId not be compensated by adjunctive chemotherapy. Certain advantages and disadvantages of cIosed wound treatment and combined antibiotic therapy are discussed.
Jawetz 3. JAWETZ, E. and GUNNXSON,J. B. An basis of combined antibiotic action. 150: 693, 1952. 4. LOWBURY, E. L. Cross infection of antibiotic-resistant organisms. Brit.
experimenta J. A. M. A., wounds with M. J., I : 985,
1955. 5. JOCSON, C. T. The diffusion of antibiotics through the synovial membrane. J. Bone @ Joint Surg., 37-A: 107, 1955. 6. ALTMEIER, W. A. and WULSIN, J. H. Antimicrobial therapy in injured patients. J. A. M. A., 173: 527, 1960. 7. JONES, W. F. and FINLAND, M. Antibiotic combinations; antibacteria action of plasma of normaI subjects after ora doses of peniciIIin v, tetracychne hydrochIoride, and a combination of both. New England J. Med., 256: 869, 1957. 8. HINTON, N. A. and ORR,J. H. The effect of combinations of antibiotics on coagulase-positive staphylococci. Canad. M. A. J., 82: 31 I, ;g6o. g. GUNNISON, J. B. and JAWETZ, E. Sensitivity tests with combinations of antibiotics: unsuitabihtv of disk method. J. Lab. ti Clin. Med., 42: 16;, 1953. IO. JAWETZ, E., GUNNISON, M. A., COLEMAN, V. R. and KEMPE, H. C. A Iaboratory test for bacteria1 sensitivity to combinations of antibiotics. Am. J. Clin. Patb., 25: 1016, 1945. I I. JAWETZ, E. Assay of antibacteria activity in serum. Am. J. Dis. Cbild.. IO?: 81. 1062. 12. GARCIA, A., JR. and GRANTHAM, S. A. Hematogenous pyogenic vertebra1 osteomyehtis. J. Bone TVJoint Surg., 42-A: 429, 1960. 13. SCHERBEL, A. L. and GARDNER, W. J. Infections involving the intervertebra disks. J. A. M. A., 174: 370, 1960. 14. JAWETZ. E. Infections with Pseudomonas aeruginosa treated with polymyxin B. Arch. Int. Med., 89: go, 1952. I 5. MCELVENNY, R. T. Mechanical suction of wounds. &rt. Bull. Nortbwestern M. School, 35: 235, 16. WAUGH, T. R. and STINCHFIELD, F. E. Suction drainage of orthopaedic wounds. J. Bone EdJoint Surg., 43-A: 939, rg6r. 17. RANTZ, L. A. Consequences of the widespread use of antibiotics. California Med., 81: I, 1954. 18. WEINSTEIN, L., G~LDFIELD, M. and CHANG, T. Infections occurring during chemotherapy: a study of their frequency, type and predisposing factors. New England J. Med., 25 I : 247, 1954. rg. COMPERE, E. L. Treatment of osteomyeIitis and infected wounds by cIosed irrigation and a detergent-antibiotic solution. Acta ortbop. scandinav., 32: 324, 1962. 20. GRACE, E. J. and BRYSON, V. TopicaI use of concentrated peniciIIin in surface active soIution. Arch. Surg.. 50: 219, 1945.
REFERENCES
DISCUSSION
I. MILLER,
R. H. and SMITH-PETERSEN, M. N. Further report on osteomyelitis at the Massachusetts General HospitaI. New England J. Med., 216: 827, 1937. 2. JAWETZ, E. Combined antibiotic action. 4th Internat. Cong. Biocbem., 5: gr, 1959.
