Empiric Therapy Regimens

Community-acquired pneumonia (CAP) is one the most common infectious diseases

addressed by clinicians. It is a major health problem in the United States and is an important
cause of mortality and morbidity worldwide. [1, 2]
CAP is defined as pneumonia acquired outside a hospital or long-term care facility. It occurs
within 48 hours of hospital admission or in a patient presenting with pneumonia who does not
have any of the characteristics of healthcare-associated pneumonia (ie, hospitalized in an
acute care hospital for 2 or more days within 90 days of 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; or attend a hospital or
hemodialysis clinic). [1, 2]
A number of pathogens can give rise to CAP, generally categorized into typical and atypical
pathogens.
Typical bacterial pathogens that cause CAP include Streptococcus pneumonia(penicillin-
sensitive/resistant strains), Haemophilus influenza (ampicillin-sensitive/resistant strains),
and Moraxella catarrhalis (all strains penicillin-resistant) and account for approximately 85%
of CAP cases. CAP is usually acquired via inhalation or aspiration of a pulmonary pathogen
into a lung segment or lobe. Less commonly, CAP results from secondary bacteremia from a
distant source, such as Escherichiacoli urinary tract infection and/or bacteremia. Aspiration
pneumonia is the only form of CAP caused by multiple pathogens (eg, aerobic/anaerobic oral
organisms). Klebsiella pneumonia CAP occurs primarily in persons with chronic alcoholism
and Staphylococcalaureus may cause CAP in patients with influenza. Pseudomonas
aeruginosa is a cause of CAP in patients with bronchiectasis or cystic fibrosis. [1]
Atypical pathogen CAP manifests a variety of pulmonary and extrapulmonary findings (eg,
CAP plus diarrhea). Atypical CAP can be divided into those caused by either zoonotic or
nonzoonotic atypical pathogens. Zoonotic atypical CAP pathogens
include Chlamydophila (Chlamydia) psittaci (psittacosis), Coxiella burnetii (Q fever),
and Francisella tularensis (tularemia). Nonzoonotic atypical CAP pathogens
include Mycoplasma pneumoniae, Legionella species, andChlamydia pneumoniae. These
organisms account for approximately 15% of all CAP cases. [1]
For all suspected CAP patients, in light of better outcomes with the earliest possible
interventions the Infectious Diseases Society of America (IDSA) recommends initial empiric
antimicrobial therapy until laboratory results can be obtained to guide more specific
therapy. [2]
Empiric therapeutic regimens for CAP are outlined below, including those for outpatients with
or without comorbidities, intensive care unit (ICU) and non-ICU patients, and penicillin-
allergic patients. [2]
Outpatient
No comorbidities/previously healthy; no risk factors for drug-resistant S pneumoniae:
Azithromycin 500 mg PO one dose, then 250 mg PO daily for 4 d or extended-release
2 g PO as a single dose or
Clarithromycin 500 mg PO bid or extended-release 1000 mg PO q24h or
 Doxycycline 100 mg PO bid
If received prior antibiotic within 3 months:
Azithromycin or clarithromycin plus amoxicillin 1 g PO q8h or amoxicillin-
clavulanate 2 g PO q12h or
Respiratory fluoroquinolone (eg, levofloxacin 750 mg PO daily ormoxifloxacin 400
mg PO daily)
Comorbidities present (eg, alcoholism, bronchiectasis/cystic fibrosis, COPD, IV drug user,
post influenza, asplenia, diabetes mellitus, lung/liver/renal diseases):
Levofloxacin 750 mg PO q24h or
Moxifloxacin 400 mg PO q24h or
Combination of a beta-lactam ( amoxicillin 1 g PO q8h or amoxicillin-clavulanate 2 g
PO q12h or ceftriaxone 1g IV/IM q24h or cefuroxime 500 mg PO BID) plus a
macrolide (azithromycin or clarithromycin)
Duration of therapy: minimum of 5 days, should be afebrile for 48-72 hours, or until afebrile
for 3 days; longer duration of therapy may be needed if initial therapy was not active against
the identified pathogen or if it was complicated by extrapulmonary infections
Inpatient, non-ICU
See the list below:
Levofloxacin 750 mg IV or PO q24h or
Moxifloxacin 400 mg IV or PO q24h or
Combination of a beta-lactam (ceftriaxone 1 g IV q24h or cefotaxime 1 g IV
q8h or ertapenem 1 g IV daily or ceftaroline 600 mg IV q12h) plusazithromycin 500
mg IV q24h
Duration of therapy: minimum of 5 days, should be afebrile for 48-72 hours, stable blood
pressure, adequate oral intake, and room air oxygen saturation of greater than 90%; longer
duration may be needed in some cases
Inpatient, ICU:
Severe COPD:
Levofloxacin 750 mg IV or PO q24h or
Moxifloxacin 400 mg IV or PO q24h or
Ceftriaxone 1 g IV q24h or ertapenem 1 g IV q24h plus azithromycin 500 mg IV
q24h
If gram-negative rod pneumonia (Pseudomonas) suspected, due to alcoholism with
necrotizing pneumoniae, chronic bronchiectasis/tracheobronchitis due to cystic fibrosis,
mechanical ventilation, febrile neutropenia with pulmonary infiltrate, septic shock with organ
failure:
Piperacillin-tazobactam 4.5 g IV q6h or 3.375 g IV q4h or 4-h infusion of 3.375 g
q8h or
Cefepime 2 g IV q12h or
Imipenem/cilastatin 500 mg IV q6h or meropenem 1 g IV q8h or
 If penicillin allergic, substitute aztreonam 2 g IV q6h plus
Levofloxacin 750 mg IV q24h or
Moxifloxacin 400 mg IV or PO q24h or
Aminoglycoside ( gentamicin 7 mg/kg/day IV or tobramycin 7 mg/kg/day IV )
Add azithromycin 500 mg IV q24h if respiratory fluoroquinolone not used
Duration of therapy: 10-14 days
If concomitant with or post influenza:
Vancomycin 15 mg/kg IV q12h or linezolid 600 mg IV bid plus
Levofloxacin 750 mg IV q24h or
Moxifloxacin 400 mg IV or PO q24h
If received prior antibiotic within 3 months:
High-dose ampicillin 2 g IV q6h (or penicillin G, if not resistant); if penicillin allergic,
substitute with vancomycin 1 g IV q12h plus
Azithromycin 500 mg IV q24h plus
Levofloxacin 750 mg IV q24h or moxifloxacin 400 mg IV/PO q24h

