Pneumoni

a
Larissa Co
yle, Pharm
.D, BCPS
Fall 2016

Objectives
0 Discuss different classifications of pneumonia
0 Review prevalent organisms common in

different types of pneumonia

0 Discuss treatment options for CAP and apply
to a patient case
0 Review treatment options for different types
of Nosocomial Pneumonia
0 Discuss treatment options for aspiration
pneumonia

Classifications for
Pneumonia
0 Community-acquired pneumonia (CAP)
0 Nosocomial Pneumonia
0 Hospital-acquired pneumonia (HAP)
0 Ventilator associated pneumonia (VAP)
0 Aspiration Pneumonia

Communi
tyacquired
Pneumoni
a
CA P

CAP Organisms Outpatient

0 Streptococcus pneumoniae
0 Mycoplasma pneumoniae
0 Haemophilus influenzae
0 Chlamydophila pneumoniae
0 Respiratory viruses

Mandell et al. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of CommunityAcquired Pneumonia in Adults. Clin Inf Dis 2007;44:S27-72.

CAP Organisms - Inpatient

Non-ICU
0 S. pneumoniae
0 M. pneumoniae
0 C. pneumoniae
0 H. influenzae
0 Legionella species
0 Respiratory viruses

ICU
0 S. pneumoniae
0 Staphylococcus

aureus
0 Legionella species
0 Gram-negative
bacilli
0 H. influenzae

Mandell et al. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of CommunityAcquired Pneumonia in Adults. Clin Inf Dis 2007;44:S27-72.

Inpatient vs. Outpatient

0 CURB-651
0 Confusion
0 Uremia
0 BUN > 19 mg/dL

0 Respiratory Rate
0 30
0 Blood Pressure
0 SBP < 90 mm Hg or DBP
60 mm Hg
0 Age
0 65 years

0 Pneumonia Severity Index

(PSI)
0 Age
0 Gender
0 Nursing home resident
0 Comorbidities
0 Mental status
0 BP, RR, HR, Temp
0 Labs: pH, glu, Na, BUN, pO2

1. Lim et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study.
Thorax. 2003 May; 58(5).:377-82.

Additional Factors
0 Reliability of taking oral medications
0 Outpatient resources

Antibiotic Selection
0 Patient factors
0 Allergies
0 Age
0 Renal or hepatic

dysfunction
0 Concomitant
medications
0 Concomitant disease
states
0 Pregnancy

0 Medication

factors
0
0
0
0

Tissue penetration
IV vs. PO
Drug interactions
Antibiotic resistance
patterns

Risk factors for Drug-Resistant

S. Pneumoniae (DRSP)
0 Age < 2 or > 65
0 Antimicrobial use w/in last 3 months
0 Alcoholism
0 Diabetes
0 Medical co-morbidities
0 Chronic heart, lung, liver, or renal disease
0 Immunosuppressive illness or therapy
0 Malignancies, asplenia
0 Exposure to child in day care center

Outpatien
t
CAP Treatm
e

nt

Outpatient Treatment
0 No risk factors for DRSP
0 Macrolide
0 Doxycycline
0 Risk factors for DRSP
0 Respiratory fluoroquinolone

0 -lactam plus macrolide

0 -lactam plus doxycycline

Macrolides
0 MOA: Interfere with bacterial protein synthesis
0 Drugs available
0 Clarithromycin (Biaxin, Biaxin XL)
0 250-500 mg PO BID or 1000 mg XL PO daily (Renal adj.)

0 Azithromycin (Zithromax) 500 mg PO on day 1, then 250

mg PO on days 2-5

0 ADRs
0 Gastrointestinal N/V/D, metallic taste
0 QT prolongation
0 Drug interactions
0 CYP450 3A4 inhibitor
0 Clarithromycin

0 Patient counseling points

0 Biaxin XL should be taken with food
0 Pregnancy Category C

Doxycycline
0 Drug class: Tetracycline
0 MOA: Interferes with bacterial protein synthesis
0 ADRs
0 N/V/D, dyspepsia, esophageal irritation/ulceration
0 Tooth discoloration

0 Drug interactions
0 BCPs, aluminum, magnesium, iron

0 Patient counseling points

0 Photosensitivity, take with full glass of water, avoid taking

at bedtime

0 Pregnancy Category D

Respiratory Quinolones
0 MOA: Inhibitors of bacterial DNA synthesis
0 Drugs available
0 Levofloxacin (Levaquin) 750 mg PO daily x 5 days (Renal adj.)
0 Moxifloxacin (Avelox) 400 mg PO daily x 10 days
0 Gemifloxacin (Factive) 320 mg PO daily x 5-7 days (Renal adj.)

