How do we diagnose acute CAP? What are the ways to treat patients with CAP? Professor Ivan Hung (Hong Kong) presents his answers in his 2015 Pneumonia Lectures. Learn more on www.waidid.org

1. Diagnosis and Management of Acute
Community Acquired Pneumonia
Dr. Ivan Hung
MBChB (Bristol), MD (HK), FRCP (Lon, Edin), PDipID (HK)
Clinical Associate Professor
Honorary Consultant
Department of Medicine, QMH
The University of Hong Kong

2. Causes
of
febrile
respiratory
illness
• Streptococcus
pneumoniae
• Staphylococcus
aureus
• Haemophilus
influenzae
• Enterobacteriaceae
(ill
health,
>65)
• Oral
aerobes/Anaerobes
(AspiraBon)
• Acinetobacter
baumannii
• Pseudomonas
aeruginosa
• Burkholderia
pseudomallei(sputum)
• Legionella
pneumophilia
(sputum,
urinary
anBgen
EIA)
• Mycoplasma
pneumoniae
• Chlamydophila
pneumoniae/psiKaci
• Coxiella
burneBi
(Q
fever)
• Mycobacterium
tuberculosis
(sputum)
• Influenza
A
H3N2,
H1N1,
H5N1,
H9N2,
H7N9)
• Influenza
B
• Influenza
C
• Adenovirus
• RSV
• Parainfluenza
1,
2,
3,
4
• Rhinovirus
Clade
A,
B,
C
• Metapneumovirus
• MERS-­‐CoV
• Coronavirus
SARS
SARS
• Coronavirus
OC43
OC43
• Coronavirus
HKU1
HKU1
• Coronavirus
229E
229E
• Enterovirus
• Bocavirus
• PROLONGED
shedding
in
children
and
immunosuppressed
hosts
BACTERIA
*BLOOD, PLEURAL
FLUID,BAL(Bronchoalveolar lavage)
VIRUSES

3. Causes
of
febrile
respiratory
illness
• Cryptococcus
• Aspergillus
• Dimorphic
fungi:
Penicillium,
Histoplasma,
Coccidioides,
• Zygomycetes
• PneumocysBs
• *usually
in
immunosuppressed
host
• Paragonimus
westermanii
• Ascaris
lumbricoides
• Strongyloides
stercoralis
• Many
others
• *
usually
eosinophilia
in
blood
PARASITESFUNGI

4. Overview of URTI
• Acute infection of URT
• Nose, sinuses, pharynx or
larynx
• Common causes:
– Influenza
– Adenovirus
– RSV
– Parainfluenza
– Rhinovirus
– Metapneumovirus
– Coronavirus
– Enterovirus
• Symptoms:
– Fever
– Malaise, myalgia
– Headache
– Nasal discharge
– Sore-throat
– Itchy eyes
• Treatment:
– Antiviral: Influenza: neuraminidase
inhibitors or adamantanes; RSV:
ribavirin
– Analgesics: paracetamol, NSAID

5. National Institute for Health and Clinical Excellence: Guidance; 2008 Jul
Antibiotics ….when?

6. Key
laboratory
tests
for
diagnosis
of
acute
community
acquired
pneumonia
• 1.
Blood
culture
• 2.
Sputum/ETA/BAL
for
gram
stain,
bacterial
culture
(fungal
&
AFB
smear
&
culture,
PCP
smear,
parasiBc
ova)
• 3.
Pleural
fluid
for
gram
stain,
bacterial
culture
(fungal/AFB
smear
&
culture)
• 4.
NPA
or
T/S
(sputum,
ETA,
BAL)
for
respiratory
virus
anBgens
(animal
-­‐
camel
/
poultry
exposure
in
endemic
areas:
RT-­‐PCR
for
MERS-­‐CoV
/
H7N9)
• 5.
Urine
for
pneumococcal
anBgenuria
• 6.
Urine
for
legionella
pneumophila
serogroup
1
anBgenuria

