ANTIBIOTIC THERAPY OF SEPTIC BURSITIS

Transcription

1 905 ANTBOTC THERAPY OF SEPTC BURSTS ts mplication in the Treatment of Septic Arthritis GEORGE HO, JR. and EUGENE Y. SU nfected olecranon, prepatellar, and infrapatellar bursae offer a unique opportunity to study the response of a closedspace infection to antibiotic therapy. Using percutaneous needle aspirations, serial bursal fluids were cultured. The length of time necessary to achieve culture sterility with antibiotic therapy (an average of 4 days in 25 patients) was correlated with the duration of symptoms prior to diagnosis (r = 0.68, P < 0.001). n patients treated within 2 weeks from onset of symptoms, bursal fluid sterility was achieved within 1 week of therapy, while longer duration of symptoms was associated with delayed response. When antibiotic therapy was continued for 5 additional days after documented culture sterility, all 19 patients in the prospective trial were cured (average followup period of 6.8 months). n septic bursitis, the effects of delay in treatment are deleterious by prolonging culturepositivity despite adequate antibiotic therapy. By analogy, delay in treatment of septic arthritis may result in the persistence of an adverse environment which can lead to further articular damage. After accurate diagnosis of septic bursitis, a therapeutic approach consisting of prompt and appropriate antibiotic usage, frequent needle drainage, and treatment du From the Rheumatology Section, Medical Service, Veterans Administration Medical Center, Brown University Program in Medicine, Providence, Rhode sland. Presented in part at the Amul Scientific Meting of the American Rheumatism Association on May 31, 1979 in Denver, COlorado. by the Veterans Administration and in part by the Rhode sland Chapter of the Arthritis Foundation. Address reprint requests to Dr. George Ho, Jr., Veterans Administration Medical Center, Davis Park, Providence, R Submitted for publication September 22, 1980; aapted in revised form March 2, ration based on the culture results of serial aspirations is effective and may be applicable in the management of certain nongonococcal bacterial joint infections. Bacterial infections of the subcutaneous bursae in the olecranon, prepatellar, and infrapatellar areas are well described entities (13). Their clinical and laboratory characteristics, as well as their dserentiation from arthritis, cellulitis, and nonseptic bursitis have been previously reported (1,4). The specific purposes of this study are twofold: to determine how long the bursal fluids remain infected (culturepositive) after initiation of antibiotic treatment and to determine whether continuation of antimicrobial agents for 5 additional days after achieving bursal fluid sterility is sufficient to cure the infection. This report details our prospective study design, treatment results, and followup information on 25 patients with septic bursitis. A successful approach to the antibiotic therapy of septic bursitis is proposed, and its implication in the treatment of certain bacterial joint infections is discussed. PATENTS AND METHODS Patient selection. Only patients with bacterial infections of the olecranon, prepatellar, or infrapatellar bursae, Proved by culturing the bursa1 fluids, are included (Table 1). Patients with underlying host defects such BS diabetes mellitus, renal or hepatic disease, or underlying malignancy or rheumatic disease were excluded because such patients may be more prone to infection and may not respond the =me manner. Limited aspects of 11 patients have been previously reported (patients A, B, J, W, and X in reference 1 and patients D, K, M, N, P, and Y in reference 4). Study design. The choice of the route of antibiotic administration was made on clinical assessment of the severity of the infection and the reliability of the patient. We classified Arthritis and Rheumatism, Vol. 24, No. 7 (July 1981)

2 906 HO ET AL Table 1. Data on the antibiotic therapy of septic bursitis MC/MBC Duration for Clinical of Route/ oxacillin, disease symptoms, Antimicrobial daily Patient Site* Bacteria pg/mlt severity days agent dose* A B C D E F G H J K L M N 0 P Q R S T U V W X Y PPB PB PPB PPB Staphylococcus aureus Group A betahemolytic Streptococcus Group A betahemolytic Streptococcus S auras Staphylococcus epidermidis _ 0.16/ / / / / / / / / /0.39 _ 0.19/ /1.56 Mild Mild Mild = olecranon bursa; PPB = prepatellar bursa; PB = infrapatellar bursa. t MC = minimal inhibitory concentration; MBC = minimal bactericidal concentration. V = intravenous; PO = oral; M = million units., penicillin G Penicillin G Nafcillin Penicillin G, penicillin G, oxacillin Dicloxacillin, penicillin G Dicloxacillin V/12 M 1V/8 gm 1V/9 M V/9 M PO/.6 M V/12 M Days needed to achieve bursal fluid sterility o each patient s disease severity according