Amoxicillin for cough

That B-lymphocytes

play

and

with

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, which has certain lipophilic regions may be the streptococcal virulence factor responsible. Once streptokinase is membrane bound,

complement

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 concentrations of penicillin are currently required to in­hibit pneumococcus. Penicillin is still considered first-line therapy in the treatment of most GAS infections despite a recognized increase in microbiologic failure rates. Eryth­romycin has been the antibiotic of choice in the penicillin-­allergic child for most GAS infections, yet impressive emergence of resistance has been documented on three continents during the last 30 years (57,58,75). Thus, antibiotic treatment of GAS infections in general will likely become much more complex.

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.

A single injection of 1.2 million units of penicillin G benzathine given intramuscularly is as effective as enteral penicillin (4) and was

the

well

This efficacy, however, is dependent upon prolonged, rather than high-dose, therapy. Penicillin has been shown effective when therapy is started within 9 days of onset of symptoms of GAS pharyngitis (90).

Other desirable features of penicillin include lower cost, lower side effects, and a narrow antimicrobial spectrum.

There has been no documentation of resistance in GAS to penicillin; the minimal bactericidal concentration of penicillin G for GAS has remained 0.005 ?g/mL (reviewed in 76).

Erythromycin remains the first alternate choice in patients who are allergic to penicillin.

Erythromycin estolate (20 - 40 mg/ kg/day) or erythromycin ethylsuccinate (40 mg/kg/day) given enterally in 2 to 4 divided doses has been shown as effective as penicillin in treatment of pharyngitis. However, documented reports of erythromycin-resistant GAS have occurred in Finland, Japan, and, most recently, in the United States (57,58,75,92). In 1970, resistance to erythromycin in Japan had increased to 70% of all isolates, corresponding to a marked increase in macrolide use during that time (30).

Use of macrolides since then has declined, and a marked decrease in rates of erythromycin resistance has followed (30).

Resistance rates fell to 46% in 1981 and are currently at 3% (1989) (30). In Finland, erythromycin resistance reached 25% and was highest among strains isolated from soft tissue infections (75). The newest macrolides, azithromycin and clarithromycin , have been shown highly effective in the treatment of GAS pharyngitis. They provide easier dosing schedules and thus improve patient compliance.

Azithromycin has been shown to be efficacious in the treatment of GAS pharyngitis when given for only 3 - 5 days. For example, a recent study comparing azithromycin (20 mg/kg, once daily for 3 days) with penicillin V (125-200 mg four times daily for 10 days) showed significantly higher bacteriologic eradication rates and lower pathogen recurrence in the azithromycin group (69): 100% of the azithromycin group had a satisfactory clinical response, defined as cure or improvement, compared with 97% in the penicillin group; 5% of the azithromycin group relapsed, compared with 2% in the penicillin group (69). However, azithromycin-resistant GAS have been reported in the United States (19), and treatment failure of azithromycin

was

high

The ability of macrolides to prevent episodes of rheumatic fever has not been studied. Amoxicillin has been shown to be effective in eradicating GAS, is more palatable, and provides easier dosing than penicillin. Oral cephalosporins have been extensively studied in the treatment of GAS pharyngitis and are highly augmentin and amoxicillin effective.

In fact, some studies have suggested greater efficacy with cephalosporins than with penicillin, possibly because of their resistance to ?-lactamase producing organisms in the pharynx (70); other studies have not supported this (76).

Cephalexin can be given at 30 mg/day, in four divided doses for 10 days; cefadroxil , 30 mg/kg/day, in two divided doses forns10 days; cefaclor , 30 mg/kg/day in three divided doses for 10 days; cefuroxime axetil, 15 mg/kg/day in two divided doses for 10 days; cefoxitin , 80 to 160 mg/kg/day or 4 to12 g/day in four divided doses for 10 days; and cefixime , 8 mg/kg/day, once a day for 10 days (76). Cefaclor has been associated with a higher incidence of serum sickness than most other antibiotics.

In addition, cephalosporins as a class are more expensive than penicillin, are associated with greater side effects in general, and have a broader spectrum of activity. In many areas, tetracycline resistance occurs in a high percentage of strains of GAS and thus, this drug is not recommended for treatment of pharyngitis.

Sulfonamides , including trimethoprim-sulfamethoxazole, are ineffective in the treatment of GAS pharyngitis, though sulfadiazine

has

Noncompliance is thought to play a major role with oral treatments but does not account for all failures, however, it is unlikely that bacteriologic failures in the treatment of GAS are due solely to ?-lactamase-flora colonizing a patient's pharynx (76). Some investigators have postulated that early treatment of GAS, within 48 h of symptoms, impairs the patient=s immune response by altering the course of the illness. In fact, studies have shown that delaying therapy for 3 to 5 days resulted in an increase in anti-streptolysin O antibodies but did not affect development of type-specific antibodies (32).

Antibodies such as anti-streptolysin O, unlike type-specific antibodies, do not confer immunity on the host.

At present, it is unclear if delaying therapy for 2 to 3 days in patients with GAS pharyngitis results in a significantly greater antibody rise. Since adequate antimicrobial therapy prevents development of suppurative and non-suppurative complications of GAS, most authors do not recommend delaying therapy. Some bacteriologic and clinical failures may also represent infection with a tolerant strain or acquisition of a new strain of GAS. In addition, GAS carriers with an intercurrent viral pharyngitis may be mistakenly diagnosed as patients with acute GAS pharyngitis and thus considered treatment failures, since penicillin is ineffective in eradication of the GAS carrier state (76).