9. No. of infected cells: determining test sensitivity
Swabs inserted: sampling posterior pharyngeal
wall / level of ear lobes
Specimens with high viral load
Timing of specimen taking: viral load usually highest
within the first 48 hours after onset of disease

10. Aspirate and swab in
Viral transport medium,
Stored at 4 (<24hr) or
-70(>24hr) degree Celsius

11. Epidemic curve of staff with influenza like illness in AE department
Clinical attack rate: 46% (17 infected / 37 staff)
M:F = 9:6
Infected doctor = 9 (50%, 9/18)
Infected frontline nurse = 5 (45%, 5/11)
Infected senior nurse = 2 (33%, 2/6)
Infected supporting staff = 1 (50%, 1/2)
Clinical symptoms:
Sneeze: 9
Nasal drip: 6
Fever: 3
Cough: 11
Sputum: 8
Sore-throat: 11
Headache: 3
Lethargy: 6
Risk factor for infection:
Lack of vaccination (p=0.051)
Infected case: none received vaccine
Non-infected case: 4 (25%)received vaccine

12. Case
1
• F/27;
Japanese
• History
of
pepBc
ulcer
disease
and
leh
ovarian
cyst
• Fever
&
cough
for
2
days
– Given
oral
cefuroxime
by
private
pracBBoner.
No
improvement
• TOCC
– Came
back
from
Japan
~2
weeks
before
symptom
onset
– Works
in
office
buildings
– No
contact
with
paBents
with
influenza-­‐like-­‐
illness
– No
clustering
• A&E
(day
2
aher
symptom
onset)
– Temp
39.5°C
– BP
107/65
– Pulse
130
Day
2
a&er
symptom
onset
(A&E)

13. Case
1
• Diagnosis
(A&E):
– community
acquired
pneumonia
• AnBbioBcs:
– AugmenBn
1g
bd
po
– Azithromycin
500mg
daily
po
• Persistent
fever
• AdmiKed
5
days
aher
symptom
onset
• Switched
to
– IV
AugmenBn
1.2g
q8h
– oral
Azithromycin
500mg
daily
Day
5
a&er
symptom
onset
(admission)

14. Case
1
• Sputum
culture:
– WBC:
3+,
commensals
• NPA:
– negaBve
for
respiratory
viruses
by
direct
immunofluorescence
• Blood
culture:
– no
growth
(taken
aher
3
days
of
AugmenBn
/
Azithromycin)
Day
7
a&er
symptom
onset
(hospitalized)

15. • Persistent
fever
without
clinical/
radiological
improvement
despite
6
days
of
AugmenBn
&
Azithromycin
• OpBons?
1. Start
Meropenem
2. Start
Doxycycline
3. Start
TB
treatment
(HREZ)
4. Start
oseltamivir
5. ConBnue
with
current
treatment
Oral
AugmenBn/
IV
AugmenBn
Oral
Azithromycin
0
1
2
3
4
5
6
7
8

16. • Persistent
fever
without
clinical/
radiological
improvement
despite
6
days
of
AugmenBn
&
Azithromycin
• OpBons?
1. Start
Meropenem
2. Start
Doxycycline
3. Start
TB
treatment
(HREZ)
4. Start
oseltamivir
5. ConBnue
with
current
treatment
• Given
piperacillin-­‐tazobactam
&
doxyccycline
– Rapid
resoluBon
of
symptoms
• Ix:
– NPA
PCR
for
Mycoplasma
pneumoniae:
posiBve
– Mycoplasma
pneumoniae
serology
• <10
(D5)
à
1280
(D21)
• Macrolide
resistance
marker
found:
A2063G
mutaBon
Oral
AugmenBn/
IV
AugmenBn
Oral
Azithromycin
0
1
2
3
4
5
6
7
8