to the following criteria: : extensive local infection with intense peribursal cellulitis or infected skin wound, usually accompanied by systemic symptoms and signs of fever greater than 37.7OC, chills, or leukocytosis of greater than /mm in the peripheral blood : moderately severe local inflammation with or without minor skin wound and systemic symptoms and signs Mild: mild to moderate local inflammation, usually without skin lesion or systemic symptoms and signs When disease severity was assessed independently by two observers in 13 consecutive patients, there were no disagreements. n general. the patients with severe infection were hospitalized and given parenteral antimicrobial agents. The patients with moderate or mild disease were treated with oral drugs and followed as outpatients. When noncompliance was anticipated, treatment consisted of parenteral agents in the hospital. Patients K, 0, V, and W were such examples in whom histories of noncompliance, dementia, seizure disorder. and alcoholism had been present, respectively. The usual antibiotic regimen consisted of 2 gm of oxacillin intravenously every 6 hours or 500 mg of oxacillin orally 4 times per day. n one instance (patient M), oral erythromycin at 2 gm per day had failed to cure the infection which oral oxacillin subsequently eradicated (4). Other exceptions included patient E who had been given nafcillin and patients and L, who had been started on dicloxacillin by their referring physicians. f the results of antibiotic sensitivity testing showed the organism to be sensitive to pencillin, or the organism was a group A betahemolytic streptococcus, pencillin was substituted for oxacillin. ts parenteral dosage was between 9,000,000 to 12,000,000 units per day in divided doses, and the oral dosage was 400,000 units penicillin G 4 times per day. The study design is illustrated in Figure 1 by the course of a representative patient. Serial bursal aspirations were performed with an [%gauge needle. All fluid analyses, as well as culture techniques, antibiotic sensitivity testing, and determinations of minimal inhibitory concentration (MC), minimal bactericidal concentration (MBC), and antibiotic levels in serum and bursal fluid were performed as previously described (1,4). n all 25 patients, bursal aspirations were usually

3 THERAPY OF SEPTC BURSTS 907 camed out daily or every other day and in no instance greater than 72 hours apart. Once the fluid became culturenegative, a subsequent aspiration was done within 48 to 12 hours if ekusion was still present to confirm culture sterility. Since an additional 48 hours were required before the confirmatory results were known, 4 to 5 days had usually elapsed from the time of the initial sterile culture. Thus, 5 additional days of antibiotic therapy after achieving fluid sterility were chosen for the prospective trial in 19 of the 25 patients. n the original design, the antibiotic dosage and its route of administration remained constant for each patient throughout the treatment. However, because of the apparent success of the treatment trial and in order to minimize the duration of hospitalization and its cost, 2 of the most recently studied inpatients (patients G and H) followed a modified approach. They received parenteral treatment until the bursal fluid became sterile, and then completed the trial as outpatients on oral medication. RESULTS Patient characteristics. All patients were men. The mean age was 50 years old (range 1787 years). Twentyone infections occurred in the olecranon bursa, 3 in the prepatellar, and 1 in the superficial infrapatellar bursa. No patients had a history of recurrent infections, and no overt defects in host resistance against bacterial infections were apparent (see Patient Selection ). Occupations predisposing to bursitis were noted in many patients. There were 4 custodians performing janitorial work, 2 operators of heavy machinery, 2 carpenters, and 1 each of the following: carpet layer, roofer, electrician, plumber, cook, and supermarket worker. Neurologic diseases that predisposed our patients to trauma included seizure disorder, ataxia from cerebellar degeneration, and dementia and organic brain syndrome requiring restraints. Skin abrasions and wounds were frequently associated with septic bursitis ( 1,4). Bursa1 fluid leukocytosis, bacteriology, and antibiotic levels. Although extremely high leukocyte counts (greater than 1 O0,000/mm3) were seen more frequently in the bursal fluids from patients with severe infections, the correlation between clinical severity and bursal fluid leukocyte concentration was generally poor. n addition, the degree of bursal fluid leukocytosis at the time of diagnosis was not useful in predicting the time necessary to eradicate the infecting organism. n some instances, the bursal fluid leukocyte