Antibiotic Therapy in

Chronic Obstructive Pulmonary Disease

By
Dr. Mahmoud Omer
• There is a liberal approach to prescription of antibiotics in
exacerbations of COPD.

• Accordingly, antibiotics were prescribed in 85% of 69 820

patients admitted for acute exacerbations of COPD to 360
hospitals throughout the United States.

Lindenauer PK, et al. Ann Intern Med 2006; 144:894-903 .

• Antimicrobials are often given either to speed up
recovery from a bacterial infection or in a defensive
manner to avoid the risk of airway infection progressing
to pneumonia.

Wilson R.Thorax 2008; 63:390–392.

• However, the frequency of bacterial detection in the sputum of
COPD patients at stable state and at exacerbation contrasts with
the marginal effect of antibiotic therapy and the significant
effect of anti-inflammatory steroid treatment,
suggesting that

suppression of inflammation might be more important than

removal of bacteria for the improvement of symptoms and
functional abnormalities associated with COPD exacerbations.

Papi A, et al. Am J Respir Crit Care Med 2006; 173:1114-21.

• The controversy of antibiotic use in acute
exacerbations has been fuelled by recent data
suggesting that viral infection is the most
common cause of acute exacerbation of COPD.

• Cameron RJ, et al. Virus infection in exacerbations of COPD requiring ventilation.

Intensive Care Med 2006; 32:1022-9.
• Wedzicha JA. Role of viruses in exacerbations of chronic obstructive pulmonary
disease. Proc Am Thorac Soc 2004; 1:115-20.
• The excessive use of antibiotics
is believed to be the main cause
of the spread of antibiotic-
resistant bacteria.

Chen DK, et al. NEJM 1999; 341:233-9.

• Anthonisen identified three cardinal symptoms:

1. Increase in dyspnea

2. Increase in sputum volume

3. Increase in sputum purulence

Anthonisen NR, et al. Ann Intern Med1987;106:196-204

Types of Exacerbations
 Antibiotics should be given to the following:

1. Patients with a Type I Anthonisen exacerbation.

2. Patients with a Type II Anthonisen exacerbation when

increased purulence of sputum is one of the two cardinal
symptoms.

3. Patients with a severe exacerbation that requires

invasive or noninvasive mechanical ventilation.
• NB. Antibiotics are generally not recommended in
Anthonisen Type II without purulence and Type III
patients.

Woodhead M et al. Guidelines for the management of adult lower

respiratory tract infections. Eur Repir J 2005;26:1138-80 .

Potential microorganisms involved in
exacerbation of COPD

Woodhead M et al. Guidelines for the management of adult lower

respiratory tract infections. Eur Repir J 2005;26:1138-80 .

 What are the risk factors for P. aeruginosa?
• At least two out of the following four are risk factors for P.
aeruginosa:

1. Recent hospitalisation

2. Frequent (more than four courses per year) or recent administration

of antibiotics (last 3 months)

3. Severe disease (FEV1 < 30%)

4. Previous isolation of P. aeruginosa during an exacerbation or

patient colonised by P. aeruginosa.
Woodhead M et al. Guidelines for the management of adult lower

respiratory tract infections. Eur Repir J 2005;26:1138-80 .

• The duration of antibiotic treatment in COPD patients
should be maintained at an average of 7-10 days.

• Courses of 5 days with levofloxacin or moxifloxacin have

been as effective as 10 days of treatment with b-lactams in
some trials.
Prophylactic Antibiotic
Therapy in COPD
• Bronchial bacterial colonization is frequent in patients with COPD. In
almost half of moderate-to-severe COPD patients potentially pathogenic
micro-organisms have been demonstrated on bronchoscopy and colonized
patients show both higher inflammation and more frequent and severe
exacerbations.

Weinreich and Korsgaard, 2008; Monsó et al. 1999, 1995; Zalacain et al. 1999
• Chronic bacterial colonization of the damaged respiratory
epithelium leads to chronic release of bacterial and host-
mediated pro-inflammatory factors that in turn damage the
epithelium more, leading to a vicious circle ending in more
severe obstruction and increased susceptibility to acute
exacerbation.

• By reducing bacterial colonization, chronic antibiotic therapy

could help in reducing progression of the disease.
Rationale of antibiotic prophylaxis in
COPD.

Ther Adv Resp Dis. 2010;4(3):135-142.

 Randomized controlled trials on antibiotic prophylaxys in
COPD.