F. E. WEST (San Diego, CaIif.): It is a pieasure to have the opportunity to discuss the paper on Pyogenic Infections in Orthopedic Surgery by Doctors Jergesen and Jawetz. For a11 of us surgeons, the treatment of pyogenic infections is a
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Pyogenic Infections serious task; and certainIy for the orthopedist, infection frequentIy presents itself as a tragedy. The loss of a joint, or the tota failure of a reconstructive procedure is a major calamity. Dr. Jergesen and Dr. Jawetz have presented a prehminary survey of their approach to this most distressing problem. In their paper the age oId axiom that where there is an estabhshed debris and a coIIection of pus, open and adequate drainage is necessary, has been modified. When infection is first seen, that is, earIy in its deveIopment, either postoperative or by spontaneous onset in bone or joint, these authors bebeve, this infection may be handied by cIosed drainage and a strong barrage of antibiotics: (I) The appropriate more toxic and nonabsorbabIe drugs, such as, neomyecin, poIymyxin and bacatracin, may be used in the area of the IocaI infection through cIosed system drainage. (2) ProperIy seIected parentera antibiotics with less toxic effects may be used by oraI or injection routes. (3) They have aIso suggested that the proper method of election of the antibiotic is by the tube diIution method, in contrast to the ordinary disc evahration methods commonly used. In regard to this last assumption, I do not believe that I am qualified to discuss the probIem, but would leave this decision to the bacterioIogists. In the report Dr. Jergesen mentions that sixtyeight cases have been so treated, but actualIy onIy twenty-five cases have been reviewed as to the resuIts of this method of treatment. The remainder of the cases are not reported in detai1. The three cases of acute hematogenous osteomyehtis of the spine, and six of recurrent infection of hematogenous osteomyelitis are of interest, but they are not convincing; I shouId expect that further evidence wiI1 be uItimateIy obtained. Among the ten cases of marked interest are four cases of postoperative infection of the knee which recovered under this form of treatment and six cases of postoperative infection foIIowing prosthetic surgery of the hip. In five of the six patients, the prosthetic device was saIvaged. It is we11 known that in instances of an acute pyogenic infection of a joint, a serviceabIe articuIation may be obtained by an earIy diagnosis, proper parentera antibiotics; and on certain occasions, a thorough cIosed irrigation of the infected joint with norma saIine soIution or an antibiotic, according to the methods previousIy described. However, the same experience has not been mine in the case of an infected postoperative hip prosthesis. The usua1 course in this situation has been the fina removal of the foreign body. In this paper, in five of six patients with such infections, the prosthesis has been saved. I shouId like to know the fina results in regards motion, function and durabiIity of these saIvaged affected joints.
The additiona report of a case of an infected intertrochanteric fracture is, I believe, of double interest. First, the proper seIection of antibiotics for a mixed type of infection; and secondIy, the heaIing of the serious fracture with a foreign body present, in face of infection, is of significant importance to emphasize the advantages of such a course of therapy. There is no question that the problem of treating acute pyogenic infections of bones, joints and postoperative reconstructive procedures is a matter of great concern. Any method which may lead to avoiding Ioss of joint motion or Ioss of operative repair demands our attention. This paper is provocative and chaIIenging. It is my opinion that through such endeavors we will ultimateIy make progress in our seIective therapy of such infections. I trust that Doctors Jergesen and Jawetz wiI1 continue to pioneer in this important heId. DR. FLOYD JERGESEN (cIosing): First of a11 I shouId like to thank Dr. West for his thoughtful and pertinent remarks. He requested a foIIow-up report concerning the outcome of the five patients in whom hip prostheses were saIvaged. I wish he had asked the question Iast week. It couId have been said that a11 five prostheses were in situ. A few days ago, we removed one from a patient with rheumatoid arthritis, not because of the infection, but because of restricted motion. This was in spite of a supplementa operation a year ago, at which time cuItures of Iarge samples of excised capsuIe were steriIe. There had been no recurrence of infection in the two year period foIIowing the first operation. Infections in the other four patients are quiescent, one to five years after operation. They have recovered varying degrees of function. The first patient was treated in 1957; and in retrospect, we were not vigorous in treatment. Recurrence of infection was noted preciseIy one year Iater; again, we treated it in a similar fashion. Two years later, a third recurrence responded favorably to treatment. The infection has been quiescent for the past two and a haIf years. Motion in the involved hip is essentiaIly complete. I shouId emphasize that the infections complicating prosthetic arthropIasty among these eight patients were treated in the acute stage and were treated soon after occurrence. In so far as I could determine, the infection ultimately had IittIe or no effect upon subsequent function when the prosthesis was retained. Dr. Stephens has asked whether or not we used continuous drip. In the Iate forties we did use continuous drip. GeneraIIy, at this time, local instiIIation twice daiIy is preferred. Suction is discontinued for three hours after each IocaI injection.
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