ERS Munich 2006 Congress

September 2 6, 2006

PG1 GRACE Postgraduate Course

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2006 by the author

Saturday, September 2, 2006

09:30 - 17:30
Hall B2a

PG 1
GRACE Postgraduate Course

CAP and HAP Guidelines: Treatment Indications and more

Dr. Mark Andrew Woodhead

Dept of Resp. Medicine
Manchester Royal Infirmary
Oxford Road
M13 9WL
Manchester
United Kingdom

Phone: 0044 161-2764381

Fax: 0044-161-2764989
Email: mark.woodhead@cmmc.nhs.uk

59

GRACE Postgraduate Course

CAP and HAP Guidelines: Treatment indications and more

Dr Mark Woodhead

Aims
1. To discuss the need for Guidelines for Respiratory Infections
2. To introduce Guideline methodologies
3. To give examples of the content of two recently published guidelines

Genetic mutation in bacteria leading to resistance to antibiotics is a naturally

occurring phenomenon due to the very high replication rate of bacteria. In natural
circumstances the possession of resistance to an antibiotic confers no survival
advantage and such organisms would not proliferate. However exposure to the
antibiotic to which the bacterium is resistant does confer such advantage and will lead
to clonal proliferation of that resistant bacterium. Antibiotics are therefore not the
cause of antibiotic resistance, but are the reason why it has become a common
problem.

Of course dead bacteria cannot proliferate, so effective antibiotic treatment does not
promote resistance. Unfortunately our routine antibiotic practice has for many years
been inappropriate. Examples of such inappropriate use is use for an illness of nonbacterial aetiology, use of an antibiotic inappropriate for the likely causative
bacterium, use of too low a dose and use of too long a course of therapy. All of these
may promote resistance. Why has this occurred?

The first reason was the perception that antibiotics were safe and that inappropriate
use did not cause harm. The second was, and to some extent remains, a lack of a
scientific evidence base to guide prescribing. The scientific literature now contains a
plethora of publications on antibiotic use, some good, and many bad. Individual

61

prescribers do not have the time to read and assimilate all of this evidence. This is
where Guidelines have a role. Guidelines have been developed for many common
conditions. To illustrate this talk I will use the recently published ERS lower
Respiratory Tract Infection Guidelines and the American Thoracic Society and
Infectious Diseases Society of America Guidelines for Ventilator-associated and
Health care-associated pneumonia

The science of Guideline writing has evolved over time. Usually they are written by
an expert body including representatives from specialties relevant to the topic in
question. They need to define the objectives of the Guideline, the target audience and
the scope of the project. An explicit literature search strategy should be developed
which is transparent so that if required the casual reader could use it. Relevant
literature must then be selected, read and the evidence contained within graded.
Evidence grading is based on the methodological robustness of the study in question.
Highest evidence is attributed to systematic reviews and randomised controlled trials,
lowest to expert opinion and consensus. From this recommendations are developed.
Where good evidence is available this is not difficult. In LRTIs the best evidence is
available for preventive strategies such as use of vaccination. Unfortunately the
decision about which antibiotic to use is often supported by relatively weak evidence.

The ERS LRTI Guidelines cover community-acquired pneumonia in the community,

in hospital and on the intensive care unit. However they also cover LRTI in the
community, exacerbations of COPD and preventive strategies. The North American
HAP Guidelines cover hospital-acquired pneumonia, ventilator associated pneumonia
and healthcare-associated pneumonia. Both Guidelines go beyond the issue of
antibiotics prescribing and in addition cover prevention, other treatments and severity
assessment. Examples will be provided in the presentation.

Finally Guidelines have to be promoted, implemented and evaluated. The latter is

most difficult. Evidence is emerging that they can change practice in a useful way. It
is predicted that they will have an impact on antibiotic resistance but evidence for this
in CAP and HAP has not yet been sought.

