TREATMENT OF SEPTIC ARTHRITIS

Transcription

1 a3 TREATMENT OF SEPTIC ARTHRITIS COMPARISON OF NEEDLE ASPIRATION AND SURGERY AS INITIAL MODES OF JOINT DRAINAGE DON L. GOLDENBERG, KENNETH D. BRANDT, ALAN S. COHEN and EDGAR S. CATHCART Surgery and needle aspiration have been evaluated as initial modes of drainage in 59 patients with acute septic arthritis. Full recovery was noted in 42y0 treated surgically at the outset. On the other hand, 67% of those treated by needle aspiration recovered without sequelae, despite the greater prevalence in this group of adverse host factors-eg, serious underlying From the Arthritis and Connective Tissue Disease Section, Boston University Medical Center, Departments of Medicine, Boston City Hospital and University Hospital, and from the Evans Department of Clinical Research and the Thorndike Memorial Laboratory. Grants in support of these investigations have been received from the United States Public Health Service, National Institute of Arthritis and Metabolic Diseases (AM and TI-AM-5285), the General Clinical Research Centers Branch of the Division of Research Resources, National Institutes of Health (RR-533), the Massachusetts Chapter of The Arthritis Foundation and The Arthritis Foundation. Don L. Goldenberg, MD: formerly, Trainee in Rheumatology, National Institutes of Health: Kenneth D. Brandt, MD: Special Research Fellow. National Institutes of Health, and Associate Professor of Medicine, Boston University School of Medicine: Alan S. Cohen, MD: Conrad Wesselhoeft Professor of Medicine, Boston University School of Medicine, Director, Thorndike Memorial Laboratory, and Chief of Medicine, Boston City Hospital; Edgar S. Cathcart, MD: Associate Professor of Medicine. Presented in part at the Thirty-seventh Annual Scientific Session of the American Rheumatism Association, Los Angeles, California, June 7-8, Address reprint requests to Alan S. Cohen, MD, Thorndike 314, Boston City Hospital, 818 Harrison Avenue, Boston, Massachusetts Submitted for publication March 21, 1974: accepted June 6, illness, concommitant extraarticular infection, prior arthritis in the infected joint, and recent antibiotic or immunosuppressive therapy. There is general agreement regarding the necessity for surgical drainage of an infected joint which has not responded to an adequate trial of closed aspiration and antibiotics (1). On the other hand, surgical drainage is also frequently employed as initial treatment of acute bacterial joint infections, despite the fact that many patients treated with appropriate antibiotics respond well when the joint is drained by repeated needle aspiration rather than by surgery (1-6). Indeed, whether the patient with septic arthritis is treated with needle aspiration or surgical drainage appears frequently to depend upon whether he has been admitted to a medical or to a surgical service, and studies of septic arthritis which have attempted to relate the therapeutic outcome to the type of joint drainage employed are sparse (7). Accordingly, we have retrospectively analyzed our own experience with sep tic arthritis and compared the results in patients treated surgically. MATERIALS AND METHODS The case records of all patients with a discharge diagnosis of infectious arthritis seen at Boston City Hospital and University Hospital in were examined. To ensure that this study included only examples of definite, acute bacterial arthritis, all cases analyzed further were a) Arthritis and Rheumatism, Vol. IS, No. 1 (January-February 1975)

2 84 GOLDENBERG ET AL seen within 14 days of the onset of joint symptoms and b) had positive synovial fluid cultures. Infections due to Neisseria gonorrhoeae, which is generally considered to be more benign than other bacterial joint infections and to respond readily to medical management, were excluded. For purposes of comparison, cases meeting the above criteria were divided into two groups according to the mode of joint drainage initially employed-medical (repeated needle aspiration) or surgical. Statistical analyses were performed by the xz method, with the Yates correction employed as indicated (8). Eighty percent of patients were followed for at least 3 months. RESULTS Fifty-nine patients with proven acute bacterial arthritis were seen in the 8-year period of this study. All received parenteral antibiotics on the basis of in vitro sensitivity studies. In 42 the infected joint was drained from the outset by repeated needle aspirations while 17 underwent immediate surgical drainage. All but one of the 17 treated with initial surgery and 34 of the 42 treated medically had monarticular arthritis. One patient in the surgically treated