Many antibiotics are available for the treatment of PT caused by GABHS. However, the recommended optimal treatment for GABHS infection is penicillin administered three times a day for 10 days (Tables 1,2 ). Oral penicillin-VK is used more often than intramuscular (i.m.) benzathine penicillin-G. However, i.m. penicillin can be given as initial therapy in those who cannot tolerate oral medication, or to ensure compliance.
An alternative medication is amoxicillin, which is as active against GABHS, but has a more reliable absrption, blood levels are higher, plasma half-life is longer and protein binding is lower, giving it theoretical advantages. Furthermore, oral amoxicillin has better compliance (better taste). Amoxicillin should not be used, however, in patients suspected of Infectious Mononucleosis; where it can produce a skin rash.
An alternative medication is amoxicillin, which is as active against GABHS, but has a more reliable absrption, blood levels are higher, plasma half-life is longer and protein binding is lower, giving it theoretical advantages. Furthermore, oral amoxicillin has better compliance (better taste). Amoxicillin should not be used, however, in patients suspected of Infectious Mononucleosis; where it can produce a skin rash.
Table 1: Oral Antibiotics for 10 days course of Treatment of Acute GABHS Pharyngo-Tonsillitis
Generic Name
|
Dosage ( in mg )
|
Pediatric (mg/kg/d) adult frequency
| |
Penicillin-V
|
25-50 250 q6-8 hrs
|
Amoxicillin
|
40 250 q8 hrs
|
Cephalexina
|
25-50 250 q6-8 hrs
|
Cefadroxyla
|
30 1000 q12 hrs
|
Cefaclora
|
40 250 q8 hrs
|
Cefuroxime-axetila
|
30 250 q12 hrs
|
Cefpodoxime-proxetila
|
30 500 q12 hrs
|
Cefdinir a,d
|
7 mg 300 q 12 hrs
14 mg 600 q 24 hrs
|
Cefprozila
|
30 250 q12 hrs
|
ceditoren
|
NA 200 q12 hrs
|
Azithromycin d
|
12 250c q24 hrs
|
Clarythromycin
|
7.5 250 q12 hrs
|
Cefixime
|
8 400 q24 hrs
|
Ceftibuten
|
9 400 q24 hrs
|
Erythromycin estolate
|
40 250 q8-12 hrs.
|
Amoxicillin-calvulanateb
|
45 875 q12 hrs.
|
Clindamycinb
|
20-30 150 q6-8 hrs.
|
a = effective also against aerobic BLPB
b = effective also against aerobic and anaerobic BLPB
c= first day dose is 500mg
d= duration of therapy 5 days
NA=not approved for children younger than 12 years
Table 2: Oral Antimicrobials in Treatment of GABHS Tonsillitis
Acute
|
Recurrent/
Chronic | |
penicillin
(amoxicillin) |
clindamycin
amoxicillin-clavulanate |
clindamycin
|
cephalosporinsb
|
metronidazole & macrolide
|
penicillin &
rifampin |
clindamycin
|
penicillin & rifampin
| |
amoxicillin-clavulanate
| ||
Macrolidesa
| ||
a GAS may be resistant
b all generations
Remark: For dosages and length of therapy see Table 2.
The frequently reported inability of penicillin to eradicate group A beta hemolytic streptococci (GABHS) from patients with pharyngo-tonsillitis (PT) despite it’s excellent in-vitro efficacy is of concern. Although about half of the patients who harbor GABHS following therapy may be carriers, the rest may still show signs of infection and represent true clinical failure. Recent studies has shown that the recommended doses of either oral penicillin V or intramuscular penicillin failed to eradicate GABHS in acute-onset pharyngitis in 35% patients treated with oral penicillin V and 37% of intramuscular penicillin (2).
Penicillin failure in eradicating GABHS tonsillitis has several explanations ( Table 3).
Table 3: POSSIBLE REASONS FOR ANTIBIOTIC FAILURE OR RELAPSE IN GABHS TONSILLITIS
· Bacterial Interactions
The presence of beta-lactamase–producing organisms that “protects” GABHS from penicillins
Co-aggregation between GABHS and Moraxella catarrhalis
Absence of members of the oral bacterial flora capable of interfering with the growth of GABHS ( through production of bacteriocins and/or competition on nutrients)
· Internalization of GABHS (survives within epithelial cells escaping eradication by penicillins)
· Resistance (i.e., erythromycin) or tolerance (i.e., penicillin) to the antibiotic used
· Inappropriate dose, duration of therapy, or choice of antibiotic
· Poor compliance with taking medication
· Reacquisition of GABHS from a contact or an object ( i.e. toothbrush, dental retainer or dental braces )
· Carrier state, not disease
These include noncompliance with 10-day course of therapy, carrier state, reinfection from another person or object, and penicillin tolerance. Some postulate that bacterial interactions between GABHS and members of the pharyngo-tonsillar bacterial flora can explain these failures. These explanation include the “shielding” of GABHS from penicillins by beta-lactamase-producing bacteria ( BLPB ) that colonize the pharynx and tonsils (3), the absence of normal flora organisms that interfere with the growth of GABHS (4), and the co-aggregation between Moraxella catarrhalis and GABHS (5).
The repeated penicillin administration can induce many of these changes. It can result in a shift in the oral microflora with selection of beta-lactamase-producing strains of S. aureus, Haemophilus spp., Moraxella catarrhalis, Fusobacterium spp., pigmented Prevotella and Porphyromonas spp. and Bacteroides spp. ( all
It is possible that BLPB can protect the GABHS from penicillin by inactivating the antibiotic. Such organisms in a localized soft-tissue infection may degrade penicillin in the area of the infection, protecting not only themselves but also penicillin-susceptible pathogens such as GABHS. Thus, penicillin therapy directed against a susceptible pathogen can be rendered ineffective.
