Treatment Challenges of Group A Beta-hemolytic Streptococcal Pharyngo-Tonsillitis

Despite its in vitro efficacy, penicillin often fails to eradicate Group A β-hemolytic streptococci (GABHS) from patients with acute and relapsing pharyngo-tonsillitis (PT).

A review of the literature details the causes of penicillin failure to eradicate GABHS PT and the therapeuticmodalities to reduce and overcome antimicrobial failure.

• The causes of penicillin failure in eradicating GABHS PT include:
• The presence of β-lactamase producing bacteria (BLPB) that "protect" GABHS from any penicillin
• The absence of bacteria that interfere with the growth of GABHS
• Co-aggregation between GABHS and Moraxella catarrhalis
• The poor penetration of penicillin into the tonsillar tissues and the tonsillo-pharyngeal cells, which allows intracellular GABHS and Staphylococcus aureus to survive. The inadequate intracellular penetration of penicillin can allow intracellular GABHS and S. aureus to persist.

In the treatment of acute tonsillitis, the use of cephalosporin can overcome these interactions by eradicating aerobic BLPB (including M. catarrhalis), while preserving the potentially interfering organisms and eliminating GABHS.

In treatment of recurrent and chronic PT, the administration of clindamycin, or amoxicillin-clavulanic acid, can eradicate both aerobic and anaerobic BLPB, as well as GABHS. The superior intracellular penetration of cephalosporin and clindamycin also enhances their efficacy against intracellular GABHS and S. aureus.

Probiotic for the treatment of recurring group A beta-hemolytic streptococci pharyngo-tonsillitis

A recent retrospective study has shown that an oral preparation of Streptococcus salivarius K12 (SsK12) may be a good option for treating patients who have group A beta-hemolytic streptococci (GABHS), especially those patients who  require frequent antibiotic therapy. The study was completed by Giuseppe Gregori, MD and colleagues, of the Primary Care Department, in the Department of Health Science at the University of Genoa, Italy, and was published in Therapeutics and Clinical Risk Management on January 2016.

The study assess retrospectively if SsK12 use in pediatric patients with recurrent group A beta-hemolytic streptococcal (GABHS) tonsillitis (RPTI) reduce the occurrence of  GABHS relapses during the treatment period, and during the following 12 months as well as compared to a group of children with GABHS RPTIs not being treated with SsK12.

There were 130 children in this study, 76 were treated with SsK12, and 54 were the control group. The investigators found that the reduction of infections observed in the SsK12-treated children was statistically higher than the controls. Additionally, the children treated with SsK12 experienced significantly fewer GABHS infections both during the initial 90 days of inclusion in the study, when the treatment group received SsK12, and in the following 9 months.

The authors noted that even though treatment with SsK12 oral preparation made the need for antibiotic therapy against GABHS infections four times less likely, the retrospective, observational study has less validity than a double-blind, controlled, prospective, and randomized investigation. They recommended that further studies and additional investigations would be performed on this topic.

Group A beta hemolytic streptococcal tonsillitis

Is tonsillectomy or adeno-tonsillectomy better than non-surgical approach for chronic/recurrent acute tonsillitis?

Tonsillectomy with or without adenoidectomy, is a common operation, but the indications for surgery are controversial. A Cochrane updated review by Burtton et al. of randomized controlled trials assessed the effectiveness of tonsillectomy (with and without adenoidectomy) in children and adults with chronic/recurrent acute tonsillitis in reducing the number and severity of episodes of tonsillitis or sore throat.

The review includes seven trials; five in children (987 participants) and two in adults (156 participants). The authors concluded that adeno-/tonsillectomy leads to a reduction in the number of episodes of sore throat and days with sore throat in children (5.1 fewer days) in the first year after surgery compared to non-surgical treatment. Children who were more severely affected were more likely to benefit as they had a small reduction in moderate/severe sore throat episodes.

In adults there were 3.6 fewer episodes (95% CI 7.9 fewer) in the group receiving surgery within six months post-surgery. The pooled mean difference for number of days with sore throat in a follow-up period of about six months was 10.6 days fewer in favor of the group receiving surgery (95% CI). Given the short duration of follow-up and the differences between studies, the authors considered the analysis found the evidence for adults to be of low quality. They concluded that insufficient information is available on the effectiveness of adeno-/tonsillectomy versus non-surgical treatment in adults to draw a firm conclusion.

The authors concluded that potential 'benefit' of surgery must be weighed against the risks of the procedure as adeno-/tonsillectomy is associated with a small but significant degree of morbidity in the form of primary and secondary haemorrhage and, even with good analgesia, and is particularly uncomfortable for adults.