count actually increased during the first several days of treatment before decreasing with clinical resolution. Staphylococcus aureus was isolated in 22 patients, group A betahemolytic Streptococcus in 2, and S epidermidis in 1. Seventyeight percent of the staphylococci were resistant to pencillin; all were sensitive to oxacillin. n those strains tested, the MC values for oxacillin ranged from 0.10 pg/ml to 0.63 pg/ml, and the MBC values were generally two times the MC values (range of zero to four times the MC) (Table 1). We have measured antibiotic concentrations in serum and bursal fluid primarily from patients receiving oral antibiotic agents (4). Paired levels of oxacillin from 2 patients (H and 0) receiving intravenous drugs were obtained. The results are summarized in Table 2. Treatment results. Linear regression analysis of culture results of serial bursal aspirations from 25 patients by means of least square showed a correlation between the duration of symptoms prior to antibiotic therapy and the subsequent time needed to sterilize the bursal fluids (r = 0.68, P c 0.001). f the 3 patients in whom the diagnosis was delayed beyond 1 week are excluded, the correlation is no longer statistically significant. The average duration required to sterilize the bursal fluids was 4 days, with a range of days. Culture Negative 1 ;, + Last Positive Culture First Negative + Positive Culture (3 (1 0 0 NotDone ~ ~ Day ( J Antibiotic Started A? J 1 B Five Additional Days Antibiotic Stopped Figure 1. Prospective approach to the therapy of septic bursitis: illustration of a case. A = days cultures remain positive after initiation of antibiotic; B = days between last positive culture and first negative culture. Duration required to eradicate organisms: A + B/2 = 5 + 2/2 = 6 days. Total antibiotic treatment duration: A + B + 5 = 12 days. T

4 ~ 908 HO ET AL Table 2. levels in paired serum and bursal fluid Hours after Serum Bursa1 fluid last dose of level, level, Patient oxacillin dml dm1 H < < * Both patients were receiving 2 gm of oxacillin intravenously every 6 hours. When the patients with streptococcal infections (C and F) and the patients with symptom duration longer than 1 week (K, M, and Y) are excluded, the remaining 20 patients with staphylococcal disease can be compared in the following ways. We analyzed the time required to sterilize the bursal fluids with respect to 1) the clinical severity of the infections, 2) the different routes of antibiotic administration, and 3) the situation where both disease severity and antibiotic route were taken into account simultaneously (Table 3). The data indicate that severe infections may require longer treatment to achieve bursal fluid sterility than moderate diseases (3.9 versus 2.8 days), that intravenous administration of higher dosages of antimicrobial agents may render the bursal fluid sterile more promptly than lower dosages of oral drugs (2.9 versus 3.8 days), and that the time required to sterilize the bursal fluids for the group with severe disease who were treated intravenously and the group with moderate infection who received oral medication is similar (3.4 versus 3.1 days). All 25 patients were cured of their infections, including the 19 who had followed the antibiotic trial in which only 5 additional days of treatment were given after bursal fluid sterility was acheved. The mean duration of antibiotic therapy in these 19 patients was 9.7 days with a range of 621 days. Subsequent clinical information was available on all 19 prospectively treated patients. The mean followup period has been 6.8 months (range 1 13 months), and there have been no recurrences of septic bursitis. However, 2 patients (R and S) with postinfectious bursitis, in whom moderate symptoms of olecranon bursitis reappeared within weeks of bacteriologic cure and in whom multiple reaspirations yielded sterile cultures, have required specific treatment. n patient R, an oral nonsteroidal antiinflammatory agent controlled the sterile inflammation, and in patient S an intrabursal injection of a corticosteroid preparation resulted in prompt resolution. Otherwise, nonseptic bursitis has recurred only in patient K. One year after the cure of his bacterial infection, he developed a sterile olecranon bursitis in the same elbow after minor trauma. He, too, Table 3. Comparisons of treatment results with respect to severity of disease and routes of antibiotic administration Average time Mean required to duration sterilize Patient Number of of symptoms, bursal fluids Statistical subgroups patients days (days f SEM) comparisont f f 0.44 NS ntravenous Oral f f 0.64 NS /intravenous f 0.96 /oral f 0.55 NS Only patients with staphylococcal infections of less than or equal to one week s duration of symp toms are included. t By Student s 1test. NS not significant.

