Pneumonia

1
Pneumonia

• Deborah Goldstein
• Georgetown ID Fellow
• February 9, 2009

2
Outline

• CAP, HAP, HCAP, VAP bugs, diagnostics, drugs
• MDR organisms, therapies
• PNA Prevention
• Questions are adapted from MYKSAP
• 1. Infectious Disease Society of
  America/American Thoracic Society Guidelines on
  Management of CAP in Adults, CID 2007
• 2. ATS Guidelines for Management of Adults with
  HAP, VAP, and HCAP, Am J Respir Crit Care Med
  2005
• Level 1 evidence from RCTs. Level 2
  nonrandomized trials (patient series, cohort
  studies). Level 3 expert opinion.

3
Pneumonia Definitions

• Community-acquired PNA (CAP)
• Cough/fever/sputum production infiltrate
• Healthcare-associated PNA (HCAP)
• PNA that develops within 48 hours of admission
  (but is not present on admission) in pts with
• Hospitalization in acute care hospital for 2 d
  in past 90 d
• Residence in NH or LTC facility
• Chronic dialysis within 30 days
• Home IV therapy, home wound care in past 30 days
• Family member with MDR pathogen
• Hospital-acquired PNA (HAP)
• PNA 48 hours after admission
• Ventilator-associated PNA (VAP)
• PNA 48-72 hours after intubation

4
Almost 1 million annual episodes of CAP in adults
65 yrs in the US
5
Drug Resistant Strep Pneumoniae

• 40 of U.S. Strep pneumo CAP has some antibiotic
  resistance
• PCN, cephalosporins, macrolides, tetracyclines,
  clinda, bactrim, quinolones
• All U.S. MDR strains are sensitive to vancomycin
  or linezolid most are sensitive to respiratory
  quinolones
• Original definitions of ß-lactam resistance were
  for meningitis (CSF drug levels are a fraction of
  plasma levels)
• PCN is effective against pneumococcal PNA at
  concentrations that would fail for meningitis or
  otitis media
• For PNA, pneumococcal resistance to ß-lactams is
  relative and can usually be overcome by
  increasing ß-lactam doses (not for meningitis!)

ATS Guidelines, 2005
6

• Pneumococcal CAP Be cautious if using PCN if
  MIC 4. Avoid using PCN if MIC 8.
• Remember that if MIC PCN-sensitive in sputum or blood (but need MIC
  

MIC Interpretive Standards for S. pneumoniae.
Clinical Laboratory Standards Institute (CLSI)
2008 28123.
7
Who is at risk for drug-resistant Strep Pneumo
CAP?

• Age 65 yrs
• ß-lactam therapy in past 3 months
• Alcoholism
• Medical comorbidities
• Immunosuppression
• Exposure to a child in day care
• Nursing home, long-term care facility, homeless
  shelter

IDSA/ATS Guidelines 2007
8
Resistant Pneumococcus

• A 44-year-old woman is hospitalized from the ER
  with left lower lobe pneumonia. Medical history
  is unremarkable except for recurrent urinary
  tract infections for which she has received
  various antibiotics.
• On admission, temp 39.2 C. IV levofloxacin is
  begun.
• One day later, her temp has decreased to 38.1 C,
  and blood cultures from the ER grow Strep pneumo
  with minimal inhibitory concentration (MIC) for
  penicillin 1 µg/mL.
• Which of the following is the most appropriate
  therapy at this time?
• Change to cefepime
• Change to vancomycin
• Change to ampicillinsulbactam
• Change to linezolid
• Continue levofloxacin

9
PCN Resistant Pneumococcus

• Answer E continue levofloxacin
• Pt has bacteremic pneumococcal PNA with MIC1, so
  PCN-sensitive, clinically improving on
  levofloxacin
• Continue levofloxacin until she meets criteria to
  change to PO
• If pt had meningitis with Strep pneumo PCN MIC
  1, PCN would NOT be appropriate therapy
• Organisms that are resistant to PCN are usually
  sensitive to fluoroquinolones and are uniformly
  sensitive to vanc and linezolid

10
CAP Atypicals

• Mycoplasma pneumoniae, Chlamydophila pneumoniae,
  Legionella Coxiella burnetii (Q fever),
  Francisella tularensis (tularemia), Chlamydia
  psittaci (psittacosis)
• Approximately 15 of all CAP
• Atypical not detectable on gram stain wont
  grow on standard media
• Unlike bacterial CAP, often extrapulmonary
  manifestations
• Mycoplasma otitis, nonexudative pharyngitis,
  watery diarrhea, erythema multiforme, increased
  cold agglutinin titre
• Chlamydophila laryngitis
• Most dont have a bacterial cell wall? Dont
  respond to ß-lactams
• Therapy macrolides, tetracyclines, quinolones
  (intracellular penetration, interfere with
  bacterial protein synthesis)