First Year of Patients no. Drug and dose Duration of

author publication treatment
goslin 1957 63 Sulphaphenazole 500 mg BID or 5 months
Tetracycline 500 mg BID

moyes 1957 86 Tetracycline 500 mg TID for 7 4 months

TID days, then 250 mg

murdoch 1959 23 Sigmamycin 1 caps QID or 3 months

Oxytetracycline 250 mg QID

francis 1960 185 Tetracycline 250 mg BID or 4 months

Phenoxymethylpenicillin 312 mg BID

pridie 1960 139 Oxytetracycline 0.5 g OD or 6 months

Phenoxymethylpenicillin 500 mg +
sulphadiamidine 2 g
johnston 1961 40 Phenethicillin 250 mg BID 6 months
First author Year of Patients no. Drug and dose Duration of
publication treatment
fletcher 1966 373 Oxytetracycline 0.5 g in years 1– 7 months per year
3, 0.5 g BID in year 4, 1 g BID in for 5 years
year 5

johnston 1969 79 Tetracycline 500 mg BID 6 months per year

for 5 years

liippo 1987 19 Trimethoprim 300 mg OD 6 months

banerjee 2005 76 Clarithromycin extended release 3 months

500 mg OD

seemungal 2008 109 Erythromycin 250 mg BID 1 year

miravitlles 2009 40 Moxifloxacin 400 mg OD 5 days

sethi 2010 1149 Moxifloxacin 400 mg OD 5 days every 8

weeks for six
courses
• Three months of oral clarithromycin given to subjects with
stable COPD does not improve health status, sputum bacterial
numbers or exacerbation rate.

• Treatment of COPD with clarithromycin during the clinical

stable state yields no clinical advantages and therefore cannot be
recommended as means of eliminating sputum bacteria or
preventing infective exacerbations.

Respir Med. 2005;99(2):208-15.

Am J Respir Crit Care Med.2008,178.1139-47.
• Erythromycin administered at 250 mg twice
daily to patients with COPD over 12 months.
Distribution of exacerbation frequencies in the two arms of the study.
Exacerbations were less frequent in the macrolide arm (P 5 0.003).
Duration of exacerbations between macrolide and placebo groups.
Patients in the macrolide arm were more likely to have shorter duration
exacerbations (P < 0.001).
.
• The macrolide erythromycin, at a dosage of 250 mg twice
daily, is associated with:
1. significant reduction in moderate to severe exacerbations in
patients with moderate to severe COPD.
2. There was no corresponding effect on FEV1 or on airway or
systemic inflammatory markers.
3. There was a statistically significant decrease in exacerbation
duration associated with macrolide use.
• Macrolides have a role in COPD and may be used to augment
therapy in patients with moderate to severe COPD.
`
• Stable patients with COPD were randomized in a double-blind,
placebo-controlled trial to receive moxifloxacin 400 mg PO
once daily (N = 573) or placebo (N = 584) once a day for 5 days.
Treatment was repeated every 8 weeks for a total of six courses.

• Patients were repeatedly assessed clinically and

microbiologically during the 48-week treatment period
• Intermittent pulsed therapy with moxifloxacin reduced
exacerbation by 25%, and by 45% in patients with
purulent/mucopurulent sputum at baseline.
• Treatment with intermittent pulsed moxifloxacin could be indicated in certain
subgroups of patients.

1. patients include those with baselin purulent/mucopurulent or purulent sputum

production, (who are not colonized by P. aeruginosa)

2. who have an unacceptable frequency of exacerbations in spite of maximal

therapy with inhaled agents for COPD

3. who experience complications such as pneumonia with these treatments.

 Conclusion
• Around 10% of the general population is affected by COPD and
the disease is deemed to increase in the next years. This means
that, should antibiotic prophylaxis be recommended worldwide,
around 30 million American and 50 million European COPD
patients would be treated with long-term antibiotics. These huge
figures require the special attention of a safety drug profile and
the possible adverse effects on the epidemiology of bacterial
resistance in the community.
• we concluded that findings on anti-inflammatory and/or
antibacterial effect may have some beneficial effects in
reducing acute exacerbations.
• However, considering the huge population possibly involved in
such prolonged treatments and the risk of adverse events in
terms of side effects and/or incidence of resistance, it will be
safer to wait for further data before antibiotic prophylaxis can
be considered in COPD as an evidence-based recommendation.

Prophylactic Antibiotic Therapy in Chronic Obstructive Pulmonary

Disease.

Ther Adv Resp Dis. 2010;4(3):135-142.