5 THERAPY OF SEPTC BURSTS 909 was successfully managed with an intrabursal steroid injection. On followup, most patients had adhered to our advice on preventive measures against occupational hazards (1). DSCUSSON Septic bursitis is a common condition that requires accurate diagnosis and appropriate treatment. nfected olecranon, prepatellar, and infrapatellar bursae, because of their superficial location, offer a unique opportunity to study the response of a closedspace infection to therapy. The specific purposes of this study are twofold: to determine how long the bursal fluids remain infected (culturepositive) after initiation of antibiotic treatment and to determine whether continuation of antimicrobial agents for 5 additional days after achieving bursal fluid sterility is sufficient to cure the infection. Because of the wide spectrum of clinical severity in bursal infections and our previous experience with a group of patients in whom oral antibiotic agents had failed to control the infection (), a nonrandomized study design was utilized whereby large parenteral doses of antimicrobial agent are instituted against more severe infections and lesser oral dosages are used for milder diseases. Thus, the selection of antibiotic dosages and routes of administration was based on clinical judgement at the time of diagnosis according to certain guidelines (see Study Design in Patients and Methods). mportant parameters in septic bursitis that might influence the duration of culture positivity from initiation of treatment include: 1) the presence of previous disease in the septic bursa and/or an underlying host defect in handling bacterial infections, 2) the inherent characteristics of the infecting organism, 3) the mode and frequency of bursal drainage, 4) the severity of the infection, 5 ) the appropriateness of antibiotic usage, and 6) the promptness of therapy or the duration of infection before the initiation of specific treatment. As will be discussed, promptness of therapy is probably the major determinant of treatment outcome in septic bursitis. n the present series, only 1 patient had a history of bursitis in the affected area, and none of the patients had underlying host defects such as diabetes mellitus, renal or hepatic disease, or underlying malignancy or rheumatic disease. Such patients may be more prone to infection and may not respond in the same manner. Among the possible pathogens, only one organism, Staphylococcus aureus, was the causative agent in the majority (22 of 25 patients), and the narrow range of MC values for oxacillin of the isolated staphylococci (Table 1) suggests that the wide variation of time required to sterilize the infected bursal fluid is not likely due to differences among the strains of individual staphylococci. The mode and frequency of bursal drainage can possibly influence the duration of culture positivity during treatment. Repeated percutaneous needle aspiraton was the only mode employed in this study, and no complications of sinus tract formation or bacterial dissemination to contiguous structures were encountered. The total number of aspirations performed in each patient depended on the time required to sterilize the bursal fluid and was therefore variable, but the frequency of aspiration was relatively constant (daily or every other day and no greater than 72 hours apart). Finally, in all instances, an appropriate antimicrobial agent that is bactericidal against penicillinaseproducing staphylococci was chosen at the time of diagnosis. Therefore, by virture of the absence of some variables (host defect and prior bursal disease) and the minimal differences in others (bacteriology and initial antibiotic choice), and by controlling still other variables by prospective design (antibiotic usage, treatment duration, and drainage mode and frequency), we have shown that in septic bursitis, the duration of infection prior to treatment is an important variable in determining the duration of culture positivity, especially in patients who had untreated infections for longer than 2 weeks. Although the final treatment outcome was good in all cases, delay in treatment of septic bursitis resulted in prolonged antibiotic course and increased patient morbidity. The most important conclusions of this