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MAJOR ARTICLE Pneumococcal Septic Arthritis: Review of 190 Cases John J. Ross,1 Charles L. Saltzman,4 Philip Carling,3 and Daniel S. Shapiro2 1 Division of Infectious Diseases, Saint Elizabeth’s Medical Center, and 2Clinical Microbiology and Molecular Diagnostics Laboratory, Boston Medical Center, Boston, and 3Department of Medicine, Carney Hospital, Dorchester, Massachusetts; and 4Department of Orthopedic Surgery, University of Iowa, Iowa City This article reports 13 cases of pneumococcal septic arthritis and reviews another 177 cases reported since 1965. Of 2407 cases of septic arthritis from large series, 156 (6%) were caused by Streptococcus pneumoniae. Mortality was 19% among adults and 0% among children. Pneumococcal bacteremia was the strongest predictor of mortality. At least 1 knee was involved in 56% of adults. Polyarticular disease (36%) and bacteremia (72%) were more common among adults with septic arthritis caused by S. pneumoniae than among adults with other causative organisms. Only 50% of adults with pneumococcal septic arthritis had another focus of pneumococcal infection, such as pneumonia. Functional outcomes were good in 95% of patients. Uncomplicated pneumococcal septic arthritis can be managed with arthrocentesis and 4 weeks of antibiotic therapy; most cases of pneumococcal prosthetic joint infection can be managed without prosthesis removal. A fatal case of septic arthritis caused by a b-lactam–resistant strain of S. pneumoniae is also presented. Pneumococcal septic arthritis is described as “rarely encountered” [1] or “unusual” [2]. However, Streptococcus pneumoniae causes septic arthritis more often than is generally thought. Ispahani et al. [3] last reviewed pneumococcal septic arthritis in this journal, reporting 32 cases and reviewing 58 cases from large series published since 1965. We present 13 previously unreported cases and review 177 cases of pneumococcal septic arthritis reported in the English-language literature since 1965 [3–59], emphasizing the frequency of bacteremia and polyarticular disease among adults, the absence of extra-articular infection in many patients, and the emerging problem of pneumococcal antibiotic resistance. We report 2 cases of pneumococcal prosthetic joint infection and a case of pneumococcal arthritis in an adult that was caused by a strain of S. pneumoniae with high-level resistance to penicillin and intermediate resistance to ceftriaxone. PATIENTS AND METHODS We identified 13 cases of pneumococcal septic arthritis from the medical records of our institutions, Boston Medical Center (formerly Boston City Hospital), the University of Iowa Hospitals (Iowa City), Carney Hospital (Dorchester, MA), and Saint Elizabeth’s Medical Center of Boston. Pneumococcal septic arthritis was defined by isolation of S. pneumoniae from synovial fluid or by pneumococcal bacteremia with purulent joint fluid, positive results of Gram staining of joint fluid, or an imaging study demonstrating sacroiliitis. RESULTS Received 21 August 2002; accepted 1 November 2002; electronically published 13 January 2003. Reprints or correspondence: Dr. John J. Ross, Div. of Infectious Diseases, Saint Elizabeth’s Medical Center, 736 Cambridge St., Boston, MA 02135 (jrossmd @cchcs.org). Clinical Infectious Diseases 2003; 36:319–27 2003 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2003/3603-0012$15.00 Epidemiology. Demographic and clinical characteristics of the 13 patients we report here are summarized in table 1, and the clinical and laboratory findings for our patients, along with 177 cases reported elsewhere since 1965, are summarized in table 2. The mean age of adults with pneumococcal septic arthritis for whom Pneumococcal Septic Arthritis • CID 2003:36 (1 February) • 319 Table 1. Patient Demographic and clinical characteristics of 13 previously unreported patients