62

References:
Guidelines for the management of adult lower respiratory tract infections. 2005 Eur
Respir J;26:1138-1180

Ventilator associated pneumonia. 2001 Eur Respir J;17:1034-1045

Guidelines for the management of adults with hospital-Acquired, ventilatorassociated, and healthcare-associated pneumonia. 2005 Am J Respir Crit Care
Med;171:388-416

Update of practice guidelines for the management of community-acquired pneumonia

in immunocompetent adults. 2003 Clin Infect Dis;37:1405-1433

EVALUATION TOOL:
1. Antibiotics cause bacterial antibiotic resistance True/False
2. Incorrect indication, dose and duration are all examples of inappropriate
antibiotic use True/False
3. Best evidence comes from cohort studies True/False
4. Recommendations based on consensus should not be part of evidence-based
guidelines True/False
5. Microbiological investigations are recommended for LRTIs managed in the
community True/False
6. Tetracycline or amoxicillin are the antibiotics of choice for LRTI in the
community True/False
7. In the management of hospital acquired pneumonia it is important to recognise
that bacterial causes are different in different hospitals True/False
8. Ceftriaxone or Fluoroquinolone or ampicillin/sulbactam or ertapenem are the
antibiotics of choice for HAP commencing within 5 days of admission
True/False
9. All hospitals should have antibiotic guidelines True/False

63

EVALUATION TOOL: ANSWERS

10. Antibiotics cause bacterial antibiotic resistance False
11. Incorrect indication, dose and duration are all examples of inappropriate
antibiotic use True
12. Best evidence comes from cohort studies False
13. Recommendations based on consensus should not be part of evidence-based
guidelines False
14. Microbiological investigations are recommended for LRTIs managed in the
community False
15. Tetracycline or amoxicillin are the antibiotics of choice for LRTI in the
community True
16. In the management of hospital acquired pneumonia it is important to recognise
that bacterial causes are different in different hospitals True
17. Ceftriaxone or Fluoroquinolone or ampicillin/sulbactam or ertapenem are the
antibiotics of choice for HAP commencing within 5 days of admission True
18. All hospitals should have antibiotic guidelines True

64

Slide 1

CAP AND HAP GUIDELINES:

___________________________________
___________________________________
___________________________________

TREATMENT INDICATIONS
AND MORE

___________________________________
___________________________________

Mark Woodhead
Manchester Royal Infirmary
Manchester, UK

___________________________________
___________________________________
___________________________________

Slide 2

CAP AND HAP GUIDELINES:

___________________________________
___________________________________
___________________________________

AIMS

___________________________________
to introduce Guideline methodology

___________________________________

to provide snapshots from 2 recent Guidelines

___________________________________
___________________________________
___________________________________

Slide 3

___________________________________
GUIDELINES FOR THE MANAGEMENT OF ADULT
LOWER RESPIRATORY TRACT INFECTIONS
2005 Eur Respir J;26:1138-1180
VENTILATOR ASSOCIATED PNEUMONIA
2001 Eur Respir J;17:1034-1045
GUIDELINES FOR THE MANAGEMENT OF ADULTS WITH
HOSPITAL-ACQUIRED, VENTILATOR-ASSOCIATED, AND
HEALTHCARE-ASSOCIATED PNEUMONIA
2005 Am J Respir Crit Care Med;171:388-416
UPDATE OF PRACTICE GUIDELINES FOR THE
MANAGEMENT OF COMMUNITY-ACQUIRED
PNEUMONIA IN IMMUNOCOMPETENT ADULTS
2003 Clin Infect Dis;37:1405-1433

65

___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

___________________________________

Slide 4
GUIDELINES FOR THE MANAGEMENT OF ADULT
LOWER RESPIRATORY TRACT INFECTIONS
2005 Eur Respir J;26:1138-1180
VENTILATOR ASSOCIATED PNEUMONIA
2001 Eur Respir J;17:1034-1045
GUIDELINES FOR THE MANAGEMENT OF ADULTS WITH
HOSPITAL-ACQUIRED, VENTILATOR-ASSOCIATED, AND
HEALTHCARE-ASSOCIATED PNEUMONIA
2005 Am J Respir Crit Care Med;171:388-416
UPDATE OF PRACTICE GUIDELINES FOR THE
MANAGEMENT OF COMMUNITY-ACQUIRED
PNEUMONIA IN IMMUNOCOMPETENT ADULTS
2003 Clin Infect Dis;37:1405-1433