group and 3 of those treated medically had proven infection in two joints, while 5 in the latter group had organisms cultured from three joints. Thus, 55 infected joints were treated by needle aspiration, while 18 were operated upon at the outset. In no case was there any suspicion that joints other than those from which positive cultures were obtained might have been infected at any time during the course of the illness. In several cases, in addition to drainage ancillary procedures were performed. Thus intraarticular antibiotic injections were used in treating four joints drained by needle aspiration. Continuous irrigation was employed for periods up to 7 days postoperatively, with 10 of the 18 joints treated surgically at the outset; antibiotics were instilled through the irrigating catheter in 7. Debridement and partial synovectomy were performed on three joints. Forty of the 42 patients treated with closed aspiration (95%) were admitted to a Medical Service, whereas 8 of the 17 treated surgically (47710) were admitted to an Orthopedics Service. Whether the patient was hospitalized on a medical or surgical ward was determined in each case by the admitting physician, who was either a medical or surgical (or orthopedic) resident. At the outset of this study it was recognized that factors other than mode of therapy may have significantly influenced the outcome, and the two treat- Table 1. Synouial Fluid Cultures, Related to Initial Mode of Joint Drainnge, in Patients with Acute Znfectious Arthritis Aspiration Surgery No. of patients Organisms Streptococcus pyogenes 10 4 Streptococcus fecalis 2 0 Staphylococcus aureus 11 8 Diplococcus pneutnoniae 5 2 Hemophilus influenza 5 1 Escherichia coli 4 1 Proteus mirabalis 3 1 Pseudomonas aeruginosa 1 Serratia marcescens - 1 Salmonella typhimurium 1 - Salmonella choleraesuis 1 - ~~ ~ *Two patients had mixed infections. Total 42 19* ment groups were therefore compared with respect to several such variables. Five major points were considered: a) general features, b) manifestations of the infection, c) host factors predisposing to septic arthritis, d) the joint disease, and e) results. General Features Sex, Race, Age. The medically treated group consisted of 25 males and 17 females; the surgically treated group, of 14 males and 3 females. Approximately 60% of each group were white and 40% black. The series included 12 children, constituting approximately 20% of each group. The mean age of the 42 medically treated patients, however, was 53 years, while that of the surgically treated group was only 36 years. Manifestations of the Infection Organisms Involved. Staphylococcus aureus and streptococci were the organisms most frequently encountered (Table 1) and were cultured from the joints of 19 and 16 patients, respectively. Streptococci accounted for 29% of the organisms recovered from patients treated by needle aspiration and 21% of those from patients treated surgically, while staphylococci represented 26y0 of the organisms recovered from medically treated patients but 42% of those isolated from the surgically treated group. Thirteen patients had infections with gramnegative bacilli, which constituted approximately 20% of all organisms recovered from patients in each group. Two patients treated surgically had mixed infections,

3 TREATMENT OF SEPTIC ARTHRITIS 85 Table 2. Predisposing Factors in Patients with Acute Infectious Arthritis Treated Initially by Aspiration or Surgical Drainage No. of patients Predisposing factors Extraarticular infection With same organism With different organism Serious underlying illness Prior antibiotic for 5 days Prior immunosuppressive agent Prior arthritis in infected joint Aspiration Surgery each involving two organisms (E coli plus serratia; Staphylococcus plus Diplococcus pneumoniae). Duration of Symptoms Prior to Evaluation. The development of septic arthritis appeared in all patients to have been heralded by pain in the infected joint, although other features, such as chills or fever, were also frequently present at the outset. In both groups the interval between the presumed onset of joint infection and admission to hospital averaged 4.3 days. According to the criteria of the study, no patients had symptoms of joint infection for more than 14 days prior to initial evaluation. Most had symptoms for less than a week. However, 6 (14%) of those treated at the outset by needle aspiration and 5 (29y0) of those treated by immediate surgical drainage were presumed to have had septic arthritis for at least 8 days prior to evaluation. Fever, Chills, Leukocytosis. The highest rectal temperature recorded in each patient during the first 