Community-acquired Pneumonia - RCP London

Community-acquiredPneumonia

Mark Woodhead

Honorary Clinical Professor of Respiratory Medicine

Conflicts of Interest

Paid member, Data Monitoring CommitteeCAPITA (pneumococcal conjugate vaccine) study. Pfizer Pharmaceuticals: 2010 – May 2012

Speaker fee / Accommodation / travel expenses only for :European Pneumo Update, 2014, 2015, 2016, 2017, 2018

• Background• Diagnosis• Causes• Severity assessment• Treatment – antibiotics• Treatment – other• Prevention

www.nice.org.uk/guidance/cg191 4

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2006-2007 2011-2012 2016-2017

Pneumonia – EnglandAdmissions

https://digital.nhs.uk/data-and-information/publications/statistical/hospital-admitted-patient-care-activity/

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>74

Pneumonia – EnglandAdmissions – by Age band

https://digital.nhs.uk/data-and-information/publications/statistical/hospital-admitted-patient-care-activity/

IllnessSeverity

Time

Clinical Presentation

PneumoniaEvolution

"The role of the doctor is to amuse the

patient, while nature takes its course"

Voltaire

IllnessSeverity

Time


PneumoniaEvolution

Key Decision Point

n = 1251 compared with adults with CAP (n=6660)

Were older (median 80 vs 78 years, p<0.001)Had more comorbid disease, Significantly fewer respiratory symptoms (fever, cough, dyspnoea, pleuritic pain), More constitutional symptoms (general deterioration, falls)

Lower 30-day inpatient mortality (14.3% vs 17.0%, adjusted OR 0.75,p=0.003)

52% miscoded as having pneumonia were treated as having CAP, …..these constitute cases of miscoding due to misdiagnosis rather than coder-related error

Daniel et al Thorax 2017 ;72:376-379

CT CAP

Upchurch et al Chest 2017

Aug 9. pii: S0012-3692(17)31392-2. doi: 10.1016/j.chest.2017.07.035

• hospital length of stay,

• ICU admission,

• mechanical ventilation, and

• shock,

were similar between groups

• In-hospital death was rare in both the CT-only and

• pneumonia on CXR groups (0% vs 2%).

CT CAP

IllnessSeverity

Time


PneumoniaEvolution

Key Decision Point

Usually pneumococcal

IllnessSeverity

Time


PneumoniaEvolution

Key Decision Point

Usually pneumococcal

PneumococcalLegionellaStaphylococcus

Little time!

Penicillin

Macrolide

Resistance in Streptococcus pneumoniae. UK

Total number of tested isolates (N) and percentages non-susceptible 2013–2016

n %

https://ecdc.europa.eu/en/home

2016

Severity Assessment

Prognostic value – predicts mortality

Assists in

• Place of care home/hospital/ICU

• Intensity of investigation

• Antibiotic therapy

• What to tell patient / family

11.7

23.4

0

5

10

15

20

25

Direct Delayed

Outcome related to ICU Transfer Mode

28-day mortality %

Renaud et al Crit Care Med 2009;37:2867-2874

Direct = straight from EDDelayed = within 3 days of admission

Severity Assessment

Mortality (%) related to CURB-65 score

0

5

10

15

20

25

30

35

0 or 1 Two 3 or more

CURB-65 score

CRB65

ATS/IDSA

1.5%

mortality

9.2%

Lim et al Thorax 2003;58:377-382, Fine et al NEJM 1997;336:243-250

1.5%

9.2%

22%

Severity assessment in hospital

• When a diagnosis of community-acquired pneumonia is made at presentation to hospital, determine whether patients are at low, intermediate or high risk of death using the CURB65 score.

• Use clinical judgement in conjunction with the CURB65 score to guide the management of community-acquired pneumonia, as follows:

• consider home-based care for patients with a CURB65 score of 0 or 1• consider hospital-based care for patients with a CURB65 score of 2 or

more• consider intensive care assessment for patients with a CURB65 score of 3

or more.[Based on prognostic cohort studies of moderate to very low quality with a large number of patients, and the experience and opinion of the GDG]

• Stratify patients presenting with community-acquired pneumonia into those with low-, moderate- or high-severity disease. The grade of severity will usually correspond to the risk of death.