Slide 5

___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

___________________________________
GUIDELINES FOR THE MANAGEMENT OF ADULT
LOWER RESPIRATORY TRACT INFECTIONS
2005 Eur Respir J;26:1138-1180

___________________________________
___________________________________
___________________________________

88 recommendations
GUIDELINES FOR THE MANAGEMENT OF ADULTS WITH
HOSPITAL-ACQUIRED, VENTILATOR-ASSOCIATED, AND
HEALTHCARE-ASSOCIATED PNEUMONIA
2005 Am J Respir Crit Care Med;171:388-416

66 major points and recommendations

Slide 6

___________________________________

___________________________________
___________________________________
___________________________________
___________________________________

___________________________________

WHY HAVE GUIDELINES?

___________________________________
___________________________________

Common conditions
Diverse conditions with diverse aetiologies

___________________________________

No single accepted management for either condition

___________________________________

Evidence that routine management may often not

conform with accepted standards

___________________________________
___________________________________

Inadequate management may lead to harm

(individual morbidity, death; society- resistance)

Publications too numerous for individual to assess

66

___________________________________

Slide 7

WHY NOT JUST ASK AN EXPERT?

___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 8

WHY NOT JUST ASK AN EXPERT?

An expert is a man who has stopped thinking
- he knows!
Frank Lloyd Wright

___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 9

WHY NOT JUST ASK AN EXPERT?

An expert is a man who has stopped thinking
- he knows!
Frank Lloyd Wright

___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

An expert is somebody who is more than

50 miles from home, has no responsibility
for implementing the advice he gives,
and shows slides
Edwin Meese III

___________________________________
___________________________________

67

Slide 10

GUIDELINE METHODOLOGY

___________________________________
___________________________________
___________________________________

Team of interested / expert individuals

___________________________________

relevant to the topic

Define objectives, scope and target audience

___________________________________

Explicit literature search strategy

___________________________________

Evidence grading

___________________________________

Recommendation grading

___________________________________

Consensus when evidence is lacking

Slide 11

RECOMMENDATION GRADES
50
45
40
35
30
25
20
15
10
5
0

1 = Systematic review or meta

analysis of RCTS
2 = 1 or more RCTs
3 = cohort studies
4 = other

___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

ERJ 2005; 26:1138-1180

Slide 12

RECOMMENDATION GRADES

No of
recommendations

A = consistent evidence clear outcome

B = inconsistent evidence unclear outcome
C = insufficient evidence - consensus

45
40
35
30

___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

25
20

___________________________________

15

___________________________________

10
5

___________________________________

0
A

ERJ 2005; 26:1138-1180

68

___________________________________

Slide 13
GUIDELINES FOR THE MANAGEMENT OF ADULT
LOWER RESPIRATORY TRACT INFECTIONS
2005 Eur Respir J;26:1138-1180

___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 14

___________________________________
No of
recommendations

___________________________________
___________________________________

Community
Hospital

14
29

AECOPD

17

___________________________________

___________________________________

21

___________________________________

Bronchiectasis
Prevention

Slide 15

___________________________________

CAP

___________________________________

___________________________________

MANAGEMENT OUTSIDE HOSPITAL

___________________________________
DIAGNOSIS

___________________________________
HOW TO DIFFERENTIATE BETWEEN PNEUMONIA AND OTHER
RESPIRATORY TRACT INFECTIONS?

___________________________________

A patient should be suspected of having pneumonia when the following signs

and symptoms are present:

___________________________________
___________________________________

an acute cough and one of the following:

new focal chest signs,
dyspnoea,
tachypnoea,
fever > 4days.

