Acute exacerbation of chronic obstructive pulmonary disease

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

on presentation

1st line – short-acting bronchodilator

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Give a short-acting beta-2 agonist (e.g., salbutamol) at an increased dose or frequency from the patient’s usual baseline treatment as first-line therapy.[1][88]

For a moderate to severe exacerbation, use a nebuliser driven on air (not oxygen).[88]
- This is to avoid worsening hypercapnia.[88]
- The driving gas for nebulised therapy should always be specified in the prescription.[88]
For a mild exacerbation, use a metered-dose inhaler (MDI) plus spacer.
People with severe dyspnoea with low inspiratory flow rates may have difficulty achieving proper technique and medication delivery from the MDI; a nebuliser may be easier for these patients to use.
You may see benefit from this initial treatment within 30 minutes.

During the COVID-19 pandemic, seek advice from a respiratory specialist and consult local guidelines before using a nebuliser.

There are currently differences of opinion between organisations in different countries on whether use of a nebuliser is an aerosol-generating procedure.
International guidelines from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend minimal use of nebulisers, advising that inhalers should ideally be used for drug delivery instead. GOLD acknowledges that nebulisers may be needed in critically ill patients with COVID-19 receiving ventilatory support. GOLD recommends using a mesh nebuliser (to keep the circuit intact and prevent virus transmission) if absolutely necessary to do so (e.g., in ventilated patients).[1] However, nebulisers are not considered to represent a significant infectious risk for COVID-19 according to Public Health England and the UK National Institute for Health and Care Excellence.[129][130]
For more detailed information on COVID-19 see our topic Coronavirus disease 2019 (COVID-19). Opens in new window

Practical tip

Observe patients while they use an MDI. It is common for patients to need advice and training on technique. If a patient is struggling to obtain the required dose, switch to a nebuliser.

Add a short-acting muscarinic antagonist (e.g., ipratropium) administered via a nebuliser if the initial dose of the short-acting beta-2 agonist does not provide sufficient and prompt benefit.[1][127]

Short-acting beta-2 agonists are typically favoured as a first-line option as they tend to have a more rapid effect than antimuscarinics.

Give ipratropium alone if the patient experiences adverse effects due to salbutamol (e.g., tremor, palpitations, headache, nausea, dizziness).

To avoid overdose, stop any long-acting muscarinic antagonist the patient may already be on for maintenance therapy (e.g., aclidinium, glycopyrronium, tiotropium, umeclidinium) while the short-acting muscarinic antagonist is given.

Continue the long-acting beta-2 agonist (the patient’s maintenance therapy) alongside the additional short-acting beta-2 agonist needed for recovery from the exacerbation.
Many patients are on a long-acting beta-2 agonist/long-acting muscarinic antagonist (with or without a corticosteroid) combination inhaler for maintenance therapy. If this is the case, stop the combination inhaler during the acute exacerbation.

Seek specialist advice on the optimal method of delivering bronchodilators (MDI or nebuliser) to adults with COPD exacerbation who are receiving mechanical ventilation via endotracheal tube.

There is insufficient evidence to recommend one route of delivery over the other.[131]

Primary options

salbutamol inhaled: (100 micrograms/dose inhaler) 2-10 puffs inhaled every 10-20 minutes or when required (each puff should be inhaled separately via a large volume spacer); 5 mg inhaled via nebuliser every 20-30 minutes or when required

salbutamol inhaled : (100 micrograms/dose inhaler) 2-10 puffs inhaled every 10-20 minutes or when required (each puff should be inhaled separately via a large volume spacer); 5 mg inhaled via nebuliser every 20-30 minutes or when required

and/or

ipratropium inhaled: 500 micrograms inhaled via nebuliser when required, may repeat dose until patient is stable (time interval between doses may be determined by physician), maximum 2 mg/day

ipratropium inhaled : 500 micrograms inhaled via nebuliser when required, may repeat dose until patient is stable (time interval between doses may be determined by physician), maximum 2 mg/day

ipratropium inhaled: 500 micrograms inhaled via nebuliser when required, may repeat dose until patient is stable (time interval between doses may be determined by physician), maximum 2 mg/day

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Show drug information for a patient with no comorbidities

Primary options

salbutamol inhaled

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

and/or

ipratropium inhaled

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

Plus – monitor comorbidities during hospital stay

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Consider – systemic corticosteroid

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Additional treatment recommended for SOME patients in selected patient group

Consider a systemic (oral or intravenous) corticosteroid.[1][88] Oral administration is preferred; however, some patients may require intravenous administration if they cannot tolerate oral therapy (e.g., if they are vomiting).