17. Case
1
Doxycyline
Azithromycin
AugmenBn

18. J
Infect
Chemother.
2010
Apr;16(2):78-­‐86.
The
problem
of
MRMP

19. J
Infect
Chemother.
2010
Apr;16(2):78-­‐86

20. MRMP
rate
in
the
world
• China:
70%-­‐90%
• Taiwan:
23%
• Japan:
87.1%
(children)
• US:
up
to
18%
• Europe:
up
to
26%
Clin
Infect
Dis.
2012;
55(12):1642–9
Pediatr
Pulmonol.
2012
Nov
20.
doi:
10.1002/ppul.22706.
MMWR
Morb
Mortal
Wkly
Rep.
2012
Oct
19;61:834-­‐8
J
AnBmicrob
Chemother.
2011
Apr;66(4):734-­‐7.
Hong Kong
Lung
DC
et
al.
Hong
Kong
Med
J.
2011
Oct;17(5):407-­‐9.
Clinical implications:
• Longer
Bme
to
resoluBon
of
fever
• More
persistent
symptoms/signs
• Longer
duraBon
of
anBbioBcs
• Higher
bacterial
load

21. Rapid
effecBveness
of
tetracyclines
Tetracyclines
be>er
than
quinolone
Clin
Infect
Dis.
2012;
55(12):1642–9

22. Case
2
• M/30
months
• Good
past
health
• All
vaccinaBons
up-­‐to-­‐date,
received
a
dose
of
pneumococcal
conjugate
vaccine
(private
pracBBoner)
• Travelled
to
Singapore
31/3
–
8/4,
– Transit
at
Vietnam
on
31/3
(3h
at
departure
hall)
– Mosquito
bite
on
5/4
• 6/4:
Fever
to
40℃
with
occasional
dry
cough
• 8/4:
Given
ventolin
for
symptom
at
HKSH
outpaBent
• 10/4:
persistent
fever,
no
symptom
improvement
à
AdmiKed
to
HKSH
– started
on
AugmenBn
9/4 13/4
WCC 11.87 2.66
ANC 5.54 0.48
Lym 4.08 1.38
Aty
Lym -­‐ 5%
Plt 285 183

24. 9/4,
13/4
Blood
culture:
sterile
13/4
Throat
Swab:
normal
flora
14/4
-­‐ Mycoplasma
IgM:
neg
-­‐ Dengue
virus
IgM/IgG:
negaBve
13/4 CXR: Right pleural effusion
— US-guided pleural aspiration
— Turbid fluid: c/st negative
— Wcc 5346, Rbc 3000, ADA 71.5
— Protein 34.9, pH 8.0
— Augmentin à Cefepime

25. Transferred
to
QMH
18/4
18/4
CT
thorax
at
HKSH
– ConsolidaBve
changes
at
RML
and
RLL
with
associated
loss
of
volume.
– Early
change
of
necroBzing
pneumonia
has
to
be
considered
– Moderate
right
pleural
effusion
with
no
mediasBnal
shih
– Prominent
pre-­‐carinal
LN
up
to
0.6x1.3cm
9/4 13/4 18/4
WCC 11.87 2.66 11.68
ANC 5.54 0.48 3.62
Lym 4.08 1.38 7.48
Atyp
lym 5%
Plt 285 183 566
Day
13
a&er
symptom
onset
(Day
2
a&er
admission
to
QMH)

26. 18/4:
Blood culture: sterile
MSU: no growth
NPA x respiratory virus IF: negative
ASOT <100
Legionella antigen: negative
Melioidosis serology: T/F
EMU, Gastric aspirate: AFB smear negative
US-guided pleural drainage:
Right pleural effusion with internal echoes and
incomplete septation, measuring <1cm in thickness,
with thickest part 1.4cm
Fluid appearance: Turbid
pH 7.0, fluid protein 56.0
LDH 606, TCC 6925, neutrophil 70%
AFB smear negative, TB-PCR
Gram stain: no organisms seen
Bacterial culture: sterile
Antibiotics:
Augmentin 10-13/4, Cefepime 13-18/4
Fortum, Vancomycin, Azithromycin 18/4
Case
3
What further investigations could be
done?