Risk of aspiration pneumonia/anaerobic lung infection/lung abscess:

See the list below:
Clindamycin 300-450 mg PO q8h or
Ampicillin-sulbactam 3 g IV q6h or
Ertapenem 1 g IV q24h or
Ceftriaxone 1 g IV q24h plus metronidazole 500 mg IV q6h or
Moxifloxacin 400 mg IV or PO q24h or
Piperacillin-tazobactam 3.375 g IV q6h or
If methicillin-resistant S aureus (MRSA) is suspected, add vancomycin 15 mg/kg IV
q12h or linezolid 600 mg IV/PO q12h
If influenza is suspected, add oseltamivir 75 mg IV or PO q12h for 5 d

New antimicrobials in CAP

Since the publication of the 2007 IDSA/American Thoracic Society (ATS) guidelines for the
management of CAP in adults, 2 intravenous antimicrobials have been approved by the US
Food and Drug Administration (FDA) for the treatment of CAP: tigecycline and ceftaroline
fosamil.
Use of tigecycline in CAP
Tigecycline was approved by the FDA in 2009 for adults with CAP caused by S
pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, H
influenza (beta-lactamase-negative isolates), and Legionella pneumophila. In a study
conducted to evaluate the efficacy of tigecycline versus levofloxacin in hospitalized patients
with CAP, tigecycline achieved cure rates similar to those of levofloxacin in hospitalized
patients with CAP. For patients with risk factors, tigecycline provided generally favorable
clinical outcomes. [3]
Data from various sources, including PubMed, the European Medicines Agency (EMEA), and
the FDA were appraised. Tigecycline was found to be noninferior compared with levofloxacin
for the treatment of patients with bacterial CAP requiring hospitalization. [4]
Although tigecycline is indicated for CAP, data from clinical trials suggest a high incidence of
adverse events, particularly gastrointestinal adverse effects, which may limit its use. [5]
Dosing for tigecycline is as follows:
Tigecycline 100 mg IV loading dose, then 50 mg IV q12h for 7-14 d
Use of ceftaroline in CAP
Ceftaroline fosamil is a parenteral cephalosporin antibacterial that was approved by the FDA
in 2010 for the treatment of adults with CAP caused by S pneumoniae, including cases with
concurrent bacteremia; S aureus (methicillin-susceptible isolates only); H influenza; K
pneumonia; Klebsiella oxytoca; and E coli.
Ceftaroline, the active form of ceftaroline fosamil, has broad-spectrum in vitro activity against
common causative gram-positive and gram-negative bacteria, including MRSA. However,
there are no clinical data supporting the use of ceftaroline fosamil for MRSA pneumonia. [5]
Ceftaroline fosamil is included in Joint Commission pneumonia core measures as one of the
recommended beta-lactam antibiotics for CAP in immunocompetent, non-ICU patients.
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Dosing for ceftaroline is as follows:
Ceftaroline 600 mg IV q12h