0 ADRs
0 Diarrhea, QT prolongation, tendonitis/tendon rupture, confusion,

hyperglycemia, hypoglycemia

0 Drug interactions
0 Warfarin (increased INR), QT prolongation drugs- Class IA and III anti-

arrhythmics

0 Patient counseling points

0 Photosensitivity, separate from aluminum, magnesium, zinc, iron,

and calcium products by 2 hours

0 Pregnancy Category C

-lactams
0 MOA: Interfere with bacterial cell wall synthesis
0 Drugs available
0 Amoxicillin (High-dose) 1 gram PO TID (renal adj.)
0 Amoxicillin/clavulanate (Augmentin ) 2 grams PO BID (renal

adj.)

0 ADRs
0 GI diarrhea, N/V, rash

0 Drug interactions
0 BCPs

0 Patient counseling points

0 Take with food to increase absorption and minimize GI

effects

0 Pregnancy Category B

Alternative Therapies
0 Other -lactams
0 Cefpodoxime (Vantin) 200 mg PO BID
0 Cefuroxime (Ceftin) 500 mg PO BID
0 Cefdinir (Omnicef) 300 mg PO BID
0 Ceftriaxone (Rocephin) 1 gm IV or IM daily

DRSP
0 If the area in which you practice has a high

percentage of macrolide-resistance to S.
pneumoniae, it is not recommended to use a
macrolide alone first-line.

WMC Antibiogram

Patient Case
CC: 49 yo male presents in clinic complaining of a cough
that produces yellow sputum, and shortness of breath
after walking short distances. Patient also states he had
a fever of 99.8 F at home
PMH: GERD, Hypertriglyceridemia, Previous smoker (20
pack years) Quit 10 years ago
Medication History: Lansoprazole 30 mg daily, Fish Oil
1000 mg daily, Multivitamin daily
Drug Allergies: Augmentin

Patient Case cont.

0 SH: Works as a high school math teacher,

married, no children
0 ROS: Patient denies chills, no chest pain
0 Physical exam: Crackles in left lower lung

field, alert and oriented X 3

0 Vaccination history: Influenza in November

2013

Patient Case cont.

0 What key factors will help determine the

course of treatment for this patient?

0 Is this patient at risk for DRSP?

Patient Case cont.

0 What is the best treatment option for this

patient?

0 What would you counsel the patient on?

Hospitaliz
ed
CAP Treatm
e

nt

Decision for ICU

admission
Septic shock
Requires vasopressors to maintain BP
Acute respiratory failure
Mechanical ventilation
Intubation

3 or more minor criteria for severe CAP

Respiratory rate > 30 breaths/min
Arterial oxygen pressure/fraction of inspired oxygen (PaO /FiO ) ratio < 250
Multi-lobar infiltrates
Confusion
Blood urea nitrogen level >20 mg/dL
Leukopenia resulting from infection
Thrombocytopenia
Hypothermia
Hypotension requiring aggressive fluid resuscitation
2

CAP: Organisms - Inpatient

Non-ICU
0 S. pneumoniae
0 M. pneumoniae
0 C. pneumoniae
0 H. influenzae
0 Legionella species
0 Respiratory viruses

ICU
0 S. pneumoniae
0 Staphylococcus

aureus
0 Legionella species
0 Gram-negative
bacilli
0 H. influenzae

Mandell et al. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of CommunityAcquired Pneumonia in Adults. Clin Inf Dis 2007;44:S27-72.

