Bell's palsy - the effect of prednisolone and/or valaciclovir versus placebo in relation to baseline severity in a randomised controlled trial.

OBJECTIVES: To evaluate the treatment effect of prednisolone and/or valaciclovir in Bell's palsy patients with different baseline severity of palsy. DESIGN: Patient data were collected from the Scandinavian Bell's Palsy Study, a prospective, randomised, double-blind, placebo-controlled, multi-centre trial. SETTING: Sixteen otorhinolaryngological centres in Sweden and one in Finland. PARTICIPANTS: Altogether, 829 patients aged 18-75 years were treated within 72 h of palsy onset. Patients were randomly assigned to treatment with prednisolone plus placebo (n = 210), valaciclovir plus placebo (n = 207), prednisolone plus valaciclovir (n = 206), placebo plus placebo (n = 206). Follow-up was 12 months. MAIN OUTCOME MEASURES: Facial function was assessed using the Sunnybrook grading scale at baseline and at 12 months. Complete recovery was defined as Sunnybrook score = 100. RESULTS: All patients, regardless of baseline severity, showed significantly higher complete recovery rates if treated with prednisolone compared with no prednisolone. In patients with severe palsy, recovery at 12 months was 51% with prednisolone treatment versus 31% without prednisolone (P = 0.02). Corresponding results were 68%versus 51% (P = 0.004) for moderate, and 83%versus 73% (P = 0.02) for mild palsy. In patient groups with moderate and mild palsy at baseline, significantly fewer prednisolone-treated patients had synkinesis at 12 months (P = 0.04 and P < 0.0001, respectively). For patients with severe palsy at baseline, prednisolone versus no prednisolone made no significant difference regarding synkinesis at 12 months. Valaciclovir did not add any significant effect to prednisolone regarding recovery rate or synkinesis at 12 months. CONCLUSION: Prednisolone treatment resulted in higher complete recovery rates, regardless of severity at baseline. Prednisolone treatment should be considered in all patients irrespective of degree of palsy.

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.

Persistence of Lactobacillus plantarum DSM 9843 on human tonsillar surface after oral administration in fermented oatmeal gruel. A pilot study.

The occurrence of Lactobacillus plantarum DSM 9843 on tonsillar scrapings was studied after single-dose administration. Six healthy volunteers gargled 100 ml of fermented oatmeal gruel containing 2 x 10(11) colony forming units (cfu) of Lb. plantarum DSM 9843 for 2 min and then swallowed it. Two healthy volunteers drank 50 ml fermented oatmeal gruel (containing 1 x 10(11) cfu of Lb. plantarum DSM 9843) mixed with 50 ml fruit juice, and in another experiment, 5 ml fermented oatmeal gruel (containing 1 x 10(10) cfu of Lb. plantarum DSM 9843) mixed with 95 ml fruit juice. Lb. plantarum DSM 9843 were found in tonsillar scrapings 4-8 h after intake of 2 x 10(11) cfu, for 5-8 h after intake of 1 x 10(11) cfu, and finally up to 4 h after intake of 1 x 10(10) cfu. On electron microscopy micrographs, short rod-shaped bacteria were visible 1 h after intake of the fermented oatmeal gruel, but not 2 h after intake. The results suggest that Lb. plantarum DSM 9843 possess an ability to adhere to tonsillar cells.

Tonsillar microbial flora: comparison of recurrent tonsillitis and normal tonsils.

Tonsillar microbial flora was studied in cultures of tonsillar core specimens from 34 patients tonsillectomized due to recurrent group A streptococcal pharyngotonsillitis (n = 17) or sleep apnoea (n = 17). Patients in the sleep apnoea subgroup, who had no history of recurrent tonsillitis and manifested no tonsillar hypertrophy at ENT examination, served as controls. Tonsillar core specimens were cultured for semi-quantitative estimation of growth of aerobic, anaerobic and facultative organisms. The recurrent tonsillitis and apnoea subgroups did not differ significantly in the mean number of isolates per patient, either of aerobic spp. (3.8 vs. 4.3) or anaerobic spp. (5.2 vs. 4.7). Nor did the two subgroups differ significantly in the proportion of patients whose specimens manifested beta-lactamase producers (71% vs. 59%), in the isolation frequency of viridans (alpha) streptococci, or in the occurrence of semi-quantitative growth estimates of 3-4+ for aerobic, anaerobic or beta-lactamase-producing spp. Thus, the study provided no support for the hypothesis that inactivation of penicillin V by beta-lactamase-producing bacteria in oral or throat flora, or the eradication of viridans streptococci with their GAS-inhibitory capacity, is an important factor with regard to recurrent group A streptococcal tonsillitis. Other possible explanations, such as poor antibiotic penetration at the site of infection, are discussed.

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.

Penetration of penicillin V to tonsillar surface fluid in healthy individuals and in patients with acute tonsillitis.

In the treatment of group A streptococcal tonsillitis, as the bacteria are located on the epithelial surface, an important determinant of outcome is the concentration of penicillin in extracellular tonsillar surface fluid. Accordingly, we investigated the concentration of penicillin in serum, and penetration to tonsillar surface fluid and saliva in nine patients with acute group A streptococcal tonsillitis and in nine healthy controls. Among the healthy subjects, despite high serum penicillin concentrations (mean, 2.04 micrograms/ml), there was no penetration to tonsillar surface fluid or to saliva, whereas erythromycin penetrated to tonsillar surface fluid in 3/6 cases. Of the nine patients with acute tonsillitis, on the first day of treatment eight manifested high concentrations of penicillin in tonsillar surface fluid (mean, 0.34 micrograms/ml--i.e. well above the minimal inhibitory concentration (MIC) for group A streptococci), but penetration to saliva was found in only two patients. On the tenth day of treatment, penicillin was not present in the saliva of any of the patients and was present in the tonsillar surface fluid of only one. The results suggest that measurable concentrations of penicillin in tonsillar surface fluid can only be obtained in the presence of inflammation with fluid exudation through the tonsillar epithelium.

