Amoxicillin for dry cough

Recently, Hackett and Stevens demonstrated that SPEA induced both TNF? and TNF? from mixed cultures of monocytes and lymphocytes (39), supporting the role of lymphokines (TNF?) in shock associated with strains producing SPEA. Kotb (49) has shown that a digest of M-protein type 6 can also stimulate T cell responses by this mechanism. Interestingly, quantitation of such V? T-cell subsets in patients with acute StrepTSS demonstrated deletion rather than expansion, suggesting that perhaps the life-span of the expanded subset was shortened by a process of apoptosis (91).

In addition, the subsets deleted were not specific for SPEA, SPEB, SPEC, or MF suggesting that perhaps an as yet undefined superantigen may play a role in StrepTSS (91). Cytokine production by less exotic mechanisms may

also

Peptidoglycan, lipoteichoic acid (84) and

killed

Exotoxins such as SLO are also potent inducers of TNF? and IL-1?.

SPEB, a proteinase precursor, has clamoxyl amoxicillin the ability to cleave pre-IL-1? to release preformed IL-1? (46).

Finally, SLO and SPEA together have additive effects in the induction of IL-1? by human mononuclear cells (39). Whatever the mechanisms, induction of cytokines in vivo is likely the cause of shock and SLO, SPEA, SPEB, SPEC as well as cell wall components, etc., are potent inducers of TNF and IL-1 (11). Finally, a cysteine protease formed from cleavage of SPEB may play an important role in pathogenesis by the release of bradykinin from endogenous kininogen and by activating metalloproteases involved in coagulation (10). The mere presence of virulence factors, such as M-protein or pyrogenic exotoxins, may be less important in Strep TSS than the dynamics of their production in vivo.

For example, Chaussee et al (11) have demonstrated that among strains from patients with necrotizing

fasciitis

In addition, the quantity of SPEA but not SPEB was higher for strains from Strep TSS patients compared to non invasive cases (11).

Recently, Cleary has proposed a regulon in GAS that controls the expression of a group of virulence genes coding for virulence factors such as M-protein and C5-peptidase (14).

Using DNA fingerprinting, differences were shown in M-1 strains isolated from patients with invasive disease compared to M-1 strains from patients with non-invasive GAS infections (15).

Such strains of GAS could acquire genetic information coding for SPEA via specific bacteriophage.

Multi-locus enzyme electrophoresis demonstrates two patterns that correspond to M-1 and M-3 type organisms which produce pyrogenic exotoxin A, a finding that fits epidemiologic studies implicating these strains in invasive GAS infections (64) in the United States.

P athogenic Mechanisms in Acute Rheumatic Fever: The pathogenesis of acute rheumatic fever involves an intimate interplay between streptococcal virulence factors and the susceptible host.

That T cells play an integral role was demonstrated by obtaining T-cell clones from valvular tissue of patients with rheumatic fever and then showing that

these

specific

That B-lymphocytes play an important role is suggested by the demonstration that antibodies raised against particular M-protein digests cross react with cardiac tissue including myosin and endothelium (71). Interestingly anti-myosin antibodies also react strongly to cardiac endothelium (36).

Thus, as antibody against M-protein develops in a patient with antecedent Group A streptococcal pharyngitis, antibody could fix complement, thereby damaging and activating the endothelium yielding cytokines and chemokines which attract and activate T-lymphocytes. Thus, molecular mimicry between specific epitopes on M-protein and cardiac tissue results in damage to endothelium on the heart valve mediated by specific B and T-lymphocytes.

P ost Streptococcal Glomerulonephritis: It is clear that only certain strains of streptococci are capable of causing post-streptococcal glomerulonephritis. The best hypothesis at the present time is that proteins with unique antigenic determinants produced only by Anephritogenic strains, intercalate into the lipid bilayer of the glomerular basement membrane during the course of pharyngitis or impetigo.

Recent studies suggest that

streptokinase

Once streptokinase is membrane bound, complement is activated directly.

Further glomerulus-bound streptokinase interacts with circulating anti-streptococcal antibodies, resulting in further complement fixation and glomerular damage (66).

Susceptibilities for commonly used antibiotics in the treatment of GAS are presented in Table 1. Susceptibilities from Coonan and Kaplan's study were obtained from 282 pharyn­geal isolates along with 43 isolates from severe or invasive group A streptococcal disease (18).

No in vitro susceptibility testing has been undertaken to investigate whether combinations of antibiotic may exert an additive, synergistic or antagonistic effect against GAS.

Despite possible changes in virulence, group A streptococci have universally remained susceptible to penicillin since its introduction. This is of considerable interest, since other strep­tococci have developed multiple antibiotic resistance, and

higher

G AS Pharyngitis: GAS infections of the pharynx are the most common bacterial infections of childhood. Treatment of GAS pharyngitis is primarily aimed at preventing non-suppurative (in particular, rheumatic fever) and suppurative complications. The drug of choice remains penicillin VK , 25 to 50 mg/kg/day in 4 divided doses for children, or 250 to 500 mg per dose, 4 times/day for adults. demonstrated that twice-a-day dosing of penicillin was as effective as three-times-a-day dosing (34).

Treatment with penicillin should be continued for 10 days since shorter courses of penicillin have shown decreased efficacy.

A clinical response is generally obtained within 24 h of beginning therapy, and most children have a negative throat culture by 48 h and can return to school at that time. Persistence of symptoms beyond this period suggests development of a suppurative complication of GAS, a lack of compliance, or the presence of another underlying disease.