Non-ICU C
AP
Treatment

Non-ICU CAP treatment

options
0 Respiratory fluoroquinolones
0 -lactam PLUS macrolide
0 -lactam PLUS doxycycline

Non-ICU CAP treatment

options
0 Respiratory fluoroquinolones
0 Moxifloxacin 400 mg IV/PO Q24 hours
0 Levofloxacin 750 mg IV/PO Q24 hours

0 -lactams
0 Cefotaxime (Claforan) 1-2 grams IV q8 hours (Renal adj.)
0 Ceftriaxone (Rocephin) 1-2 grams IV Q24 hours
0 Ampicillin (Principen) 1-2 grams IV q6-8 hours (Renal

adj.)
0 Ertapenem (Invanz) 1 gram IV Q24 hours (Renal adj.)

0 Macrolides
0 Azithromycin (IV and PO)
0 Clarithromycin (PO)

Influenza
0 Treatment
0 Symptoms less than 48 hours
0 Symptoms > 48 hours when hospitalized or have pneumonia
0 Check annual resistance rates and CDC recommendations
0 Oseltamavir (Tamiflu) 75 mg PO BID x 5 days
0 Renal dosage adjustment required
0 ADRs N/V, psychosis (mainly in pediatrics)
0 Zanamavir (Relenza) 2 inhalations (10 mg) BID x 5 days
0 CI: Pulmonary disease, mechanical ventilation
0 Increased risk of bronchospasm and decreased lung function

Patient Case
0 CC: A 67 yo male is brought to clinic by his daughter. He is

complaining of shortness of breath, wheezing, and

weakness. The patient also says he has been having chills,
he has been sweating, and coughing up yellow sputum
0 PMH: Diabetes type 2, atrial fibrillation, chronic kidney

disease, hypothyroidism, and chronic anemia

0 Medication History: Aspirin, warfarin, valsartan,

lansoprazole, simvastatin, metoprolol, digoxin, glimepiride,

folic acid, calcium carbonate, and levothyroxine

Patient Case cont.

0 Allergies: NKDA
0 PE: Lungs wheezing and crackles in bases

bilaterally. Patient is alert and oriented X 3

0 Vital signs: Temp: 98.2 F, BP 150/39, HR 92

RR 18, and O2 sat 90%

Patient Case cont.

0 Additional information:
0 Chest X-ray Bibasilar infiltrates
0 EKG Sinus rhythm
0 Labs:
137 102 54
226
4.2
26 1.7

7.9

193

8.8
26

Patient Case cont.

0 What is his CURB-65 score?

0 What is the best antimicrobial therapy choice

for this patient?

CAP ICU
Treatment

CAP - ICU
0 -lactam
0 Ceftriaxone (Rocephin)
0 Cefotaxime (Claforan)
0 Ampicillin/sulbactam (Unasyn) 1.5 - 3 grams IV q6

hours (Renal adj.)

0 PLUS
0 Azithromycin (Zithromax) or
0 Respiratory fluoroquinolone

0 For penicillin-allergic patients

0 Aztreonam (Azactam) plus respiratory fluoroquinolone

Aztreonam (Azactam)
0 MOA: Interfere with bacterial cell wall synthesis
0 Monobactam
0 Low incidence of cross-reactivity with -lactams
0 Bacterial coverage
0 Aerobic gram negatives only
0 Dose: 2 grams IV q8-12 hours
0 ADRs: Increased LFTs, phlebitis
0 Pregnancy Category B
**Use may be based on antibiogram susceptibility data**

CAP-ICU: Pseudomonas
Risk
0 Severe structural lung disease
0 Bronchiectasis
0 Repeated exacerbations of severe COPD
requiring frequent steroid or antibiotic use

CAP-ICU: Pseudomonas Risk

**2 or 3 drug combination**
Anti-Pneumococcal, anti-Pseudomonal -lactam (Pick 1)
Piperacillin-tazobactam (Zosyn )
Cefepime (Maxipime)
Imipenem (Primaxin) or Meropenem (Merrem)
Plus one of the following agents or combinations:
Anti-Pseudomonal quinolones with atypical coverage
Ciprofloxacin or levofloxacin (750-mg dose)

or
Aminoglycoside (anti-Pseudomonal) and azithromycin (atypical)
or
Aminoglycoside (anti-Pseudomonal) and an anti-Pneumococcal
fluoroquinolone (atypical)

