# Presentation: 794428

## ARE ANTIBIOTICS USEFUL IN EXACERBATIONS OF CHRONIC BRONCHITIS?

- JV HIRSCHMANN, MD
- SEATTLE VA MEDICAL CENTER
- UNIVERSITY OF WASHINGTON

## EXACERBATIONS OF CHRONIC BRONCHITIS

- Definitions
- chronic bronchitis
- current or previous smokers
- chronic sputum production
- acute exacerbations
- increased cough, dyspnea
- increased sputum +/- color change

## EXACERBATIONS

- Frequency: average 1-2 per year
- Causes: non-infectious
- 	air pollution
- 	changes in barometric pressure
- 	exposure to fumes, dust, smoke
- 	exposure to cold air

## EXACERBATIONS

- Viruses (20-65%)
*Mycoplasma pneumoniae* <1%
*Chlamydia pneumoniae* <5%
- ?Other bacteria
- 	*Haemophilus influenzae*
*	**Streptococcus pneumoniae*
*	**Moraxella catarrhalis*

## ANTIBIOTIC TRIALS: EXACERBATIONS

**Randomized, double-blind, placebo-controlled**
**Large numbers (100s)**
**Microbiology**
**Chest films to exclude pneumonia**
**Standardized therapy**
**	****bronchodilators**
**	****systemic corticosteroids**

## ANTIBIOTIC TRIALS: EXACERBATIONS

- Stratified by severity
- 	exacerbations
- 	underlying disease
- Outcome criteria, assessed early
- 	dyspnea, other symptoms
- 	exercise capacity, PFTs
- 	return to usual activities

## ANTIBIOTIC TRIALS: EXACERBATIONS

- Long-term follow-up:
- 	recurrent attacks
- 	pulmonary function
- Careful record of adverse drug effects
- Appropriate analysis
- 	statistical significance
- 	_clinical_ significance

## ANTIBIOTICS IN COPD

- 11 placebo-controlled trials
- 8 no benefit
- 3 favor antibiotics

## META-ANALYSIS

- 6 placebo-controlled trials
- 	advantage to antibiotics
- 		PEFR 10L/min
- 		average PEFR: 200L/min
- 		meaningless difference
- 			physiological, clinical
- 							**JAMA 1995; 273: 957**

## CANADIAN STUDY

**173 patients   362 attacks 1981-4**
**Increased dyspnea, sputum volume, purulence**
**	****all three (40%)         placebo****	****	****antibiotic**
**success****	****	****45%****	****	****	****   65%**
**no resolution****	****23%****	****	****	****   20%**
**deterioration****	****32%****	****	****	****   15%**
**	****	****	****	****	****	****Ann Intern Med 1987;106:196**

## CANADIAN STUDY

- Weaknesses of study
- 	no microbiology
- 	no chest films (30% febrile)
- 	no stratification for corticosteroids
- 		40% received them
- 		no systematic assignment
- 		no standard dose or duration

## DANISH STUDY

- 270 patients  1986-8
- 				placebo       amoxicillin
- PEFR				no
- MD evaluation         difference
- 	(8 days)
- 			Scand J Prim Health Care 1992;10:7

## SYSTEMIC STEROIDS IN EXACERBATIONS

- Faster improvement, fewer failures
**	****Inpatients**
**	****	****Ann Intern Med 1980; 92:753**
**	****	****N Engl J Med 1999; 340:1941**
**	****	****Lancet 1999; 354:456**
**	****	****Am J Respir Crit Care Med 2002; 165:698**
**	****Outpatients**
**	****	****Am J Respir Crit Care Med 1996;154:407**

## DUTCH STUDY

- Systemic steroids +/- antibiotics
- 	71 patients 1988-91
- 	all received steroids
- 	amoxicillin, SMX-TMP, placebo
- 		symptoms, PEFR, future relapse
- 			no difference
- 						Thorax 1995; 50:758

## CANADIAN STUDY

- Patients receiving steroids
- 		placebo			antibiotic
- 		     73                        72
-  no significant difference in outcome

