Penicillin treatment failure in group A streptococcal tonsillopharyngitis: no genetic difference found between strains isolated from failures and nonfailures.

Despite penicillin (pcV) treatment, tonsillopharyngitis caused by group A streptococci (GAS) is associated with bacterial failure rates as high as 25%. The reason for this rate of failure is not fully understood. One explanation might be that certain DNA profiles of GAS strains are responsible for treatment failures. Using arbitrarily primed polymerase chain reaction (AP-PCR), we compared the DNA profiles of GAS strains from 4 patients with several treatment failures following pcV treatment of tonsillopharyngitis with the profiles of strains of the same T type from patients who were clinically and bacteriologically cured after a single course of pcV. The isolates were obtained during the same time period and from the same geographic area. Thirty-seven strains of T types 4, 12, and R28 were investigated. Eleven different DNA profiles could be detected with the AP-PCR technique. Five DNA profiles were identified as T type 12, 3 as T type 4, and 3 as T type R28. The DNA profiles of the strains from the 4 patients with several treatment failures differed, but all isolates from each one of these patients exhibited the same or a very similar profile. The DNA profiles of the failure strains were also represented in nonfailure strains. Treatment failure in these 4 patients therefore seems to be due to insufficient eradication of GAS, rather than to reinfection with a new strain. The finding that the same DNA profile can be present in both failure and nonfailure strains suggests that the treatment failure may be to some extent host-related and not only due to bacterial factors.

Clindamycin in recurrent group A streptococcal pharyngotonsillitis--an alternative to tonsillectomy?

Fifty-three patients with bacterial treatment failure after a 10-day course of treatment with phenoxymethyl penicillin (pcV) for group A streptococcal (GAS) pharyngotonsillitis were randomly assigned to continued treatment with pcV, or to treatment with clindamycin instead. The patients were then followed for 1 year with throat cultures and clinical examination every third month and in the event of symptoms of sore throat. In the first 3-month period, 15/22 patients in the pcV group yielded one or more positive cultures for GAS, all of the same T-type as in the original throat culture, as compared to 3/26 in the clindamycin group (p < 0.001). All three cases in the clindamycin group were due to a new T-type and thus were re-infections. In the pcV group, owing to repeated treatment failure, 12/22 patients were switched to treatment with clindamycin within the 3-month period following the second treatment. During the remainder of the 1-year follow-up period, sporadic cases of GAS-positive throat cultures occurred in both groups, but there was no significant difference in frequency between the two groups. It is concluded that, in patients with GAS pharyngotonsillitis and failure after pcV treatment, a 10-day course of clindamycin can protect the patient from recurrence for at least 3 months and might be an alternative to tonsillectomy.

Treatment failure in streptococcal pharyngotonsillitis. An attempt to identify penicillin tolerant Streptococcus pyogenes.

Penicillin tolerance in group A streptococci has been suggested to cause treatment failures in pharyngotonsillitis. In the present study, group A streptococci from patients with pharyngotonsillitis, who healed (n = 33) or failed (n = 25) on phenoxymethylpenicillin therapy for 10 days, as well as isolates obtained following the first (n = 25) and second (n = 7) failure were tested for penicillin tolerance by a plate-screening method. For most strains, the survival rate after a 6-h exposure of log-phase bacteria (10(4) CFU) to a phenoxymethylpenicillin concentration of 4 times the minimum inhibitory concentration (MIC) was below 0.1%. Five strains from cases of failure, exhibiting survival rates of 0.2-0.5%, were subjected to time killing kinetic tests with phenoxymethylpenicillin at 12 times the MIC. At 6 h each of the strains from failures showed survival rates below 0.03%. One single group A strain, previously selected in our laboratory, showed a survival rate of 0.4-1.2%, which was close to tolerance as defined. Four streptococcal strains, earlier reported as tolerant, showed survival rates of > 1% but were found to be group G. Penicillin tolerance does not significantly contribute to failures in penicillin therapy of group A streptococcal pharyngotonsillitis, but seems to be a common property of group C and G streptococci.

Clindamycin in persisting streptococcal pharyngotonsillitis after penicillin treatment.

239 patients with streptococcal pharyngotonsillitis completed treatment with phenoxymethyl penicillin 12.5 mg per kg body weight b.i.d. for 10 days. At examination after completing therapy, throat specimens from 53 patients (22%) yielded growth of group A streptococci of the same. T-type as the initial culture (bacterial treatment failure). 20 of these 53 (38%) had symptoms and signs of tonsillitis (clinical and bacterial treatment failure). 48 of the patients with bacterial failure were randomly allocated to phenoxymethyl penicillin or clindamycin in an open design; 22 of them received a second course of phenoxymethyl penicillin for 10 days and 26 were given clindamycin, 6.5 mg per kg body weight b.i.d. (children) or 300 mg t.i.d. (adults) for 10 days. After completing their treatment, 14 of 22 patients (64%) given phenoxymethyl penicillin harboured the same T-type as in the previous two cultures, while group A streptococci were not recovered from any of the 26 patients receiving clindamycin. In patients with clinical failure after phenoxymethyl penicillin treatment, a new course with this drug is not motivated. In that situation clindamycin seems to be an efficient choice.

Penicillin tolerance in group A streptococci and treatment failure in streptococcal tonsillitis.

Penicillin tolerance in Streptococcus pyogenes has been suggested as a possible cause of therapeutic failure in streptococcal phryngitis treated with penicillin. In 144 patients with acute group A streptococcal tonsillitis treated with phenoxymethyl penicillin 12.5 mg per kg body weight b.i.d. for 10 days the same T-type was recovered after treatment in 21%. The recovery rate was higher for non-tolerant strains, 23%, than for tolerant strains, 10% (p greater than 0.05). Of patients with a non-tolerant strain 17% had both clinical and bacterial treatment failure in comparison with 5% infected with a tolerant strain (p greater than 0.05). Reinfection with a new serotype occurred in altogether 3%. The present data did not indicate that penicillin tolerance in group A streptococci is of significance in acute tonsillitis treated with phenoxymethylpenicillin for 10 days.