with pneumococcal septic arthritis. Sex, age Affected joint Streptococcus pneumoniae serotype Sample with positive culture results Predisposing factors Other site of infection Therapy, outcome 1 M, 1 month Elbow NA Blood, joint Prematurity None I&D, 3 weeks iv antibiotics; cured 2 F, 2 years Elbow NA Joint None None Arthrocentesis, 1 week iv antibiotics, 2 weeks oral antibiotics; cured 3 F, 43 years Elbow 9N Joint EtOh, trauma None Arthrocentesis, 2 weeks iv antibiotics, 2 weeks oral antibiotics; decreased ROM 4 M, 51 years Knee, shoulder, ankle, SC NA Blood, joint Smoking, recent URTI Endocarditis Arthrocentesis, 8 weeks iv antibiotics; MVR 5 M, 51 years Knee 12F Joint EtOh, smoking None Arthrocentesis, 2 weeks iv antibiotics, 2 weeks oral antibiotics; decreased ROM 6 F, 51 years Shoulder 6A Blood, joint EtOh, smoking, RA None Signed out AMA; lost to follow-up 7 M, 52 years Knee, shoulder NA Blood, joint EtOh, trauma, CHF None I&D, 8 weeks iv antibiotics, 1 week oral antibiotics; cured 8 M, 60 years Shoulder 23F Blood, joint EtOh, smoking, gout None I&D, 6 weeks iv antibiotics; decreased ROM 9 M, 65 years Knees 17F Blood, joint, CSF CHF, DM, COPD, CRI, EtOh Pneumonia, meningitis Arthrocentesis, 4 weeks iv antibiotics; cured 10 M, 66 years Wrists, ankles, knee NA Blood, joint EtOh, cirrhosis, CHF, CRI Pneumonia Died of sepsis 11 F, 73 years Hip prosthesis NA Blood, joint OA, COPD Pneumonia Died of sepsis 12 F, 74 years Knees 23F Blood, joint, CSF MGUS, OA Pneumonia, meningitis I&D, 6 weeks iv antibiotics; cured 13 F, 79 years Hip prosthesis NA Blood, joint CHF, COPD, OA None Arthrocentesis, 6 weeks iv antibiotics; infection suppressed with indefinite oral antibiotics NOTE. AMA, against medical advice; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; CRI, chronic renal insufficiency; DM, diabetes mellitus; EtOh, alcohol abuse; I&D, incision and drainage; MGUS, monoclonal gammopathy of undetermined significance; MVR, mitral valve replacement; NA, not available; OA, osteoarthritis; RA, rheumatoid arthritis; ROM, range of motion; SC, sternoclavicular; URTI, upper respiratory tract infection. age data were available was 59 years. Most children with pneumococcal septic arthritis were !2 years old (62 [78%] of 80 children). Pneumococcal septic arthritis in adults was equally common in men (53 [51%] of 104 adults) and women (51 [49%] of 104 adults). Septic arthritis was slightly more common among boys (29 [60%] of 48 children) than among girls (19 [40%] of 48 children). Antecedent upper respiratory infection occurred in 14 (18%) of 80 children and 11 (10%) of 105 adults. Five (6%) of 80 children and 6 (6%) of 105 adults reported recent trauma to the affected joint. Fifty-six (93%) of 60 children and 43 (65%) of 66 adults presented with a temperature 138.0C. Laboratory findings. Serum leukocytosis (WBC count 9 111 ⫻ 10 cells/L) was observed in 41 (95%) of 43 children and 55 (61%) of 90 adults for whom WBC counts were available. Gram staining of joint fluid showed S. pneumoniae in 14 (38%) of 37 children and 61 (77%) of 79 adults. Cultures of joint fluid for S. pneumoniae were positive in 70 (88%) of 80 children and 82 (84%) of 98 adults. Joint fluid was usually purulent, with a mean WBC count of 127,000 cells/mm3 (range, 5500– 362,000 cells/mm3). Differential counts showed a predominance of neutrophils, with a mean of 92% polymorphonuclear 320 • CID 2003:36 (1 February) • Ross et al. leukocytes (range, 73%–100%). These values were similar for adults and children. Joint involvement. Most adults with pneumococcal septic arthritis have knee involvement (table 3). Thirty-five (32%) of 108 adults had monoarticular involvement of a knee joint, and 26 adults with polyarticular septic arthritis had knee involvement. Therefore, 56% of adults with pneumococcal septic arthritis had involvement of at least 1 knee. Other adults with monoarticular arthritis had involvement