For penicillin-allergic patients

Aztreonam (Azactam) + an aminoglycoside + an antiPneumococcal fluoroquinolone

WMC Antibiogram

CAP-ICU: MRSA Risk

0 End-stage renal disease
0 Injection drug abuse
0 Prior influenza infection

CAP-ICU: MRSA Risk

Vancomycin
MOA: Inhibits bacterial cell wall synthesis
Pharmacokinetic dosing
Maintain trough levels between 15 and 20 mg/L
Dosing: 15 - 20 mg/kg IV q8-12 hours

IV formulation only
0 ADRs: nephrotoxicity, red man syndrome,

phlebitis, long term use - neutropenia

0 Pregnancy Category: C

CAP-ICU: MRSA Risk

Linezolid (Zyvox)
MOA: Inhibits bacterial protein synthesis
May be first choice in patients when vancomycin
trough levels are difficult to maintain, Vancomycin
MIC > 1 mg/L, or necrotizing pneumonia
Now available as generic
Dose: 600 mg IV/PO q12 hours
ADRs: myelosuppression, serotonin syndrome
(weak MAOI), peripheral neuropathy
Pregnancy Category: C

Duration of treatment
0 Minimum of 5 days, usually 7 to 10 days
0 Afebrile for 48 to 72 hours

Infants an
d
Children

Decision for
Hospitalization
0 Respiratory distress
0 Hypoxia
0 SpO2 less than 90%
0 Infants less than 6 months of age
0 Pathogen with increased virulence
0 Poor follow-up or poor observation at home

Bradley et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: Clinical practice guideline
By the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. CID 2011; 53 (7):e25-76.

Diagnostics
0 Blood cultures
0 Sputum cultures
0 Testing for viral pathogens**
0 CBC
0 Pulse oximetry**
0 Chest X-ray

Treatment - Outpatient
0 Pre-school aged children
0 No antimicrobials required Most are viral
0 Infants and pre-school aged children
0 Amoxicillin or amoxicillin/clavulanate
0 Allergies to amoxicillin: 2nd or 3rd generation
cephalosporins, levofloxacin, or linezolid
0 School-aged children and adolescents
0 Same as above
0 If concerned with atypical pathogens, may add a
macrolide

Treatment - Inpatient
0 Infants or school-aged children IMMUNIZED
0 Ampicillin or Penicillin G
0 Infants or children NOT IMMUNIZED, high level

Strep resistance to PCN, life-threatening,

empyema
0 Ceftriaxone or cefotaxime
0 Suspect atypical organisms
0 Add macrolide (IV or PO)
0 Suspect Staph aureus
0 Add vancomycin or clindamycin

Treatment - Influenza
0 Consider anti-virals for influenza viruses
0 Oseltamivir
0 FDA approved in children 2 weeks of age and
older
0 Dosing based on weight
0 Available in capsules and suspension
0 Zanamivir
0 FDA approved in children 7 years of age and
older

Nosocomi
al
Pneumoni
a

Classifications for
Pneumonia
Nosocomial Pneumonia
Hospital-acquired pneumonia (HAP)
Occurs 48 hours after admission
Ventilator Associated Pneumonia (VAP)
Occurs 48 hours after endotracheal intubation

Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia. Clin Infect Dis. (2016) 63 (5): e61-e111

VAP

VAP Diagnosis
0 Noninvasive respiratory sampling (tracheal

aspirate)vs. Invasive respiratory sampling

(bronchoalveolar lavage)
0 No significant differences in the 28-day mortality,

overall mortality, ICU LOS, DOT, vent days, or antibiotic

changes between the methods

0 If invasive quantitative culture yields results

below the diagnostic threshold (PSB with <10 3 or

a BAL with <103), antibiotics should be withheld
Similar outcomes between patients treated with and without

antibiotics

Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia. Clin Infect Dis. (2016) 63 (5): e61-e111

VAP - Common
Pathogens
0 Enteric gram negative bacilli (20-40%)
0 K Klebsiella pneumoniae
0 E E.coli
0 E Enterobacter species
0 P Proteus species
0 S - Serratia
0 Staphylococcus aureus (20-30%)
0 Pseudomonas aeruginosa (10-20%)
0 Acinetobacter baumannii (5-10%)
http://www.pharmamicroresources.com/2016/06/susceptibility-of-multidrug-resistant.html