Clindamycin has been extremely effective in the treatment of GAS.

It is unaffected by the activity of ?-lactamases, but is more expensive than penicillin and has been associated with development of pseudomembranous colitis in some patients. In patients with

recurring

Usually, a 10 day course of amoxicillin/clavulanate , clindamycin, or an oral cephalosporin eradicates the GAS. Therapies shown to be effective in eliminating the carrier state include clindamycin (20 mg/kg/day in 3 divided doses over 10 days), amoxicillin/clavulanate given for 10 days, oral rifampin (20 mg/kg every 24 h for 4 doses) started during the last 4 days of a 10 day course of oral penicillin (88), and a combination of penicillin plus rifampin (oral rifampin 10 mg/kg every 12 h for 8 doses, with one dose of intramuscular benzathine penicillin G) (88).

In addition, topical application of ?-streptococci may eliminate the carrier state (73). Tonsillectomy may help reduce

the

section

S carlet Fever: Scarlet fever is characterized by high fever, circumoral pallor and a diffuse erythematous rash over the neck, trunk, face and limbs. There is a sandpaper consistency to the rash which blanches with pressure.

A white coating over the tongue resolves quickly leaving a strawberry appearance to the tongue owing to the swollen papillae.

The

the

Scarlet fever can also result from GAS infections at other sites, such as the skin (8).

Patients in modern times resolve the illness in 5-7 days and by 10-14 days there may be impressive desquamation of the skin particularly over the hands and feet.

S oft-Tissue Infections Due to GAS: The second most common clinical manifestation of GAS is a localized, relatively benign, amoxicillin and mucinex infection of the skin. Recent reports have documented increased frequency and severity of invasive group A streptococcal infections of the skin and soft tissues, associated with group A streptococcal serotypes M-1 and M-3 (7).

This is of considerable

interest

Strains of group A streptococci that cause skin infections normally differ from those that cause pharyngitis and can be identified by their M serotypes.

The most common streptococcal M serotypes that cause pharyngitis (types 1, 3, 5, 6, 12, 18, 19, 24 and others), including M-1 and M-3, have rarely been identified in skin lesions (8). In contrast, "skin strains" have been found to colonize the pharynx but are rarely associated with acute episodes of pharyngitis (8). G AS Pyoderma (Streptococcal Impetigo, Impetigo Contagiosum, Ecthyma): Pyoderma is a term for a localized purulent infection of the skin and is used synonymously with streptococcal impetigo and impetigo contagiosa. Pyoderma is most common in children aged 2 to 5 years and occurs most commonly among economically disadvantaged children in tropical or subtropical climates but can occur in northern climates during the summer months.

It normally results from direct inoculation of the skin surface with GAS following minor trauma, abrasions, or insect bites. pyogenes from skin lesions of patients with pyoderma.

Penicillin

was

Erythromycin is an alternative for penicillin-allergic patients but must be used with caution in regions where erythromycin-resistant strains of S.

Mupirocin ointment (applied to skin lesions 3 times daily for 10 days) has achieved cure rates comparable to those with enteral therapy but is more expensive. While rheumatic fever is not an associated complication of pyoderma, skin infections caused by nephritogenic strains of group A streptococci are the major antecedent of post-streptococcal glomerulonephritis (reviewed in (7)). E rysipelas: Erysipelas is an acute inflammation of the skin with involvement of cutaneous lymphatic vessels. It is most commonly found in infants and adults over 30 years of age. Historically, erysipelas most commonly involved the face. However, recent reports document up to 85% of infections involving the legs and feet (7). It is often preceded by a sore throat and commonly occurs at the site of a wound or surgical incision, especially when involving the trunk or extremities. The lesions are associated with fever and toxicity and are noted to spread outward.

The rash itself is a scarlet-red or salmon color with well-defined borders. Facial erysipelas may spontaneously resolve in 4 to 10 days (7). Superficial infections may be treated orally for 10 days, while more aggressive infections require parenteral therapy.

Typical antimicrobial regimens include clindamycin , nafcillin , or a third generation cephalosporin. C ellulitis : Streptococcal cellulitis is an acute inflammation of the skin and subcutaneous tissues resulting from infection of burns, wounds, or surgical sites or following minor trauma. Symptoms include fever and toxicity and may be associated with lymphangitis or bacteremia. Cellulitis can be differentiated from erysipelas by noting that the skin lesion of cellulitis is not raised and the demarcation between involved and uninvolved skin is indistinct. Therapy should

consist

In patients who are penicillin allergic, a first generation cephalosporin may be used.

Therapy can be given orally, unless there is evidence of lymphangitic spread. If lymphangitis is noted, parenterally administered antimicrobials should be used until there is marked clinical improvement. Oral antimicrobials can then be used to complete 10 days of therapy. N ecrotizing Fasciitis (Streptococcal Gangrene): GAS necrotizing fasciitis is a rapidly progressing infection of the deep subcutaneous tissues and fascia with extensive and rapidly spreading necrosis.

Infections often spare the skin, but 50% of patients may have associated myonecrosis.

Necrotizing fasciitis is often associated with severe systemic involvement and an associated high mortality rate (7,80,87).