Amoxicillin clav 875

The transmission in non-hospitalized patients is usually via the oral route from droplets from primary cases or from ingestion of milk contaminated with toxin producing strains of GAS.

Reductions in incidence and mortality rates of ARF in the United States had begun prior to the discovery of penicillin, primarily because of improved housing, sanitation, and delivery of health care. The recent increase in incidence of ARF in the United States has occurred primarily in children of middle c­lass families (89). However, the use of penicillin in the treatment of GAS pharyngitis dramatically reduced the incidence of ARF.

Mucoid colonies of group A streptococci have been associated with cases of rheumatic fever in North America but not in de­veloping countries.

Five serotypes have predominated: M-1, M-3­, M-18, M-5, and M-6.

Types M- 5 and M-18 have been re­ported as most consistently mucoid (77,87,89). S treptococcal Toxic Shock Syndrome (StrepTSS): Several population-based studies of StrepTSS have documented the annual incidence of 1-5 cases per 100,000 population (74) with most cases being sporadic in nature, however, larger epidemics of invasive Group A streptococcal infections have also been described in some settings. In 1994, an epidemic of related invasive infections occurred in Wannamingo, Minnesota (16) with an annualized prevalence of 24 cases per 100,000 population. In Missoula, Montana in 1999, the incidence of invasive infections reached 30 cases per 100,000 population. In addition to community-based infections, invasive Group A streptococcal infections have also been described in hospitals, convalescent centers and among hospital employees and family contacts of patients with invasive infections (11,25,31). Some of these studies have documented the same M-type and identical RFLP patterns in strains from primary and index cases (11,25,31,44).

In addition, carriage of Group A streptococcus by healthcare personnel has been associated with the spread of life threatening Group A streptococcal infections in the obstetrics/gynecology and ear-nose-throat wards of American hospitals (1).

Such infections have also originated in outpatient surgical settings and within the home environment.

It has been estimated that the risk of secondary cases may be approximately 200 times greater than the risk among the general population (23) There is ample data from studies conducted over several decades that Group A streptococcus is quickly and efficiently transmitted from index cases to susceptible individuals and that transmission may result in colonization, pharyngitis, scarlet fever, rheumatic fever or invasive Group A streptococcal infections. The risk for secondary cases is likely related to close or intimate contact and crowding as well as host factors such as 1. active viral infections such as varicella or influenza; 2. recent surgical wounds and childbirth (author's unpublished observations); 3.

absence of type specific opsonic antibody against the Group A streptococcus causing the index case; and 4. absence of neutralizing antibody against pyrogenic exotoxin A or B (59).

The portals of entry for streptococci are the vagina, pharynx, mucosa and skin in 50% of cases (87). Interestingly, a specific portal cannot be defined in the remaining 50% (87). Rarely, patients with symptomatic pharyngitis develop StrepTSS. Surgical procedures such as suction lipectomy, hysterectomy, vaginal delivery, bunionectomy and bone pinning provide a portal of entry in some cases. Numerous cases have developed within 24 - 72 hours of minor non-penetrating trauma resulting in hematoma, deep bruise to the calf or even following muscle strain (87).

Virus infections such as varicella and influenza have provided portals in other cases (87).

In some cases the use of non-steroidal anti-inflammatory agents may have either masked the presenting symptoms or predisposed to more amoxicillin for urethritis severe streptococcal infection and shock (87). Most cases of StrepTSS occur sporadically, though outbreaks of severe Group A streptococcal infections have been described in closed environments such as nursing homes (2,42), and hospital environments (25,31).

Each type of streptococcal infection presents with its own unique set of clinical manifestations. Thus, each type of infections will be described below in the section on specific antimicrobial treatment. The diagnosis of GAS infection may be suspected on clinical grounds, but rests on the demonstration of the organism in samples of pharyngeal exudates, blood, tissue, or body fluids using criteria described under Microbiology above.

Rapid strep tests have proven useful for the office diagnosis of streptococcal pharyngitis, though the specificity and sensitivity vary widely (reviewed in (76)).

A negative rapid strep test should be followed with a pharyngeal culture.

An antecedent streptococcal infection may be diagnosed by a 4-fold increase in antibody against streptolysin O (ASO), hyaluronidase, or DNAse B (56). Anti-Phagocytic Properties: M-protein contributes to invasiveness through its ability to impede phagocytosis of streptococci by human polymorphonuclear leukocytes (PMNL) (52). Conversely, type specific antibody against the M-protein enhances phagocytosis (52). Following infection with a particular M-type, specific antibody confers resistance to challenge with viable GAS of that M-type (52). Recently, Boyle has shown that GAS protease cleaves the terminal portion of the M-protein, rendering the organism more susceptible to phagocytosis by normal serum but more resistant to phagocytosis in the presence of type specific antibody (72). While M types 1 and 3 strains have accounted for the vast majority of strains isolated from cases of StrepTSS, many other M types, including some non-typeable strains, have also been isolated from such cases. M types 1 and 3 are also commonly isolated from asymptomatic carriers, and patients with pharyngitis or mild scarlet fever (45,48).

M echanisms of Fever Induction: Pyrogenic exotoxins induce fever in humans and animals

and

Pyrogenic exotoxin C has been associated with mild cases of scarlet fever in the United States (author's observations) and in England (41). The roles of two newly described pyrogenic exotoxins, SSA (60) and MF (67), in the pathogenesis of Strep TSS have not been elucidated. Cytokine Induction: There is strong evidence suggesting that SPEA, SPEB and SPEC, as well as a number of staphylococcal toxins (TSST-1, and staphylococcal enterotoxins A, B, and C) act as superantigens and stimulate T cell responses through their ability to bind to both the Class II MHC complex of antigen presenting cells and the V ? region of the T cell receptor (61). The net effect is induction of T cell proliferation (via an IL-2 mechanism) with concomitant production of cytokines (e.g., IL-1, TNF?, TNF?, IL-6, IFN?) that mediate shock and tissue injury.

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 contribute to the genesis of shock and organ failure.

Peptidoglycan, lipoteichoic acid (84) and killed organisms (37,63) are capable of inducing TNF? production by mononuclear cells in vitro (40,63,77). Exotoxins such as SLO are also potent inducers of TNF? and IL-1?.

SPEB, a proteinase precursor, has 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 keflex amoxicillin 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 and StrepTSS, 40% and 75% produced SPEA or SPEB, respectively. 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 clones were responsive to specific epitopes of type 5 M-protein (35).