National Institute for Health and Care Excellence and Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend a 5-day treatment course.[1][88]
Latest evidence shows no benefit from prolonged therapy.[132] [ ]
Corticosteroids are associated with risk of pneumonia, sepsis, and death and should only be used in patients with significant exacerbations.[1]
Avoid use of a corticosteroid with a fluoroquinolone antibiotic, because co-administration could exacerbate fluoroquinolone-induced tendinitis and tendon rupture.[133]

Manage your patient’s diabetes when they are taking corticosteroids

Giving corticosteroids to someone with diabetes will worsen their glycaemic control, so test blood glucose four times a day (based on expert opinion).

Synthetic corticosteroids can cause hyperglycaemia by affecting carbohydrate metabolism and inducing insulin resistance.[153]
For patients with diabetes, use the same doses of corticosteroid as for patients without diabetes, but adjust diabetes medication, as their glycaemic control will get worse.
If hyperglycaemia does occur, follow your hospital protocol. The Joint British Diabetes Societies for Inpatient Care has produced an algorithm for this clinical scenario and a separate one for patients with diabetes who have COVID-19.[153]
- Aim for a target blood glucose of 6 to 10 mmol/L (108-180 mg/dL) in hospital inpatients in general, with an acceptable range of 6 to 12 mmol/L (108-216 mg/dL). The targets should be individualised. Certain groups are particularly at risk of hypoglycaemia (e.g., those living with frailty or receiving end-of-life care).
- If your patient has type 1 diabetes, check daily for ketones if their capillary blood glucose is >12 mmol/L (>216 mg/dL).[153]

When you taper the corticosteroid dose, glycaemic control will likely improve, which may require weaning of titrated diabetic medication back to the pre-corticosteroid regimen.[153] Communicate on a clear strategy for titration to the general practice team on discharge.

The duration of action for a particular corticosteroid will determine the period of effect on glycaemic control.
- Intravenous corticosteroids (e.g., hydrocortisone) typically have shorter half-lives, which means glycaemic control returns to pre-corticosteroid levels within 24 hours.
- Oral corticosteroids (e.g., prednisolone) may take a few days.

Monitor for psychiatric complications of corticosteroids

Corticosteroids are indicated as an immediate treatment in certain acute conditions, as well as some chronic conditions, but it is important to be aware that corticosteroids may have adverse psychiatric effects.

Although all patients should be monitored for these effects, the risk of depression, mania, panic disorder, or suicide during corticosteroid therapy has been reported to be higher in people who are already living with these conditions, but not consistently so.[154]

If the clinical situation allows:

Check previous response to corticosteroids
- Past incidence of psychiatric complications during corticosteroid therapy may increase the risk of recurrence in subsequent treatments.[154]
Consider referral for psychiatric advice on whether to offer prophylactic medication to reduce the risk of psychiatric adverse effects if a patient has a recent history of mood or cognitive disorder.[154]

Monitor for psychiatric adverse effects.

These may vary in severity and include among others:[155]
- Anxiety and insomnia
- Severe mood disorders, including manic states
- Cognitive impairment.
Effects seem to be dose-related and are more common with long-term regimens, long-acting formulations, and in older patients.[154] This also stands true for patients who have neuropsychiatric adverse effects related to discontinuing long-term corticosteroid therapy.[156]
Manic episodes and delirious states are the most common psychiatric adverse effects when starting corticosteroid treatment, whereas depression is most common during chronic therapy.[154][157]
Be mindful of a possible withdrawal reaction, which may present with weakness, fatigue, gastrointestinal symptoms, and delirium, as well as with psychiatric complications such as depression, when discontinuing corticosteroids.[156]

If your patient develops psychiatric complications related to corticosteroids, liaise with the psychiatry team for advice on appropriate management (based on expert opinion).

This may include adjusting dose or earlier discontinuation of the corticosteroid therapy if the clinical situation allows.[154]

Evidence: Corticosteroids

Evidence shows no benefit from prolonged therapy of corticosteroids.