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.

High recovery of Haemophilus influenzae and group A streptococci in recurrent tonsillar infection or hypertrophy as compared with normal tonsils.

One hundred and twenty-six patients who underwent tonsillectomy because of recurrent acute tonsillitis, tonsillar hypertrophy or sleep apnoea were evaluated by tonsillar core culturing. The sleep apnoea patients served as controls, since none of them had tonsillar hypertrophy at ENT examination or any history of recurrent acute tonsillitis, and thus their tonsillar core flora could be regarded as normal. The isolation rate of H. influenzae was much lower among sleep apnoea controls (2.7 per cent) than among either the patients with recurrent acute tonsillitis (20.3 per cent) or those with tonsillar hypertrophy (36.7 per cent) (p less than 0.05), as was that of group A streptococci, 5.4 per cent versus 16.9 and 20 per cent, respectively (though the latter differences were not statistically significant). The isolation frequencies of B. catarrhalis, pneumococci, group C and G streptococci did not differ between the three groups. The high tonsillar core recovery rates of H. influenzae and group A streptococci both in patients with recurrent acute tonsillitis and in those with tonsillar hypertrophy, as compared with normal controls, suggests the possible involvement of these bacteria in both conditions.

Protective effect of heterologous gram-positive vaccine against lethal upper respiratory tract infection with type M50 group A streptococci in mice.

Type M50 group A streptococci are exceptional for their virulence in mice. However, intranasal (i.n.) vaccination with heat-killed group A streptococci, either of type M50 or M55, or an M12 strain deficient in M-protein, protected mice against i.n. challenge with M50 streptococci (82, 88 and 83% survival, respectively). Significant resistance against M50 streptococci was also noted by i.n. application of heat-killed Lactobacillus fermenti (81% survival) as well as two strains of pneumococci (50 and 79% survival). In contrast, no protective effect was obtained using heat-killed trypsin-treated M55 streptococci. Nor did vaccination with Escherichia coli and Pseudomonas aeruginosa induce protection against type M50. Thus, M protein was not required for immunity against type M50. The results call for a revision of the hitherto accepted view that M proteins are the only candidates for mucosal vaccines against group A streptococci.

Colonization by Haemophilus influenzae and group A streptococci in recurrent acute tonsillitis and in tonsillar hypertrophy.

One hundred patients subjected to tonsillectomy because of recurrent acute tonsillitis or tonsillar hypertrophy were evaluated bacteriologically both with ordinary throat culturing and cultures from tonsillar cores. In 26% of the patients H. influenzae was isolated and in 20% beta-haemolytic group A streptococci. Growth of B. catarrhalis was obtained in 10% and group C-, group G streptococci or pneumococci in less than 5% each. None of the group A streptococcal strains proved tolerant to penicillin. A much higher isolation rate of H. influenzae was found in cultures obtained from tonsillar core tissue (23%) than from ordinary throat cultures (2%). This was also the fact, though to a lower extent, regarding group A streptococci. H. influenzae and group A streptococci were isolated as often in patients with tonsillar hypertrophy as in patients suffering from recurrent acute tonsillitis, suggesting a role of these bacteria in both conditions.

Antibody response to pneumococcal vaccination as related to tonsillectomy.

In each of twelve matched pairs of patients undergoing tonsillectomy one patient was vaccinated with Pneumovax, a pneumococcal polysaccharide antigen, prior to tonsillectomy, the other patient being vaccinated after tonsillectomy. Sera were tested for antibody response to three different pneumococcal types of IgG, IgA and IgM classes. The patients with intact tonsils at vaccination did not develop higher antibody response than did those tonsillectomised prior to vaccination. On the contrary, in the case of pneumococcus type 6A, the IgM antibody response in tonsillectomised patients was significantly higher than that in patients with intact tonsils at vaccination (p = 0.021). Thus, the present study did not support the notion that tonsillectomy affects antibody response against pneumococcal vaccination. The palatine tonsils' role as an immunologically reactive organ is also discussed.

Clinical and laboratory findings in patients with acute tonsillitis.

In 82 patients with acute tonsillitis studied, beta-hemolytic group A streptococci were isolated from 30 (37%), and group C or G streptococci from 12 (15%). In the 40 patients with non-streptococcal tonsillitis there was a significantly higher isolation rate of pneumococci, H. influenzae and/or B. catarrhalis, as compared with those with beta-hemolytic streptococci. Patients were classified regarding clinical status according to standardized criteria as severe, moderate, or mild. The patients with group A streptococcal tonsillitis were significantly more often classified clinically as 'severe' and had significantly shorter duration of symptoms before seeking medical care, as compared with those with non-streptococcal tonsillitis. Significant increases in white blood cell count and in anti-DNase B were found in the patients with group A streptococcal tonsillitis, whereas their antistreptolysin O levels did not increase significantly. C-reactive protein concentrations were consistently higher in the patients with group A streptococcal tonsillitis. No evidence of polyclonal beta-lymphocyte stimulation was found when measuring antibodies against pneumococci and group B streptococci. The findings show clinical and simple laboratory tests to be useful aids in distinguishing group A streptococcal tonsillitis from non-streptococcal tonsillitis, and that other bacteria may be involved in non-streptococcal tonsillitis.