[Based on the experience and opinion of the GDG]

www.nice.org.uk/guidance/cg191

Low intermediate High Low intermediate High

CRB65 CURB65

Pneumonia Patient Distribution by Mortality Risk Score

Lim et al Thorax 2003;58:377-382

n = 718

1.2% 8.1% 31% 1.5% 9.2% 22%

**

Low intermediate High Low intermediate High

CRB65 CURB65

Antibiotic Choice by Mortality Risk Score

Lim et al Thorax 2003;58:377-382

n = 718

1.2% 8.1% 31% 1.5% 9.2% 22%

**

AmoxicillinB-lactam + macrolideB-lactam + macrolide

• Offer a 5-day course of a single antibiotic to patients with low-severity community-acquired pneumonia.

• Consider amoxicillin in preference to a macrolide or a tetracycline.




• Consider dual antibiotic therapy with amoxicillin and a macrolide for patients with moderate-severity community-acquired pneumonia.

• Consider dual antibiotic therapy with a beta-lactamase stable beta-lactam and a macrolide for patients with high-severity community-acquired pneumonia.


Horita et al Respirology 2016;21:1193-1200

JAMA Intern Med. 2014;174(12):1894-1901. doi:10.1001/jamainternmed.2014.4887

We did not find noninferiority of β-lactam monotherapy inpatients hospitalized for moderately severe community-acquired pneumonia

N Engl J Med 2015;372:1312-23. DOI: 10.1056/NEJMoa1406330

…..empirical treatment with beta-lactam monotherapy was non-inferior tostrategies with a beta-lactam–macrolide combination or fluoroquinolonemonotherapy with regard to 90-day mortality

Outcome = % not reaching clinical stability

Outcome = mortality

Macfarlane et al J Infect 1983;7:111-117

One third of patients made an complicated / delayed recovery or died……

…There appear to be good reasons for using ampicillin and erythromycin together….

15 consecutive patients were studied…..there were no deaths, and 10 patients made an uncomplicated recovery

BTS AUDIT 2014-20156786 cases at 158 hospitals

Antibiotic – CURB65 3 - 5

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Guideline Audit

Other

B-L + M

B-lactam

35% under treated with B-lactam alone

Timely diagnosis and treatment

• Put in place processes to allow diagnosis (including X-rays) and treatment of community-acquired pneumonia within 4 hours of presentation to hospital.

• Offer antibiotic therapy as soon as possible after diagnosis, and certainly within 4 hours to all patients with community-acquired pneumonia who are admitted to hospital.

[Based on observational cohort studies of low to very low quality with a large number of patients]


Time to first antibiotic (hours)

first antibiotic dose within 4 h of admission was associated

with a 16% lower adjusted 30-day IP

mortality compared with later antibiotic administration

Time to First Antibiotic

Daniel P, et al. Thorax 2016 Jun;71(6):568-70

< 4 4-8 8-12 >12

16

17

18

19

20

2009 2010 2011 2012 2014

35

40

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50

2009 2010 2011 2012 2014

0

20

40

60

80

2009 2010 2011 2012 2014

%

30-day mortality

CURB-65 0 - 1

Antibiotic within 4 hours

OR (AOR) for mortality from 2009 (reference) to 2014

AOR 0.86 (95% CI 0.68 to 1.08)

p for trend=0.004

24,187 cases in 218 hospitals

Daniel P, et al. Thorax 2016;71:1061–1063

• Multicentre, non-inferiority randomized clinical trial • Hospitalized patients diagnosed as having CAP 4 teaching hospitals in Spain

control group duration of antibiotics was determined by physicians as usual in clinical practice.