of the hip (7%), shoulder (6%), ankle (5%), or elbow (3%). Polyarticular disease was more common among adults (36%) than among children (7%). Among children, involvement of the hip joint was most common (24%), followed by involvement of the knee (21%), elbow (18%), and ankle (15%). Comorbid conditions and risk factors. Comorbid conditions and risk factors are summarized in tables 4 and 5. Most adults and children 12 years old with pneumococcal septic arthritis had underlying medical conditions. Such conditions were present in 85% (92 of 108) of adults with pneumococcal septic arthritis and 83% (15 of 18) of children aged 2–16 years. However, only 10% (5 of 52) of children !2 years old had comorbid conditions. Table 2. Clinical findings and demographic characteristics for 190 patients (82 children and 108 adults) with pneumococcal septic arthritis. Finding or characteristic Children, n/N (%) Adults, n/N (%) Sex Male 29/48 (60) 53/104 (51) Female 19/48 (40) 51/104 (49) 14/80 (18) 11/105 (10) Recent URTI (immediately before onset of arthritis) Antecedent trauma 5/80 (6) 6/105 (6) Temperature 138C 56/60 (93) 43/66 (65) 0/80 (0) 14/105 (13) Prosthetic joint Pneumonia 2/80 (3) 38/105 (36) Meningitis 3/80 (4) 16/105 (15) Endocarditis No extra-articular infection 0/80 (0) 6/105 (6) 75/80 (94) 53/105 (50) Bacteremia Without extra-articular infection With extra-articular infection 42/45 (93) 35/75 (47) 3/45 (7) 40/75 (53) Mortality Associated with monoarticular arthritis 0/73 (0) 10/69 (14) Associated with polyarticular arthritis 0/7 (0) 10/39 (26) WBC count 111 ⫻ 109 cells/mm3 41/43 (95) 55/90 (61) Gram stain 14/37 (38) 61/79 (77) Culture 70/80 (88) 82/98 (84) Positive results of testing of joint fluid for Streptococcus pneumoniae NOTE. n/N, no. of patients with finding or characteristic/no. of patients for whom data were available; URTI, upper respiratory tract infection. Major risk factors in adults included rheumatoid arthritis (22%), alcoholism (20%), osteoarthritis (14%), prosthetic joints (14%), coronary disease (10%), corticosteroid use (9%), and multiple myeloma or monoclonal gammopathy (8%). Risk factors in children with pneumococcal septic arthritis included sickle cell anemia (10%), hemophilia (9%), HIV infection (9%), and X-linked agammaglobulinemia (3%). Underlying focus of pneumococcal disease. The vast majority of children with pneumococcal septic arthritis (75 [94%] of 80 children for whom adequate data were available) had no underlying extra-articular pneumococcal infection. Three (4%) of these 80 children had meningitis, and 2 (3%) had pneumonia. One-half of the adults with pneumococcal septic arthritis had no underlying extra-articular focus (53 [50%] of 105 adults for whom adequate data were available). Thirtyeight (36%) of these 105 adult patients had pneumococcal pneumonia, 16 (15%) had meningitis, and 6 (6%) had endocarditis. Eight adult patients had 11 extra-articular site of infection: 4 had pneumonia and meningitis, 2 had meningitis and endocarditis, 1 had pneumonia and endocarditis, and 1 had pneumococcal pneumonia, endocarditis, and meningitis (Austrian syndrome). Predictors of mortality. The overall mortality was 19% (20 of 108) among adults and 0% (0 of 82) in children. By univariate analysis (x2 test), mortality was predicted by pneumococcal bacteremia (mortality was 24% among patients with bacteremia [18 of 74 patients] and 6% among patients without bacteremia [2 of 31 patients] for whom adequate data were available; P p .03). Mortality was higher among patients 160 years old (26% [14 of 53 patients]) than among those ⭐60 years old (12% [6 of 51 patients]), but the difference was not statistically significant (P p .06 ). Mortality was higher among patients with polyarticular disease (26% [10 of 39 patients]) than among those with monoarticular disease (14% [10 of 69]), but the difference was not statistically significant (P p .15). Alcoholism, rheumatoid arthritis, invasive pneumococcal disease at another site, leukopenia, and leukocytosis did not predict higher mortality. Therapy and outcomes. Of 108 adults with septic arthritis, 88 survived and 20 died. Survivors were treated with intravenous antibiotics for an average duration of 30.1 days, followed by oral antibiotics for an average duration of 30.6 days. Four patients with infected prosthetic joints were treated with indefinite oral antibiotic suppression (they were excluded from the analysis of duration of therapy). Four patients in older series were treated with intra-articular antibiotics. Of the patients who survived, 40 patients (45%) were treated with operative incision and drainage, 32 patients (36%) were treated with arthrocentesis, and 13 patients (15%) were treated with arthroscopic drainage. Functional outcomes and mortality Table 3. Joint involvement in 190 patients (82 children and 108 adults) with pneumococcal septic arthritis. Adults, no. (%) Children, no. (%) 35 (32) 17 (21) Hip 8 (7) 20 (24) Shoulder 7 (6) 6 (7) Ankle 5 (5) 12 (15) Elbow 3 (3) 15 (18) Sacroiliac 3 (3) 3 (4) Wrist 2 (2) 3 (4) Sternoclavicular 2 (2) 0 Metatarsophalangeal 2 (2) 0 Type of involvement, joint Monoarticular Knee Acromioclavicular 1 (1) 0 Metacarpophalangeal 1 (1) 0 Polyarticular Total 39 (36) 108 6 (7) 82 Pneumococcal Septic Arthritis • CID 2003:36 (1 February) • 321 Table 4. Comorbid conditions and risk factors in 108 adults with pneumococcal septic arthritis. Condition or risk factor Patients, no. (%) Rheumatoid arthritis 24 (22) Alcoholism 22 (20) None (otherwise healthy) 16 (15) Osteoarthritis 15 (14) Prosthetic joint 15 (14) Coronary disease 11 (10) Corticosteroid use 10 (9) HIV infection 8 (7) COPD 8 (7) Malignancy 8 (7) CHF 7 (6) SLE, other vasculitis 7 (6) Splenectomy 6 (6) Multiple myeloma 6 (6) Gout 5 (5) Monoclonal gammopathy 3 (3) Diabetes mellitus 3 (3) Hemophilia 2 (2) Bone marrow transplant 2 (2) Active tuberculosis 2 (2) Aseptic necrosis of hip 2 (2) Unspecified immunodeficiency 2 (2) Miscellaneousa 5 (5) NOTE. CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; SLE, systemic lupus erythematosus. a Miscellaneous conditions included clubfoot, hereditary spherocytosis, epilepsy, sleep apnea, and malnutrition (1 patient each). were similar among the 3 treatment groups. Three patients with minimal effusions were treated without drainage, including 2 patients with sacroiliitis and 1 patient with metacarpophalangeal arthritis who received only antibiotic therapy, and all had good outcomes [16, 33, 49]. Functional outcomes for adults with pneumococcal septic arthritis were good. Fifty-seven (74%) of 77 surviving patients for whom follow-up data were available regained baseline joint function. Sixteen patients (21%) had mild limitation of range of motion, without disability. Four patients (5%) had significant disability involving destruction of at least 1 knee joint; a shoulder joint was destroyed in one of these patients and an elbow in another [4, 30, 56]. Seven adults (9%) developed pneumococcal osteomyelitis. All 82 children with pneumococcal septic arthritis survived. They were treated with intravenous antibiotics for a mean of 16.4 days and with oral antibiotic therapy for a mean of 11.6 322 • CID 2003:36 (1 February) • Ross et al. days. Eighteen of these children (22%) developed osteomyelitis. Of 54 children for whom detailed treatment information was available, 31 (57%) were treated with operative incision and drainage; 19 (35%) were treated with arthrocentesis; and 2 (4%) were treated with arthroscopy. In addition, 2 patients were treated without drainage. Follow-up information was available for 47 children: 38 (81%) of these children regained normal joint function, 4 (9%) had mild or moderate restrictions of joint range of motion but no significant disability, and 5 (11%) had severe disability. Prosthetic