A Cochrane review compared the efficacy of short-duration (7 or fewer days) and conventional longer duration (longer than 7 days) systemic corticosteroid treatment of adults with acute exacerbations of COPD.[132]

Eight studies with 582 participants were included.
Corticosteroid treatment was given at equivalent daily doses for 3 to 7 days for short-duration treatment and for 10 to 15 days for longer-duration treatment.
Patients treated for 7 or fewer days did not have a higher rate of treatment failure.
Time in hospital and lung function at the end of treatment were not different.
No differences in side effects or death were noted between treatments.

The balance of risks and benefits of corticosteroids for people with milder exacerbations is uncertain.

Note that there may be guidance in future over which patients to prescribe corticosteroids to, in an effort to reduce their prescription.
At the moment there is no consensus owing to a lack of peer-reviewed data.
Recent studies suggest that systemic corticosteroids may be less effective in treating exacerbations in patients with lower levels of blood eosinophils.[55][110][111][112]

Primary options

prednisolone: 30 mg orally once daily

prednisolone : 30 mg orally once daily

prednisolone: 30 mg orally once daily

hydrocortisone sodium succinate: 100 mg intravenously every 6 hours; convert to oral prednisolone as soon as possible to complete course

hydrocortisone sodium succinate : 100 mg intravenously every 6 hours; convert to oral prednisolone as soon as possible to complete course

hydrocortisone sodium succinate: 100 mg intravenously every 6 hours; convert to oral prednisolone as soon as possible to complete course

Plus – monitor comorbidities during hospital stay

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Consider – oxygen

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Additional treatment recommended for SOME patients in selected patient group

Check arterial blood gas and pulse oximetry on presentation and then after 30 to 60 minutes to ensure satisfactory oxygenation and monitor for carbon dioxide retention and acidosis.[1][96]

Administer the oxygen in a controlled fashion via a Venturi mask to deliver 24% to 28% oxygen.[96]
Titrate controlled oxygen to a target saturation of 88% to 92% as COPD patients are considered at risk for hypercapnic (type 2) respiratory failure.[1][96][100]
Document the fraction of inspired oxygen (FiO₂) or O₂ flow rate.

Repeat arterial blood gas (ABG) if the patient's clinical condition deteriorates or they fail to respond to initial therapy.

Avoid excessive oxygen use in patients with COPD due to the risk of hypercapnic (type 2) respiratory failure.

It is likely that there are at least six mechanisms responsible for oxygen-induced hypercapnia:[96]
- V/Q mismatch
- Ventilatory drive
- Haldane effect (the ability of deoxyhaemoglobin to carry more carbon dioxide than oxyhaemoglobin[136])
- Absorption atelectasis
- Higher density of oxygen compared with air
- Rebreathing can occur if low oxygen flow rates are used through a face mask.
Risk factors for hypercapnic respiratory failure include:
- Previous respiratory failure
- Morbid obesity[96]
- Chest wall deformities, such as severe kyphoscoliosis[96]
- Neuromuscular disorders[96]
- Fixed airflow obstruction associated with bronchiectasis[96]
- Concurrent obstructive sleep apnoea.
The risk of respiratory acidosis in patients with hypercapnic respiratory failure is increased if the PaO₂ is above 10.0 kPa (75 mmHg) due to previous excessive oxygen use.[96]

Use a Venturi mask in preference to nasal prongs as they offer a more accurate delivery of oxygen.[1]

More evidence is needed on the use of high-flow oxygen therapy by nasal cannula in patients with acute exacerbations of COPD.[1]

Practical tip

Beware that hypercapnic respiratory failure may occur as a consequence of high oxygen delivery in an ambulance when attempting hypoxaemia correction.[128] Note that nasal prongs and standard Hudson masks do not deliver controlled oxygen.

Gradually reduce oxygen therapy as the patient recovers.[96]

Discontinue oxygen therapy once the patient can maintain their target oxygen saturation on room air.[96]

Bear in mind that some patients will be on long-term oxygen therapy as part of their usual treatment and this will need to be maintained.

Plus – monitor comorbidities during hospital stay

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Consider – ventilation

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Additional treatment recommended for SOME patients in selected patient group

Start non-invasive ventilation (NIV) for patients who have acute hypercapnic respiratory failure (pH <7.35, PaCO ₂ >6.5 kPa), despite optimal medical therapy, [100] and have no contraindications.[128]

NIV:[1][150] [ ] [Evidence B]
- Improves survival
- Improves gas exchange
- Reduces the work of breathing
- Reduces the need for intubation
- Decreases length of hospital stay.

