How is long-term azithromycin being used by respiratory physicians in Australia?


By Sunalie Silva

15 Feb 2021

Long-term, low-dose azithromycin is effective but underused in patients with persistent asthma and other obstructive airway disease (OAD), according to findings from a study of real-world prescribing patterns of the macrolide in Australia.

Investigators from Hunter Medical Research Institute (HMRI) in NSW who carried out the evaluation said most patients responded positively to the treatment, and there was a significant reduction in the proportions of patients requiring emergency department visits (48% versus 32%; p<0.001) and hospital admissions (35% versus 31%; p<0.001) after starting azithromycin.

The findings are based on the audit of 91 patient records from two hospitals. The most common therapeutic regimen was 250mg daily for more than one year (73%),  with less use of a 500mg thrice weekly regimen (18%).

Patients were older adults, not current smokers and had chronic airway disease typically with persistent asthma and often in combination with another airway disease such as COPD or bronchiectasis.  Patients often reported bothersome chronic cough and/or sputum with abnormal chest radiology.

The study investigators said the findings provided a case definition for patients receiving long-term low-dose azithromycin who note that, despite reported efficacy, an optimal treatment regimen of azithromycin in OADs had not yet been established.

Optimal dosage regimen

In an interview with the limbic, lead author Dr Dennis Thomas, post doctoral fellow at HMRI, said it appeared the macrolide was not being prescribed at optimal doses and was also underused, given that most patients responded positively to the treatment, and healthcare utilisation reduced significantly after starting azithromycin.

“In our current study we found that most people were using 250mg daily but in my opinion the most promising investigated regimen is actually 500mg thrice weekly for a minimum duration of six months, based on our experience and other previous studies  – the guidelines also recommend the regimen as well,” he said

One reason the drug may be underused was fear of antimicrobial resistance (AMR), Dr Thomas suggested.

“The potential for AMR is an ongoing concern for any antibiotic use and that might be one of the reasons for the under use of azithromycin we’re currently seeing here.”

“However previous work conducted by our team found that although azithromycin increased macrolide resistance there was no increase in systemic infection – in fact it reduced respiratory infection. So we need to further investigate the clinical implications of macrolide resistance – whether there is any clinical implication and also if there is impact onto the community.”

Treatment withdrawal after attaining a stable therapeutic benefit or a certain period of treatment might help reduce the drug burden to the patient and AMR risk to the community, he added.

Meanwhile the study also identified some gaps in clinical practice. Although the guidelines recommended microbiological assessment of sputum, ECG before and after starting treatment and using validated tools such as ACQ and CAT15 to determine treatment effect, investigators said their findings suggested these assessments were not routinely practiced. 

“We found that only 32% of patients had an ECG carried out both before treatment initiation and at one month from treatment initiation. These may have been carried out and undocumented but it is important to highlight because there were a small number of patients in our study, which is consistent with other studies who experienced prolongation of QTc.”

Azithromycin-related adverse events were identified in seven participants: diarrhoea and gastrointestinal issues reported in fou4 patients while one case each of hepatitis, nausea and increased gamma GT reported.

The full paper can be found here.

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