Eva Grahn

Evaluation of Beta-lactamase Activity and Microbial Interference in Treatment Failures of Acute Streptococcal Tonsillitis

Out of 169 patients with streptococcal tonsillitis treated with phenoxymethylpenicillin, 13 (8%) developed a new clinical infection with the same streptococcal strain within 2 weeks of completing the therapy (clinical treatment failure) and 24 (14%) were clinically healthy but harboured the same streptococcal strain after treatment (bacterial treatment failure). Patients with clinical treatment failure showed beta-lactamase activity in their saliva pellet significantly more often than patients with bacterial treatment failure, healed streptococcal tonsillitis or non-streptococcal tonsillitis as well as healthy controls. In an interference study, clinical treatment failures were compared with healthy streptococcal carriers, i.e. persons living in the same household and harbouring the same beta-streptococcal strain. 11/12 healthy carriers had alpha-streptococci with interfering activity against their own beta-streptococcal strain, while the corresponding figure for the clinical treatment failures was 2/13. Furthermore, 6/12 healthy carriers had beta-streptococci inhibiting their own alpha-strains, while the streptococci in 11/13 clinical treatment failures had this ability. The beta-lactamase activity and the interference between alpha- and beta-streptococci may be a contributory cause to treatment failure in streptococcal tonsillitis.

Alpha-Streptococci as Supplementary Treatment of Recurrent Streptococcal Tonsillitis: A randomized Placebo-controlled Study

Recurrences are a common finding after antibiotic treatment of acute group A streptococcal tonsillitis. This has been attributed to several factors, among others a disturbed normal throat flora and especially a lack of alpha-streptococci. It thus seems logical in patients with recurrent streptococcal tonsillitis, to restore the normal alpha-streptococcal flora by reimplantation of alpha-streptococci. This was performed in a double blinded, randomized, placebo-controlled study. 36 patients with recurrent streptococcal group A tonsillitis were treated with antibiotics followed by either placebo (19 patients) or a pool of 4 selected alpha-streptococcal strains (17 patients) with good interfering activity against clinical isolates of beta-streptococci. No patient recurred during the first 2 months of follow-up in the alpha-treated group, but 7 in those treated with antibiotics and placebo. After 3 months 1 in the patient group treated with antibiotics and alpha-streptococci and 11 in the placebo-treated group recurred. These results are statistically highly significant and show that recolonisation with alpha-streptococci seems to offer a new way to lower the rate of recurrence in streptococcal throat infections.

Penicillin Tolerance in Beta-Streptococci Isolated from Patients with Tonsillitis

Beta-streptococci isolated from patients with acute tonsillitis were tested for penicillin tolerance defined as an MBC/MIC ratio greater than or equal to 16. 11/18 strains recovered from patients with clinical treatment failure were tolerant to penicillin in comparison with 0/15 strains from successfully treated patients. The MBC/MIC ratio was less than 16 for all strains versus cefadroxil but above that ratio for many strains versus clindamycin, doxycycline and erythromycin. We suggest that penicillin tolerance may be one reason to treatment failures in individuals with streptococcal tonsillitis and that other antibiotics could be used to treat these patients since penicillin tolerance is not correlated to a general increase in antibiotic resistance.

Interfering α-streptococci as a protection against recurrent streptococcal tonsillitis in children

Recurrent streptococcal tonsillitis/pharyngitis is a great problem, especially in certain epidemiological situations. Patients treated with antibiotics often have a disturbed normal throat flora and may lack, e.g., alpha-streptococci known in vitro to have an interfering activity against group A streptococci. Thirty-one patients with recurrent streptococcal tonsillitis were given antibiotics for 10 days. At the end of this treatment they were sprayed in their mouths with four selected alpha-streptococcal strains known to have strong growth inhibiting activity in vitro against most beta-streptococci group A. The follow-up period after this colonization was 3 months. After alpha-streptococcal treatment, none of the patients attracted a new tonsillitis during the follow-up period while 8% of the controls had a second tonsillitis. Treatment of streptococcal tonsillitis/pharyngitis with antibiotics followed by recolonization with alpha-streptococci seems to hinder further recurrences.

Is Penicillin the Appropriate Treatment for Recurrent Tonsillopharyngitis? Results from a Comparative Randomized Blind Study of Cefuroxime Axetil and Phenoxymethylpenicillin in Children

The efficacy of cefuroxime axetil compared with phenoxymethylpenicillin (PcV) was studied in group A beta-haemolytic streptococci (GAS) culture-proven tonsillitis in children aged 3-12 years with a history of at least 1 episode of tonsillopharyngitis requiring antibiotic therapy during the previous 3 months. This was a comparative, randomized, investigator-blind, multicentre study. A total of 236 children received either cefuroxime axetil suspension or PcV syrup. Inclusion criteria were a positive, rapid, group A strep test verified by bacteriological culture and clinical signs and symptoms of tonsillopharyngitis. Cefuroxime axetil treatment gave a significantly higher bacteriological eradication rate and clinical cure rate than PcV. At day 2-5 post treatment the eradication rates were 99/114 (87%) for cefuroxime axetil vs 61/109 (56%) for PcV (p < 0.001). The clinical cure rates were 98/114 (86%) and 73/109 (67%) respectively (p < 0.01). Up to 21-28 days post-treatment, 9/114 (8%) cefuroxime axetil patients and 37/109 (34%) PcV patients were treatment failures or had recurrence/reinfection of GAS tonsillopharyngitis (p < 0.001). More than 90% of the patients who experienced bacteriological treatment failure at either the first or second follow-up had the same serotype isolated pre- and post-treatment. During the study period, 21/114 (18%) patients in the cefuroxime axetil group and 50/109 (46%) patients in the PcV group received additional antibiotics (p < 0.001). No serious adverse events were noted and the mild adverse events were equally distributed among the patients in the 2 study groups: 15% for cefuroxime axetil and 14% for PcV.