11
Atypical PNA

• A 63-year-old man is brought to the ER with 4
  days of fevers, cough, confusion, and mild
  diarrhea. His wife reports he just returned from
  a business trip where he stayed in a hotel.
• In the ER Temp 103, BP 142/70, RR 24.
• Exam Ill-appearing. Rales at the left base.
• CXR LLL consolidation.
• Labs WBC 26K, Hct 44, BUN/Cr 42/2.3, AST 107,
  ALT 110, Na 130
• All of the following would be appropriate therapy
  EXCEPT
• Azithromycin
• Doxycycline
• Levofloxacin
• Moxifloxacin
• Imipenem

12
CAP Legionella

• Answer E Imipenem. Imipenem has very broad
  coverage, but NO ATYPICALS.
• Consider in returning travelers from hotels,
  cruise ships within the past 2 weeks
• Extrapulmonary CNS (headache, AMS), GI
  (diarrhea, abd pain), cardiac (relative
  bradycardia), hepatic (transaminitis), renal
  (incr. creatinine), muscle involvement (incr.
  CPK), low Na, low phos
• Infects alveolar macrophages (intracellular)
• Tx Fluoroquinolones or azithromycin
• Legionella Urine Ag sensitivity 70-90,
  specificity 99.
• Detects only Serogroup 1.
• Serogroup 2, 3 cause 5-20 of disease.
• Gold standard culture on BCYE agar.

13
CAP CA-MRSA

• CA-MRSA PNA remains rare in most communities but
  is anticipated to be an emerging threat
• May cause severe disease with abscess, empyema
  formation necrotizing or cavitary PNA
• Risk factors for CA-MRSA PNA ESRD, IVDU, prior
  antibiotic therapy (especially quinolones), prior
  influenza
• Linezolid at least as effective as vancomycin
  for treatment of MRSA PNA
• Do not use Daptomycin (inactivated by lung
  surfactant)
• Negative gram stain and culture prior to
  antibiotics is adequate to withold or stop tx for
  MRSA

IDSA/ATS Guidelines 2007
14
Who is at risk for Pseudomonal PNA?

• Immunocompromised pts (HIV, solid organ or bone
  marrow transplant, neutropenic, chronic oral
  steroids)
• Alcoholics
• Frequent prior antibiotic use
• Recent hospital admission
• Structural lung abnormalities
• Cystic fibrosis, bronchiectasis, severe COPD
• Rare in previously healthy pts
• Gram stain/sputum culture (if good quality) is
  usually adequate to exclude need for empiric
  coverage

15
Who is at risk for which pathogens?

• PNA in nursing home/long term care facility
  residents mirrors PNA in hospitalized pts
• Pseudomonas, Acinetobacter, MRSA
• Chronic hemodialysis
• Increased risk of MRSA (not Pseudomonas or
  Acinetobacter)
• COPD
• Increased risk for Pseudomonas (not MRSA)

16
Remember these associations

• Alcoholism Strep pneumo, oral anaerobes, K.
  pneumo, Acinetobacter, MTB
• COPD/smoking H. influenzae, Pseudomonas,
  Legionella, Strep pneumo, Moraxella catarrhalis,
  Chlamydophila pneumoniae
• Aspiration Klebsiella, E. Coli, oral anaerobes
• HIV S. pneumo, H. influ, P. aeruginosa, MTB,
  PJP, Crypto, Histo, Aspergillus, atypical
  mycobacteria
• Recent hotel, cruise ship Legionella
• Structural lung disease (bronchiectasis)
  Pseudomonas, Burkholderia cepacia, Staph aureus

17
CAP Diagnostics

• Outpatients testing is OPTIONAL
• Most pts do well on empiric therapy
• Inpatients low yield of sputum blood cultures,
  so perform only if result will change antibiotic
  management or test will be high yield....
• Blood cultures for probable pathogen in 5-14
  of hospitalized CAP
• Sputum gram stain usually poor quality. Only
  14 yield causative organism
• Sputum culture collect prior to antibiotics for
  best yield
• Pneumococcal Urine Ag Sensitivity 50-80,
  specificity 90
• Influenza rapid nasal swab sensitivity 50-70,
  specificity 100

18

• Blood sputum culture, pneumococcal urine Ag
  severe CAP, chronic disease, immune defects
• Legionella urine Ag severe CAP, pts with
  recent travel

IDSA/ATS Guidelines 2007
19
Outpatient CAP therapy

• Previously healthy, without risk factors for DRSP
  (age 65 yrs, recent ß-lactams, alcoholism,
  medical comorbidities, immunosuppression, nursing
  home....)
• Macrolide (azithro, clarithro, erythromycin)
  (level 1)
• Doxycycline (level III)
• Heart/ lung/ liver/ kidney disease, DM, EtOH,
  malignancies, asplenia, immunosuppression,
  antibiotics in past 3 months or any DRSP risk
• Respiratory quinolone (Moxi, Levo 750 mg) (level
  1) OR
• ß-lactam PLUS macrolide (level 1)
• ß-lactam Amox 1g TID OR Augmentin 2g bid (high
  dose PCNs to overcome Strep pneumo resistance).
  Alt cefuroxime 500 mg bid.