VAP - Risk Factors for MDR

pathogens
0 Intravenous antimicrobial therapy in

preceding 90 days
0 Current hospitalization of 5 days or more
prior to VAP
0 Septic shock at time of VAP
0 ARDS preceding VAP
0 Acute renal replacement therapy prior to VAP

Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia. Clin Infect Dis. (2016) 63 (5): e61-e111

VAP - Risk factors for MRSA

0 Intravenous antimicrobial therapy in

preceding 90 days
0 ICU where percentage of Staph aureus
isolates are MRSA in >10-20% of patients
0 Prevalence of MRSA in ICU is unknown

https://www.cdc.gov/HAI/organisms/staph.html

VAP - Treatment Options

0 One to three antimicrobials depending on risk

factors
1. Agent active against GN organisms (including

Pseudomonas) and Staph aureus

2. Add MRSA coverage if MRSA risk
3. Add second gram negative agent from a different
drug class

MDR risk factor

Primary antibiotic selected has >10% resistance to
gram negative organisms
Susceptibility patterns in unit unknown, or patient
has structural lung disease

Critical Care Antibiogram

VAP Monotherapy
0 Cephalosporin
Cefepime (Maxipime)

0 Carbapenems
Imipenem (Primaxin)
Meropenem (Merrem)

-Lactam/lactamase inhibitor
Piperacillin/tazobactam (Zosyn )

Fluoroquinolone
Levofloxacin (Levaquin)

VAP Double GNR

coverage

Pick one from Column A and one from Column B

Column A
Column B
0 Cephalosporins
Cefepime
Ceftazidime
0 Carbapenems
Imipenem
Meropenem
0 -Lactam/lactamase inhibitor
Piperacillin/tazobactam
0 Monobactam
Aztreonam

0 Fluoroquinolones
Ciprofloxacin
Levofloxacin
0 Aminoglycosides
Amikacin
Tobramycin
Gentamicin
0 Polymyxins
Colistin
Polymyxin B

Anti-Pseudomonas
cephalosporins
Cefepime (Maxipime) - 4th generation cephalosporin

Dose: 2 grams IV q8 hours, can also use

extended infusion over 3 hours

ADRs rash, N/V/D
Ceftazidime (Fortaz) - 3rd generation cephalosporin

Dose: 2 grams IV q8 hours

ADRs N/V/D

Renal dosage adjustments required

Pregnancy Category B

Anti-Pseudomonas
carbapenems
Imipenem (Primaxin)
500 mg IV q6 hours
Meropenem (Merrem)
1 gram IV q8 hours
Can also use extended infusions
Renal dosage adjustments required
ADRs seizures, rash, phlebitis, nausea, diarrhea
Pregnancy Category C, B

-Lactam/lactamase
inhibitor
Piperacillintazobactam (Zosyn)
4.5 grams IV q6 hours or 3.375 grams IV

extended infusion over 4 hours every 8 hours

0 Renal adjustment required

0 Cautions: may inhibit tubular secretion of other

drugs, may prolong neuromuscular blockade

0 ADRs Diarrhea, headache, N/V, platelet
inhibition, pancytopenia
0 Pregnancy Category B

Other Anti-Pseudomonas
agents
Anti-Pseudomonal fluoroquinolones
Ciprofloxacin 400 mg IV q8 hours
Levofloxacin 750 mg IV q24 hours
Aminoglycosides
Amikacin 15-20 mg/kg IV q24 hours
Gentamicin 5-7 mg/kg IV q24 hours
Tobramycin 5-7 mg/kg IV q24 hours
Polymyxins
Colistin (Polymyxin E)
Polymyxin B

Aminoglycosides
0 MOA: Interfere with bacterial protein synthesis
0 Once Daily dosing Preferred
0 Random levels 10- 12 hours post infusion
0 Level typically <2 mg/L