Interference of α-hemolytic streptococci isolated from tonsillar. Surface on β-hemolytic streptococci (Streptococcus pyogenes). A methodological study

The interference between alpha-streptococcal strains obtained from patients with repeated tonsillitis and a collection of group A streptococcal strains were studied. For this purpose three in vitro methods were designed and compared. The results obtained by a simple plating technique suitable for screening purposes were found to correlate well with those using more laborious techniques. In a limited scale some of the alpha- and beta-streptococcal combinations were tested under in vivo conditions using a tissue cage model allowing repeated sampling. In most instances agreement between the results of the in vitro and in vivo methods was registered. Several alpha-strains having inhibitory capacity to the majority of a collection of group A streptococci belonging to different serotypes were found, but also alpha-strains with an inhibitory activity restricted to few group A isolates within a certain serotype. Also beta-streptococcal strains with growth inhibiting activity towards some alpha-strains were found. As the methods were chosen to eliminate many of the unspecific inhibitory factors and the beta-hemolytic test strains showed a pattern of inhibition that varied for each of the reference alpha-strains the activity is most likely attributed to bacteriocin-like substances.

Effects of active addition of bacterial cultures in fermented milk to patients with chronic bowel discomfort following irradiation

Radiotherapy is a cornerstone in the treatment of malignancies in the pelvis. Consequently, there is usually exposure of the intestine and especially the lower colon and rectum, with ensuing disturbances in bowel habits at different times following radiotherapy. The main problem is diarrhoea associated with lactose intolerance, bile salt absorption and fat malabsorption. Bacterial contamination has also been described. In the present study we have evaluated the influence of the active administration of specific bacterial cultures in fermented milk, which inhibit the growth of potentially pathogenic micro-organisms, to 40 consecutive patients with chronic alteration in their bowel habits caused by previous radiotherapy of pelvic malignancies. The results suggest that intake of fermented milk products could be of value in decreasing chronic bowel discomfort following radiotherapy of pelvic malignancies. However, a more extensive study is warranted in order to very the significance of the results and to find the optimal product.

Pharmacokinetics of Phenoxymethylpenicillin in Tonsils

The pharmacokinetics of phenoxymethylpenicillin in tonsillar tissue was studied in 33 patients who underwent tonsillectomy, mainly because of repeated tonsillitis or peritonsillitis. The patients were operated on 30-240 min after an oral penicillin dose of 12.5 mg/kg body weight. The mean serum concentration was 2.8 micrograms/ml for 10 patients operated upon 80-95 min after drug administration. The mean tissue concentration for these patients at the same time was 0.6 micrograms/g. The mean concentration of penicillin in tissue after 240 min was 0.05 micrograms/g. 19% of the serum concentration was recovered in the tonsillar tissue. No significant difference between penicillin concentration in the centre or surface of the tonsils was found. The tissue concentration was calculated to be above 0.03 micrograms/ml for at least 4-5 h. 30% of the patients harboured penicillinase producing bacteria on their tonsils, mainly Staphylococcus aureus. These patients had a lower tissue concentration than those lacking the bacteria, but the difference was not statistically significant (p = 0.095).

Penicillin Concentration in Saliva and Its Influence on Bacterial Interference

The aim of the investigation was to study the influence of various penicillin levels on the interference between alfa- and beta-streptococci based on antibiotic levels registered after oral intake of penicillin tablets. It was found that penicillin was released from ordinary sugar coated tablets already in the mouth resulting in concentrations in saliva above the MIC of most penicillin sensitive microorganisms during the first 2 min. This was followed by a decrease of the alfa-streptococcal flora. It was also shown that penicillin levels above the MIC of alfa-streptococci resulted in prolonged survival of beta-streptococci as compared to that noted at penicillin levels above the MIC of beta-streptococci but below that of the alfa-strains. At this latter level a synergistic effect between penicillin and interfering alfa-streptococcal strains could be demonstrated.

The effect of penicillin on bacterial interference in vivo

The study was designed to analyse the effect of penicillin on interference between alfa-streptococci and group A streptococci in vivo. Tissue cages were implanted subcutaneously in 9 rabbits and inoculated with 10(5) cfu of alfa- and beta-streptococci together as well as separately. Both streptococci were recovered 96 h after the inoculation in the untreated rabbits. Alfa-streptococci inhibiting the growth of beta-streptococci in vitro retained this capacity under the experimental in vivo conditions. Higher penicillin concentration did not increase the killing rate of beta-streptococci grown separately while a faster killing was observed with low penicillin levels in the presence of inhibiting alfa-streptococci, indicating synergistic effect.