Oral probiotic therapy with Streptococcus salivarius prevents recurrent streptococcal pharyngitis and/or tonsillitis

Streptococcus salivarius K12 has been shown to inhibit the in-vitro growth of Group A beta hemolytic streptococcal (GABHS) due to bacteriocins release. Di Pierro and colleagues from Velleja Research in Mialno, Italy have tested the Streptococcus salivarius K12 for its efficacy in preventing GABHS pharyngitis and/or tonsillitis in adults.

Forty adults with a diagnosis of recurrent GABHS pharyngitis and/or tonsillitis were enrolled in the study. Twenty of these subjects received one tablet containing Streptococcus salivarius K12 (Bactoblis®) a day for 90 days. The other 20 subjects served as untreated controls. The individuals were followed for  6-month to evaluate the effects of the treatment.

The 20 adults who completed the 90-day course of Bactoblis® showed a reduction in their episodes of streptococcal pharyngeal infection (about 80%). The 90 days treatment was also associated with an approximately 60% reduction in the incidence of reported pharyngitis in the 6-month period following use of the product. The product was well tolerated by the subjects with no treatment-related side effects or drop-outs reported. The study illustrated that the prophylactic administration of Streptococcus salivarius K12 to adults with a history of recurrent GABHS pharyngitis and/or tonsillitis reduced the number of episodes of GABHS oral infections.

Using a probiotic tablet

New guideline for the treatment of pharyngitis

New guideline from the Infectious Diseases Society of America (IDSA) recommend that physicians should prescribe antibiotics only for patients with sore throats who have positive test results for a group A streptococcal (GAS) infection.

The recommendations include:

1. Because the clinical features alone do not reliably differentiate between GAS and viral pharyngitis swabbing the throat and testing for GAS by rapid antigen detection test (RADT) and/or culture should be performed except when clear viral features like rhinorrhea, cough, oral ulcers, and/or hoarseness are present. In children and adolescents (and not in adults), negative RADT tests should be backed up by a throat culture.

2. Diagnostic studies for GAS pharyngitis are generally not indicated for children <3 years old and adults because acute rheumatic fever is rare in these groups.

3.  Routine follow-up throat cultures or RADT are not generally recommended.

4. Diagnostic testing or empiric treatment of asymptomatic household contacts of those with acute GAS pharyngitis is not routinely recommended.

5.   Those with acute GAS pharyngitis should be treated with an appropriate antibiotic at an appropriate dose for duration likely to eradicate the organism. Ten days treatment with penicillin or amoxicillin is recommended for those non-allergic to them.

6.  Treatment of penicillin-allergic patients  include a first generation cephalosporin (for those not anaphylactically sensitive) for 10 days, clindamycin or clarithromycin for 10 days, or azithromycin for 5 days.

7.  Adjunctive therapy with analgesic/antipyretic agent may be useful in the management of GAS pharyngitis. Corticosteroid is not recommended and aspirin should be avoided in children.

8.  GAS carriers do not generally require antimicrobial therapy because they are unlikely to spread GAS pharyngitis to their close contacts and are at little or no risk for developing suppurative or nonsuppurative complications.

9.  Tonsillectomy is not recommended solely to reduce the frequency of GAS pharyngitis.

Does Helicobacter pylori play a role in chronic tonsillitis?

Several studies confirmed the presence of Helicobacter pylori in chronically inflamed tonsils.. However, other reports did not find this organism. The difference in results in various studies might be due to different laboratory methods. A recent study by Farivar et al. used a polymerase chain reaction (PCR) in evaluating the role of this organism in chronic tonsillitis.

The authors detected H. pylori DNA in 21.35% of 103 specimens. There was no significant relationship between the presence of H. pylori, sex, age, and place of residence.

The finding of this organism in about 1 of 5 chronically inflamed tonsils require more studies that may shed light about the association of this organism with this condition. These include the use of antimicrobial effective against H. pylori, in treating this condition.

                                                           
                                                             Helicobacter pylori

Increasing incidence of methicillin-resistant staphylococcus aureus in retropharyngeal abs

Because of a recent increase in retropharyngeal abscess cases due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), a retrospective evaluation of the microbiology, clinical manifestations and treatment outcome of  retropharyngeal abscess  over the past 6-years (2004-2010) was performed at Children's Hospital of Michigan, Detroit, Michigan. The Findings were compared to those of a previous 11 year study (1993-2003) period.