Provide non-invasive mechanical ventilation to patients with any of the following:[1]

Respiratory acidosis (pH <7.35 and PaCO ₂ >6.5 kPa).[100]
- Acidaemia implies a severe exacerbation and predicts in-hospital and 30-day mortality.[101]
- The evidence is less clear for patients with arterial pH ≤7.25. In these patients NIV may be used as a ceiling of care treatment for severe hypercapnic acidaemic ventilatory failure.
Severe dyspnoea (as shown by use of respiratory accessory muscles, paradoxical motion of the abdomen, or retraction of intercostal spaces).
Persistent hypoxaemia despite supplemental oxygen.

Follow your hospital’s protocol for initiation of NIV and subsequent management.

This should include recommendations on pressures, oxygen titrations, and frequency of ABGs.

In general:

Monitor oxygen saturations continuously.[100]
Take intermittent measurements of PaCO ₂ and pH. [100]
Use ECG monitoring if the patient has a pulse rate >120 bpm or if there is dysrhythmia or possible cardiomyopathy.[100]
Frequently assess the patient to monitor for any complications occurring.

The British Thoracic Society sets out specific timeframes as measurable markers of good practice for the use of acute NIV in the UK.[91][102]

For patients who meet the criteria for acute NIV, start it within:
- 60 minutes of the blood gas result associated with the clinical decision to go ahead with NIV
- 120 minutes of hospital arrival for patients who present acutely.
Review the patient’s clinical progress within 4 hours of starting NIV.
- This should be done by a healthcare professional with appropriate training and competence.
A consultant with training and competence in acute NIV should review the patient’s clinical progress within 14 hours of starting acute NIV.

If possible, perform a blood gas analysis within 30-60 minutes of starting acute NIV.

Although the BTS recommends performing a blood gas analysis within 2 hours of starting NIV,[102] in practice, specialists recommend ideally waiting only 30-60 minutes to check for changes in PaCO ₂ and pH.
Arrange review by a specialist healthcare professional with expertise in managing patients on NIV within 30 minutes if the blood gas measurements have failed to improve.

Plan with senior colleagues what to do if the patient deteriorates,[100] including ‘ceilings of care’,[88] and consider DNACPR (‘Do Not Attempt Cardiopulmonary Resuscitation’) for patients not suitable for escalation to an intensive care unit.

See Diagnostic recommendations for specific advice on care planning.

Admit the patient to an intensive care unit if they have:[1]

Severe dyspnoea with a poor response to initial emergency therapy
Changes in mental status
Persistent or worsening hypoxaemia (PaO ₂ <40 mmHg or 5.3 kPa) and/or severe or worsening respiratory acidosis (pH <7.25) despite supplemental oxygen and non-invasive ventilation
Need for invasive mechanical ventilation
Haemodynamic instability (need for vasopressors).

Only consider invasive ventilation after careful consideration and discussion with the senior medical team.[1]

This is not purely a clinical decision and there are no absolute numerical thresholds to adhere to. You will need to take many factors into account, including the patient’s own wishes regarding resuscitation.
Compare the patient’s functional status to their baseline and consider their overall fitness for ventilation.
Indications for invasive mechanical ventilation include:[1]
- Unable to tolerate NIV
- When NIV has failed
- Post respiratory arrest or cardiac arrest
- Diminished consciousness or inadequately controlled psychomotor agitation
- Massive aspiration or persistent vomiting
- Persistent respiratory secretions that cannot be removed
- Severe haemodynamic instability, not successfully treated with fluid and drugs
- Severe arrhythmias
- Hypoxaemia and unable to tolerate NIV.
Complications associated with mechanical ventilation include:[1]
- Ventilator-associated pneumonia
- Barotrauma
- Volutrauma
- Respiratory weakness after prolonged ventilation (weaning and tracheostomy may be required to manage this).

When assessing suitability for intubation and ventilation, take into account:[88]

Functional status
BMI
Need for oxygen when stable
Comorbidities
Previous admissions to intensive care units
Age
FEV ₁.
- Do not use age or FEV ₁ in isolation when assessing suitability for intubation and ventilation.