joints. Fourteen patients had pneumococcal infections of prosthetic joints [3, 8, 11, 25, 27, 31, 37, 53, 59], including 2 of our previously unreported patients. Outcome information was not available for 1 patient. Of the remaining 13 patients, 3 died of pneumococcal sepsis. All 3 patients who died were women with infected hip prostheses and large thigh abscesses whose conditions deteriorated after prosthesis removal and surgical drainage. (One of these was patient 11 in our series, discussed below.) Two patients developed loosening of the hip prostheses, which were removed and reimplanted after long courses of intravenous antibiotics. One of these patients also had bilateral infection of knee prostheses, which were drained and left in place. She continued to receive oral suppressive antibiotics. The remaining 8 patients, who did not have abscesses, were cured with a combination of long-term antibiotics and drainage. Four of these patients were maintained on indefinite suppression with oral penicillin. DISCUSSION Prevalence, and clinical and laboratory features. Our experience and review of the literature suggest that the pneumococcus is a relatively common cause of septic arthritis. At Boston City Hospital in 1979–1994, S. pneumoniae accounted for 3% of cases of bacterial septic arthritis (table 6). Data on the etiology of septic arthritis from 9 large series [60–68] and the present study indicate that S. pneumoniae is the third most Table 5. Comorbid conditions in 70 children with pneumococcal septic arthritis. Condition None (otherwise healthy) Patients, no. (%) 50 (71) Sickle cell anemia 7 (10) Hemophilia 6 (9) HIV infection 6 (9) X-linked agammaglobulinemia 2 (3) Hereditary spherocytosis 1 (1) Bone marrow transplantation 1 (1) Unspecified immunodeficiency 1 (1) Table 6. Species of 265 isolates from patients with septic arthritis at Boston City Hospital, 1979–1994. Organism Isolates, no. (%) Staphylococcus aureus 139 (52) Staphylococcus epidermidis 25 (9) Streptococcus pyogenes 22 (8) Streptococcus agalactiae 9 (3) Streptococcus pneumoniae 8 (3) Neisseria gonorrhoeae 7 (3) Haemophilus influenzae 4 (1) Enterobacter cloacae 3 (1) Escherichia coli 2 (!1) Salmonella serotype Typhi 1 (!1) Neisseria meningitidis Polymicrobial infection 1 (!1) 22 (8) Other streptococcal species 5 (2) Other gram-negative bacilli 5 (2) Miscellaneous 12 (4) common pathogen in septic arthritis (after Staphylococcus aureus and Streptococcus pyogenes), causing 6% of cases (table 7). Pneumococcal septic arthritis is equally common in men and women. More boys than girls developed pneumococcal septic arthritis, which is related to the higher incidence among young men with hemophilic arthropathy and HIV disease. Gram staining of synovial fluid found S. pneumoniae in 77% of adults with pneumococcal septic arthritis, a frequency that is much higher than the 33% of patients for whom Gram staining revealed other causes of bacterial septic arthritis [69]. Joint involvement. Joint involvement in adults with pneumococcal septic arthritis was similar to that in adults with septic arthritis caused by other organisms [69]. Although Ispahani et al. [3] found that the knee is involved less commonly in pneumococcal septic arthritis than in septic arthritis caused by other organisms, we found that this joint is involved with similar frequency if knee involvement in polyarticular disease is taken into account. Other large joints, including the hip, shoulder, elbow, and ankle, are occasionally infected. In children with pneumococcal septic arthritis, hip involvement (24%) was most common, followed by knee (21%), elbow (18%), and ankle (15%). This contrasts with bacterial arthritis in children in general, in which knee involvement is seen in 35%–46% of patients [21, 70, 71], followed by hip, ankle, and elbow involvement. (Involvement of large joints other than the knee in septic arthritis is more