a potential risk factor in this population. STSS has also been well described as a complication
of wounds, varicella, and influenza A. A controversial association of invasive group A
streptococcal infections such as STSS with prior NSAIDs use has been suggested (116). The link
has been proposed to be depression of the cellular immune response by NSAIDs. Clinically,
STSS shares many features with TSS. Fever, hypotension, myalgias, liver abnormalities,
diarrhea, emesis, renal dysfunction, and hematological abnormalities may be present in TSS
caused by either staphylococci or streptococci. Diffuse macular erythroderma likewise is
frequently present in disease caused by both bacteria and is often accompanied by mucous
membrane findings, such as conjunctival injection and delayed desquamation of palms and
soles.
Nonetheless, certain important differences exist between STSS and TSS. The skin is often
the portal of entry in STSS, with soft tissue infections developing in 80% of patients (108). The
initial presentation of STSS is often localized pain in an extremity, which rapidly progresses
over 48 to 72 hours to manifest both local and systemic signs of STSS. Cutaneous signs may
include localized edema and erythema, a bullous and hemorrhagic cellulitis, NF or myositis,
and gangrene. Soft tissue involvement of this nature is distinctly uncommon in staphylococcal
TSS.
Blood cultures are positive in 60% of patients with STSS (108), compared with less than
3% in TSS. Mortality in streptococcal TSS is between 30% and 80%, whereas in staphylococcal
TSS ranges from 3% to 5% (117,118).
Treatment
Group AStreptococcusis susceptible to penicillin and otherb-lactam antibiotics in vitro;
however clinical treatment failure occurs when penicillin is used alone in severe group A
Streptococcusinfections (119). This may be attributed to the large inoculum size, the so-called
Eagle effect (120,121). These large inocula reach the stationary growth phase very quickly.
Penicillin and otherb-lactam antibiotics are ineffective in the stationary growth phase because
of reduced expression of penicillin-binding proteins in this phase. Moreover, toxin production
is not inhibited byb-lactam antibiotics during the stationary growth phase. The greater efficacy
of clindamycin is multifactorial, it inhibits protein synthesis, and its efficacy is unaffected by
inoculum size or the stage of bacterial growth. Clindamycin also suppresses synthesis of
penicillin-binding proteins and has a longer post antibiotic effect thanb-lactam antibiotics.
Lastly, clindamycin causes suppression of LPS-induced monocyte synthesis of TNF (121–124).
Prompt antimicrobial therapy with high-dose penicillin and clindamycin should be instituted.
Suppression of STSS toxin has been demonstrated in vitro with linezolid (125). Aggressive
fluid resuscitation is needed because of intractable hypotension and diffuse capillary leak.
Human polyspecific intravenous IgG (IVIG) has been suggested as a potential adjunctive
therapy for invasive group A streptococcal diseases mainly because of its ability to neutralize a
wide variety of superantigens and to facilitate opsonization of streptococci. An observational
cohort study of IVIG in patients with STSS reported decreased mortality rates in patients
treated with IVIG compared with controls (67% vs. 34%) (126). A double-blind placebo trial
was prematurely terminated because of slow recruitment. Analysis of the primary end point
revealed a reduced mortality in IVIG-treated group compared with placebo-treated patients
(10% vs. 36%), though statistical significance was not achieved. A significant increase in
plasma-neutralizing activity against superantigens expressed by autologous isolates was noted
in the IVIG group after treatment (127). If IVIG is to be used, it should be given early and more
than one dose should be used, because batches of IVIG have variable neutralizing activity
(128). In addition, prompt surgical exploration and debridement of deep-seated streptococcal
infection should be performed (see discussion under sect. ”Necrotizing Fasciitis”).
For management of TSS, antistaphylococcal agents are selected with consideration of
susceptibility testing. Supportive care includes aggressive IV fluid resuscitation and
vasopressors as needed. The suspected focus of infection requires specific attention.
Specifically, management includes the removal of any vaginal device in menstrual cases and
the removal of packed dressings in conjunction with drainage and debridedment in cases
associated with postsurgical wounds.
314 Sharma and Saravolatz