Streptococcal toxic shock

91 Infectious Diseases Newsletter 8(12) December 1989 therapy, a presumptive diagnosis of infection is established and the antibiotic regimen should be continued for an adequate duration. Also, clinical evaluation should be continued in search for the source of infection. However, if no lysis of fever occurs with the empiric antibiotic regimen, then the naproxen test is recommended. Prompt and complete lysis of fever with the naproxen test and sustained normal temperature while taking naproxen is highly suggestive of the diagnosis of neoplastic fever. In a patient exhibiting these signs, clinical improvement should be closely monitored to rule out the possibility of

false response. However, persistent fever with the naproxen test should suggest nonneoplastic etiology, such as unidentified bacterial or fungal infection, and the patient should be further investigated. The naproxen test should be used judiciously because premature use of an antipyretic in a febrile patient without adequate antibiotic therapy may be detrimental to the patient's recovery if a serious infection is present. Further clinical trials of the naproxen test by other independent investigators are welcomed.

Bibliography Azeemuddin SK, Vega RA, Kim TH: The effect of naproxen on fever in children

with malignancies. Cancer 59:19661968, 1987. Chang JC: How to differentiate neoplastic fever from infectious fever in patients with cancer: Usefulness of the naproxen test. Heart Lung 16:122-127, 1987. Chang JC: Naproxen test in the differential diagnosis of fever of undetermined origin in patients with cancer. Cancer Therapy Control 1:57-66, 1989. Chang JC: Neoplastic fever: A proposal for diagnosis. Arch Intern Med 149:1728-1730, 1989. Chang JC, Gross HM: Utility of naproxen in the differential diagnosis of fever of undetermined origin in patients with cancer. Am J Med 76:697-703, 1984. Chang JC, Gross HM: Neoplastic fever responds to the treatment of an adequate dose of naproxen. J Clin Oncol 3:552558, 1985.

Streptococcal Toxic Shock H. Bradford Hawley, MD Department of Infectious Diseases, WrightState University School of Medicine, Dayton, OH

In Greek, "coccus" is defined as a round berry that can be used to make a scarlet dye. All clinicians are acquainted with the propensity for both streptococci and staphylococci to cause erythema in a variety of tissues. Furthermore, it is well known that production of various toxins by these bacteria is responsible for the erythema. More recently, the similarities of toxins elaborated by streptococci and staphylococci have become apparent at a molecular level with the demonstration of the homology shared by Staphylococcus aureus enterotoxin B and Streptococcus pyogenes exotoxin A. It should then come as no surprise that group A beta-hemolytic streptococci have recently been found to be the causative agents for a syndrome resembling toxic shock caused by Staphylococcus aureus. The syndrome is a multisystem illness associated with an erythematous, generalized rash and shock. The streptococcal infection may start as an area of cellulitis or pharyngitis, but rapidly progresses (in 12 to 72 hours)

to the severe generalized illness. Fever is a prominent sign and is often quite high (104°F to 105°F). The generalized erythema is particularly prominent on the face. In many cases, flaccid yellow bullae will develop thrombocytopenia and a purpuric skin rash that may progress to peripheral gangrene; numerous platelet transfusions are sometimes necessary during the acute stages of the illness to avoid serious hemorrhagic complications. The illness can affect several organs and severe cases are usually accompanied by renal failure, pulmonary infiltrates and effusions, and hypotension that appears to be a result of the leakage of fluid from the vasculature and cardiac failure. The mortality of published cases appears to be high (approximately 50%) and some survivors lose portions of extremities following gangrene. In the reported cases the etiologic agent was most often identified by cultural methods. Positive cultures may come from a variety of sources including throat culture, soft tissue aspirates of the margin of cellulitis, © 1989 Elsevier Science Publishing Co., Inc. 0278-2316/89/$0.00 + 2.20

and aspirates of bullae and blood cultures; the latter two sources appear to have the highest yield. When cultures are negative acute and convalescent serum samples tested for anti-DNase B may be useful. The anti-DNase B titers rise later than antistreptolysin O titers peaking in 4 to 6 weeks. A fourfold or greater rise in titer is considered significant. In the preantibiotic era clinicians sometimes encountered a fulminant illness referred to as toxic scarlet fever. The description of this illness appears to be identical to that recently described as streptococcal toxic shock. In the time period between the reports of toxic scarlet fever and toxic shock we find thrombocytopenia and peripheral gangrene being reported in a few patients with staphylococcal and streptococcal bacteremia. At the time when toxic scarlet fever was seen, streptococci commonly produced type A toxin. Modem streptococci are more commonly associated with toxin types B and C. To date, the streptococci isolated from patients with toxic shock have rarely been studied for

