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You are assessing a toddler who has presented with paroxysmal cough with a whoop and post-tussive vomiting. A clinical diagnosis of “whooping cough” is made and this is duly confirmed on pernasal swab cultures that reveal the growth of Bordetella pertussis.
From history, you note that he is allergic to penicillin and has been given erythromycin for a previous episode of tonsillo-pharyngitis. His mother recalls that he suffered severe abdominal pain when taking it and did not complete the course. You wonder whether newer macrolides such as azithromycin or clarithromycin could be effective alternatives to erythromycin for the treatment of pertussis.
Structured clinical question
In a child diagnosed with whooping cough [patient] are azithromycin or clarithromycin [intervention] compared with erythromyicin [comparison] as effective in eradicating infection with fewer side effects [outcome]?
Primary source: Medline via Pubmed using keywords Pertussis OR Whooping Cough and combining the search with Azithromycin, Clarithromycin separately. This was verified by an alternative search method using MeSH heading “Whooping Cough” and subheading “drug therapy” [MeSH]. Five relevant articles were found.
Secondary sources: Cochrane database and Best Bets. No further papers were identified.
See table 4.
Antimicrobials are usually administered when pertussis is suspected or confirmed. If the disease is already established (paroxysmal phase), antibiotics have little or no effect on the clinical course of the illness except to render the patient non-infectious to others. This is important, so as to limit the spread of infection especially to the unimmunised and young infants. A 10–14 day course of erythromycin is the long established treatment for whooping cough.1 It is known to reduce transmission and hasten clearance of B pertussis.3 However, gastrointestinal side effects seem quite limiting in a large proportion of patients treated with it.7 This may have a bearing in ensuring compliance. Newer macrolides—clarithromycin and azithromycin—are superior to erythromycin in terms of absorption, acid stability, and tissue penetration. They have longer half-lives, enabling less frequent dosing and shorter treatment courses.5 They are also known to have fewer side effects.
From the available evidence it can be seen that the newer macrolides are at least as effective as erythromycin in eradicating B pertussis infection. A significant reduction in adverse gastrointestinal side effects and a better compliance have been shown. No serious side effects have been observed with these agents so far. Transient elevation in alanine aminotransferase (ALT) has been shown in one study.3
Regarding prophylaxis, the current UK guideline is to administer a seven day course of erythromycin, if a clinically suspected or confirmed case of pertussis is identified. The aim is to protect those at risk from pertussis: infants, especially neonates; all household contacts who are unimmunised; and contacts who are 5 years or older if they did not receive a pre-school pertussis booster. There is no evidence of any benefit from chemoprophylaxis given more than 21 days from the date of onset of the primary case. Unimmunised or partially immunised cases and contacts should complete their course of vaccine.8 Clarithromycin and azithromycin are potential, but not proven alternatives to erythromycin for prophylaxis at present.
CLINICAL BOTTOM LINE
A five day course of azithromycin or a seven day course of clarithromycin is as effective as a 10–14 day course of erythromycin to eradicate B pertussis infection. (Grade A)
Azithromycin and clarithromycin have fewer gastrointestinal side effects than erythromycin. (Grade A)
Patient compliance is better on the newer macrolides compared to erythromycin. (Grade A)