0 Monitoring for traditional dosing:

0 Peak 30 minutes after infusion
0 8 10 mg/L for gentamicin and tobramycin
0 20 30 mg/L for amikacin

0 Troughs 30 minutes before infusion

0 <1 mg/L for gentamicin and tobramycin
0 <10 mg/L for amikacin

0 ADRs: ototoxicity, nephrotoxicity, neuromuscular toxicity

0 Pregnancy Category D

Polymyxins
0 MOA: Disrupts bacterial cell wall membrane
0 Colistin (Polymyxin E)
0 Systemic Dose: 5 mg/kg loading dose (max 300 mg) based
on ideal body weight, then 2.5 mg/kg IV every 12 hours
0 Inhaled Dose: 75 mg in 3 ml NS via nebulizer every 12 hours
0 Polymyxin B
0 May be preferred over colistin
0 Systemic Dose: 1.25 1.5 mg/kg IV every 12 hours
0 Avoid inhaled
0 Renal dosage adjustment required
0 ADRs: Nephrotoxicity (Colistin:19-33%), neurotoxicity

(Colistin: 3.5%)

MDR
Organism
s

Susceptibilities known
0 For patients not in septic shock or high risk for

mortality, recommendation is to use one agent to

which the organism is susceptible
0 If patient is still in septic shock and high risk of
mortality, continue with dual gram negative coverage
0 Aminoglycosides are not recommended as
monotherapy even when susceptibilities are known
0 Avoid use of polymyxins unless only antimicrobial
agent susceptible
0 MDR GNR only sensitive to aminoglycosides and
polymyxins, use systemic and inhaled therapy

ESBLs
Extended Spectrum Beta-lactamase producing
GNR bacilli
0 ESBL enzyme that breaks open the beta-lactam ring

rendering the antibiotic ineffective

0 Select agent based on susceptibilities
0 Most common preferred agent
0 Carbapenems empiric choice until susceptibility known

0 Other antimicrobials depending on susceptibility and MIC

0 Cefepime
0 Piperacillin-tazobactam
0 Fluoroquinolones
0 Aminoglycosides
0 Polymyxins
0 Ceftolozane/tazobactam and ceftazidime/avibactam

Acinetobacter
0 Gram negative coccobacillus found in water and

soil and thrives in tropical and humid environments

0 Preferred therapy
0 Carbapenems
0 Ampicillin/sulbactam

0 Other options based on susceptibilities

0 If only susceptible to polymyxins
0 Systemic and inhaled therapy
0 Avoid use of tigecycline
0 Increased risk of mortality

Inhaled Antimicrobials
Aminoglycosides/Polymyxin
0 Aminoglycosides
0 Tobramycin
0 Dose: 300 mg nebulized BID

0 Amikacin
0 Dose: 500 mg nebulized BID
0 ADRs: Tinnitus, hoarseness, hearing loss,

bronchospasm (pretreat with albuterol)

0 Colistin
0 Dose: 75-150 mg nebulized BID
0 ADRs: bronchospasm
0 Mix just prior to administration to prevent fatal
pulmonary toxicity
Le et al. Use of aerosolized antimicrobial agents. Pharmacotherapy 2010;30(6):562-584.

HAP

HAP - Diagnosis
0 Microbiology
0 Respiratory culture
0 Sputum
0 Induced Sputum
0 ET aspirate

0 Blood culture

Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia. Clin Infect Dis. (2016) 63 (5): e61-e111

HAP - Common
Pathogens
0 Enteric gram negative bacilli (16%)
0 Staphylococcus aureus (16%)
0 MRSA (10%)
0 MSSA (6%)
0 Pseudomonas aeruginosa (13%)
0 Acinetobacter baumannii (4%)

HAP Risk factor for MDR

pathogen
0 Intravenous antimicrobial therapy in

preceding 90 days

HAP - Risk factors for MRSA

0 Intravenous antimicrobial therapy in

preceding 90 days
0 ICU where percentage of Staph aureus
isolates are MRSA in >20% of patients
0 Prevalence of MRSA in ICU is unknown

Critical Care Antibiogram

HAP Risk factors for

mortality
0 Requires mechanical ventilation
0 Septic shock
0 Sepsis Life threatening organ dysfunction caused
by a dysregulation host response to infection
0 Organ dysfunction SOFA score 2 (RR 22, acute
mental status changes, and SBP 100 mm Hg
0 Septic shock sepsis with circulatory and metabolic
abnormalities, increasing the risk of mortality
0 Clinical Definition: Persistent hypotension requiring

vasopressors to having an MAP 65 mm Hg and serum

lactate > 2 mmol/L despite volume resuscitation.

