Use of newer macrolides in pertussis
| Citation | Study group | Level of evidence | Outcome | Key results | Comments |
|---|---|---|---|---|---|
| Langley et al (2004) | 477 children (6 mth–16 y) with clinical symptoms of pertussis were randomised to receive either azithromycin (10 mg/kg on day 1 followed by 5 mg/kg once a day for 4 more days) or erythromycin estolate (40 mg/kg/day in 3 divided doses for 10 days) | Multicentre randomised controlled trial (level 1b) | Bacteriologic eradication: Negative cultures at the end of treatment | Azithromycin group: 53/53 v erythromycin group: 53/53 (eradication 100%. 95% CI 93.3 –100) | Group assignment not blinded after randomisation Positive Nasopharyngeal (NP) cultures for pertussis were found in 58/239 (azithromycin group) and in 56/238 (erythromycin group) Post treatment cultures not available on all subjects |
| Relapse: Positive cultures a week after end of treatment | Azithromycin group: 0/51 (0%; 95% CI: 0–7.0) v erythromycin group: 0/53 (0%; 95% CI: 0–6.7) | ||||
| Adverse GI events: (parent completed diary) | Azithromycin v erythromycin groups: Overall incidence of GI side effects was 18.8% v 41.2%, NNT = 4.46 | ||||
| Nausea (2.9% v 8.4%; 95% CI: −8.9% to −2.0%; NNT 18.1), vomiting (5.0% v 13.0%; 95% CI: −4.9% to −1.4% ; NNT = 12.5) | |||||
| Diarrhoea (7.1% v 11.8%; 95% CI: −9.0% to −0.3%; NNT = 21.2) | |||||
| No serious adverse events were recorded in either group | |||||
| Compliance: (inspection of medication containers) | 90% in the azithromycin group v 55% in the erythromycin group | ||||
| Lebel and Mehra (2001) | 153 children (<16 y) with clinical symptoms of pertussis received either clarithromycin 7.5 mg/kg/dose twice a day for 7 days (n = 76) or erythromycin (13.3 mg/kg/dose three times a day for 14 days (n = 77) | Prospective randomised single blind trial. (level 1b) | Bacteriologic eradication: Negative post treatment cultures | Negative post treatment cultures recorded in 31/31 on clarithromycin (100%; 95% CI: 88.8–100) v 22/23 with erythromycin (96%; 95% CI: 78.1–99.9%) | 35/76 in the clarithromycin group and 27/77 in the erythromycin group had positive cultures of B pertussis |
| 90% of subjects were appropriately immunised against pertussis Post treatment cultures not available on all subjects | |||||
| Adverse GI events | Seen in 45% of those on Clarithromycin Vs 62% of those on Erythromycin. (p = 0.035; NNT = 5.8) | ||||
| Compliance: (inspection of medication containers) | Mean percent of drug taken by the Clarithromycin group was 98.5% Vs 88.8% by the Erythromycin group (p<0.001) | ||||
| Pichichero et al (2003) | 34 subjects (29 culture positive and 5 pcr positive) were all given azithromycin (10 mg/kg on day1 followed by 5 mg/kg once a day for 4 more days) | Prospective, open labelled, non comparative trial (level 2b) | Bacteriologic eradication: Negative cultures/PCR at days 2–3 of treatment and days 14–21 post treatment | 1/34 (3%) had positive cultures at 2–3 days on treatment Bacteriologic eradication 97% at 2–3 days and 100% by 14–21 days after starting treatment | Study group heterogeneous. No subset analysis available 5 of the 34 subjects were adults (parents of children), 12 were between 10–20 y of age and 17 were from the age of 6 mth to 10 y |
| Adverse events | No serious adverse events recorded 10% patients had GI side effects (nausea, loose stools, and abdominal discomfort) | ||||
| Compliance | Reported 100% | ||||
| Bace et al (1999) | 37 subjects with culture proven pertussis. Mean age of patients 7.5 mth (range 2–18 mth). 60% of them were not immunised against pertussis. All received azithromycin. Dose: 10 mg/kg on day1 followed by 5 mg/kg once a day for 4 more days (n = 17) v 10 mg/kg once daily for 3 days only (n = 20) | Prospective, open labelled, non-comparative trial (level 2b) | Bacteriologic eradication: Negative cultures on day 7, 14 after commencement of treatment. | Positive cultures on day 7: 2/19 in the 3 day group (10.5%) v 0/16 in the 5 day group. 100% bacterial eradication was seen on day 14 (0/16 v 0/16) in both groups | Allocation criteria to either regime unclear |
| Relapse: Positive cultures on day 21 after start of treatment | 1/14 patients on the 3 day course (7.1%). None on the 5 day course | Relationship of transaminitis to dose used unclear | |||
| Adverse events | Transient increase in liver enzyme ALT noted in up to 20.6% of all subjects | ||||
| Aoyama et al (1996) | 17 patients (0– 13 y) with culture proven pertussis 8/17 received azithromycin (10 mg/kg once a day for 5 days) while 9/17 received clarithromycin (10 mg/kg/day in two divided doses for 7 days). Each study subject was matched with two historical controls treated with erythromycin (40–50 mg/kg/day in three divided doses for 14 days) 58.8% of subjects were not immunised against pertussis | Two separate open labelled trials using historical controls (level 4) | Bacterial eradication: negative culture on 1 week after treatment | 8/8 with azithromycin (100%, 95% CI: 68.8–100%) v 13/16 (81%, 95% CI: 54.4–96%) among controls given erythromycin 9/9 with clarithromycin (100%, 95% CI: 71.1–100%) v 16/18 (88.8%, 95% CI: 65.3–98.6%) among controls given erythromycin | Historical controls Allocation criteria to medications unclear Small study group |
| Relapse: positive culture at 2 weeks after treatment | None in either study or control groups | ||||