# Clinical summary: chronic *Pseudomonas aeruginosa* in non-CF bronchiectasis

**Patient context:** 88-year-old man with bronchiectasis and chronic *P. aeruginosa* infection.  
**Isolates (as reported):**
- Strain A — susceptible to tobramycin and amikacin  
- Strain B — susceptible to meropenem  
- Both — intermediate to ciprofloxacin; caller also reported intermediate sensitivity involving ceftazidime (“restrazol/ceftazidime” on the call — confirm exact agent on the lab report)

**Purpose:** GP/clinic reference for long-term suppression strategy, nebulised regimens, exacerbation antibiotics, evidence, guidelines, and age-related cautions.  
**Not a substitute for respiratory specialist initiation and shared care.**

---

## 1. Optimal long-term treatment strategy (given this susceptibility)

**Preferred approach for chronic *P. aeruginosa* with frequent exacerbations:**

1. Optimise **airway clearance** (and treat reversible contributors).
2. Start **long-term inhaled (nebulised) antipseudomonal antibiotic** under respiratory specialist care.
3. Formally review response (exacerbation rate, sputum, tolerance) at about **3–6 months**, then at least **6-monthly**. Stop if ineffective or poorly tolerated.
4. **Do not use long-term oral ciprofloxacin** for suppression when isolates are intermediate — unpredictable efficacy, rapid resistance selection, and high fluoroquinolone toxicity risk at age 88.
5. Oral **macrolide** (e.g. azithromycin three times weekly) is an alternative if inhaled therapy is not tolerated, or as add-on if exacerbations remain frequent (after ECG/QTc, LFTs, and exclusion of NTM).

**How this susceptibility profile steers choice:**

| Finding | Implication |
|--------|-------------|
| Tobramycin-susceptible strain | Nebulised **tobramycin** is microbiologically reasonable (and often PBS-accessible in Australia). |
| Meropenem-susceptible strain | Reserve **IV meropenem** for moderate–severe **exacerbations**, not long-term outpatient suppression. |
| Intermediate ciprofloxacin | Avoid chronic fluoroquinolone suppression (oral or inhaled ciprofloxacin programmes). |
| Intermediate ceftazidime (if confirmed) | Do not rely on ceftazidime as sole empiric IV agent for severe exacerbations without specialist/micro input; consider based on full antibiogram (e.g. meropenem-susceptible strain). |

**Guideline-aligned first choices for suppression:**
- **BTS 2019:** inhaled **colistin** first-line; inhaled **gentamicin** second-line.  
- **Australia (practical):** specialist often chooses **PBS nebulised tobramycin** (cyclical) for access, or **continuous colistin** if available/preferred and renal/ototoxicity risk favours avoiding aminoglycosides.

---

## 2. Nebulised antibiotic options — regimens

### A. Colistimethate sodium (colistin) — guideline-preferred (BTS)

| Item | Detail |
|------|--------|
| **Indication** | Long-term suppression of chronic *P. aeruginosa* in non-CF bronchiectasis with frequent exacerbations (usually off-label for non-CF). |
| **Dose** | **1–2 million IU (MU) twice daily**, continuous (not month-on/month-off). Many protocols start at **1 MU BD**. |
| **Diluent** | Reconstitute with **0.9% sodium chloride** (plastic ampoules preferred for no-needle technique). Typical: **1 MU in ~2.5–3 mL**; **2 MU in ~4 mL**. Water for injection is an alternative where protocols allow. |
| **Mixing** | Add diluent to powder; **gently swirl/roll — do not shake** (frothing impairs nebulisation). Allow to stand briefly; solution may be slightly hazy. |
| **Nebuliser** | Jet nebuliser (e.g. **PARI LC Plus**, Sidestream) with suitable compressor, **or** **I-neb** Adaptive Aerosol Delivery (used in PROMIS / Promixin pathways). |
| **Order of therapies** | Bronchodilator → airway clearance / hypertonic saline (if used) → **antibiotic last**. Mouth rinse after. |
| **First dose** | **Supervised** (risk of bronchospasm); consider pre-dose bronchodilator and pre/post spirometry where feasible. |
| **Duration** | Long-term while beneficial; specialist review of efficacy/toxicity. Some services use alternate-month cycling with another inhaled agent — only if specified by the initiating clinician. |
| **AU note** | Colistin (e.g. Tadim) is often **off-label** for non-CF BE and may need hospital/specialist supply pathway. |

### B. Nebulised tobramycin — alternative when isolate is susceptible (often AU-practical)

| Item | Detail |
|------|--------|
| **Rationale here** | At least one strain **susceptible to tobramycin**; PBS Authority listing for proven *P. aeruginosa* often makes this the most accessible funded inhaled option in Australia. |
| **Dose** | **Tobramycin 300 mg / 5 mL** nebuliser solution **twice daily**. |
| **Cycle** | Typical CF-style cycle extrapolated to non-CF BE: **28 days on / 28 days off**, ongoing while beneficial. |
| **Nebuliser** | Dedicated jet nebuliser (commonly **PARI LC Plus** or equivalent); do not mix with other nebulised drugs in the same chamber unless the product information allows. |
| **Monitoring (esp. age 88)** | Baseline and periodic **renal function**; watch for **ototoxicity / vestibular** symptoms; supervised first doses for bronchospasm. Prefer **colistin or macrolide** if significant CKD or hearing impairment. |
| **Evidence note** | Supportive smaller RCTs (bacterial density ± hospitalisation benefit); exacerbation-reduction evidence is weaker than PROMIS for colistin. |