27. Pleural fluid
Urine
…confirmed with PCR of pleural fluid!
Diagnosis:
S pneumoniae pneumonia with parapneumonic effusion

28. • Complicated
Pneumococcal
pneumonia:
– Sputum
culture:
non-­‐specific
– Blood
culture
posiBvity:
<10-­‐
20%
– Pleural
effusion
• Direct
examinaBon:
sensiBvity
70-­‐74%
• Low
culture
sensiBvity
• previous
anBbioBc
use
(>90%
in
paBents
with
parapneumonic
effusion)

29. Detects C-polysaccharide wall antigen of S. pneumoniae

31. CSF Urine
Sensitivity 95.4% 57.1%
Specificity 100% 86.3%
PPV 100% 15%
NPV 99.7% 97.9%

33. • Cross-­‐reacBvity
reported
in:
– Streptococcus
viridans,
Enterococcus
faecalis
(PF)
Porcel
et
al.
Chest.
2007;131:1442-­‐1447
– Streptococcus
oralis
(CSF)
Alonso-­‐
Tarrés
C
et
al.
Lancet.
(2001)13;358(9289):
1273-­‐4.
– Streptococcus
sanguis,
S
miNs
(PF)
Flores
et
al,
Eur
J
Pediatr
(2010)
169:581-­‐584
– Streptococcus
oralis
– Streptococcus
salivarius
(PF)
Ploton
et
al.
Pathol
Biol.(2006)54:498-­‐501

34. Pros
Easy to perform
Less affected by antibiotics treatment
Bedside test
Rapid
Cons
Antibiotics susceptibility cannot be done
Serotyping not possible
Cost ($1500 for 12)
Cross-reactivity

35. Case
3
• Elderly
male,
NS/social
drinker,
• PH:
hypertension
X
30yr,
DM
for
15
yr
now
on
insulin,
mild
coronary
artery
disease
(LAD),
hyperlipidemia,
gout
• Chronic
renal
failure
on
CAPD
• Acute
onset
of
fever
and
shortness
of
breath
for
1
day,
given
two
doses
of
ciproxfloxacin
250mg
q12h
by
family
physician.
He
had
no
bowel
moBon
for
one
day.
• Referred
to
QMH
with
worsening
of
symptoms
• Drug
list:
– Cadura
1mg
bd
– Adalat
GITS
90mg
bd
– Betaloc
75mg
bd
– Hydralazine
75mg
tds
– Lipitor
20mg
nocte
– CaCO3
2000/1000mg
bd
with
meals
– Renagel
1200mg
bd
– Lanthanum
carbonate
500mg
bd
– Mircera
50
micrograms
q10days
– Lasix
120mg
daily
– Natrilix
SR
1
tab
daily
– NaHCO3
900mg
daily
– CarBa
100mg
daily
– ForBfer
1
tab
daily

36. Case
3
• PaBent
given
IV
AugmenBn
1.2
gm
q12h
aher
blood
culture
by
nephrologist
• Though
no
coffee
ground
or
melena,
upper
endoscopy
by
gastroenterologist
because
Hb
dropped
from
11
(last
blood
checking
at
OPD)
to
7
• Endoscopy
aborted
because
of
desaturaBon
to
70%;
RR
30/min.
Admit
to
ICU
by
intensivist;
• Had
diarrhea
7X
watery
in
24hr
aher
admission
• Consulted
microbiologist/ID
Day 4 after symptom onset
(admission)