20
Outpatient CAP

• A 35-year-old woman with mild asthma has a 3-day
  history of fever, productive cough, and wheezing.
  Her 5-year old son recently had cough and fever
  to 38.9 C. She has a 10-pack-year smoking
  history and quit 3 years ago.
• Temp 38.2 C, HR 100, BP 115/75, RR 16/min, 94
  RA
• Bronchial breath sounds and a few crackles in the
  lateral right lower chest, mildly audible
  wheezing.
• WBC 11,900/µL, 80 neutrophils, 2 bands.
• CXR right middle lobe consolidation.
• Which of the following is most appropriate at
  this time?
• A. Await results of sputum culture before
  beginning therapy
• Begin trimethoprimsulfamethoxazole
• Begin ciprofloxacin
• Begin azithromycin
• Begin gentamicin

21
Outpatient CAP

• Answer D Start azithromycin
• Likely pathogens Strep pneumo, atypicals
  (Mycoplasma, Chlamydophila, Legionella)
• Her mild asthma does not put her at risk for
  community-acquired pneumonia due to unusual
  pathogens
• CAP in an outpatient without other risk factors
• Macrolide (azithro, clarithro, erythro), or
  doxycycline
• Sputum gram stain, culture not high yield in
  outpatients
• Bactrim poor Strep pneumo coverage, almost no
  atypical coverage
• Cipro poor Strep pneumo coverage but covers
  atypicals

22
CAP Outpatient therapy duration

• No standardized recommendation for duration of
  therapy
• Treat for a minimum of 5 days (often 7-10 days)
• Pts should be afebrile for 48-72 hrs before
  stopping therapy
• Azithromycin
• Long tissue half life
• Trials as short as 3-5 days in outpatient CAP
  have been successful
• Levaquin
• At least 5 days

23
PNA Outpatient or Inpatient?

• CURB-65
• 5 indicators of increased mortality confusion,
  BUN 7, RR 30, SBP 65
• Mortality 2 factors?9, 3 factors?15, 5
  factors?57
• Score 0-1?outpt. Score 2?inpt. Score 3?ICU.
• Pneumonia Severity Index (PSI)
• 20 variables including underlying diseases
  stratifies pts into 5 classes based on mortality
  risk
• No RCTs comparing CURB-65 and PSI
• Not routinely used in GUH clinical practice
  though guidelines give them level 1, strong
  rating

IDSA/ATS Guidelines 2007
24
PNA Medical floor or ICU?

• 1 major or 3 minor criteria severe CAP?ICU
• Major criteria
• Invasive ventilation, septic shock on pressors
• Minor criteria
• RR30 multilobar infiltrates confusion BUN
  20 WBC
  hypotension requiring aggressive fluids,
  PaO2/FiO2
• No prospective validation of these criteria!

IDSA/ATS Guidelines 2007
25
CAP Inpatient therapy

• General medical floor
• Respiratory quinolone (level 1) OR
• IV ß-lactam PLUS macrolide (IV or PO) (level 1)
• ß-lactams cefotaxime, ceftriaxone, ampicillin
  ertapenem
• May substitute doxycycline for macrolide (level
  3)
• ICU
• ß-lactam (ceftriaxone, cefotaxime, amp-sulbactam)
  PLUS EITHER quinolone (level 1) OR azithro (level
  2)
• PCN-allergic respiratory quinolone PLUS
  aztreonam
• Pseudomonal coverage (level 3)
• Antipneumococcal, antipseudomonal ß-lactam
  (pip-tazo, cefepime, imi, mero) PLUS EITHER
  (cipro or levo) OR (aminoglycoside AND Azithro)
  OR (aminoglycoside AND respiratory quinolone)
• CA-MRSA coverage Vanc or Linezolid (level 3)

26
CAP Inpatient Therapy Pearls

• Give 1st dose Antibiotics in ER (no specified
  time frame)
• Switch from IV to oral when pts are
  hemodynamically stable and clinically improving
• Discharge from hospital
• As soon as clinically stable, no active medical
  problems
• Duration of therapy is usually 7-10 days
• Treat for a minimum of 5 days (level 1)
• Before stopping therapy afebrile for 48-72
  hours, hemodynamically stable, RR
  90, normal mental status
• Treat longer if initial therapy wasnt active
  against identified pathogen or if complications
  (lung abscess, empyema...)