Singer et al. The Third International Consensus Definitions for Sepsis and Septic Shock. JAMA 2016;315 (8):801-810.

HAP - Monotherapy
0 Choose one of these to provide coverage for

gram negative bacilli and MSSA

0 Piperacillin-tazobactam (Zosyn)
0 Cefepime (Maxipime)
0 Imipenem (Primaxin)
0 Meropenem (Merrem)
0 Levofloxacin (Levaquin)

HAP MRSA risk

Choose an agent from column A for gram negative
bacilli coverage and one agent from column B for MRSA
coverage
Column A
Column B
0 Piperacillin-tazobactam
0
0
0
0
0
0
0

(Zosyn)
Cefepime (Maxipime)
Ceftazidime (Fortaz)*
Levofloxacin (Levaquin)
Ciprofloxacin (Cipro)*
Imipenem (Primaxin)
Meropenem (Merrem)
Aztreonam (Azactam)*

0 Vancomycin
0 Linezolid

*Poor or no activity against Staphylococcus aureus

HAP Mortality and MRSA

risk
Choose an antimicrobial from each column for a total of 3 antimicrobials
Column A

Column B

Column C

Piperacillintazobactam

Levofloxacin

Vancomycin

Cefepime

Ciprofloxacin

Linezolid

Ceftazidime

Amikacin

Imipenem

Tobramycin

Meropenem

Gentamicin

Aztreonam+

Aztreonam+

+Aztreonam can be used as primary or secondary gram negative coverage

Patient Case
HPI: 70 yo male admitted to WMC 4 days ago
for an acute CVA. He was started on apixaban
2 days ago. His PMH includes atrial fibrillation
and GERD. Yesterday he had a fever of 38.2C
with a new productive cough. Today, he
became increasingly SOB and hypoxic. His O2
Sat was 86%, but improved to 94% with 4 L
O2. Lactate level was checked and was 3.4.
He was given IV fluids and transferred to the
critical care unit for a higher level of care.

Patient Case cont.

0 PMH:Treated one month ago with oral

moxifloxacin for sinusitis

0 Medications: Metoprolol, pantoprazole,

apixaban
0 PE: Lungs decreased breath sounds on the

left
Heart: irregular rate

Patient Case cont.

0 Chest Xray: Left lower lobe infiltrate
0 Vital signs: BP 110/79 HR 95 RR 20 O2 Sat

94% 4L NC
0 Labs:
139
4.3

95
27

83
30 17.8
1.5

24511.5
34.8

0 Blood Cultures were drawn prior to antibiotics

and sputum culture is pending

Patient Case cont.

0 What are your treatment options for empiric

therapy?

Patient Case cont.

0 The sputum cultures are positive for Klebsiella

pneumoniae. Should the patient remain on the same

therapy?
Drug

Susceptibility

MIC

Ampicillin

>=32

Ampicillin/sulbactam

Cefazolin

<=4

Ciprofloxacin

<=0.25

Imipenem

<=1

Piperacillin/tazobacta
m

<=4

Tobramycin

<=1

Patient Case cont.

0 What if his culture results looked like this? What would be

your therapy choice?

Drug

Susceptibility

MIC

Ampicillin

>=32

Ampicillin/sulbactam

>=32

Cefazolin

>=64

Ciprofloxacin

>=4

Imipenem

>=16

Piperacillin/tazobacta
m

>=64

Tobramycin

<=1

Colistin

0.25

Duration of therapy
0 7 days of therapy
0 May require longer duration of therapy depending

on patient response

Aspiration
Pneumoni
a

Risk Factors
0 History of loss of consciousness
0 Drug or alcohol overdose
0 Seizures, CVA, head trauma
0 Esophageal motility disorders
0 Dysphagia from neurologic deficits
0 Mechanical disruption
0 Tube feedings, tracheostomy

Common Pathogens
0 Aerobic bacteria
0 Gram negative bacilli
0Klebsiella
pneumoniae
0E.coli
0 S. pneumoniae
0 S. aureus

0 Anaerobic bacteria
0 Peptostreptococcus

spp.
0 Fusobacterium
0 Bacteroides spp.
0 Peptococcus spp.