### C. Other inhaled agents (usually not first choice here)

- **Gentamicin** nebulised (~80 mg BD) — BTS second-line to colistin.  
- **Aztreonam** (AIR-BX) — not established; more adverse events.  
- **Inhaled ciprofloxacin** (ORBIT / RESPIRE programmes) — mixed phase 3 results, not marketed; **poor fit** with intermediate ciprofloxacin isolates.

---

## 3. Role of meropenem

**Meropenem is for exacerbations, not chronic outpatient suppression.**

| Use | Guidance |
|-----|----------|
| **When** | Moderate–severe exacerbation, failed oral options, inability to take oral therapy, or when susceptibility / severity favours an IV antipseudomonal β-lactam. |
| **Why relevant here** | One strain is **meropenem-susceptible** — useful IV choice for that isolate when IV therapy is needed. |
| **How** | Specialist/hospital-directed IV course (often ~14 days for *Pseudomonas* exacerbations per BTS/TSANZ-style practice); duration individualised. |
| **Not for** | Long-term home “suppression,” continuous outpatient IV without a clear plan, or replacement of inhaled maintenance therapy. |
| **Elderly** | Adjust for renal function; monitor for cytopenias, seizures risk at high doses/renal impairment, *C. difficile*. In frail elderly, β-lactam monotherapy is often preferred over adding systemic aminoglycoside unless multi-resistant organism or specialist advice says otherwise (TSANZ). |

After the IV course, resume / continue the **inhaled maintenance** strategy and airway clearance.

---

## 4. Key trials substantiating each approach

### Colistin — PROMIS-I and PROMIS-II  
*(Haworth et al., Lancet Respir Med 2024)*

| | PROMIS-I | PROMIS-II |
|--|----------|-----------|
| **Population** | Non-CF bronchiectasis, chronic *P. aeruginosa*, ≥2 exacerbations requiring oral antibiotics or ≥1 requiring IV in prior year | Same |
| **Intervention** | Colistimethate via **I-neb**, BD, 12 months | Same |
| **Primary endpoint** | Mean annual exacerbation rate | Same |
| **Main finding** | **0.58 vs 0.95** (rate ratio **0.61**, 95% CI 0.46–0.82, p=0.0010); fewer severe exacerbations; QoL improved | Overall **no difference** (0.89 vs 0.89); trial disrupted/terminated early due to COVID; pre-pandemic period more consistent with PROMIS-I |
| **Takeaway** | Strongest modern phase 3 support for nebulised colistin; supports guideline use despite PROMIS-II inconsistency. |

**Earlier:** Haworth et al., *AJRCCM* 2014 — colistin 1 MU BD via I-neb; primary time-to-exacerbation not met in ITT; benefit in adherent subgroup; reduced bacterial density.

### Inhaled ciprofloxacin — ORBIT-3 / ORBIT-4  
*(Haworth et al., Lancet Respir Med 2019)* — **poor fit for intermediate ciprofloxacin**

| | Detail |
|--|--------|
| **Drug** | Nebulised liposomal + free ciprofloxacin (ARD-3150), once daily, **28 on / 28 off** × 48 weeks |
| **Population** | Non-CF BE + chronic *P. aeruginosa* |
| **Primary** | Time to first pulmonary exacerbation |
| **ORBIT-4** | Median 230 vs 158 days, HR 0.72, p=0.032 |
| **ORBIT-3** | 214 vs 136 days, HR 0.99, p=0.97 (NS) |
| **Status** | Not approved/marketed; **not preferred** when isolates are ciprofloxacin-intermediate |

*(Related: RESPIRE-1/2 ciprofloxacin DPI — mixed results; not marketed.)*

### Aztreonam — AIR-BX1 / AIR-BX2  
*(Barker et al., Lancet Respir Med 2014)* — **failed to establish a role**

| | Detail |
|--|--------|
| **Regimen** | AZLI 75 mg TID, two cycles of 4 weeks on / 4 weeks off |
| **Primary** | QOL-B respiratory symptoms at 4 weeks |
| **AIR-BX1** | +0.8, p=0.68 (NS) |
| **AIR-BX2** | +4.6, p=0.011 but below clinically meaningful MID (~8); more AEs/discontinuations with AZLI |
| **Takeaway** | Not recommended as standard long-term therapy in non-CF BE. |