24 hours of hospitalization was noted. (In the few cases where oral temperatures were measured, for purposes of comparison 1 F was added to approximate the rectal temperature.) Temperatures of at least 100 F during the first day of hospitalization were more common in the medically treated patients than in those treated surgically (P < 0.01) and occurred in 40 of the 42 treated by needle aspiration (95%) and 10 of the 17 treated surgically (59%). Chills were somewhat more common in the medically treated patients, although the difference between the two groups was not statistically significant. Where a statement concerning their occurrence was recorded, chills were noted in 10 of 28 in this group (3673, but in only 2 of 12 (17y0) treated surgically. On the other hand, the mean peripheral blood leukocyte count, approximately 14,000 cells/ mm3, was comparable in the two groups. Blood Cultures. Blood cultures were obtained from every patient, with the exception of 3 in the surgically treated group and at least two specimens were obtained from 80% of all patients. Of those from whom blood cultures were obtained, bacteremia was documented in 57% of those treated medically, but in only 24% of those treated surgically. In both groups most patients with negative cultures had been receiving antibiotic therapy (see below). No episodes of hypotension, suggesting bacteremic shock, were recorded in any patient and none was considered to have had endocarditis. Host Factors Predisposing to Septic Arthritis Concurrent Extraarticular Infection. Twentysix of the 42 patients treated by needle aspiration (62%) had culture-proven extraarticular infection concurrent with their episode of septic arthritis (Table 2). In 17 the extraarticular infections were caused by the same organism recovered from synovial fluid. In 4, moreover, the organism recovered from the joint was recovered from two extraarticular sites: 10 patients had urinary tract infections; 2 had pharyngitis, pneumonia, biliary, or gastrointestinal infections; and one each had meningitis, otitis media, and an infected decubitus ulcer. In addition, 9 patients in this group had extraarticular infections with an organism different from that cultured from the joint: 4 had pneumonia, 3 skin infections, and 2 pharyngitis. In contrast, extraarticular infections were much less prevalent (P < 0.01) in the group treated surgically and were noted in only 3 of the 17 (18%). Two (pharyngitis, skin abscess) were caused by the bacterium recovered from the synovial fluid, while the third, a case of pneumonitis, was due to an organism different from that isolated from the joint. Underlying Chronic, Debilitating Disease. To indicate the further contrast between the two groups, 11 patients treated medically, but none treated surgically, had a documented serious underlying illness when the episode of septic arthritis developed: 4 patients had malignant disease, 2 diabetes mellitus, 2 cirrhosis, and one each had sickle cell anemia, paraplegia, and chronic azotemia (P < 0.05) (Table 2). Recent Antibiotic or Immunosuppressive Therapy. Since recent antibiotic therapy could have facilitated emergence of resistant strains of bacteria, and immunosuppressive therapy might have modified host responses to infection, the frequency of their use in patients in the present series was examined. Although

4 86 GOLDENBERG ET AL Table 3. joint Involvement, Related to Initial Mode of Joint Drainage, in 59 Patients with Acule Infectious Arthrilis Joint involved Knee Shoulder Wrist Ankle Elbow Hip Interphalangeal Aspiration Surgery Total Total the difference was not statistically significant, 10 of the 42 patients treated at the outset with needle aspiration, but only 1 treated initially by surgery, had been receiving antibiotics for at least 5 days prior to the onset of their symptoms of septic arthritis. None treated by surgical drainage, but 3 treated initially by needle aspiration (including 2 who were also receiving antibiotics) were receiving immuosuppressive drugs: 1 had been taking prednisone for acute leukemia; the second was receiving prednisone, nitrogen mustard, and vincristine for treatement of metastatic oat cell carcinoma; and the third was receiving azathioprine and prednisone following renal transplantation (Table 2)- Prior Disease in the Infected Joint. X-ray evidence of mild degenerative joint disease was common and was consistent with the age distribution of the series. However, symptoms in the infected joint prior to the onset of septic arthritis were noted in only 15 patients (6 with rheumatoid arthritis, 5 with posttraumatic degenerative joint disease, and one each with