27
Inpatient CAP

• 73-year-old man with COPD and type 2 DM has 1 day
  of increasing cough, dyspnea, fever, and chills.
  He has a 60-pack-year smoking history.
• Temp 38.0 C, HR 100, BP 135/85, RR 20, O2 sat
  86 RA.
• Exam obese, mild respiratory distress.
• Decreased breath sounds bilaterally, scattered
  rhonchi, crackles at left base.
• Labs WBC 9,700, 72 neutrophils, 10 bands, BUN
  40, Cr 2.4
• CXR patchy infiltrate at the left lung base.
• The patient is hospitalized.
• Which of the following is the most appropriate IV
  therapy?
• A. Ceftriaxone plus azithromycin
• B. Ampicillinsulbactam
• C. Ticarcillin plus tobramycin
• D. High-dose penicillin
• E. Trimethoprimsulfamethoxazole

28
Inpatient CAP

• Answer A ceftriaxone and azithromycin
• The pt is hospitalized.
• Does he need DRSP coverage? Yes.
• Age 60, DM, COPD
• Does he need Pseudomonal coverage? No.
• Not immunocompromised, not on chronic steroids,
  not alcoholic, no recent prior antibiotic use or
  hosp admission, no structural lung abnormalities
  (his COPD is not severe)
• General medical floor respiratory quinolone OR
  (ß-lactam PLUS macrolide)
• ICU without pseudomonal coverage ß-lactam PLUS
  (macrolide OR quinolone)
• The other 4 choices do not cover atypicals

29
Inpatient CAP

• A 72-year-old male smoker with COPD was
  hospitalized 2 days ago with fever, cough,
  dyspnea and patchy left lower lobe PNA.
• Initial WBC 14,300/µL. O2 sat 94 on 2L.
• IV levofloxacin was started on admission.
• Hospital day 3 Pt has been afebrile for the past
  18 hours. He has good oral intake, his cough has
  decreased, and he is no longer dyspneic. WBC
  9,600. O2 sat 92 on RA.
• Repeat CXR no change in size of LLL infiltrate.
• Which of the following is most appropriate at
  this time?
• A. CT scan of the chest
• B. Consultation for fiberoptic bronchoscopy
• C. Replacement of IV levofloxacin with PO
  levofloxacin
• D. Addition of IV ceftriaxone

30
Inpatient CAP

• Answer C switch IV to PO levofloxacin
• This pt with CAP is responding well to therapy
  resolution of fever, cough, and dyspnea by day 3.
  His leukocytosis normalized. Pt has a
  functioning GI tract and can take oral
  medication.
• A stable CXR does not indicate treatment failure.
• Only two thirds of pts show radiographic clearing
  of pneumonia by the fourth week of therapy.

31
Inpatient CAP

• A 79-year-old woman who lives at home is
  hospitalized for CAP. She had an apparent upper
  respiratory tract infection 7 days ago and
  developed left-sided pleuritic chest pain and
  shaking chills 1 day before admission. Three
  weeks ago, she had a UTI treated with Cipro.
• Exam Temp 38.7 C, HR 110, BP 90/60, RR 24/min.
• Crackles, diminished breath sounds at the left
  lung base, and egophony.
• WBC 31,000, 85 neutrophils, 7 bands. CXR left
  lower lobe infiltrate.
• According to the hospital's antibiogram, local
  isolates of Strep pneumo are often multi-drug
  resistant 30 of isolates are resistant to
  penicillin and 30 are resistant to macrolides.
• Which of the following is the most appropriate
  therapy for this patient at this time?
• Intravenous vancomycin plus ceftriaxone
• Intravenous ceftriaxone plus azithromycin
• Intravenous levofloxacin
• Oral telithromycin

32
CAP

• Answer B Intravenous ceftriaxone plus
  azithromycin
• Avoid Levaquin because her previous use of cipro
  predisposes her to fluoroquinolone-resistant
  pneumococcus.
• Also, limit use of fluoroquinolones as first-line
  therapy for CAP to limit the massive increase in
  fluoroquinolone resistance.
• Does she need vancomycin? No.
• Ceftriaxone is adequate for PNA even in the
  setting of possible PCN-resistant Strep pneumo.
• Does she need atypical coverage with
  azithromycin? Yes. Vancomycin does NOT cover
  atypicals.
• Telithromycin is a ketolide (derived from
  macrolide class) not yet recommended for CAP due
  to hepatotoxicity.

