There has been a marked increase in the incidence of severe group-A streptococcal infections in children and adults in the past decade3,4,7,13. Necrotizing fasciitis, bacteremia, and streptococcal toxic shock syndrome are the most common complications reported11. The estimated overall mortality rate associated with these severe infections has ranged from 30 to 80 per cent in series ranging in size from seven to fifty patients14. Early recognition of the potential severity of these infections is crucial to the successful management of these patients.
We report the first case, to our knowledge, of a patient who had streptococcal toxic shock syndrome in association with a severe group-A streptococcal infection of the knee after a total knee arthroplasty and review the diagnosis, pathophysiology, and treatment of this syndrome.
*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.
†Infectious Disease Medicine, London Health Sciences Centre, University Campus, P.O. Box 5339, London, Ontario N6A 5A5, Canada.
A thirty-seven-year-old man sought medical attention at another institution three hours after the sudden onset of severe pain and swelling in the right knee and right inguinal area in association with generalized myalgia and arthralgia, malaise, and profound weakness. The patient had had a right total knee arthroplasty because of traumatic osteoarthrosis one year previously and had sustained minor abrasions on both knees five days before the time of presentation. He had excruciating pain in the right knee and was very anxious and agitated. The measurement of vital signs revealed a temperature of 37.3 degrees Celsius, a pulse rate of 100 beats per minute, a blood pressure of 150/80 millimeters of mercury (20.00/10.66 kilopascals), and a respiratory rate of twenty-eight breaths per minute. Laboratory findings included a white blood-cell count of 9.4 x 109 per liter with 94 per cent neutrophils, a hemoglobin level of 147 grams per liter, and a platelet count of 198 x 109 per liter (normal range, 150 to 450 x 109 per liter). Blood was drawn for culture, and the right knee was aspirated. The patient was managed with analgesics and intravenous administration of fluids, and antibiotic therapy with vancomycin (one gram administered intravenously every twelve hours) was initiated. He was transferred to our institution six hours later, at which time the blood pressure was 110/70 millimeters of mercury (14.66/9.33 kilopascals).
On admission to University Hospital, the patient had a temperature of 38.9 degrees Celsius, a pulse rate of 124 beats per minute, and a respiratory rate of twenty-four breaths per minute. An abrasion that was draining a small amount of serosanguineous fluid was noted on the right knee. Synovial fluid again was aspirated from the right knee, and a gram stain of a smear from the fluid revealed many white blood cells and gram-positive cocci resembling streptococci. Laboratory findings included a white blood-cell count of 15.8 x 109 per liter with 95 per cent neutrophils, a hemoglobin level of 121 grams per liter, a platelet count of 181 x 109 per liter, a serum sodium level of 131 millimoles per liter (normal range, 133 to 148 millimoles per liter), and a serum creatinine level of 103 micromoles per liter (normal range, seventy to 141 micromoles per liter). The level of protein in the synovial fluid was 50.6 grams per liter (normal range, 10.7 to 21.3 grams per liter), and the level of glucose in the synovial fluid was 0.4 millimole per liter (normal, more than 2.2 millimoles per liter). The partial thromboplastin time and the international normalized ratio were normal. The intravenous administration of fluids was continued, and the intravenous administration of cefazolin (two grams every eight hours) was begun.
The patient was taken to the operating room the same day, and a large amount of pus was discovered when the knee was opened. A synovectomy was performed, and gentamicin-laden polymethylmethacrylate beads were inserted. All components of the prosthesis were intact. Postoperatively, the patient continued to have a temperature that spiked from 37 to 40 degrees Celsius and averaged more than 38.5 degrees Celsius. He remained tachycardic with a pulse rate of 110 to 120 beats per minute. The patient noted some decrease in pain after the initial drainage procedure but complained of severe thirst despite the intake of a large volume of fluid. On the second day of hospitalization, the patient was noted to have an erythematous rash on the face and on the proximal portion of the right thigh. The cultures of synovial fluid and blood that had been performed at the referring hospital were positive for Streptococcus pyogenes (group-A Streptococcus). The antibiotic treatment was changed to penicillin G (four million units administered intravenously every four hours) and clindamycin (600 milligrams administered intravenously every eight hours). The organism was found to be susceptible to both of these antibiotics in addition to cefazolin, erythromycin, and vancomycin. The organism also grew on culture of specimens that had been obtained at University Hospital by swabbing of the skin abrasion and aspiration of the right knee. It subsequently was serogrouped and typed for the M protein (M) and T-agglutination pattern (T) and was found to be serotype M12/T12. The M protein is an important virulence factor and when its typing is combined with that of the T protein, a non-virulence factor, a particular strain of group-A Streptococcus can be identified.
When group-A streptococcal infection was confirmed, it became evident that the patient was exhibiting manifestations of streptococcal toxic shock syndrome2,5,15. As a result, the vital signs were monitored carefully and the intravenous and oral administration of fluid was continued (total daily intake, approximately seven liters). Tests of capillary blood gases, performed on the second day of hospitalization with the patient breathing room air, showed a partial pressure of oxygen of fifty-three millimeters of mercury (7.06 kilopascals) (normal range, seventy-five to 100 millimeters of mercury [10.00 to 13.33 kilopascals]), a partial pressure of carbon dioxide of thirty-four millimeters of mercury (4.53 kilopascals), a pH of 7.48, and a concentration of bicarbonate of twenty-six millimoles per liter. A diagnosis of adult respiratory distress syndrome was made on the basis of these findings. The patient was given 40 per cent oxygen by means of a mask, and the partial pressure of oxygen improved to 101 millimeters of mercury (13.46 kilopascals).