gout, pseudogout, psoriatic arthritis, and aseptic necrosis), all except one of whom were treated by medical drainage (Table 2). Specific Characteristics of the Joint Disease Joints Infected. In both groups the knee was the joint most frequently involved (Table 3), followed by the shoulder, wrist, and other large joints of the extremities. All seven wrist infections were treated medically, while four of the five hip infections in the series were treated by initial surgical drainage. Route of Joint Infection. In 3 patients, all of whom were treated with immediate surgical drainage, it appeared likely that the organism had been directly implanted into the joint. One had undergone meniscectomy 2 weeks before the onset of a mixed infection Table 4. Initial Synozial Fluid Analysis in Patients with.4cute Infeclious Arthritis Treated Initially by Aspiration or Surgical Drainage Aspiration Surgery Patients Fluids analyzed 52 7 Mean leukocyte count (mm3) 98, ,000 Mean percentage of polymorphanuclear leukocytes Positive gram stain 16/ Poor mucin Blood-sytiovial fluid glucose 16/ differential greater than 40 mg/100 ml 10/ with E coli and Serratia, another had been stabbed in the knee 1 week prior to Pseudomonas infection, and the third had sustained a compound tibia1 fracture 1 week before the onset of a staphylococcal knee infection. In the other 56 patients the infecting organism was presumed to have reached the synovium by hematogenous spread. Of these, 14 were treated surgically and the remaining 42, medically. Synovial Fluid Analysis. Arthrocentesis was performed at the time of initial evaluation of every patient. In 10 of the cases treated surgically, the fluid was cultured hut not analyzed further. However, at least the total leukocyte count and differential of 52 fluids from all 42 patients treated medically were recorded. The mean leukocyte count (approximately 100,000 cells/mm3) and mean percentage of polymorphonuclear leukocytes (approximately 94%) in the initial synovial fluid analysis were essentially identical when the two groups were compared (Table 4). The available data confirmed that the synovial fluids from the two groups were similar also in other respects-eg, the mucin clot was poor in all 18 on which the test was performed. Approximately half of all Gram stains performed were positive in both groups and, in two-thirds of the cases in both groups where results were available, the difference between blood and synovial fluid glucose concentrations was greater than 40 mg/100 ml. Treatment and Results The therapeutic outcome could be divided into three categories: a) good results-ie, complete recovery; b) poor results-ie, flexion deformity oe loo or greater, ankylosis, secondary osteomyelitis or persistent effusion; c) death.

5 TREATMENT OF SEPTIC ARTHRITIS 87 32t NEEDLE ASPIRATION SURGICAL DRAINAGE 0 Deceased Fig 1. Trealment of acute infectious arthritis. Results related to mode of treatment. Results were good in 28 of the 42 patients (67%) whose joints were drained by closed aspiration and poor in 9 (21%). Five (12%), including 2 with widespread malignant disease and 1 with hepatic failure, died (Figure 1). Included among the 9 with poor results were 7 who were initially treated by needle aspiration but subsequently subjected to surgical drainage. All 7 have been considered herein as failures of needle drainage, even though 4 seemed to have been responding adequately to medical treatment (ie, synovial fluid cultures had become sterile and a marked decrease in synovial fluid leukocyte counts and percentage of polymorphonuclear cells had occurred) when surgery was elected. The outcome in patients operated upon at the outset was not as good as in those treated medically: 7 (42%) recovered completely, results were poor in 9 (53%) and 1 (6%) died. The difference in outcome between the two groups, however, was not statistically significant. In view of the uncontrolled variables existing in the two treatment groups, an attempt was made to compare results in subgroups matched with respect to factors such as concurrent extraarticular infection, underlying chronic disease, recent antibiotic or immunosuppressive therapy, and prior arthritis. Unfortunately, the number of patients treated by initial surgical drainage in whom the above factors existed was too small to permit such comparison. On the other hand, all 5 patients treated by needle aspiration, but only 5 of 13 treated surgically, in whom no such factors were present recovered without sequelae in the infected joint. Table 5. Outcome in Infected Joint, Related to Znitial Mode of Droinage, in Patients with Acute Infectious Arthritis ankylosis, 