33
Severe CAP

• A 62-year-old man is evaluated in the ER with 3
  days of fever, progressive dyspnea, and cough.
  History of HTN, coronary artery disease, and MI 3
  years ago.
• Exam respiratory distress. T 39.4. HR 120. BP
  88/60. RR 24. O2 sat 82 RA. Scattered crackles
  and rhonchi are heard throughout both lung
  fields.
• CXR patchy infiltrates in the right upper and
  lower lobes and left lower lobe.
• Sputum and blood cultures are obtained, IV fluids
  and supplemental oxygen are started, and IV
  levofloxacin and ceftriaxone are begun. The
  patient is admitted to the ICU.
• Which of the following should also be done at
  this time?
• A. Request fiberoptic bronchoscopy
• B. Schedule a CT scan of the chest
• C. Order urine specimen for Legionella antigen
• D. Add intravenous vancomycin

34
Severe CAP, ICU

• Answer C Order Legionella urine antigen
• Pt admitted to ICU because he met several minor
  criteria for severe CAP
• RR30 multilobar infiltrates confusion BUN
  20 WBC
  hypotension requiring aggressive fluids,
  PaO2/FiO2
• Legionella testing is indicated in severe CAP
• Bronchoscopy does not typically provide useful
  information in the initial evaluation of CAP in
  an immunocompetent host unless an endobronchial
  lesion is suspected.
• There is no need for vanc as levofloxacin is
  adequate Strep pneumo coverage

35
CAP

• A 62-year-old man comes to the ER with 2 days of
  fever, cough, and yellow-green sputum production.
  The patient had severe PNA when he was 40,
  following which he developed a daily cough and
  whitish-yellow sputum production. He typically
  receives one or two courses of antibiotics each
  year when his sputum increases in volume and
  becomes darker. He is a lifelong nonsmoker.
• Exam Temp 38.7 C. Coarse breath sounds at the
  posterior base of the right lung, with scattered
  crackles and rhonchi.
• WBC 13,500, 74 neutrophils, 12 bands.
• CXR patchy right lower lobe infiltrate. (A chest
  film 2 years ago showed nonspecific increased
  markings at the right lung base).
• In choosing antibiotics, which organism should
  you cover?
• Mycobacterium tuberculosis
• Respiratory syncytial virus
• Nocardia brasiliensis
• Pseudomonas aeruginosa
• Chlamydophila pneumoniae

36
CAP

• Answer D Pseudomonas aeruginosa
• This pt has underlying bronchiectasis, which
  developed after a severe episode of CAP 22 yrs
  ago he now has chronic cough and sputum
  production and baseline CXR abnormalities that
  suggest bronchiectasis
• Bronchiectasis is a risk factor for Pseudomonas
  aeruginosa CAP
• Bronchiectatic airways may be chronically
  colonized with many organisms, including
  Pseudomonas
• Illness is too acute in onset to be suggestive of
  MTB
• Nocardia lung infections occur most often in
  immunosuppressed patients
• Chlamydophila pneumoniae causes CAP but is not
  associated with bronchiectasis or chronic airway
  colonization

37
CAP Influenza

• Inhale small aerosolized particles from coughing,
  sneezing?1-4 day incubation? uncomplicated
  influenza (fever, myalgia, malaise,
  rhinitis)?PNA
• Adults 65 account for 63 of annual
  influenza-associated hospitalizations and 85 of
  influenza-related deaths
• CXR findings often subtle
• Respiratory isolation for suspected or documented
  influenza
• Bacterial PNA (S. pneumo, S. aureus) may follow
  viral PNA

Murata Y. Recognizing viral causes of CAP.
Journal of Resp Dis 2008.
38
www.cdc.gov/flu/weekly, 2/8/09
39
Influenza Therapy

• 06-08 widespread resistance to Adamantanes
  among influenza A strains not recommended
• Neuraminidase inhibitors
• 70-90 effective for prophylaxis
• Give within 48h of symptom onset to reduce
  duration/severity of illness, and viral shedding

Red carried by GUH inpt pharmacy
40
Influenza Resistance

• 07-08 11 of influenza A (H1N1) was
  oseltamivir-resistant
• 08-09 98 of influenza A (H1N1) is
  oseltamivir-resistant all sensitive to
  zanamivir, amantadine, rimantadine
• Oseltamivir-resistant virus same severity of
  illness
• Influenza A (H3N2) and Influenza B viruses still
  sensitive to oseltamivir
• Proportion of all U.S. influenza that is H1N1 is
  unknown!
• CDC 12/08
• Suspected influenza A (H1N1) virus infxn or
  exposure zanamivir (alternate oseltamivir
  rimantadine)
• GUH substitute amantadine for rimantadine
• Influenza B oseltamivir or zanamivir