study are 1) the time required to sterilize infected bursal fluid is prolonged in patients who had long duration of symptoms prior to the institution of definitive antibiotic therapy and 2) a treatment regimen consisting of 5 additional days of antibiotic administration after the achievement of bursal fluid sterility provides curative therapy. Our data (Table 3) also suggest that severe infections may require longer duration of treatment than moderate diseases, and higher dosages of antimicrobial agents given intravenously may shorten the duration of necessary therapy. Further comparative studies. however, are necessary to validate these points. n the present study, 2 patients with severe infections were successfully managed with parenteral oxacillin initially until sterilization of bursal fluid, followed by oral agents to complete the antibiotic treatment. n light of recent reports on the successful treatment of serious bone and joint infections in children with oral

6 9 10 HO ET AL antimicrobial agents under suitably controlled and closely monitored conditions (5,6), our parenteral/oral antibiotic regimen in compliant adults can provide the benefit of a shorter period of hospitalization in addition to the gains of lesser risk of nosocomial infection and greater patient comfort through avoidance of intravenous therapy (7). From the present study and our previous experience (1,4) other conclusions include the following: 1) antibacterial agents (penicillin and oxacillin) administered systemically penetrate well into the bursal fluid, therefore eliminating the need for intrabursal instillation of these drugs, and 2) needle aspirations provide effective drainage of the closedspace bursal infection, obviating the need for open drainage. Similar observations on these modalities have been made in the management of certain bacterial joint infections (8 10). ndeed, both bursae and diarthrodial joints are closed spaces lined with synovial membrane. n addition, S auras is the most common pathogen in septic bursitis (l), analogous to its well known predominance in nongonococcal bacterial arthritis of adults (11). The pathogenesis of these infections, however, is different, because septic arthritis commonly occurs via the hematogenous route of bacterial dissemination, whereas septic bursitis probably results from direct introduction of bacteria through the overlying skin (1). Also, the responses of olecranon, prepatellar, and infrapatellar bursae to specific disease stimuli may be different from those of synoviallined peripheral joints (12). Host factors also differ in these closedspace infections since bacterial joint infections (especially those caused by gramnegative bacilli) occur more commonly in the compromised host (1 l), while septic bursitis usually involves adults who are predisposed to trauma but are otherwise healthy (1). Perhaps the most important difference, however, is that articular cartilage and bone are at great risk of permanent damage from septic arthritis, in contrast to septic bursitis from which such complications are rare (13,14). The amount of articular destruction in bacterial ioint infection is certainlv the net result of manv factors. Delay in treatment per se, as well as certain specific situations such as underlying joint disease or gramnegative infections, are associated with a poorer outcome (11). Pathogenetically, articular cartilage damage may be related to the intense polymorphonuclear cell infiltration of the synovial membrane (15) with resultant liberation of proteolytic enzymes and other nonenzymatic substances such as superoxide radicals (16) and the local acidosis within the joint cavity (17). Even when adequate antibiotic levels are achieved, other factors may contribute to the persistence of infectionfor example, the decreased effectiveness of gentamicin in acidic synovial fluids (17) or the protection from the bactericidal action of nafcillin by the intracellular sequestration of staphylococci (1 8). While many of these factors are interrelated, the initial delay in treatment is clearly of central importance in allowing the continued intraarticular proliferation of bacteria before institution of appropriate antibiotic therapy. n septic arthritis, it is generally accepted that poor results