Treatment Options
0 Community-acquired
0 Ampicillin/sulbactam
0 Moxifloxacin
0 Levofloxacin plus Clindamycin/Metronidazole
0 Piperacillin/tazobactam
0 Ceftriaxone +/- Metronidazole
0 Hospital-acquired
0 Piperacillin/tazobactam
0 Carbapenem
0 PCN Allergy:
0 Clindamycin + Aztreonam
0 Levofloxacin + Metronidazole
Marik PE; Aspiration pneumonitis and aspiration pneumonia. N Engl J Med; 2001; Vol. 344; pp. 665-71

Clindamycin (Cleocin)
0 MOA: Inhibits protein synthesis
0 Activity against anaerobic bacteria as well as

gram positive organisms

0 Dose
0 600 mg IV q8 hours, then 300 mg PO q6-8

hours

0 ADRs
0 C. diff colitis, N/V/D, abdominal pain,
esophagitis
0 Pregnancy Category B

Metronidazole (Flagyl)
0 MOA: Metabolite disrupts DNA and inhibits

nucleic acid synthesis

0 Strictly for anaerobic bacteria
0 Dose
0 500 mg IV/PO q8 hours

0 ADRs
0 Peripheral neuropathy, disulfiram-like reaction,
neurotoxicity, N/V, dry mouth
0 Pregnancy Category B Avoid in first

trimester

Controver
sies
New Dat
a

HCAP Retired definition

Health-care associated pneumonia (HCAP)
Hospitalized in an acute care hospital for two
or more days within 90 days of the infection
Resided in a nursing home or long-term care
facility
Received recent intravenous antibiotic
therapy, chemotherapy, or wound care
within the past 30 days of the current
infection
Attended a hospital or hemodialysis clinic
Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare-associated Pneumonia. Am J
Respir Crit Care Med. 2005;171:388-416.

HCAP
0 Meta-analysis comparing pathogens isolated

in CAP and HCAP patients

0 No correlation between MDR pathogens

identified
0 No increase in mortality

0 Pharmacoepidemiolgical cohort study

0 No decrease in mortality in those treated with
anti-MRSA and anti-Pseudomonas coverage
CID 2014;58(3):330-9.
J Antimicrob Chemother 2015; 70 (5):1573-9.

CAP-START
NON-ICU CAP study

0 Primary objective (non-

0 Weaknesses
inferiority)
0 Different -lactams
0 90 Day Mortality
allowed in different
groups
0 Demographics
0 Few patients had
0 Median age 70 yrs
documented atypical
0 Treatment
organisms
groups/Results
0 Almost 40% in the 0 lactam alone (N=656)
lactam alone group
9%
also received atypical
coverage during the
0 lactam + macrolide
study
(N=739) 11.1%
0 Fluoroquinolone
NEJM 2015;372:1312-23.
alone(N=888) 8.8%

IDSA guideline updates

0 Nosocomial
0 Summer 2016
0 Removal of HCAP criteria and treatment
0 Removal of early onset vs late onset HAP/VAP
0 Removal of double gram negative coverage for

everyone
0 Removal of MRSA coverage for everyone

0 CAP
0 Expected Summer 2017
0 Role of macrolides

Conclusions
0 Different organisms are prominent in the different

types of pneumonia
0 Treatment for CAP is different for outpatients vs.
inpatients
0 Additional antibiotics should be included in empiric
therapy for patients at risk of Pseudomonas and/or
MRSA
0 Antibiotic resistance patterns in your
community/institution could affect treatment
options available

Additional Questions

Contact Information
Larissa Coyle, Pharm.D, BCPS
Clinical Pharmacy Specialist Infectious
Disease
Winchester Medical Center
Pharmacy Department
540-536-2022
lcoyle@valleyhealthlink.com