One hundred eleven children with retropharyngeal abscess were treated representing a 2.8 fold increase in incidence (per 10,000 admissions) over the previous 11-year period. A total of 116 isolates (93 aerobes, 23 anaerobes) were isolated from 66 drained specimens (2/3 of the total). The study showed increased frequency of isolation of MRSA with an associated increase of S. aureus mainly CA-MRSA. S. aureus was recovered from 25 (38%) of 66 specimens compared to 2 (4.9%) of 41 in the previous 11 years; 16 (64%) of 25 were MRSA compared to none in the previous 11 years. Children whose abscess grew MRSA were younger (mean 11 months) than the others (mean 62 month) (p< 0.001). Five children had mediastinitis; all caused by MRSA. All MRSA isolates were susceptible to clindamycin.This is likely due to the overall increase in CA-MRSA infections in pediatric patients. Treatment with ceftriaxone and clindamycin in addition to surgical drainage was effective in most patients.

Is recurrent tonsillitis in adults different from one in children?

 Brook and Foote compared the microbial flora of recurrently inflamed tonsils removed from 25 children with recurrent episodes of tonsillo-pharyngitis were compared to flora of tonsils removed from 23 adults suffering from similar illness. More bacterial isolates in each tonsil were found in adults (10.2 per tonsil) than in children (8.4 per tonsil). The difference between these groups was due to a higher recovery rate in adults of anaerobic Gram-negative bacilli. Conversely, Group A beta-hemolytic streptococci were isolated in seven (28%) children as compared to their isolation in only one (4%) adult.

More isolates of beta-lactamase-producing organisms (BLPO) per tonsil were recovered in adults. Forty-three BLPO were detected in 21 (91%) of the 23 tonsils removed from adults as compared to only 16 (64%) of the children (1.2 isolates per patient) (P=0.04).

These findings suggest that the cause of recurrent tonsillitis in adults may differ from that in children. The differences in the tonsillar microbiology may be due to the effect of many more courses of antimicrobials given over the years to adults and the changes in tonsillar tissue that occur in this age group.

Methicillin Resistant Staphylococcus aureus is isolated in greater frequency in tonsillitis

An increase in the recovery of methicillin resistant S. aureus (MRSA) was recently noted in various infections. The rate of recovery MRSA in tonsils that were removed because of recurrent Group A -b-hemolytic streptococci (GABHS) tonsillitis was not previously reported. A recent study by Brook &  Foote demonstrated for the first time the recovery of MRSA from 16% of the tonsils removed from 44 children because of recurrent GABHS tonsillitis.

The emergence of MRSA in the tonsillar flora in children with recurrent GABHS tonsillitis may contribute to the difficulty in eradicating GABHS with penicillins and other antimicrobials that are ineffective against this organism. MRSA are generally resistant to beta-lactam antimicrobials ( i.e. penicillins) and generally susceptible to clindamycin, trimethoprim-sulfamethoxazole, and vancomycin. The MRSA present in the tonsills may serve as a potential source for the spread of these organisms to other body sites as well to other individuals.

Since most of the MRSA ( 5 of 7 isolated in the study) were also beta-lactamase producers their presence could potentially interfere with the eradication of GABHS by penicillin. MRSA that is also able to produce beta-lactamase can survive treatment with beta-lactam antibiotics and continue to “shield” GABHS from penicillins through the production of the enzyme beta-lactamase. Most of the S. aureus isolated from the tonsilar cores of our patients  ( 19 of 26 or 73% ) were, however, beta-lactamase producers and not MRSA. These organisms are susceptible to beta-lactamase resistant penicillins as well as most cephalosporins.

Why does penicillin not work in Group A streptococcal tonsillitis?

Despite its excellent efficacy in the test tube, penicillin frequently does not work and fail to eradicate Group A beta-hemolytic streptococci (GABHS) from patients with acute and relapsing pharyngo-tonsillitis (PT) is cause for concern.  Over the past 50 years, the rate of penicillin failure has consistently increased from about 7% in 1950 to almost 40% in 2000.

Various explanations exist for the failure of penicillin to eradicate GABHS PT (see page).  One possibility is the poor penetration of penicillin into the tonsillar tissues as well as into the epithelial cells. Other explanations relate to the bacterial interactions between GABHS and other members of the pharyngo-tonsillar bacterial flora.  For example, it is hypothesized that beta-lactamase secreted by beta-lactamase-producing bacteria (BLPB), which colonize the pharynx and tonsils, may “shield” GABHS from penicillins. Another possibility is the coaggregation between Moraxella catarrhalis and GABHS, which can facilitate colonization by GABHS. Normal bacterial flora can interfere with the growth of GABHS, and the absence of such competitive bacteria makes it easier for GABHS to colonize and invade the pharyngo-tonsillar area.

Beta-lactamase producing organisms "protecting" penicillin susceptible bacteria from penicillin

Therapeutic strategies that allow overcoming the above mechanisms are available and are based on extensive clinical research. This website describes the research and therapeutic option for patients who fail penicillin therapy.  

Streptococcal tonsillitis