2' osteornyelitis, contracture, Aspiration Surgery chronic effusion Patients* _. Normal Joints infected Results Good 37 (SOC%) 8 (47%) Po0I-f 9 (20%) 9 (55%) $Excludes patients who died. +Ankylosis, secondary osteomyelitis, flexion contracture, persistent effusion. It was possible, however, to relate results in the two treatment groups to certain other factors, such as the infecting organism, the route of infection, the duration of illness before treatment was instituted, and the specific joint involved. Thus, 8 patients with Staphylococcus aureus infection were treated surgically. One died, 1 recovered without sequelae, and 6, including all 4 with hip infections, healed with local complications. On the other hand, 2 of 11 patients with Staphylococcus aureus arthritis treated by needle aspiration also died. However, results in the survivors were better than in those with staphylococcal arthritis treated surgically: 7 recovered completely while only 2 healed with complications. In contrast, patients with gram-negative bacillus infection did poorly regardless of the mode of drainage. All 3 treated surgically and 6 of 9 treated medically recovered with sequelae in the infected joint, with 1 dying and only 2 recovering fully. The prognosis of streptococcal arthritis, however, was relatively good, regardless of the mode of drainage. Although 2 died, 12 of 14 treated with needle aspiration aid 3 of 4 treated surgically recovered completely. Within the surgically treated group, none of the 3 patients whose septic arthritis arose as a result of surgical infection or a penetrating wound recovered fully. All developed significant flexion contracture or ankylosis. Delays in treatment may also have adversely influenced the results. Although therapy was instituted in all cases within 2 weeks, 11 patients were symptomatic for 8 days or longer prior to treatment. Recovery was complete in only 3 of these patients (27y0) but in 32 (54%) of the 48 in whom treatment was begun 7 days or less after the onset of symptoms. However, patients whose poor results could have been attributed to such delays constituted a similar proportion (approximately 20y0 of each of the two treatment groups.

6 88 GOLDENBERG ET AL Finally, since more than one joint was infected in some patients, the data were also considered with regard to the outcome in each infected joint (Table 5). (For these purposes patients who died were excluded from analysis, since all deaths occurred before adequate time had elapsed to determine therapeutic outcome in the infected joint.) In the surviving patients 37 of 46 joints (80y0) drained by needle aspiration, but only 8 of 17 (47y0) treated by initial surgical drainage, showed complete recovery (P < 0.05). All 7 wrist infections in the series were treated by needle aspiration with a uniformly good outcome, and wrists accounted for 13Y0 of all joints drained by needle aspiration. In contrast, all but one of the 5 hip infections were treated surgically, with poor results in each case, and hips accounted for 22yo of all joints drained surgically. Five of the 7 knees (ie, the joints most frequently infected) drained surgically at the outset recovered completely (71%). Four of 30 patients whose knee infections were treated with needle aspiration died. However, in the surviving patients 23 of 29 knees (SOYo) healed without sequelae. DISCUSSION Successful treatment of patients with acute infectious arthritis requires appropriate antimicrobial therapy and removal of purulent material from the joint. The latter is of twofold importance: first, pus may limit the effectiveness of antibiotics; second, both the elevation of intraarticular pressure resulting from the effusion and the products of inflammation released from synovial fluid leukocytes may cause destruction of the articular cartilage (9-13). Classically, drainage of purulent joint effusions has been accomplished surgically. Since the advent of effective antimicrobial therapy, however, drainage by needle aspiration has also been used successfully in treating many patients with acute bacterial joint infection (7,1617). Today, there is general agreement that most cases of gonococcal arthritis respond well to antibiotic therapy without surgical drainage (18-20). Still, because of fear that closed aspiration will fail to provide adequate drainage for nongonococcal joint infections, many physicians continue to rely empirically upon surgery, either initially or at a very early stage (2122). The decision concerning the mode of drainage in any patient with joint infection must be individualized. Initial surgical drainage is generally advocated for infections of the hip, since this