___________________________________
___________________________________

If pneumonia is suspected, a chest X-ray should be performed

to confirm the diagnosis. [C1]
GUIDEL INE S F OR TH E MANAGEM ENT OF ADULT LOW ER R ES PIRATOR Y TRACT INF ECTI ONS , ERJ 2005

69

Slide 16

___________________________________

MANAGEMENT OUTSIDE HOSPITAL

___________________________________
DIAGNOSIS

___________________________________
___________________________________

SHOULD THE PRIMARY CARE PHYSICIAN TEST FOR A

POSSIBLE MICROBIOLOGICAL AETIOLOGY OF LRTI?

___________________________________

Microbiological investigations are not usually recommended in

primary care.[C1 C3]

___________________________________
___________________________________
___________________________________

GUIDEL INE S F OR TH E MANAGEM ENT OF ADULT LOW ER R ES PIRATOR Y TRACT INF ECTI ONS , ERJ 2005

Slide 17

___________________________________

MANAGEMENT OUTSIDE HOSPITAL

___________________________________
TREATMENT

___________________________________
___________________________________

SHOULD SYMPTOMATIC ACUTE COUGH BE TREATED?

___________________________________

Both dextromethorphan and codeine can be prescribed in patients

with a dry and bothersome cough. [C1]

___________________________________

Expectorant, mucolytics, antihistamines and bronchodilators

should not be prescribed in acute LRTI in primary care. [A1]

___________________________________
___________________________________
GUIDEL INE S F OR TH E MANAGEM ENT OF ADULT LOW ER R ES PIRATOR Y TRACT INF ECTI ONS , ERJ 2005

Slide 18

___________________________________

MANAGEMENT INSIDE HOSPITAL

___________________________________
COMMUNITY-ACQUIRED PNEUMONIA

___________________________________
___________________________________

WHO SHOULD BE ADMITTED TO HOSPITAL?

The decision to hospitalise remains a clinical decision.

___________________________________

However, this decision should be validated against at least one objective

tool of risk assessment.
Both the Pneumonia Severity Index (PSI) and the CURB index
are valid tools in this regard. In patients meeting a PSI of IV and V and/or
a CURB of two or more, hospitalisation should be seriously considered. [A3]
Additional requirements of patient management as well as social factors not
related to pneumonia severity must be considered as well.

GUIDEL INE S F OR TH E MANAGEM ENT OF ADULT LOW ER R ES PIRATOR Y TRACT INF ECTI ONS , ERJ 2005

70

___________________________________
___________________________________
___________________________________

Slide 19

___________________________________

MANAGEMENT INSIDE HOSPITAL

___________________________________

COMMUNITY-ACQUIRED PNEUMONIA
WHO SHOULD BE CONSIDERED FOR ICU ADMISSION?

___________________________________

Criteria of acute respiratory failure, severe sepsis or septic shock and

radiographic extension of infiltrates should prompt consideration of the
admission to the ICU or an intermediate care unit.

___________________________________
___________________________________

The presence of at least two of

systolic blood pressure < 90 mmHg,
severe respiratory failure (PaO2/FIO2 < 250),
Involvement of > 2 lobes on
chest radiograph (multilobar involvment)

___________________________________
___________________________________

or one of
requirement for mechanical ventilation or
requirement of vasopressors > 4 hours (septic shock)

___________________________________

indicates severe CAP and can be used to guide ICU referral. [A3]
GUIDEL INE S F OR TH E MANAGEM ENT OF ADULT LOW ER R ES PIRATOR Y TRACT INF ECTI ONS , ERJ 2005

Slide 20

___________________________________

MANAGEMENT OUTSIDE HOSPITAL

___________________________________
TREATMENT

___________________________________
WHICH ANTIBIOTICS SHOULD BE USED IN PATIENTS WITH LRTI?
Tetracycline and amoxicillin are antibiotics of first choice.

___________________________________
___________________________________

In case of hypersensitivity a newer macrolide like azithromycin,

roxithromycin or clarithromycin is a good alternative in countries with
low pneumococcal macrolide resistance.