37. Case
3
• Microbiology
&
ID:
– Temp:
39
C,
p
– BP
160/90,
RR
25/min
– P:
120/min,
irregular
(80
regular
aher
digoxin/amiodarone)
– SaO2:
70%
on
room
air;
95%
while
on
CPAP
– Slow
mentaBon,
pallor+,
facial
puffiness,
bilateral
ankle
edema,
scratch
mark+
– No
exit
site
erythema
or
tunnel
tract
/
abdominal
tenderness,
PD
fluid
clear;
– Decreased
air
entry
to
leh
posterior
chest;
coarse
inspiratory
crepitus
• Hb
7.5,
WBC
8.6,
N
7.4,
L
0.65,
Plt
160,
• Urea
36.2,
Cr
1299,
Na
135,
K
5.1,
A/G
28/33,
ALP
34,
ALT
13,
AST
28,
Ca
2.1,
PO4:
1.68
• LDH
405(221),
troponin
0.21
(N<0.5
AMI),
CPK
131
(355)
• RetrospecBve
quesBoning:
history
of
travel
to
a
Hotel
and
zoo
for
1
day(9
Dec)
in
Guangzhou
6
days
before
admission(18
Dec)
Day 5 after symptom onset

38. Case
3
• RecommendaBons:
1. Microbiological
workup
for
causes
of
acute
community
acquired
typical
&
atypical
pneumonia
with
history
of
zoonoBc
contact
in
a
uraemic
paBent
on
CAPD
2. Empirical
IV
levofloxacin
0.5
gm
q48h,
meropenem0.5gm
q24h,
one
dose
zanamivir
0.6
gm
Bll
anBgenuria
&
viral
PCR
back
3. Acute
leh
heart
failure:
draw
fluid
out
by
increased
PD
Day 6 after symptom onset
(LLZ consolidation despite
dialysis)

39. InvesBgaBons
&
what
to
do
next?
• Blood
culture:
negaBve
• Cold
aggluBnin:
negaBve
• Sputum
not
produced
Bll
day
4
aher
admission
(21
Dec)
• NPA
viral
anBgen
by
IF:
negaBve
(19
Dec)
• Resplex
II
RT-­‐PCR
for
10(16)
viruses:
influenza
A(M,
pH1,
H3),
and
B,
adenovirus,
parainfluenza
1-­‐3,
respiratory
syncyBal
virus
A
and
B,
human
metapneumovirus,
human
rhinovirus.
coronavirus
(229E,
OC43,
NL63,
HKU1),
coxsackie/echo
virus,
bocavirus
and
adenoviruses
(B,
E):
negaBve
• Urine
anBgen
EIA(Binax)
for
legionella
pneumophila
serogroup1
&
streptococcus
pneumoniae
C
polyssacharide:
negaBve
(20
Dec)
• Urinalysis:
proteinuria
100mg/dL;
glucose:
250mg/dL;
occult
blood:
small;
RBC:
<30/ul
• Stool
culture
&
clostridium
difficile
cytotoxin:
negaBve
• PD
fluid:
normal
cell
count
&
culture
negaBve

40. Recent
travel,
acute
CAP,
diarrhea:
Real-­‐Bme
PCR
for
legionella
pnemophila
22
Dec
2011
NPA
on
Day
1
&
Sputum
sample
on
Day
4
are
posiBve;
Stop
meropenem
&
zanamivir;
ConBnue
levofloxacin
alone;
NoBfy
epidemiologists
of
CHP
Legionella antigenuria EIA: negative 2X; Early use of
ciprofloxacin? Renal failure & inability to concentrate
bacterial antigen?

42. No
response
to
Beta-­‐lactams;
Respond
to
Fluoroquinolones
Marcolides
Tetracyclines
by
2
to
3
days;
*
*

44. Legionellosis
in
what
host
• Risk
factors
for
Legionnaires‘
disease
include
1.
increasing
age,
2.
smoking,
3.
male
sex,
4.
chronic
lung
disease,
5.
hematologic
malignancies,
6.
end-­‐stage
renal
disease,
7.
lung
cancer,
8.
immunosuppression,
9.
diabetes
and
10.
HIV/AIDS
• Health
advice
to
paBents
with
immunosuppressed
condiBons:
1. eat
and
drink
boiled
items,
2. use
sterile
or
off-­‐boiled
water
for
nebulizers,
3. rinse
mouth
with
off-­‐boiled
water,
4. flush
iniBal
stream
and
avoid
nebulizaBon
5. consider
inline
bacterial
filter
in
very
immunosuppressed
hosts