Uranga et al JAMA Intern Med. 2016 Sep 1;176(9):1257-65

Usual Antibiotic

intervention group

treated with antibiotics for minimum 5 days,

stopped at this point if temperature was ≤ 37.8°C

for 48 hours and ≤ than 1 clinical instability,

Admission Day 5

Randomised

Antibiotic

duration

(median days)


Antibiotic

duration

(median days)


n 150 162 p

30-day mortality (%) 2.2 2.1 NS

Day 10 clinical success(%) 48.6 56.3 .18

Day 30 clinical success(%) 88.6 91.9 .33

Day 10 Mean symptom score 18.6 17.9 .69

Low-severity community-acquired pneumonia


[Based on moderate to very low quality evidence from randomised controlled trials, a cost analysis with limitations, and the experience and opinion of the GDG]

Moderate- and high-severity community-acquired pneumonia

• Consider a 7- to 10-day course of antibiotic therapy for patients with moderate- or high-severity community-acquired pneumonia.

[Based on the experience and opinion of the GDG]


Oseltamivir and zanamivir cause small reductions in the time to first alleviation of influenza symptoms in adults. The use of oseltamivir increases the risk of nausea, vomiting, psychiatric events in adults and vomiting in children.

Oseltamivir has no protective effect on mortality among patients with 2009A/H1N1 influenza.

Prophylaxis with either NI may reduce symptomatic influenza in individuals and inhouseholds.

The balance between benefits and harms should be considered when making decisions about use of NIs for either prophylaxis or treatment of influenza.

Heneghan CJ, et al Health Technol Assess 2016;20(42)

Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70–0·93; p=0·0024).

Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41–0·56; p<0·0001).

There was an increase in the mortality hazard rate with each day’s delay ininitiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18–1·28]; p<0·0001 for the increasing HR with each day’s delay)

Muthuri et al Lancet Respir Med 2014;2: 395–404

Meta-analyses

Salluh 2010

Nie 2012

Siemieniuk 2015

Horita 2015

Chen 2015

Marti 2015

Wan 2016

Bi 2016

Wu 2018

Briel 2018

Original Studies

Wagner 1955

Bennett 1963

Klastersky 1971

McHardy 1972

Marik 1993

Confalonieri 2005

El Ghamrawy 2006

Mikami 2007

Snijders 2010

Fernandez-Serano 2011

Meijvis 2011

Sabry 2011

Nafae 2013

Blum 2015

Torres 2015

Steroid Treatment for CAP

Among patients with septic shock undergoing mechanical

ventilation, a continuous infusion of hydrocortisone did not

result in lower 90-day mortality than placebo

35% of 3698 cases had pulmonary infection

Mortality 28%

Venkatesh et al N Engl J Med 2018;378:797-808

….90-day all-cause mortality was lower among those who

received hydrocortisone plus fludrocortisone than among

those who received placebo

59% of 1240 cases had pulmonary infection

Mortality 45%

Annane et al N Engl J Med 2018;378:378:809-818

Rochberg et al Crit CareMed 2018;146:1411-1420

Conclusion: In critically ill patients with sepsis,

corticosteroids possibly result in a small reduction in mortality

while also possibly increasing the risk of neuromuscular weakness

the use of corticosteroids in sepsis may result in a small absolute

reduction in mortality of approximately 2% …. but the CI

around the estimate includes no effect

Our panel make a weak recommendation to give corticosteroids to people with all types

and severity of sepsis, based on new evidence.

Because we are not certain that they are beneficial, it is also reasonable not to prescribe

them.

Patients’ values and preferences may guide this decision-making process.

Lamontagne et al Brit Med J 2018; 362:k3284 doi: 10.1136/bmj.k3284

CPAP (NIV) in CAP

Confalonieri et al AJRCCM,1999;160:1585-1591

CPAP Control

All 6/28 (21%) 17/28 (61%) 0.35 (0.16-0.76)

without COPD 6/16 (37.5%) 8/17 (47.1%) 0.80 (0.35-1.79)

with COPD 0/12 (0%) 6/11 (54.5%) 0.07 (0.00-1.13)

Need for Intubation OR

NIV and CPAP compared with usual care

• No recommendation made.

• No studies were found comparing NIV (Bi-level CPAP) to CPAP or usual care.Two RCTs comparing CPAP to usual care were identified

• The GDG noted that the number of patients included in the available studies was small, with a degree of imprecision around many of the results. The evidence from the post hoc subgroup analysis of patients with CAP with and without COPD should be interpreted with caution as it included a very small sample size.