Assess your patient’s level of frailty

Assess your patient’s level of frailty to help to identify whether they may need further assessment and enhanced care and to shape your management plans so they match what is important to your patient.[158]

Practical tip

Frailty is a distinctive health state related to the ageing process in which multiple body systems gradually lose their in-built reserves.[159]

Ask your patient (with input from caregivers if relevant) about their capability 2 weeks BEFORE this acute episode.
Use the Clinical Frailty Scale if your patient is ≥65 years old. NHS Specialised Clinical Frailty Network: Clinical Frailty Scale Opens in new window
- This tool is a practical aid to identify frailty, but should not be relied on in isolation.
- If your patient scores 5 or higher, refer for a comprehensive geriatric assessment, if clinically appropriate, within 72 hours of acute presentation.[160][161] If a geriatrician review is unavailable, seek senior advice on appropriate local referral for holistic review.
- A higher frailty score is associated with an increased risk of adverse outcomes.[162]
Look for non-specific complaints, such as delirium and falls.

Practical tip

A comprehensive geriatric assessment is a multidimensional, multidisciplinary process that identifies medical, social, and functional needs and the development of an integrated/co-ordinated care plan to meet those needs.[163]

Help to implement multidisciplinary care and tailor the management approach according to what the patient values most.[164]

Set an escalation plan/consider ceiling of care

In consultation with your patient (and their family or carers if applicable), agree an escalation plan as early as possible (based on expert opinion). This applies to all patients, but may be particularly relevant to patients living with frailty and/or with certain comorbidities, such as dementia, stroke, heart failure, COPD and late-stage CKD (based on expert opinion).

An escalation plan should include:[165]
- Resuscitation status (i.e., ‘Do Not Attempt Cardiopulmonary Resuscitation’ [DNACPR] decision)
- Ceiling of care (e.g., suitability for intubation or intensive care admission).
It should take account of advance care plans, including legally binding advance directives.[165]
It should be guided by your conversations with the patient about their individual wishes, including discussion to help them reach an informed decision about the likely benefit-risk balance of higher intensity interventions.

In some situations, a patient with dementia or other significant comorbidities (particularly if they are acutely unwell) will lack the mental capacity to make decisions for the escalation plan.

Assess and document mental capacity (the ability to make a specific decision at the specific time that the decision needs to be made).[166] Follow the appropriate legislation in your region.
In England and Wales, health professionals must comply with the 2005 Mental Capacity Act.[167] Assessments should follow the principles in the Act.[167]
If your patient is assessed to lack mental capacity, consult with their next of kin to make ‘best interests’ decisions, bearing in mind what is known about the patient’s own previously expressed preferences.[167] According to the 2005 Mental Capacity Act in England and Wales, if a patient is ‘unbefriended’ (i.e., has nobody to represent their best interests who is not paid to provide care) and a decision is not time-critical, an independent mental capacity advocate (IMCA) should be sought to perform this role.[168]

Tracheal intubation animated demonstration

How to insert a tracheal tube in an adult using a laryngoscope.

Bag-valve-mask ventilation animated demonstration

How to use bag-valve-mask apparatus to deliver ventilatory support to adults. Video demonstrates the two-person technique.

Plus – monitor comorbidities during hospital stay

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Consider – antibiotic therapy

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Additional treatment recommended for SOME patients in selected patient group

Give antibiotics to any patient who needs ventilation (invasive or non-invasive) or patients experiencing exacerbations with:[1]

Increase in sputum purulence, plus
Increase in sputum volume, and/or
Increased dyspnoea.

As well as the severity of symptoms, particularly sputum colour changes and increases in volume or thickness beyond the patient’s normal day-to-day variation, the National Institute for Health and Care Excellence (NICE) urges you to also consider:[95]

Whether the patient needs to go into hospital for treatment
Previous exacerbation and hospital admission history
Risk of developing complications
Previous sputum culture and susceptibility results
Risk of antimicrobial resistance with repeated courses of antibiotics.

Choose an antibiotic based on local resistance patterns, any previous culture results for the individual patient[1] and local antibiotic guidelines.

Duration of therapy will tend to be 5 to 7 days, but consult your local guidelines.[1]
- More recent guidance from the American College of Physicians recommends limiting antibiotic treatment to 5 days in patients with COPD exacerbations and acute uncomplicated bronchitis.[141]
When used appropriately, antibiotics can:[1]
- Shorten recovery time
- Reduce the risk of early relapse and treatment failure
- Shorten the length of hospital stay.