common in children than in adults.) Polyarticular septic arthritis is more common in adults when S. pneumoniae is the causative organism than when other bacteria are the cause. A total of 36% of cases of pneumococcal septic arthritis in adults are polyarticular, compared with only ∼10%–20% of cases of bacterial arthritis caused by other pathogens [66, 69, 72]. This may be related to the high rate of bacteremia among patients with pneumococcal septic arthritis. Bacteremia was seen in 71% of adults (75 of 105 patients) with pneumococcal septic arthritis reviewed in the present study, compared with 27%–33% of patients with septic arthritis in general [62, 69]. Comorbid conditions and risk factors. The major risk factors for adult pneumococcal arthritis are rheumatoid arthritis and alcoholism. Alcohol increases the risk of aspiration and upper airway bacterial colonization, decreases pulmonary macrophage phagocytosis, and alters surfactant biochemistry [73]. Alcoholism is implicated as a risk factor in up to 70% of cases of pneumococcal bacteremia [74]. Rheumatoid arthritis predisposes to septic arthritis because it is associated with increased synovial permeability, phagocytic defects from drugs or disease, and skin breakdown and cellulitis [75]. In one recent study, rheumatoid arthritis was the most common risk factor for septic arthritis [66]. In rheumatoid patients with septic arthritis, fever and leukocytosis are often blunted or absent, resulting in delayed diagnosis, higher mortality, and worse functional outcomes [76]. Use of tumor necrosis factor antagonists to treat rheumatoid arthritis has recently been implicated in pneumococcal necrotizing fasciitis and septic arthritis [59, 77]. Up to 59% of adults with septic arthritis have underlying joint disorders [66]. In the present series, ⭓1 joint disorder was seen in 52% of adults (56 of 108), Table 7. Organisms isolated in 2407 cases of septic arthritis. Organism Isolates, no. (%) Staphylococcus aureus 1066 (44) Streptococcus pyogenes 183 (8) Streptococcus pneumoniae 156 (6) Haemophilus influenzae 104 (4) Mycobacterium tuberculosis 101 (4) Escherichia coli 91 (4) Coagulase-negative staphylococci 84 (3) Neisseria gonorrhoeae 77 (3) Streptococcus agalactiae 69 (3) Pseudomonas aeruginosa 36 (1) Neisseria meningitidis 28 (1) Salmonella species 25 (1) Other gram-negative rods 110 (5) Other b-hemolytic streptococci 104 (4) Polymicrobial Fungi 4 (!1) Miscellaneous NOTE. 33 (1) 136 (6) Data are from table 6 and [60–68]. Pneumococcal Septic Arthritis • CID 2003:36 (1 February) • 323 most commonly rheumatoid arthritis but also osteoarthritis, prosthetic joints, gout, aseptic necrosis of the hip, and hemophilic arthropathy. HIV infection was a risk factor for septic arthritis in 7% of adults and 9% of children in the present series. This is not surprising, given the frequency with which bacteremic pneumococcal infection occurs in HIV-positive patients [78] and the presence of underlying hemophilic arthropathy in many. Pneumococcal bacteremia and the pathogenesis of septic arthritis. Septic arthritis is an uncommon complication of pneumococcal bacteremia. We identified 1003 episodes of pneumococcal bacteremia that occurred at Boston City Hospital in 1979–1994. Six episodes were complicated by septic arthritis, an incidence of 0.6%. This is similar to rates reported by other authors: 0.3% (1 case of arthritis in 325 episodes of pneumococcal bacteremia) [79], 0.45% (2 cases in 444 episodes) [80], and 0.7% (2 of 294 patients) [78]. Septic arthritis usually arises from hematogenous seeding of a joint. In many cases, a primary focus is not identified. For S. aureus, the most common cause of septic arthritis, an extraarticular focus of staphylococcal infection is found in only 52% of patients [62]. It has long been known that pneumococcal arthritis may be “primary,” or not associated with extra-articular disease. Bulkley