___________________________________

National/Local resistance rates should be considered when choosing a

particular antibiotic. When there are clinically relevant bacterial resistance
rates against all first choice agents, treatment with
levofloxacin or moxifloxacin may be considered. [C4]

___________________________________
___________________________________

GUIDEL INE S F OR TH E MANAGEM ENT OF ADULT LOW ER R ES PIRATOR Y TRACT INF ECTI ONS , ERJ 2005

Slide 21

___________________________________

MANAGEMENT INSIDE HOSPITAL

TREATMENT OPTIONS FOR HOSPITALISED PATIENTS WITH MODERATE
COMMUNITY-ACQUIRED PNEUMONIA (IN NO SPECIAL ORDER) [C4]
PREFERRED (IN REGIONS
WITH
LOW PNEUMOCOCCAL
RES IS TANCE RATES )

ALTERN ATIVE (IN REGIONS WITH

INCREAS ED PN EUMOCOCCAL
RES IS TANCE RATES OR MAJOR?
INTOLERANCE TO PREFERRED DRUGS )

Penicillin G macrolide

Levofloxacin #
M oxifloxacin #

Aminopenicillin macrolide *#

___________________________________
___________________________________
___________________________________
___________________________________

Aminopenicillin / lactamaseinhibitor #
macrolide *

___________________________________
___________________________________

Non-antipseudomonal
cephalosporin II or III macrolide *

___________________________________

# Can be applied as s equenti al treatment using t he s ame drug

* new macrolides preferred to er ythromycin
wit hin the fluor oquinolones, moxifloxacin has the highes t antipneumoc occal acti vit y
Experienc e with ket olides is limit ed but they may off er an alt ernati ve when or al treatment is adequat e
For recommended dos ages see main doc ument Appendi x A3.
GUIDEL INE S F OR TH E MANAGEM ENT OF ADULT LOW ER R ES PIRATOR Y TRACT INF ECTI ONS , ERJ 2005

71

___________________________________

Slide 22

___________________________________
PREVENTION BY METHODS OTHER THAN VACCINATION

___________________________________
DOES ANTIBIOTIC TREATMENT OF UPPER RESPIRATORY TRACT INFECTIONS
PREVENT LRTI?
Treatment of URTI with antibiotics will not prevent LRTI [A 1].

___________________________________
___________________________________

DOES THE TREATMENT WITH INHALED STEROIDS OR LONG ACTING

BETA-2-AGONISTS PREVENT LRTI ?
The regular use of inhaled steroids [B 1] or of long-acting beta-2-agonist [C 4]
as a preventive approach for LRTI is not recommended (this does not mean that
they might not prevent exacerbations of COPD which is an issue beyond
the scope of this document).

___________________________________
___________________________________
___________________________________

GUIDEL INE S F OR TH E MANAGEM ENT OF ADULT LOW ER R ES PIRATOR Y TRACT INF ECTI ONS , ERJ 2005

Slide 23

___________________________________
___________________________________
GUIDELINES FOR THE MANAGEMENT OF ADULTS WITH
HOSPITAL-ACQUIRED, VENTILATOR-ASSOCIATED, AND
HEALTHCARE-ASSOCIATED PNEUMONIA
2005 Am J Respir Crit Care Med;171:388-416

___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

___________________________________

Slide 24
Hospital-acquired pneumonia (HAP) pneumonia that occurs
48 hours or more after admission, which was not incubating
at the time of admission

___________________________________
___________________________________

Ventilator-associated pneumonia (VAP) pneumonia that

arises more than 48-72 hours after endotracheal intubation

___________________________________
___________________________________

Healthcare-associated pneumonia (HCAP) pneumonia

occurring within 90 days of hospital stay, nursing home or LTCF
resident, received recent intravenous antibiotic therapy,
chemotherapy or wound care within 30days or attended a
hospital or haemodialysis clinic
Am J Respir Crit Care Med;171:388-416

72

___________________________________
___________________________________
___________________________________

___________________________________

Slide 25

___________________________________

Four Major Principles

___________________________________
1. Avoid inadequate treatment
2. Variable bacteriology between hospital sites and over time
3. Avoid antibiotic overuse accurate diagnosis and

