Translating Evidence into Everyday Care

Introduction

I still remember the clinic in 2010 when a patient with non-CF bronchiectasis told me, “Doctor, I measure my life in antibiotic courses, not in months.” That single sentence catalysed one of the most satisfying pieces of research I have ever been involved in. Working as a respiratory consultant at Whiston Hospital (St Helens & Knowsley Teaching Hospitals NHS Trust), we set out to see whether a simple, inexpensive oral macrolide—azithromycin—could become a disease-modifying therapy for patients trapped in a vicious cycle of infection, inflammation and lung damage.

The Problem We Faced

Bronchiectasis unrelated to cystic fibrosis (non-CF BE) affects roughly 1 in 1,000 adults in the UK, but its impact is disproportionately large: chronic cough, daily sputum, recurrent infective exacerbations, hospital admissions, accelerated decline in lung function and a measurable fall in quality of life. Each flare means more antibiotics, more corticosteroids, more time off work and, most importantly, further irreversible airway injury.

The British Thoracic Society (BTS) bronchiectasis statement in 2010 acknowledged that macrolides possessed “disease-modifying activity” but stopped short of a firm recommendation because robust pragmatic UK data were lacking. We decided to generate that data ourselves.

How We Did the Study

Over 12 months we prospectively captured every patient in our service who had been placed on maintenance azithromycin, usually after ≥3 exacerbations needing rescue antibiotics in the preceding year. We recorded dose, duration, exacerbations, rescue antibiotic use, adverse events and microbiology. In total 137 patients were analysed, of whom 90 had classical non-CF bronchiectasis (CT-confirmed); the remainder had chronic suppurative lung disease such as persistent post-infective bronchiolitis, primary ciliary dyskinesia and immune-deficiency-related lung disease.

Key findings that swayed our practice:

• Exacerbation-free interval more than tripled: Mean time to next exacerbation without azithromycin was 64 days (range 30–360) versus 304.5 days (range 14–582) on azithromycin (p<0.001).
• 48 patients (35%) required zero rescue antibiotics after initiation.
• Dose matters: 250 mg once daily outperformed 500 mg three times weekly and caused fewer gastrointestinal side-effects; all treatment failures due to side-effects occurred in the higher pulsed-dose group.
• Withdrawal = rebound: When azithromycin was stopped electively (usually at patient request or because “they felt better”), the majority experienced a prompt return to pre-treatment flare frequency. We no longer discontinue unless there is a compelling reason.
• Microbiological safety signal: No increase in atypical mycobacterial isolation or macrolide-resistant pneumococci during the observation period. (Longer surveillance is still warranted.)

The abstract was accepted for oral presentation at the European Respiratory Society Congress in Amsterdam, September 2011. Walking off that stage, I suspected our local protocol would never be the same—and it hasn’t been.

Translating Evidence into Everyday Care

Within six months we had embedded the following pragmatic pathway:

1. Confirm structural disease with high-resolution CT.
2. Optimise airway clearance and treat reversible exacerbating factors (immunoglobulin replacement, reflux control, vaccination).
3. If ≥3 confirmed exacerbations per year, offer azithromycin 250 mg PO daily, after baseline ECG (QTc <450 ms) and LFT screen.
4. Review at 3 months: if ≥50% reduction in exacerbations or patient-reported benefit, continue. If not, stop.
5. Re-evaluate annually; monitor one sputum sample every 6–12 months for atypical mycobacteria and resistant flora.

Patients appreciate the clarity: “We have a plan, not just tablets.”

What Has Happened Since 2011?