An increase in in vitro resistance of GABHS to penicillin was observed when GABHS was inoculated with S. aureus, Haemophilus spp., and pigmented Prevotella and Porphyromonas spp. Bacteroides sp. protected a penicillin-sensitive GABHS from penicillin therapy in mice. Both clindamycin and the combination of penicillin and clavulanic acid (a beta-lactamase inhibitor), which are active against both GABHS and AGNB, eradicated the infection.
Penicillin therapy can also reduce the number of aerobic and anaerobic bacteria that can interfere with the growth of GABHS. The oro-pharyngeal flora of over 85% of individuals who are not tonsillitis prone contains numerous types of organisms that are capable of interfering with the in-vitro growth of potential pathogens. In contrast only 25%-30% of children who suffer from recurrent tonsillitis harbor interfering organisms.
Acute pharyngo-tonsillitis
Even though antibiotics other than penicillin were found to be more effective in the bacteriological and clinical cure of GABHS PT, penicillin is still recommended by some guidelines as the antibiotics of choice. The antibiotics found to be more effective included cephalosporins, lincomycin , clindamycin , macrolides , and amoxicillin-clavulanate . Some of these agents were more effective than penicillin in acute (cephalosporins, macrolides ) and others (lincomycin , clindamycin , and amoxicillin-clavulanate in recurrent GABHS PT.
There are patients where more effective antimicrobials that are less likely to fail to eradicate GABHS should be considered. Individual medical, economical and social issues should be considered in each patient prior to selecting an antimicrobial for the treatment of GABHS PT.( Table 4) These include the existence of a high probability for the presence in the pharyngo-tonsillar area of BLPB and the absence of interfering organisms, the recent failure of penicillin therapy, or a history of recurrent GABHS PT.
Table 4: Indications for the use of antimicrobial other than a penicillin for GABHS tonsillitis
• Presence of beta-lactamase-producing bacteria ( recent antibiotic exposure, Winter, region )
• Absence of “Interfering Flora“ (recent antibiotic therapy)
• Recurrent GABHS tonsillitis
• Past failures to eradicate GABHS
• High failures of penicilins in the community
• Co-morbidities
• When failure is a medical, economical, or social hardship
• Penicillin allergy ( non-type I)
The macrolides are also an alternative choice in therapy of PT. Compliance with the newer macrolides (clarithromycin and azithromycin) is better compare with erythromycin, because of their longer half life, and reduced adverse gastrointestinal side effects. However, the increased use of macrolides for the treatment of various respiratory and other infections has been associated with increased GABHS resistance to these agents. Resistance of GABHS to macrolides reached up to 70% in Finland Italy Japan Turkey USA USA
The success rate of treatment of acute GABHS tonsillitis was consistently found to be higher with cephalosporins than with penicillin. The cephalosporins increased efficacy may be due to their activity against aerobic beta lactamase producing bacteria (BLPB) such as S. aureus, Haemophilus spp. and Moraxella cattarrhalis. Another possible reason is that the non-pathogenic interfering aerobic and anaerobic bacteria which compete with GABHS, and help to eliminate them, are less susceptible more resistant to cephalosporins than to penicillin. These organisms are therefore more likely to survive cephalosporin therapy.
The length of therapy of acute tonsillitis with medication other than penicillin has not been determined by large comparative controlled studies. However, certain new agents have been administered in shorter courses of 5 or more days ( Table 1). Early initiation of antimicrobial therapy results in faster resolution of signs and symptoms. However, spontaneous disappearance of fever and other symptoms generally occurs within 3 to 4 days, even without antimicrobials. Furthermore, acute rheumatic fever can be prevented even when therapy is postponed up to 9 days.
Prevention of recurrent tonsillitis due to GABHS by prophylactic administration of daily oral or monthly benzathine penicillin should be attempted in patients who suffered from rheumatic fever. American Heart Committee guidelines on the prevention of rheumatic fever should be followed, and if any family members are carrying GABHS, the disease should be eradicated and the carrier state monitored.
When C. diphtheriae infection is suspected, erythromycin is the drug of choice, and penicillin or rifampin are alternatives. Supportive therapy of PT includes antipyretics and analgesics such as aspirin or acetaminophen, and attention to proper hydration.
Recurrent and chronic pharyngo-tonsillitis
Penicillin failure in treatment of recurrent and chronic tonsillitis is even higher than the failure of therapy of acute infection. Several clinical studies demonstrated the superiority of lincomycin, clindamycin, and amoxicillin-clavulanic acid over penicillin. (see table below) These antimicrobial agents are effective against aerobic as well as anaerobic BLPB and GABHS in eradicating recurrent tonsillar infection. However, no studies showed them to be superior to penicillin in treatment of acute tonsillitis. A study in 774 patients with acute recurrent GABHS pharyngotonsillitis, that compared oral clindamycin 300 mg BID and oral amoxicillin/clavulanic acid 1 g BID achieved comparable rates of bacteriologic eradication at 12 days and 3 months and comparable clinical cure rates at 3 months. Patients who received clindamycin had significantly greater clinical cure rates at 12 days (92.6% vs 85.2%).
Other drugs that may also be effective in the therapy of recurrent or chronic tonsillitis are penicillin plus rifampin and a macrolide (e.g., erythromycin) plus metronidazole (see Table 2). Referral of a patient for tonsillectomy should be considered only after these medical therapeutic modalities have failed.
Studies comparing penicillin treatment of GABHS PT with other antimicrobials