41
HCAP, HAP, VAP

• Healthcare-associated PNA (HCAP)
• PNA within 48 hours of admission in pts with
• Hospitalization in acute care hospital for 2
  days in past 90 days
• Residence in NH or LTC facility
• Chronic dialysis within 30 days
• Home IV therapy, home wound care in past 30d
• Family member with MDR pathogen
• Hospital-acquired PNA (HAP)
• 48 hours after admission
• Ventilator-associated PNA (VAP)
• 48-72 hours after intubation

42
Organisms in HAP, VAP

• Pts with no known risk factors for MDR pathogens
• Strep pneumo, H. influenzae, MSSA
• Sensitive enteric GNR E. Coli, Klebsiella,
  Enterobacter, Proteus, Serratia
• Risk Factors for MDR organisms
• Pts with ANY Risk factors for HCAP
• Antibiotics in the past 90 days
• Current hospitalization 5 days
• High frequency of antibiotic resistance

43
Multi-drug Resistant Organisms

• Common MDR Organisms
• Pseudomonas aeruginosa
• MRSA
• SPACE Organisms Serratia, Proteus,
  Acinetobacter, Citrobacter, Enterobacter
• ESBL Klebsiella, E Coli
• Stenotrophomonas maltophilia
• Burkholderia cepacia

ATS Guidelines, 2005
44
HAP, HCAP, VAP MRSA

• Standard of therapy vancomycin
• Failure rates 40 with vanc 1g iv bid due to
  inadequate dosing
• Aim for vanc trough 15 mg/L (no prospective
  trials validate this, though)
• 2 RCTs Linezolid equivalent to vanc in HAP, VAP
  (may even be superior)
• 1 RCT Synercid (quinupristin-dalfopristin)
  worse outcomes than vanc in HAP
• Remember daptomycin is inactivated by pulmonary
  surfactant. DO NOT USE in PNA.

ATS Guidelines, 2005
45
HAP

• 72-year-old NH resident with COPD, DM transferred
  to ICU on day 12 of admission. Intubated for
  respiratory distress.
• Temp 38.6, BP 130/80. WBC 3.0.
• Sputum gram stain many WBC, GNR. Cx pending.
• All of the following are likely etiologies
  EXCEPT
• Pseudomonas aeruginosa
• Vancomycin-resistant Enterococcus
• Acinetobacter baumanii
• ESBL E. Coli
• Serratia marsescens

46
HAP Organisms

• Answer is B VRE
• Enterococcus is very rare cause of pneumonia
• Question Part 2 The patients sputum culture
  grows Klebsiella pneumoniae, ESBL.
• What is the best treatment option?
• A. Aztreonam
• B. Levofloxacin
• C. Tobramycin
• D. Meropenem

47
Extended Spectrum ß-lactamases

• Answer D Meropenem
• ESBL resistance is plasmid-mediated
• ESBLs hydrolyze extended-spectrum cephalosporins
  with an oxyimino side chain
• RESISTANT Ceftriaxone, ceftazadime, cefepime
• RESISTANT Aztreonam
• ESBLs cannot inactivate cephamycins
• SENSITIVE 2nd gen cephalosporins cefoxitin,
  cefotetan
• ESBLs most common in Klebsiella, E. Coli
• Tx No RCTs, but carbapenems associated with
  improved bacteria clearance and improved survival

48
HAP/VAP Risk Factors

• 1. Intubation and mechanical ventilation increase
  the risk of HAP 6-21 fold
• Reduce vent duration vent weaning protocols,
  decreased sedation. Noninvasive ventilation.
• 2. Leakage of bacteria around the endotracheal
  tube cuff or aspiration of oropharyngeal
  pathogens ? colonization of lower resp tract ?
  PNA
• Limit sedatives and paralytic agents that depress
  cough
• Semi-recumbent (30-45), not supine! especially
  during enteral feeding
• 3. Antihistamines, antacids?decrease gastric
  acidity

49
HAP, VAP Therapy Pearls

• Start empiric antibiotics early. Delay in
  starting appropriate antibiotics ? increased
  mortality
• Choose initial Abx based on risk factors for
  specific pathogens, local patterns of Abx
  resistance and organism prevalence
• Do not change Abx in first 48-72 hrs unless pt
  deteriorates or culture results dictate it
• If not clinically improved at 48-72 hrs, adjust
  antibiotic therapy
• Narrow antibiotics when culture results are known