___________________________________
___________________________________
___________________________________

pathogen directed therapy

4. Prevention strategies for modifiable risk factors

___________________________________
___________________________________

Am J Respir Crit Care Med;171:388-416

Slide 26

___________________________________
HAP, VAP or HCAP Suspected

___________________________________

Obtain lowe r respiratory tract sample for culture

(quantitative or semi quantitative) & microscopy
Begin empiric antimicrobial therapy using algorithm and
local microbiologic data (unless low clinical suspicion and
Negative microscopy of LRT sample)

___________________________________
___________________________________
___________________________________
___________________________________

Days 2 & 3: Check cultures & assess clinical response:

(Temperature, WBC, CXR, Oxygenation, sputum purulence,
Haemodynamic changes and organ function)
Clinical Improvement at 48-72 hours?

Am J Respir Crit
Care Med;171:
388-416

HAP, VAP or HCAP Suspected

Am J Respir Crit
Care Med;171:
388-416

Slide 27

Clinical Improvement at 48-72 hours?

NO

___________________________________
___________________________________

___________________________________
___________________________________
___________________________________
___________________________________

YES

___________________________________
Cultures -

Cultures +

Cultures -

Cultures +

Search for other

Pathogens,
Complications,
Other Diagnoses
or Other Sites of
infection

Adjust antibiotic
Therapy, search
For other
Pathogens,
Complications
Or other signs
Of infection

Consider
Stopping
antibiotics

De-escalate
Antibiotics, if
Possible.
Treat selected
Patients for
7-8 days and
reassess

___________________________________

73

___________________________________
___________________________________

Slide 28

Am J Respir Crit
Care Med;171:
388-416

___________________________________
HAP, VAP or HCAP Suspected

___________________________________

Late onset (5days) or risk factors for

multidrug resistant pathogens
NO

___________________________________
___________________________________

YES

___________________________________
Limited Spectrum
Ceftriaxone or
Fluoroquinolone or
Ampicillin / sulbactam or
Ertapenem

Slide 29

Broad Spectrum
Antipseudomonal cephalosporin
or
Antipseudomonal carbapenem
or
-lactam/- lactamase inhibitor
Plus
Antipseud fluoroquinolone or aminoglyc
(MRSA linezolid or vancomycin)

GUIDELINE IMPLEMENTATION

___________________________________
___________________________________
___________________________________

___________________________________
___________________________________
___________________________________

relevance

___________________________________

what is already available

___________________________________

layout (question/answer, algorithm etc)

dissemination

___________________________________

ownership

___________________________________
___________________________________

research

Slide 30

CONTROLLED TRIAL OF CRITICAL

TREATMENT PATHWAY FOR CAP
Prediction rule, Levofloxacin, Iv- oral Switch and Discharge Criteria
(n = 1743 ; 19 hospitals)

___________________________________
___________________________________
___________________________________
___________________________________

Speed of Recovery (SF36)

Clinical Outcomes
PSI I-III Inpatient (%)
Admitted Mean PSI score
Median Stay (days)
Single Antibiotic (%)

CASES
=
=
31
103
5.0
64

CONTROLS
=
=
49*
94
6.7*
27*

(Marrie et al JAMA 2000;283:749-755)

74

___________________________________
___________________________________
___________________________________
___________________________________

___________________________________

Slide 31
GUIDELINES FOR THE MANAGEMENT OF ADULT
LOWER RESPIRATORY TRACT INFECTIONS
2005 Eur Respir J;26:1138-1180

___________________________________
___________________________________
___________________________________
___________________________________

GUIDELINES FOR THE MANAGEMENT OF ADULTS WITH

HOSPITAL-ACQUIRED, VENTILATOR-ASSOCIATED, AND
HEALTHCARE-ASSOCIATED PNEUMONIA
2005 Am J Respir Crit Care Med;171:388-416

___________________________________
___________________________________
___________________________________

75