The field has moved rapidly, largely in the direction our data had pointed:

• 2015 Australian BLESS trial (n=117) showed 250 mg azithromycin three times weekly reduced exacerbations by 62% over 12 months, with modest hearing loss incidence (5%).
• 2018 British Thoracic Society Guideline for Bronchiectasis upgraded its stance: “Consider long-term macrolide therapy in adults with bronchiectasis who have ≥3 exacerbations per year despite standard care.” Daily or three-times-weekly dosing is acceptable.
• 2019 Cochrane systematic review (11 trials, 1,249 patients) concluded macrolides cut exacerbation risk by ~40% and modestly improve quality-of-life scores.
• 2020 European Respiratory Society (ERS) / Multisociety Guideline recommends azithromycin (250 mg daily or 500 mg three times weekly) as first-choice macrolide for adults with frequent exacerbations, provided baseline ECG and audiology are documented and surveillance cultures are arranged.
• 2022 NICE bronchiectasis evidence update echoed the ERS position, encouraging shared-decision discussions and noting cost-effectiveness (£1,700 per quality-adjusted life-year).

In parallel, real-world safety databases have flagged a small but measurable rise in macrolide-resistant Streptococcus pneumoniae and occasional non-tuberculous mycobacteria (NTM) isolation. Most centres now advocate:

• Sputum acid-fast bacilli culture before initiation.
• Six-monthly audiometry if available (formally recommended in Australia).
• Prompt reassessment if new infiltrates or cavitary change appear on follow-up imaging.

Practical Take-Aways for Clinicians

• Patient selection: Target those with recurrent infective flares (≥3 per year) or rapid lung-function decline despite optimal airway clearance.
• Dose choice: 250 mg daily is effective, generally well tolerated and cheaper than intermittent high-dose schedules. I rarely start with 500 mg three times weekly unless gastrointestinal intolerance dictates.
• Baseline work-up: HRCT, spirometry, sputum culture (including AFB), serum IgG/A/M, IgE and Aspergillus precipitins, ECG. Correct vitamin-D deficiency; it modulates innate immunity.
• Conversations about risk: Hearing disturbance (<5%), transient nausea or loose stools (10%), QT prolongation (rare but avoid concomitant QT-prolonging drugs). Re-emphasise NTM surveillance.
• Review early and often: At 3 months, if no meaningful clinical benefit, stop. Benefit usually plateaus by 6–12 months; thereafter review every 6–12 months.
• Don’t stop suddenly: Tapering is unnecessary, but monitor for rebound flares; counsel patients to seek early review if symptoms return.

What About Children or Other Suppurative Diseases?

Paediatric data are encouraging but less robust; most UK centres extrapolate adult evidence cautiously. In primary ciliary dyskinesia, azithromycin is now standard care to preserve lung function. In persistent post-infective bronchiolitis and immune-deficiency lung disease, our series—and subsequent reports—suggest similar benefits, although formal trials are still needed.

Looking Forward

Our 2011 cohort study was practice-changing for us, yet questions remain:

• Can biomarkers (calprotectin, neutrophil elastase activity, genomic signatures) predict super-responders?
• Would dual immunomodulatory agents (macrolide plus low-dose doxycycline or inhaled statin) synergise?
• Could ultra-long-acting macrolides (e.g., solithromycin) deliver the same benefit with once-weekly dosing?
• How do we balance population antimicrobial stewardship with individual patient gain?

We are currently piloting a remote monitoring platform where patients report daily symptom scores and weekly spirometry via smartphone; machine-learning algorithms flag early exacerbation patterns, allowing “treat-early” rather than “rescue-late” paradigms. Early data mirror the azithromycin story—simple interventions, rigorously applied, trump flashy technology without evidence.

Conclusion

I began this journey trying to give my patients fewer “antibiotic birthdays.” Azithromycin 250 mg daily delivered that for many, and successive multicentre trials have since legitimised what we observed on the ground. Used judiciously—with proper patient selection, baseline checks and ongoing surveillance—maintenance azithromycin is no longer novel; it is a cornerstone of modern bronchiectasis care. Yet each prescription still reminds me of that patient who measured life in antibiotic courses. Today, when I see her in follow-up, she measures it in holidays, grandchildren and, most pleasingly, in years.