Give oral antibiotics first-line if the patient is able to tolerate oral medications, and if the severity of the exacerbation does not require intravenous antibiotics.[1][95]

If a patient is started on intravenous antibiotics, review them by 48 hours and consider stepping down to oral therapy where possible.[95]
NICE recommends amoxicillin, doxycycline, or clarithromycin as suitable first-line oral options. Alternative oral options include amoxicillin/clavulanate, levofloxacin, and trimethoprim/sulfamethoxazole. Suitable first-line intravenous options include amoxicillin, amoxicillin/clavulanate, clarithromycin, trimethoprim/sulfamethoxazole, or piperacillin/tazobactam.[95]
It is worth noting that you must not prescribe fluoroquinolones (e.g., levofloxacin) for mild to moderate acute exacerbation of COPD unless other antibiotics are considered inappropriate. This is due to reports of disabling, long-lasting, or potentially irreversible adverse reactions affecting the musculoskeletal and nervous systems.[133][142] Avoid fluoroquinolones in patients who have previously had serious adverse effects with a fluoroquinolone antibiotic. Avoid use of a corticosteroid with a fluoroquinolone, because co-administration could exacerbate fluoroquinolone-induced tendinitis and tendon rupture.[133]

Look for improvements in dyspnoea and sputum purulence to measure success of antibiotic treatment.[1]

Additional considerations in the community:

Give the patient/their family specific advice about when to seek further medical help, in particular:[95]
- If symptoms worsen rapidly or significantly
- If symptoms do not start to improve within an agreed time (e.g., 2-3 days if taking antibiotics)
- If the patient becomes systemically very unwell.
Give advice on possible adverse effects of antibiotics (particularly diarrhoea).[95]
Explain that their respiratory symptoms may not be fully resolved when the course has been completed.[95]
Reassess the patient if their symptoms worsen rapidly or significantly. In particular:
- Beware symptoms and signs of:
  - Pneumonia
  - Cardiorespiratory failure
  - Sepsis.
- Refer the patient to hospital if you suspect a more serious illness (e.g., sepsis or cardiorespiratory failure).
Consider antibiotic-resistant bacteria and send a sputum sample for microscopy, culture, and Gram stain if symptoms have not improved following antibiotic treatment and these tests have not been done already.[95]
- Only request sputum microscopy, culture, and Gram stain in severe disease and if hospitalisation is being considered. This is not a routine investigation in primary care.[88]
Seek specialist advice for patients:[95]
- Whose symptoms do not improve after repeated courses of antibiotics
- Who have bacteria that are resistant to oral antibiotics
- Who cannot take oral medications.
  - Other options may be to give intravenous antibiotics at home or in the community, rather than in hospital, where appropriate.
Some patients will keep antibiotics at home for use in an exacerbation as part of their existing action plan.

Evidence: Efficacy of antibiotics[143]

Antibiotics offer a large and consistent beneficial effect across outcomes of patients admitted to an intensive care unit (ICU), but for inpatients and outpatients the effects are inconsistent.

A Cochrane review of 19 trials with 2663 participants looked at the effects of antibiotics in the management of acute COPD exacerbations on:

Treatment failure (observed 7 days to 1 month after treatment initiation)
Mortality
Adverse events
Length of hospital stay.

In the study:

Three groups of patients were considered:
- Outpatients (mild to moderate exacerbation)
- Inpatients (severe exacerbation)
- ICU patients (very severe exacerbation)
In outpatients, there was low-quality evidence that antibiotics do significantly reduce the risk for treatment failure between 7 days and 1 month after treatment initiation (RR 0.72, 95% CI 0.56 to 0.94).
In inpatients (excluding ICU), moderate-quality evidence does not show that antibiotics significantly reduce the risk of treatment failure in inpatients with severe exacerbations (RR 0.65, 95% CI 0.38 to 1.12).
In ICU patients:
- A trial of 93 patients showed a large and statistically significant effect of antibiotics on treatment failure (RR 0.19, 95% CI 0.08 to 0.45).
- Antibiotics significantly reduced length of hospital stay (mean difference ‐9.60 days, 95% CI ‐12.84 to ‐6.36 days).
Length of hospital stay (in days) was similar in the antibiotics and placebo groups for inpatients.
The authors conclude that there is a beneficial effect across outcomes of patients admitted to an ICU, but that for inpatients and outpatients the effects of antibiotics are inconsistent.[143]

Evidence: Choice of antibiotic

Choose an antibiotic regimen based on local resistance patterns, any previous culture results for the individual patient,[1]and local antibiotic guidelines.