NIV, CPAP and usual care compared with elective intubation

• No suitable studies were identified

• No recommendation made.


A CRP that fails to fall by 50% or more within 4 days of admission is

independently associated with

increased 30 day mortality (OR 24.5; 6.4-93.4), P .0001;

mechanical ventilation and/or inotropic support (OR 7.1; 2.8-17.8), P .0001

and complicated pneumonia (OR 15.4; 6.32-37.6), P .0001.

REPEAT CRP WITHIN 4 DAYS OF ADMISSION

Chalmers et al Am J Med 2008;121:219-225

0

5

10

15

20

25

30 d mortality AV / inotropes complications

Day 4 CRP decreased by >49%

Day 4 CRP decreased by < 50%

%

Monitoring in hospital

• Consider measuring a baseline C-reactive protein concentration in patients with community-acquired pneumonia on admission to hospital, and repeat the test if clinical progress is uncertain after 48 to 72 hours.

[Based on low to very low quality observational cohort studies, and the experience and opinion of the GDG]


Instabilities

Temp > 37.8

Resp Rate > 24/min

Heart Rate > 100/min

SBP ≤ 90

SaO2 < 90%

Altered mental status

Can’t maintain oral intake

PREDICTION OF SAFE HOSPITAL DISCHARGE IN CAP

N = 680

130 (19%) 1 instability

at discharge

0

10

20

30

40

50

60

Mor

talit

y

Rea

dmission

s

Major

Eve

nts

not B

TN

0 1 2

No of

instabilities

Halm et al Arch Int Med 2002;162:1278-1284

Safe discharge from hospital

• Do not routinely discharge patients with community-acquired pneumonia if in the past 24 hours they have had 2 or more of the following findings:• temperature higher than 37.5°C• respiratory rate 24 breaths per minute or more• heart rate over 100 beats per minute• systolic blood pressure 90 mmHg or less• oxygen saturation under 90% on room air• abnormal mental status• inability to eat without assistance.

• Consider delaying discharge if their temperature is higher than 37.5°C.[Based on evidence from moderate to very low quality prognostic cohort studies at low risk of bias]


Older adults receiving the influenza vaccine may experience less influenza over a single season compared with placebo, from 6% to 2.4% (risk ratio (RR) 0.42, 95% confidence interval (CI) 0.27 to 0.66; low-certainty evidence

The study providing data for mortality and pneumonia was underpowered to detect differences in these outcomes. No data on hospitalisations were reported

The available evidence relating to complications is of poor quality, insufficient, or old and provides no clear guidance for public health regarding the safety, efficacy, or effectiveness of influenza vaccines for people aged 65 years or older. Society should invest in research on a new generation of influenza vaccines for the elderly.

Demicheli V, et al.CochraneDatabase of Systematic Reviews 2018, Issue 2. Art.No.:CD004876. DOI: 10.1002/14651858.CD004876.pub4

Okasha et al Thorax 2018;73:262-269

Pneumococcal disease infections caused by serotypes in Prevenar 13 vaccine

www.gov.uk/government/collections/pneumococcal-disease-guidance-data-and-analysis

www.gov.uk/government/collections/pneumococcal-disease-guidance-data-and-analysis

Pneumococcal disease infections caused by serotypes not in Prevenar 13 vaccine

Dosage and schedule

PCV13 contains polysaccharide from thirteen common capsular types 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F. These are conjugated to protein (CRM197).For infants under one year of age: first dose at eight weeks of age, second at 16 weeks of age (at least two months after the first dose), third dose after their first birthday (at least 2 months after the last PCV13 dose)

Unimmunised or partially immunised children aged one year and up to two years of age: a single dose of PCV13

PPV23contains purified capsular polysaccharide from each of 23 capsular types of pneumococcus (PPV23) 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33FAdults over 65 years and at-risk groups aged two years or over: a single dose of PPV23

PCV10 Not currently recommended in the UK National Immunisation Programme.

Involve your Clinical Audit Department in 2018 BTS CAP Audit (www.brit-thoracic.org.uk)

Thank you

http://www.brit-thoracic.org.uk/

Community-acquired Pneumonia - RCP London

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