ATS Guidelines, 2005
50
HAP, VAP Antibiotics

• If early-onset PNA (organisms
• Bugs Strep pneumo, H. influenzae, MSSA, E. coli,
  K. pneumo, Enterobacter, Proteus, Serratia
• Drugs Ceftriaxone, cipro/levo/moxi,
  amp-sulbactam or Ertapenem
• If late-onset PNA (5d) and RFs for MDR
  organisms
• Bugs P. aeruginosa, ESBLs, Acinetobacter, MRSA
• Drugs (antipseudomonal cephalosporin or
  carbepenem or ß-lactam/ß-lactam inhibitor) PLUS
  (antipseudomonal quinolone OR aminoglycoside)
  PLUS (Linezolid or vanc)
• (Cefepime/Ceftazadime or Imipenem/Meropenem or
  pip-tazo) PLUS (Cipro/Levo OR Amik/Gent/Tobramycin
  ) PLUS (Linezolid or vanc)

ATS Guidelines, 2005
51
HCAP Management

• An 82-year-old woman was admitted to the hospital
  for CAP. She lives alone and was hospitalized 2
  months ago for urosepsis treated with cipro.
• On admission, she was clinically stable with
  right middle and lower lobe consolidations.
  Ceftriaxone was started but she deteriorated with
  worsening dyspnea, progressive hypoxemia, and
  persistent fever.
• 48 hours after admission, she is transferred to
  the ICU for respiratory failure
• Exam HR 124, RR 40, O2 sat 85 on 100
  nonrebreather.
• Rhonchi in all lung fields. Normal cardiac exam.
  No leg swelling.
• CXR diffuse bilateral infiltrates.
• She is intubated. Blood, urine, and endotracheal
  tube aspirate cultures are sent.
• Which is the appropriate next step in managing
  this patient?
• A. Bronchoscopy with protected specimen brushing
  
• B. Doppler ultrasonography of the lower
  extremities
• C. Change of antibiotics to vancomycin,
  cefepime, and ciprofloxacin pending cultures
• D. CT scan of the sinuses, and aspiration of
  maxillary sinus fluid

52
HCAP

• Answer C Change of antibiotic therapy to
  vancomycin, cefepime, and ciprofloxacin pending
  culture results
• Her recent hospital admission 2 months ago puts
  her at risk for HCAP with MRSA and Pseudomonas
• Her HCAP worsened after 48 hours ceftriaxone
  therapy
• She now needs broader coverage for MRSA and
  Pseudomonas
• (Antipseudomonal cephalosporin or carbepenem or
  ß-lactam/ß-lactam inhibitor) PLUS
  (antipseudomonal quinolone OR aminoglycoside)
  PLUS (Linezolid or vanc)
• (Cefepime/Ceftazadime or Imipenem/Meropenem or
  Zosyn) PLUS (Cipro/Levo OR Amik/Gent/Tobramycin)
  PLUS (Linezolid or vanc)
• Bronchoscopy with protected specimen sampling has
  not been shown to improve outcomes beyond that
  achieved by lower respiratory tract cultures

53
VAP 8 days vs. 15 days of antibiotics

• Traditionally, VAP was treated for 14-21d because
  shorter therapy was thought to have higher
  relapse rate
• Prospective, randomized, double-blind trial of
  401 pts in 51 French ICUs, 1999-2002
• Excluded neutropenics, AIDS, immunosuppressants,
  long-term steroids
• VAP diagnosed by BAL culture
• Randomized to 8 or 15 days of antibiotics

Chastre J, et al. Comparison of 8 vs 15 days of
antibiotic therapy for ventilator-associated PNA
in adults, JAMA 2003.
54
VAP 8 vs. 15 days of antibiotics

• Pseudomonas 18, Strep 14, MSSA 12, EColi 7,
  MRSA 7....
• No difference in mortality (18 vs. 17),
  recurrent infection rate (29 vs. 26), of
  mechanical ventilation-free days, length of ICU
  stay
• Among pts who developed recurrent infections, MDR
  pathogens emerged more often in pts who had
  received 15d antibiotics
• Pts w/VAP caused by Pseudomonas,
  Stenotrophomonas, Acinetobacter had higher rates
  of recurrent infection in the 8-day group, but no
  increase in mortality
• Conclusion treat VAP for 8 days when you have a
  documented pathogen, except in immunocompromised
  pts. Consider extended therapy in Pseudomonas,
  Steno, Acinetobacter VAP.

Chastre J, et al. Comparison of 8 vs 15 days of
antibiotic therapy for ventilator-associated PNA
in adults, JAMA 2003.
55
What dose in HAP, VAP, HCAP?