### Tobramycin nebulised in non-CF bronchiectasis

| Trial | Findings |
|-------|----------|
| **Barker 2000** (*AJRCCM*) | Tobramycin 300 mg BD × 28 days — significant ↓ sputum *P. aeruginosa* density; clinical improvement reported |
| **Drobnic 2005** (*Ann Pharmacother*) | 300 mg BD, cyclic — ↓ hospitalisations/hospital days and bacterial density; no clear reduction in exacerbation rate / FEV1 / QoL; bronchospasm in some |
| **Overall** | Supports microbiological effect and possible healthcare-use benefit; **weaker exacerbation-prevention evidence** than PROMIS colistin |

---

## 5. Guideline positions

| Guideline | Position relevant to this patient |
|-----------|-----------------------------------|
| **BTS 2019** (*Thorax* 2019;74 Suppl 1) | If ≥3 exacerbations/year and chronic *P. aeruginosa*: **inhaled colistin first (B)**; inhaled gentamicin second-line; macrolide as alternative or add-on. Eradication regimens for *new* growth differ from chronic suppression. Prophylaxis should be specialist-initiated; 6-monthly review. |
| **ERS (updated clinical practice guideline, Eur Respir J 2025)** | **Strong recommendation** for long-term inhaled antibiotics in chronic *P. aeruginosa* at high exacerbation risk (≥2 exacerbations/year **or** ≥1 severe **or** 1 exacerbation + severe daily symptoms). Conditional against routine long-term oral **non-macrolide** antibiotics. Define treatment period and reassess response. |
| **TSANZ 2023** (*Respirology* 2023;28:339–349) | Do **not** routinely use long-term inhaled antibiotics in *stable* disease. **Consider** inhaled antibiotics (aminoglycosides or colistin) in adults with *P. aeruginosa* and ≥3 exacerbations/year; specialist advice; individualise. |

---

## 6. Practical cautions — 88-year-old

1. **Nephrotoxicity / ototoxicity (tobramycin, gentamicin, systemic aminoglycosides):** check baseline eGFR/creatinine; recheck periodically; ask about hearing, tinnitus, imbalance. Prefer **colistin or macrolide** if significant renal impairment or known hearing loss.  
2. **Bronchospasm:** common with nebulised antibiotics — **first dose supervised**; pre-treat with bronchodilator if reactive; stop if severe.  
3. **Fluoroquinolones:** avoid long courses — tendon, CNS, QT, aortic, hypoglycaemia risks; intermediate MIC further argues against chronic cipro.  
4. **Meropenem IV:** renal dose adjustment; *C. difficile*; not a maintenance drug.  
5. **Macrolide fallback:** ECG for QTc; exclude NTM before long-term azithromycin; drug interactions.  
6. **Polypharmacy / cognition / dexterity:** assess ability to reconstitute and nebulise BD; involve carers/pharmacy support; simpler PBS tobramycin ampoules may be easier than reconstituting colistin powder for some patients.  
7. **Monitoring plan:** sputum culture periodically (in vitro resistance may not equal clinical failure for inhaled agents); exacerbation count; weight/nutrition; vaccine status; 6-monthly specialist review while on long-term inhaled antibiotics.

---

## One-page action plan for this case

1. Confirm full lab report (exact MICs; clarify “restrazol/ceftazidime”).  
2. Refer / confirm with respiratory: start **long-term nebulised suppression** + airway clearance.  
3. Agent choice:  
   - **Colistin 1 MU BD continuous** (dilute in 0.9% NaCl; jet nebuliser or I-neb; supervised first dose), **or**  
   - **Tobramycin 300 mg BD, 28 on / 28 off** if PBS access and renal/hearing acceptable (isolate susceptible).  
4. **Do not** use long-term oral ciprofloxacin for suppression.  
5. For **exacerbations** needing IV therapy: use susceptibility-guided IV agents (e.g. **meropenem** for the meropenem-susceptible strain); then return to inhaled maintenance.  
6. If inhaled therapy fails/intolerable: consider **azithromycin** thrice weekly after QTc/NTM screen.  
7. Review efficacy and toxicity at **3–6 months**, then at least **6-monthly**.

---

## Core citations

- ERS adult bronchiectasis CPG, *Eur Respir J* 2025 (doi:10.1183/13993003.01126-2025)  
- BTS Guideline for bronchiectasis in adults, *Thorax* 2019;74(Suppl 1)  
- TSANZ position statement, *Respirology* 2023;28:339–349  
- Haworth et al. PROMIS-I/II, *Lancet Respir Med* 2024  
- Haworth et al. colistin I-neb, *AJRCCM* 2014;189:975–982  
- Haworth et al. ORBIT-3/4, *Lancet Respir Med* 2019  
- Barker et al. AIR-BX1/2, *Lancet Respir Med* 2014  
- Barker et al. nebulised tobramycin, *AJRCCM* 2000  
- Drobnic et al. nebulised tobramycin, *Ann Pharmacother* 2005  
- UK shared-care / APC colistin nebulisation protocols (Colomycin reconstitution practice)

*Prepared for clinic reference. Verify local PBS/hospital formulary and specialist protocol before prescribing.*