Respiratory tract infections in primary care - aspects of diagnosis and treatment

Sammanfattning: Background Primary health care is accountable for most of the antibiotic prescriptions in humans. In Sweden, most of these antibiotics are used for respiratory tract infections, and pharyngotonsillitis (acute sore throat) is the single respiratory tract infection that leads to most antibiotic prescriptions. The first line treatment for pharyngotonsillitis with presence of group A streptococci is penicillin V 1000 mg three times daily for 10 days. Though, effectiveness of shorter penicillin V treatment for pharyngotonsillitis is unknown. Antibiotic treatment can induce ecological changes in the intestinal microbiota, including emergence of antimicrobial resistance. Previous studies on side-effects from penicillin V therapy, including antimicrobial resistance in the intestinal microbiota, are lacking. To restrict the use of antibiotics, two point-of-care tests have become very popular in Swedish primary care: the C reactive protein (CRP) and rapid antigen detection test for group A streptococci (GAS). They have capacity to restrict unnecessary use of antibiotics in primary care, when used according to the guidelines. However, concentration of CRP in primary care patients with influenza-like illness has not been investigated earlier, and the reliability of rapid tests for GAS after recent penicillin V treatment for pharyngotonsillitis has been questioned. Aim The overall aim of the thesis was to contribute to a safe reduction in antibiotic use and to investigate the benefit of two popular near-patient tests in patients with common RTIs. We set out to: i) determine if a shorter but more intense penicillin V treatment could give a clinical cure rate of GAS pharyngotonsillitis comparable to the currently recommended treatment; ii) compare the presence of GAS in rapid antigen detection test (RADT) and throat culture among patients recently treated with penicillin V for pharyngotonsillitis; iii) evaluate penicillin V effects on the microbiota with a focus on the emergence of β-lactam resistance; iv) examine if CRP can predict presence of influenza A in primary care patients presenting with influenza-like symptoms. Methods The first paper was a randomised controlled non-inferiority trial, comparing penicillin V 800 mg x 4 for 5 days to 1000 mg x 3 for 10 days. The second paper was an observational study comparing the results from RADT and culture for GAS at a follow-up visit within 21 days from inclusion. In the third paper we explored some clinically relevant changes in cultures of faecal swab samples from patients, before and after pencillin V treatment for pharyngotonsillitis. The fourth paper was a cross-sectional study in patients with an influenza-like illness for less than 72 h. The main outcome measures were capillary blood CRP and PCR test for detection of influenza A or B in the upper respiratory tract. Results and conclusions We found penicillin V for 5 days to be non-inferior to the 10-day treatment regarding clinical cure. Hence, it is possible to maintain the clinical effectiveness with a shorter penicillin V treatment for GAS pharyngotonsillitis. The most reported side-effects from treatment were diarrhoea and vulvovaginal symptoms. With the 10-day treatment 35% of patients reported gastrointestinal side-effects and 25% of female patients reported vulvovaginal symptoms. The incidence of these side-effects was lower with the 5-day treatment. We found penicillin V treatment to induce several alterations in the faecal microbiota that are generally considered signs of ecological disturbance, including a significant increase of resistance towards ampicillin and third generation cephalosporins. These findings emphasise the importance to restrict the use of penicillin V. Further, we found no significant difference between the results of RADT and throat culture for GAS after recent penicillin V treatment for pharyngotonsillitis. Thus, we conclude that RADT for GAS is reliable also after recent penicillin V treatment. Finally, we found that the CRP concentrations in patients with influenza-like illness of different confirmed aetiology had a great overlap. We found no association between CRP and confirmed influenza A. We conclude that the CRP concentration cannot predict influenza A in patients with influenza-like illness. The results of this thesis is relevant in other primary care settings. It may influence the future treatment recommendation for pharyngotonsillitis and the clinical use of two popular rapid tests. The demonstrated ecological disturbances in the microbiota from penicillin V treatment ought to raise awareness of the risks from treatment and may guide the design of future studies in the field.