The platelet count decreased to 134 x 109 per liter, and the levels of liver transaminases increased to approximately twice the normal levels within twenty-four hours after admission.
In view of the lack of clinical improvement and the concern regarding the possible deterioration to irreversible toxic shock syndrome, the patient was returned to the operating room on the second day after admission and was managed with incision, drainage, radical débridement with removal of the prosthesis, and insertion of an antibiotic-laden polymethylmethacrylate spacer. He continued to have a fever of more than 38.5 degrees Celsius for three days postoperatively, but by the fourth postoperative day the temperature had decreased to between 37 and 38 degrees Celsius. A fine desquamation from the facial rash was noted on the fifth day after admission. Clinically, the patient continued to complain of severe fatigue and was very anxious. On the fourth day of hospitalization, the partial pressure of capillary oxygen with the patient breathing room air was still only fifty-nine millimeters of mercury (7.86 kilopascals). However, the patient gradually improved over the next six days in the hospital, during which time there was a concomitant improvement in the laboratory parameters. He was discharged from the hospital and continued to receive two grams of cefazolin intravenously every twelve hours for five weeks at home. Ultimately, he had a successful arthrodesis of the knee with no recurrence of the group-A streptococcal infection.
In the past decade, there has been a resurgence in the number of recognized severe group-A streptococcal infections worldwide. The case of our patient is somewhat unusual in that it involved a joint with a prosthesis that probably was seeded secondary to bacteremia that resulted from a minor abrasion on the knee. It is now recognized that severe group-A streptococcal infections can occur after minor trauma (for example, muscle strain, bruises, or abrasions) and can result in local invasion (for example, necrotizing fasciitis) or systemic spread with bacteremia, or both11.
Quintiliani and Engh, in 1971, reported the cases of seven orthopaedic patients who had a severe group-A streptococcal infection. Five of these infections occurred postoperatively. Four of the patients died, and the authors provided excellent descriptions of necrotizing fasciitis and toxic shock syndrome.
Our patient had symptoms of a severe streptococcal infection and toxic shock syndrome5,15 that followed a rapid, progressive course over several hours. At the time of presentation, the patient complained of severe weakness and dizziness. Severe hypotension was prevented with the intensive intravenous administration of fluids within approximately three hours after the onset of symptoms. Our patient had positive results on culture of blood, as did twelve (60 per cent) of the twenty patients who had streptococcal toxic shock syndrome in the study by Stevens et al.13. He also had evidence of multiple organ failure in association with adult respiratory distress syndrome11, which often is noted in patients who have streptococcal toxic shock syndrome. Finally, the patient had a rash on the face and on the right thigh with subsequent desquamation; these findings were similar to those noted in eleven (9 per cent) of the 128 patients who had streptococcal toxic shock syndrome in the study by Hoge et al.
Intensive treatment of toxic shock syndrome is necessary. Our patient was managed with intravenous administration of vancomycin within four hours after presentation and then received high doses of penicillin G and clindamycin. The addition of clindamycin has been recommended for patients who have a severe group-A streptococcal infection because of evidence that beta-lactam drugs alone, including penicillin G, may be less effective in the treatment of such an infection12. Intravenous administration of immunoglobulin also has been suggested as adjunctive therapy in instances of toxic shock syndrome and has been noted to be effective in anecdotal reports1,8.
The major concerns for our patient were progression to irreversible toxic shock syndrome and local spread of the infection with resultant necrotizing fasciitis, which can be life-threatening. Although we are not aware of any data that support early removal of the prosthesis in instances of group-A streptococcal infection, there is ample evidence that removal of the prosthesis is necessary in order to eradicate organisms consistently10. Therefore, an early decision was made to perform a radical débridement with removal of the prosthesis. The clinical condition and the laboratory parameters began to improve approximately five days after the operation.
Various hypotheses have been proposed to explain the increased incidence of severe group-A streptococcal infections. This resurgence probably has resulted from changes in the virulence factors of group-A streptococci (pyrogenic exotoxins A and B and M proteins) as well as in the immunological characteristics of the patients. The virulence factors appear to act as superantigens that can stimulate helper T-cells to proliferate directly without classic antigen processing6. The T-cells then produce excessive quantities of cytokines, including tumor necrosis factor, interleukin-1, and interleukin-6, which cause marked inflammatory effects14. It has been postulated that patients who are susceptible to these severe infections lack antibodies to these superantigens, which enables the infection to be established, to become invasive, and to cause marked inflammation of local tissues as well as systemic problems such as multiple organ failure11. In our patient, the group-A Streptococcus that was isolated was serotype M12, which is one of the serotypes most commonly detected in our region4. In other series, serotypes M1 and M3 have been the most common13.
In summary, a rapidly progressing infection of the knee that develops after a total joint arthroplasty and is associated with severe systemic manifestations should alert one to the possibility of a group-A streptococcal infection and streptococcal toxic shock syndrome. In view of the complications associated with this type of infection, we recommend radical débridement with removal of the prosthesis, careful monitoring of the patient, intensive fluid resuscitation, administration of high-dose penicillin G and clindamycin, and possible intravenous immunoglobulin therapy.