joint frequently cannot be evacuated satisfactorily via needle aspiration. Surgical drainage should be employed in treating any infected joint whenever the presence of large amounts of fibrin, tissue debris, or loculations prevent adequate drainage by needle aspiration. However, while there is no question about the need for surgical drainage of an infected joint that has not responded to an adequate trial of needle aspiration, controversy currently exists concerning the preferable mode of drainage to be employed initially, save for hip infections. The present study provides some information concerning this issue. The uncontrolled variables (eg, age, infecting organism, joint involved, antibiotic employed, etc) encountered in the above cases were inevitable in a retrospective study of this type. Obviously, an analysis in which they were eliminated would allow the most meaningful comparison between the two therapies. Unfortunately, no such study is available in the literature. Indeed, this report is among the first to attempt to examine results of treatment of septic arthritis in relation to the initial mode of joint drainage employed (7). In view of the findings, certain of these variables are notable for their presence: Thus, the two treatment groups differed significantly with respect to the joints involved (Table 3). Most notable in this respect were hip infections, which accounted for 22% of all joints drained surgically but only 2yo of those drained by needle aspiration. Since none of the hips treated surgically healed without sequelae, the prominence of hip infections among patients in the surgical group adversely affected their results. Results of surgical treatment of hip infections reported by others have been generally poor (7,14,23, 24). No data exist, however, to indicate that needle drainage of the infected hip would yield a more favorable outcome. Notably, all hip infections treated surgically in the present series were due to Staphylococcus uuyeus. However, 7 patients with staphylococcal infections of other joints, who were treated medically, recovered without sequelae, suggesting that the site of infection was more significant than the organism in determining outcome in the above patients with hip infections. While results in the surgical group may have been compromised by the relatively high proportion of hip infections and, in some instances, by the fact that organisms were inoculated directly into traumatized joints, a number of other factors weighed against those treated medically. Thus, patients in the latter

7 TREATMENT OF SEPTIC ARTHRITIS 89 group tended to be older, more likely to have had positive blood cultures, and to have recently received antibiotics or immunosuppressive therapy. In addition, the medically treated group had a greater prevalence of prior arthritis in the joint, which became infected (P < 0.05); of chronic, serious, underlying illness (P < 0.01); and of concurrent extraarticular infection (P < 0.01) (Table 2). Infectious arthritis is a serious illness, with appreciable mortality; 10% of patients in the present series did not survive. Of those undergoing immediate surgery, complete recovery was seen in only 42% (Figure 1). Even if patients with hip infections (which appear to carry a poorer prognosis than infections in other joints [see above]) are excluded, the proportion of good results in this group rises only to 540/,. Given the results with surgical drainage, the significance of the present study lies in the observation that, despite the presence of numerous factors that might have been expected to affect adversely the results, 67y0 of patients treated by needle aspiration recovered completely. While the difference in therapeutic outcome between the two groups did not achieve statistical significance, the difference in outcome in infected joints of surviving patients was more marked: complete recovery was seen in 80% of all joints for which needle aspiration was elected, but in only 47% treated by initial surgery (P < 0.05) (Table 5). Again, even if the four hips drained surgically are excluded, only 54y0 of joints treated by initial surgery healed without sequelae. Thus, results with needle aspiration compared most favorably with those following surgical drainage. Indeed, from the above data, needle drainage appeared in general to be the preferable initial mode of treatment. The period of observation in the above study was relatively brief. Information was not available, therefore, concerning the ultimate outcome in those joints in which results were not satisfactory. It is also not possible to anticipate whether degenerative arthritis will eventually