A review of 19 randomised controlled trials (RCTs) found that macrolides, fluoroquinolones, and amoxicillin/clavulanate may be considered equivalent for the treatment of patients with an acute bacterial exacerbation of chronic bronchitis in short-term effectiveness.[144]

Treatment success was lower for macrolides compared with fluoroquinolones (OR 0.47, 95% CI 0.31 to 0.69).
Fewer fluoroquinolone recipients experienced a recurrence of acute exacerbation after resolution of the initial episode, compared with macrolide recipients, during the 26-week period following therapy.
Amoxicillin/clavulanate was associated with more adverse effects (mainly diarrhoea) than fluoroquinolones (OR 1.36, 95% CI 1.01 to 1.85).

An analysis of five RCTs involving 287 patients found that there were no differences between patients with acute exacerbation of chronic bronchitis receiving semisynthetic penicillins (e.g., amoxicillin, ampicillin) and those receiving trimethoprim-based regimens (e.g., trimethoprim, trimethoprim/sulfamethoxazole, trimethoprim/sulfadiazine) in:[145]

Treatment success (intention-to-treat patients: n = 26; OR 1.68, 95% CI 0.91 to 3.09; clinically evaluable patients: n = 246; OR 1.59, 95% CI 0.79 to 3.20).
Number of drug-related adverse events in general (n = 186 patients; OR 0.37, 95% CI 0.11 to 1.24).

Primary options

amoxicillin: 500 mg orally three times daily, may increase to 1000 mg three times daily in severe infections; 500 mg intravenously every 8 hours, may increase to 1000 mg every 6 hours in severe infections

amoxicillin : 500 mg orally three times daily, may increase to 1000 mg three times daily in severe infections; 500 mg intravenously every 8 hours, may increase to 1000 mg every 6 hours in severe infections

doxycycline: 200 mg orally on the first day, followed by 100 mg once daily thereafter, may increase to 200 mg once daily in severe infections

doxycycline : 200 mg orally on the first day, followed by 100 mg once daily thereafter, may increase to 200 mg once daily in severe infections

doxycycline: 200 mg orally on the first day, followed by 100 mg once daily thereafter, may increase to 200 mg once daily in severe infections

clarithromycin: 500 mg orally (immediate-release)/intravenously twice daily

clarithromycin : 500 mg orally (immediate-release)/intravenously twice daily

clarithromycin: 500 mg orally (immediate-release)/intravenously twice daily

Secondary options

amoxicillin/clavulanate: 500/125 mg orally three times daily; 1.2 g intravenously every 8 hours

amoxicillin/clavulanate : 500/125 mg orally three times daily; 1.2 g intravenously every 8 hours

amoxicillin/clavulanate: 500/125 mg orally three times daily; 1.2 g intravenously every 8 hours

trimethoprim/sulfamethoxazole: 160/800 mg orally twice daily; 160/800 mg intravenously every 12 hours, may increase to 240/1200 mg every 12 hours in severe infections

trimethoprim/sulfamethoxazole : 160/800 mg orally twice daily; 160/800 mg intravenously every 12 hours, may increase to 240/1200 mg every 12 hours in severe infections

trimethoprim/sulfamethoxazole: 160/800 mg orally twice daily; 160/800 mg intravenously every 12 hours, may increase to 240/1200 mg every 12 hours in severe infections

Also known as cotrimoxazole. Should only be considered in acute exacerbations of COPD when there is bacteriological evidence of sensitivity and good reason to prefer this combination to a single antibiotic.[95]

piperacillin/tazobactam: 4.5 g intravenously every 8 hours, may increase to 4.5 g every 6 hours in severe infections

piperacillin/tazobactam : 4.5 g intravenously every 8 hours, may increase to 4.5 g every 6 hours in severe infections

piperacillin/tazobactam: 4.5 g intravenously every 8 hours, may increase to 4.5 g every 6 hours in severe infections

levofloxacin: 500 mg orally once daily for 5 days

levofloxacin : 500 mg orally once daily for 5 days

levofloxacin: 500 mg orally once daily for 5 days

These drug options and doses relate to a patient with no comorbidities.