• Higher doses provide better pseudomonal coverage,
  adequate lung penetration
• Vanc 15 mg/kg q12 (not 1g iv q12)
• Levofloxacin 750 mg iv qd (not 500mg)
• Cipro 400 mg iv q8 (not q12)
• Cefepime 2g iv q8
• Ceftazidime 2g iv q8
• Meropenem 1g iv q8
• Piperacillin/Tazobactam 4.5g iv q6h (not 3.375 iv
  q6)

ATS Guidelines, 2005
56
CAP Prevention Influenza Vaccine

• Annual, inactivated, IM
• Influenza vaccine reduces incidence of
  influenza, risk of influenza-related
  hospitalization/mortality, and risk of bacterial
  CAP
• All persons 50 yrs old
• High-risk persons 6 mos - 49 yrs old (chronic
  heart/lung disease including asthma DM renal
  dysfunction hemoglobinopathies
  immunocompromising conditions/medications)
• Residents in long-term care facilities
• Pregnant women
• Health care workers
• Household contacts of high-risk persons

57
CAP Prevention Pneumovax

• Give pneumovax to prevent pneumococcal PNA, but
  even more to prevent complications and mortality
  from invasive infection (bacteremia, meningitis)
• The 23-valent pneumococcal polysaccharide vaccine
  is recommended for
• All persons 65 yrs old
• High-risk persons 2-64 yrs old (Chronic
  heart/lung/kidney/liver disease, DM, CSF leaks,
  alcoholism, asplenia, immunocompromising
  conditions/medications, Native Americans, Alaska
  natives, long-term care facility residents)
• Current smokers
• Contraindicated in pregnancy
• One-time revaccination after 5 yrs for adults 65
  (if first dose given before age 65), asplenics,
  and immunocompromised persons

58
Unusual Pneumonias
History is KEY Travel, pets, occupational
exposures, hobbies, sick contacts, geographic
location, season
59
Remember these associations

• Exposure to bat or bird droppings Histoplasma
  capsulatum
• Exposure to birds Chlamydophila psittaci (if
  poultry avian influenza)
• Exposure to rabbits Francisella tularensis
• Exposure to farm animals or parturient cats
  Coxiella burnetti (Q fever)
• Travel to or residence in southwestern United
  States Coccidioides species, Hantavirus
• Travel to or residence in Southeast and East
  Asia Burkholderia pseudomallei, avian influenza,
  SARS
• In context of bioterrorism Bacillus anthracis
  (anthrax), Yersinia pestis (plague), Francisella
  tularensis (tularemia)

60
Tularemia

• Francisella tularensis
• Rabbits, squirrels, rodents
• Hunters, landscapers
• More common in South-central Western states
• 1st Doxycycline
• Alt gentamicin, streptomycin

61
Psittacosis

• Chlamydophila psittaci
• Exposure to birds
• Bird owners, pet shop employees, vets
• 1st Tetracycline
• Alt Macrolide

Alex
62
Q fever

• Coxiella burnetti
• Exposure to farm animals or parturient cats
• 1st Tetracycline, 2nd Macrolide

63
Histoplasmosis

• Histoplasma capsulatum
• Exposure to bat (guano) or bird droppings
• Caves (spelunking), construction sites
• 1st itraconazole
• Alt Amphotericin B

64
Travel-related PNAs

• Southwestern US
• Coccidioides spp.
• Hantavirus
• Plague

• Southeast East Asia
• Avian influenza
• SARS
• Burkholderia pseudomallei
• Cruise ship stay
• Hotels
• Legionella
• Influenza

65
HAP Diagnosis

• Clinical signs (new fever, purulent sputum,
  leukocytosis, positive culture of sputum or
  tracheal aspirate) AND new or progressive
  radiographic infiltrate
• Tracheobronchitis clinical signs without
  infiltrate
• Associated with longer length of ICU stay, longer
  duration of mechanical ventilation no increase
  in mortality
• Antibiotics may reduce incidence of subsequent
  PNA
• Tracheal colonization in intubated pts in absence
  of clinical findings is NOT infxn ? no
  antibiotics
• 3 RCTs No mortality benefit to bronch culture
  vs. endotracheal aspirate culture (1 RCT
  mortality benefit to bronchoscopy)

66
CAP Viral

• Viruses cause 1-29 of CAP
• Healthy adults self-limited URIs
• Elderly, immunocompromised, cardiopulmonary
  disease severe LRTIs
• 1 Influenza A, B
• Respiratory syncytial virus (RSV), Parainfluenza
  virus (PIV), Human metapneumovirus (hMPV)
• Immunocompromised Coronavirus, Adenovirus,
  Rhinovirus
• CXR diffuse, interstitial, alveolar infiltrates,
  lobar consolidation.
• Dx Antigen testing for Influenza. Convalescent
  serologic titers. Viral PCR.
• Tx Supportive. Steroids. Empiric antibiotics.
  Antivirals? Very little literature in adults.