92 Infectious Diseases Newsletter 8(12) December 1989 toxin production. The strains studied have all been found to be heavy toxin producers, usually types A or B. Perhaps a reversion to more strains with type A toxin production will be found to be epidemiologically significant in the incidence of streptococcal toxic shock. It appears that the patients with streptococcal toxic shock have no antibody to the erythrogenic toxins, an immune status identical to that seen in scarlet fever patients. I am unaware of any recent studies in adults looking at the prevalence of antibody to streptococcal erythrogenic toxins. It is therefore not known if a substantial proportion of the adult population may be susceptible to this illness, or if the percentage of those susceptible is on the increase. Many of our newer antimicrobial agents have been developed to combat gram-negative bacilli and, although they maintain some activity against gram-positive cocci, the activity is often less than that of earlier developed penicillins and cephalosporins. One of the reported cases of streptococcal toxic shock occurred in a man initially treated with ceftazidime for a wound infection following trauma to the forearm. It is uncertain if early specific therapy with an agent such as penicillin would have aborted this se-

vere infection. Quinolones have been lauded for their broad spectrum of antibacterial activity and the usage of this class of oral antibiotics has dramatically increased. It must be noted that quinolones have limited activity against streptococci and it remains to be seen if streptococcal infections will be seen more frequently as a result of empiric treatment with quinolones. At present, early diagnosis and treatment with intravenous penicillin combined with intensive support measures afford the best prognosis to patients with streptococcal toxic shock. Support measures may be heroic with multiple platelet transfusions, vasopressors and central monitoring, renal dialysis, and surgical debridement or amputation. Awareness and better reporting methods may provide us with more accurate information regarding the incidence of this syndrome. More data will also be necessary to determine the prevalence of susceptible adults lacking toxin antibodies. Lastly, more attention must be paid to the streptococci themselves if we are to learn which erythrogenic toxin types are most important to the development of this syndrome and if the type of toxin produced is changing in the current group A beta-hemolytic streptococci.

Selected References 1. Rahal JJ Jr, MacMahon E, Weinstein L: Thrombocytopenia and symmetrical peripheral gangrene associated with staphylococcal and streptococcal bacteremia. Ann Intern Med 69:35-43. 1968. 2. Ortbals DW, Glew RH, Santa Cruz DJ: An unusual cutaneous manifestation of group A streptococcal bacteremia. South Med J 71:1421-1423. 1978. 3. Schlievert PM, Bettin KM, Watson DW: Production of pyrogenic exotoxin by groups of streptococci: Association with group A. J Infect Dis 140:676681, 1979. 4. Wannamaker LW: Streptococcal toxins. Rev Infect Dis 5(suppl 4):$723-$732, 1983. 5. Cone LA, Woodard DR, Schlievert PM, et al: Clinical and bacteriologic observations of a toxic shock-like syndrome due to Streptococcus pyogenes. N Engl J Med 317:146-149, 1987. 6. Bartter T, Dascal A, Carroll K, et al: "Toxic strep syndrome": A manifestation of group A streptococcal infection. Arch Intern Med 148: !421 - 1424, 1988. 7. Stollerman GH: Changing group A streptococci: The reappearance of streptococcal "toxic shock." Arch Intern Med 148:1268-1270, 1988. 8. Chesney PJ: Clinical aspects and spectrum of illness of toxic shock syndrome: Overview. Rev Infect Dis ll(suppl 1):S1-$7, 1989.

COMMENTS ON CURRENT PUBLICATIONS

Yarchoan R, Mitsuya H, Thomas R, et al: In vivo activity against HIV and favorable toxicity profile of 2',3'-dideoxyinosine. Science 245:412-415, 1989. The purine analogue 2',3'-dideoxyinosine (ddI), which has antiretroviral activity in vitro, was administered for up to 42 weeks in 26 patients with AIDS or ARC. Eight dose regimens were studied. The drug was orally bioavailable and penetrated into the cerebrospinal fluid. At higher doses, patients had increases in their circu-

lating T-4 cells and decreases in HIV p24 antigen. These patients also had evidence of improved immunologic function and reduced viremic symptomatology. The most notable adverse effects directly attributable to ddI administration at the doses used in this study included increases in serum uric acid (due to hypoxanthine release), mild headaches, and insomnia.

Comment It has become increasingly clear that early chemotherapeutic intervention in HIV infection is necessary in order to © 1989 Elsevier Science Publishing Co., Inc. 0278-2316/89/$0,00 +

2.20

prevent progression of the asymptomatic infection to ARC or AIDS. Currently, zidovudine (AZT), which is 3'-azido-2' ,3'-dideoxythymidine, has been shown to reduce the morbidity and mortality of patients with ARC or AIDS, but can also cause substantial toxicity such as bone marrow suppression in 40% to 80% of AIDS patients. Obviously, additional antiretroviral drugs are needed. The results of this pilot study are promising. In particular, circulating T-4 cells had an average increase of >200 T-4 cells, which may reduce the risk