develop in any of the infected joints in these patients. The extent to which the mode of drainage itself may have factored into the above results also cannot be measured, nor do the data permit any determination as to whether ancillary procedures performed in conjunction with surgical drainage-eg, synovectomy, irrigation of the joint via catheter, or instillation of intraarticular antibiotics-influenced results. It has been shown, however, that intraarticular antibiotics themselves incite a chemical synovitis (6). Moreover, recent studies have indicated that direct administration 06 antibiotics into the joint is usually unnecessary, since adequate synovial fluid concentrations are generally achieved following parenteral administration of most of the commonly employed antibiotics (25-28). In conclusion, there is experimental (29) as well as clinical (6,23,24) evidence that the outcome in patients with infectious arthritis is directly related to the rapidity with which appropriate treatment is instituted. Ward et al (2) have emphasized that results are notably poorer in patients with symptoms for more than 1 week prior to institution of therapy than in those with symptoms for a shorter period before treatment. Although all patients in the present series were treated within 2 weeks of onset, the observation that recovery was complete in only 8 of the 11 with symp toms of infection for more than 7 days prior to treatment emphasizes the necessity of diagnosing and initiating treatment of infectious arthritis as promptly as possible. REFERENCES 1. Schmid FR, Parker RH: Ongoing assessment of therapy in septic arthritis. Arthritis Rheum 12: , Ward J, Cohen AS, Bauer W: The diagnosis and therapy of acute suppurative arthritis. Arthritis Rheum 3: , Borela L, Goobar JE, Summitt RL, et al: Septic arthritis in childhood. J Pediatr 62: , Nelson JD, Kootz WC: Septic arthritis in infants and children: a review of 117 cases. Pediatrics 38: , Baitch A: Recent observations of acute suppurative arthritis. Clin Orthop 22: , Argen RJ, Wilson CH, Wood P: Suppurative arthritis, clinical features of 42 cases. Arch Intern Med 117: , Chartier Y, Martin WJ, Kelly PG: Bacterial arthritis: experiences in the treatment of 77 patients. Ann Intern Med 50: , Hill AB: Principles of Medical Statistics. New York, Oxford University Press, Phemister DB: The effect of pressure on articular surfaces in pyogenic and tuberculous arthrides and its bearing upon treatment. Ann Surg 80: , Lack CH: Chondrolysis in arthritis. J Bone Joint Surg 41B: , Ziff M, Bribetz HJ, Lospalluto J: Effect of leukocyte and synovial membrane extracts on cartilage mucoprotein. J Clin Invest 39: , Curtiss PH, Jr, Klein L: Destruction of articular carti-

8 GOLDENBERG ET AL lage in septic arthritis. I. In vitro studies. J Bone Joint Surg 45A: , Curtiss PH, Jr, Klein L: Destruction of articular cartilage in septic arthritis. 11. In vivo studies. J Bone Joint Surg 47A: , Watkins MB, Samilson RL, Winters DM: Acute suppurative arthritis. J Bone Joint Surg 38A: , Cohen AS, Kim IC: Acute suppurative arthritis. Modern Trends in Rheumatology, chap 23. Vol 1. Edited by AGS Hill. New York, Appleton, 1966, pp Schmid FR: Principles of diagnosis and treatment of infectious arthritis, chap 6. Arthritis and Allied Conditions. Eighth edition. Edited by JL Hollander, DJ McCarty, Jr. Philadelphia, Lea and Febiger, 1972, pp Ortiz AC, Miller WE: Treatment of a septic joint. South Med J 54: , Keiser H, Ruben FL, Wolinsky E, et al: Clinical forms of gonococcal arthritis. N Engl J Med 279: , Cooke CL, Owen DS, Irvy R, et al: Gonococcal arthritis: a survey of 54 cases. JAMA 217: , Holmes KK, Counts GW, Beaty HN: Disseminated gonococcal infection. Ann Intern Med 74: , Clawson DK, Diinn AW: Management of common bacterial infections of bones and joints. J Bone Joint Surg 49A: , Curtiss PH, Jr: Cartilage damage in septic arthritis. Clin Orthop 64:87-89, Kelly PJ, Martin WJ, Coventry MB: Bacterial (suppurative) arthritis in the adult. J Bone Joint Surg 52A: , Samilson RL, Bersani FA, Watkins MB: Acute suppurative arthritis in infants and children. Pediatrics 21: , Nelson JD: Antibiotic concentrations in septic joint effusions. N Engl J Med 284: , Parker RH, Schmid FR: Antibacterial activity of synovial Huid during treatment of septic arthritis. Arthritis Rheum 14:96-104, Baciocco EA, Iles RL: Ampicillin and kanamycin concentrations in joint fluid. Clin Pharmacol Ther 12: , Chou A, Hecht R, Winters R: Gentamycin and carbenecillin penetration into the septic joint. N Engl J Med 285: , Orchard RA, Stamp WC: Early treatment of induced suppurative arthritis in rabbit knee joints. Clin Orthop 59: , 1968