noted in 1914 [81] that 16% of cases of pneumococcal septic arthritis were not associated with another focus of pneumococcal disease. One-half of the patients with pneumococcal septic arthritis reviewed here did not have an underlying focus of pneumococcal disease, such as pneumonia or meningitis. Presumably, septic arthritis arose from joint seeding during transient bacteremia with a mucous membrane source. Children experience transient pneumococcal bacteremia without an identifiable focus [82], but this phenomenon also occurs in adults. In 12,000 South African gold miners followed up for 4 years in a trial of pneumococcal vaccination, 217 episodes of pneumococcal bacteremia were documented. Twenty-nine of these episodes (13%) were not associated with focal infection, and 14 of these patients recovered without antimicrobial therapy [83]. In one study of pneumococcal bacteremia, 38 (9%) of 424 episodes that occurred in adults were not associated with a specific source [80]. Bacteremia predicted mortality in patients with pneumococcal septic arthritis. The high mortality associated with pneumococcal bacteremia has long been recognized [84] and has not decreased since 1960 [74, 85–88]. Prosthetic joints. Septic arthritis is 15 times more common in prosthetic joints than in native joints [89], and up to 17% of cases of septic arthritis occur in prosthetic joints [68]. The mortality associated with pneumococcal septic arthritis of prosthetic joints (23% [3 of 13 adults]) was similar to the mortality associated with pneumococcal arthritis of native joints (18% 324 • CID 2003:36 (1 February) • Ross et al. [17 of 95 adults]). Of the 10 surviving patients, 9 were able to retain at least 1 infected prosthetic joint; 5 of these patients received long-term suppressive antibiotic therapy, although 4 were treated with shorter courses of antibiotics and did not experience relapse. Therapy and outcome. Our experience and the recent report of James and Thomas [56] support administration of courses of antibiotic therapy lasting a total of 3–4 weeks for uncomplicated pneumococcal septic arthritis, including 1–2 weeks of intravenous therapy. Intra-articular antibiotics are no longer recommended because of the potential for chemical synovitis [72]. The favorable outcomes seen in patients who survive pneumococcal septic arthritis were known in the preantibiotic era. In 1939, Heffron [90] wrote that “provided treatment is undertaken early, complete return of joint function is to be expected.” A total of 95% of adults and 90% of children in our review had a return to baseline joint function or mild limitation of range of motion. By comparison, 150% of patients with staphylococcal septic arthritis have serious residual joint damage [2]. In a recent study, 32% of all patients with septic arthritis and 46% of patients with septic arthritis caused by S. aureus had poor outcomes [67]. Outcomes were similar whether patients were treated with surgical incision and drainage, arthrocentesis, or arthroscopic drainage. Repeated needle aspirations are adequate for the initial drainage of infected joints. Surgical drainage is indicated when patients do not respond to arthrocentesis, when loculated joint fluid prevents adequate needle aspiration, or when the hip joint is involved [1, 69, 72]. Some data indicate that outcomes may be worse in patients who undergo surgery for septic arthritis, although this could be accounted for by the retrospective nature of the studies and the selection of more severely affected patients for surgery [67, 91]. The 4 adults in the present review with poor outcomes all had preexisting joint pathology (2 had rheumatoid arthritis, 1 had gout, and 1 had hemophilic arthropathy), and the diagnosis of septic arthritis was delayed in 1 patient. Of the 5 children with poor outcomes, 3 had septic arthritis of the hip, which is strongly associated with worse