with loss of joint function, secondary osteomyelitis, and recurrences are more common in patients whose treatment was delayed more than 7 days after the onset of symptoms (1 1). This study on septic bursitis confirms that an initial delay in treatment is associated with the persistence of an adverse environment (i.e., longer duration of culturepositivity) despite subsequent antimicrobial therapy. Our data, therefore, further support the general concept that in closedspace infections such as septic bursitis and septic arthritis, optimal therapy requires not only choosing the most efficacious antimicrobial agent or agents but initiating such antibiotic treatment as promptly as possible. We believe our overall approach in septic bursitis of individualizing therapy according to culture results of serial aspirations combined with a parenteral/ oral antibiotic regimen in compliant patients provides adequate therapy and minimizes patient morbidity. Furthermore, we believe that a similar approach to treating certain nongonococcal septic arthritides is justified and warranted. ACKNOWLEDGMENTS We are indebted to Ms Maryellen Price for her technical assistance, Donald P. Comveau, PhD for his assistance in statistical analysis, and Ms Lori R. Fratantuono for her secretarial assistance. REFERENCES 1. Ho G Jr, Tice AD, Kaplan SR. Septic bursitis in the prepatellar and olecranon bursae: an analysis of 25 cases. Ann ntern Med 89:2127, Thompson GR, Manshady BM, Weiss JJ: Septic bursitis. JAMA , Canoso JJ, Sheckman PR: Septic subcutaneous bursitis: report of sixteen cases. J Rheumatol6:96102, HO G Jr, Tice AD: Comparison on nonseptic and septic bursitis: further observations on the treatment of septic bursitis. Arch ntern Med 139: , Nelson JD, Howard JB, Shelton S: Oral antibiotic therapy for skeletal infections of children. 1. Antibiotic concentra

7 THERAPY OF SEPTC BURSTS 91 1 tions in suppurative synovial fluid. J Pediatr 92:131134, Tetzlaff TR, McCracken GH Jr, Nelson JD: Oral antibiotic therapy for skeletal infections of children. 11. Therapy of osteomyelitis and suppurative arthritis. J Pediatr 92:485490, Nelson JD: Oral antibiotic therapy for serious infections in hospitalized patients. J Pediatr 92:175176, Nelson JD: Antibiotic concentrations in septic joint effusions. N Engl J Med 284:349353, Parker RH, Schmid FR: Antibacterial activity of synovial fluid during therapy of septic arthritis. Arthritis Rheum 14:96104, Goldenberg DL, Brandt KD, Cohen AS, Cathcart ES: Treatment of septic arthritis: comparison of needle aspiration and surgery as initial modes ofjoint drainage. Arthritis Rheum , Goldenberg DL, Cohen AS: Acute infectious arthritis: a review of patients with nongonococcal joint infections. Am J Med 60:369377, Canoso JJ, Yood RA: Subcutaneous bursae react differ ently than synovial joints to specific disease stimuli. Arthritis Rheum 22597, Smason JB: Posttraumatic fistula connecting prepatellar bursa with knee joint. J Bone Joint Surg 54A: Simonelli C, Zoschke D, Bankhurst A, Messner R: Septic bursitis. Ann ntern Med , Goldenberg DL, Cohen AS: Synovial membrane histopathology in the diaerential diagnosis of rheumatoid arthritis, gout, pseudogout, systemic lupus erythematosus, infectious arthritis and degenerative joint disease. Medicine 57:239252, Greenwald RA, Moy WW: nhibition of collagen gelatin by action of the superoxide radical. Arthritis Rheum 22: , Ward TT, Steigbigel R T Acidosis of synovial fluid correlates with synovial fluid leukocytosis. Am J Med 64: , Beam TR Jr: Sequestraton of staphylococci at an inaccessible focus. Lancet 2: MDDLETON AWARD Norman Talal, MD, Professor of Medicine, University of San Francisco, California, and Chief of the Clinical mmunology and Arthritis Section at the Veterans Administration Medical Center in San Francisco, has won the 1980 William S. Middleton Award. The award is given to a VA investigator who has contributed to the enhancement of medical care by outstanding achievements in medical research. The recipient was recognized for his accomplishments in immunology, particularly as they relate to the study of autoimmunity and lymphoid malignancy in inbred strains of mice and in patients with rheumatic disorders. Dr. Talal is the first rheumatologist to receive this prestigious award.