## CONCLUSIONS

- Available studies inadequate
- Benefits for antibiotics unproven
- 	overall
- 	subgroups
- 	with current therapy, including 	steroids
- Need for appropriate study now

## PROSPECTIVE STUDY

- 71 patients with exacerbations
- 	failure <4 weeks after treatment
- 		antibiotic  		13%
- 		no antibiotic 	14%
- 						Q J Med 1995;88:61

## COPD EXACERBATIONS

**101 patients  2.5 years  1995-8   504 exacerbations**
**Treatment: antibiotics +/- steroids**
**	****antibiotics: no effect**
**	****steroids**
**	****	****faster recovery**
**	****	****longer time to next episode**
**	****	****	****	****     ****Am J Resp Crit Care Med**** 2000; 161:1608       **

## ANTIBIOTIC VS ANTIBIOTIC

- 			**Microbiologic     Clinical ****	****% resistant**
**	****	****	****cure****	****	****         success**
**grepafloxacin    97%****	****            83%****	****	****            2%**
**amoxicillin         89%                 85%****	****	****          31%**
**	**
**    ****	****	****	****	****	****	**** ****J Antimicrob Chemo 1997; 40:63**

## ANTIBIOTIC VS ANTIBIOTIC

- 			**Microbiologic     Clinical ****	****% resistant**
**	****	****	****cure****	****	****         success**
**levofloxacin       94%****	****	****92%****	****	****            2%**
**cefaclor****	****        87%               92%****	****	****          23%**
**	****	****	****	****	****	****Infect Dis Clin Pract 1998;7:101**

## CLINICAL SUCCESS WITH CLARITHROMYCIN

- Susceptible bacteria	86**%**
- Resistant bacteria		88**%**
- J Antimicrob Chemo 1999; 44:501

## “PATHOGENS” IN EXACERBATIONS

- 50-80%: no pathogens isolated
- 	expectorated sputum
- 	protected bronchoscopic specimen

## “PATHOGENS” IN EXACERBATIONS

- 			38 pts    1975-7
- 			*H. influenzae**	**  S. pneumoniae*
- Remission	 11%			8%
-   (628)
- Exacerbation   12%		      14%
- 	(77)
- 				Br J Dis Chest 1980; 74:228

## “PATHOGENS” IN EXACERBATIONS

- 				25 pts       1968-72
- 			*H. influenzae**	**	**S. pneumoniae*
- Remission	   60%			  33%
- (1267)
- Exacerbation	   57%			  37%
-    (86)
- 	  			Am Rev Resp Dis 1976;113:465

## COPD EXACERBATIONS

*Moraxella catarrhalis*
- 5-10% of exacerbations
- usually with *H. influenzae* or pneumococcus
*Haemophilus parainfluenzae*
- common in COPD
- _less_ frequent in exacerbations than remissions

## NEW STRAINS IN EXACERBATIONS

- New strains associated with attacks
- 	*H. influenzae, S. pneumoniae, *
*	**M. catarrhalis*
- 67% of new strains: no attack
- New strains: only 15% of attacks
- Other explanation: attacks increase colonization with new strains
- 					N Engl J Med 2002; 347:465

## COPD EXACERBATIONS

- “Purulent” sputum contains mainly eosinophils
- Bronchial biopsies
- marked increase in eosinophils
- mild increase in neutrophils
- Not the findings expected in bacterial infection

## ANTIBIOTICS IN COPD: MECHANICAL VENTILATION

- 45 ofloxacin, 45 placebo
- Mortality: 4% vs 22%
- Almost all from pneumonia
- 				Lancet 2002;358:2020

## ANTIBIOTICS IN COPD: MECHANICAL VENTILATION

- <1% of exacerbations
- Patients poorly treated
- 	aminophylline 	65%
- 	beta-adrenergic agents 45%
- 	anticholinergic agents 0%
- 	systemic corticosteroids 0%
- Preventing pneumonia in untreated ventilated patients