outcomes in children [21]. Mortality among adults was 19%, 26% in those 160 years old. This is comparable to the mortality of 14% associated with nongonococcal arthritis in adults [62]. The mortality of bacterial septic arthritis is known to be age dependent, increasing from 5% among those !65 years old to 32% among those ⭓65 years old [67]. We noted a lower mortality among adults (19% compared with 32%) than was seen in the series by Ispahani et al. [3]; this difference likely can be explained by the fact that our patient population was younger. Only 53% of the patients reviewed in our study were 160 years old, compared with 80% in the other series. Impact of antibiotic resistance. Since 1989, 7 children [45, 58, 92] and 4 adults [28, 46, 53] have been reported who had penicillin-resistant pneumococcal septic arthritis. Of the 7 pediatric patients, 4 had strains of S. pneumoniae that were resistant to penicillin but sensitive to ceftriaxone, using current breakpoints for nonmeningeal isolates; all patients were successfully treated with ceftriaxone or cefotaxime (1 patient also received vancomycin). Three pediatric patients had strains with high-level ceftriaxone resistance, and these patients responded to vancomycin-containing regimens (one patient also received ceftriaxone, and another also received clindamycin). Three adults were infected with pneumococcal strains manifesting intermediate resistance to penicillin, and 1 patient had a strain with high-level penicillin resistance and intermediate resistance to ceftriaxone. One patient whose infection was intermediately resistant to penicillin was treated with penicillin alone, and another was treated with vancomycin and rifampin, with good outcomes in both cases. (The regimens for the other 2 patients were not specified, but both patients achieved clinical cure.) Patient 11 in our series was a 73-year-old woman who was admitted to another facility with left lower lobe pneumonia. Despite receiving cefuroxime therapy, she developed increasing right hip pain over the course of 10 days and was transferred to Boston Medical Center, where vancomycin therapy was initiated. Examination revealed exquisite tenderness on manipulation of the hip, with erythema, edema, and bulla formation over the old right-hip arthroplasty scar. She was taken to the operating room for arthroplasty removal and debridement, with findings of a grossly infected hip prosthesis and a pus collection from the anterior thigh to the knee. Surgical wound cultures and blood cultures grew S. pneumoniae, with a penicillin MIC of 2 mg/mL (resistant), a ceftriaxone MIC of 2 mg/mL (intermediately resistant), and a vancomycin MIC of 1 mg/mL (sensitive) by Etest. Postoperatively, the patient’s condition deteriorated, and she died as a result of multisystem organ failure. The clinical significance of penicillin resistance in the pneumococcus is unclear. In one study, mortality was not higher among adults with pneumonia with strains of S. pneumoniae that were resistant to penicillin and third-generation cephalosporins. However, few strains demonstrated high-level resistance, and some “cephalosporin-resistant” strains would not be considered resistant by current breakpoints [93]. A recent Canadian study did show an increase in mortality that was associated with high-level pneumococcal b-lactam resistance [94]. Pneumococcal serotyping was available for 38 isolates; 34 (89%) were represented in the 23-valent pneumococcal vaccine. Many cases of pneumococcal septic arthritis are, therefore, potentially vaccine preventable. Acknowledgments We thank Kathy Browne, Megan Sandel, and Michael G. Worthington for their assistance and support. References 1. Smith JW, Hasan MS. Infectious arthritis. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett’s principles and practice of infectious diseases. 5th ed. 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