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

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

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  

PARASITES FUNGI

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

 

National Institute for Health and Clinical Excellence: Guidance; 2008 Jul

Antibiotics ….when?

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                        

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

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

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

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)  

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)  

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)  

•  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  

•  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  

Case  1  

Doxycyline  

Azithromycin  

AugmenBn  

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

The  problem  of  MRMP

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

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    

Rapid  effecBveness  of  tetracyclines  

Tetracyclines  be>er  than  quinolone  

Clin  Infect  Dis.  2012;  55(12):1642–9    

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

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

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)  

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?

Pleural fluid Urine

…confirmed with PCR of pleural fluid!

Diagnosis: S pneumoniae pneumonia with parapneumonic effusion

•  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)      

Detects C-polysaccharide wall antigen of S. pneumoniae

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

•  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  

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

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

 

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)

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

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)

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  

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?

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

*

*

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