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Journal of Pharmacy Practice

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An Update for Community-Acquired Bacterial Pneumonia Pharmacotherapy : What's New and Where
Does It Fit?
Heather F. DeBellis, Melissa C. Jones and Scott E. Kincaid
Journal of Pharmacy Practice 2012 25: 569 originally published online 11 October 2012
DOI: 10.1177/0897190012460829
The online version of this article can be found at:
http://jpp.sagepub.com/content/25/6/569

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New York State Council of Health-system Pharmacists

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An Update for Community-Acquired


Bacterial Pneumonia Pharmacotherapy:
Whats New and Where Does It Fit?

Journal of Pharmacy Practice


25(6) 569-575
The Author(s) 2012
Reprints and permission:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/0897190012460829
http://jpp.sagepub.com

Heather F. DeBellis, PharmD, CDE1,


Melissa C. Jones, PharmD, BCPS1 and Scott E. Kincaid, PharmD, BCPS1

Abstract
In 2007, 1.2 million people in the United States were hospitalized with pneumonia, and more than 52 000 died from the disease.
Community-acquired bacterial pneumonia (CABP) can be caused by a variety of organisms as a result of patient factors such as
comorbidities, epidemiologic conditions, or the setting in which the infection was contracted. Treatment of CABP differs depending on the types of bacteria that are suspected. In the last several years, due to the concern regarding multidrug-resistant organisms (MDROs), 2 new antibiotics have been developed and approved for use in CABP. Ceftaroline fosamil (Teflaro) was approved
by the US Food and Drug Administration (FDA) in October 2010 and tigecycline (Tygacil) in March 2009. In clinical trials, both
agents have been shown to be efficacious and are generally well tolerated. Although these agents have received approval as therapy for CABP, it is the responsibility of physicians and pharmacists to prudently use these antimicrobials where they are truly
needed. Until these agents show superiority over conventional therapy for selected patient populations, given the wide variety
of pharmacotherapy that can prove efficacious for pneumonia, the new agents should be reserved for patients who have known
risk factors for MDROs. Further studies are warranted for these agents in the setting of CABP.
Keywords
pneumonia, tigecycline, ceftaroline fosamil

Introduction
In 2007, 1.2 million people in the United States were
hospitalized with pneumonia and more than 52 000 died from
the disease. Community-acquired bacterial pneumonia (CABP)
in the outpatient setting is caused mainly by Streptococcus
pneumoniae but can also be attributed to such organisms as
Mycoplasma pneumoniae, Haemophilus influenza, Chlamydophila pneumoniae, and certain respiratory viruses. The cause
of hospital-acquired pneumonia is similar; however,
Legionella, Staphylococcus aureus, and other bacteria could
be the culprit. The causative organisms can vary due to comorbid or epidemiologic conditions, such as diabetes, alcoholism,
chronic lung or renal disease, or the recent use of antibiotics.1
According to the current Infectious Disease Society of
America/American Thoracic Society (IDSA/ATS) treatment
guidelines for CABP, there are several empiric treatment
options for CABP in the outpatient setting. Outpatients who are
otherwise healthy should receive monotherapy with a macrolide or doxycyline. In those with comorbid conditions, a
respiratory fluoroquinolone (levofloxacin, moxifloxacin, or
gemifloxacin) or a beta-lactam plus a macrolide are recommended. If a patient is admitted to the hospital, a respiratory
fluoroquinolone or a macrolide plus a beta-lactam are

recommended. Additional antibiotics can be added depending


on the bacteria suspected.1
In the last several years, due to the concern regarding
multidrug-resistant organisms (MDROs), 2 new antibiotics
have been developed and approved for use in CABP. Ceftaroline fosamil (Teflaro) was approved by the US Food and Drug
Administration (FDA) in October 2010. Ceftaroline fosamil is
a broad-spectrum, beta-lactam antibiotic, with activity against
methicillin-resistant Staphylococcus aureus (MRSA) and
multidrug resistant S pneumoniae. It also has gram negative
coverage against Escherichia coli, Proteus mirabilis, H influenza, and Neisseria meningitidis. It has no activity against
anaerobes. The drug has a high affinity for penicillin-binding
protein 2a, which may lend itself to the inhibition of MRSA.
Ceftaroline fosamil is still susceptible to beta-lactamase
producing bacteria; therefore, there are ongoing studies with

South University School of Pharmacy, Savannah, GA, USA

Corresponding Author:
Heather F. DeBellis, PharmD, CDE, South University School of Pharmacy,
709 Mall Boulevard, Savannah, GA 31406, USA
Email: hdebellis@southuniversity.edu

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Journal of Pharmacy Practice 25(6)

the drug in conjunction with a beta-lactamase inhibitor to


expand its antimicrobial coverage. Ceftaroline fosamil is
available as an intravenous (iv) formulation and is dosed at
600 mg every 12 hours for 5 to 7 days. Dosage adjustments are
required for those patients with a creatinine clearance less than
50 mL/min.2 Adverse events were minimal in clinical trials
with nausea reported in 4% and diarrhea in 5% of patients.3
Tigecycline (Tygacil), approved in March 2009, is the first
broad-spectrum, iv, glycylcycline antibiotic for the treatment
of CABP.4 It is a synthetic analogue of the tetracyclines,
designed to overcome resistance that is seen with tetracycline.
It has broad spectrum coverage against gram-positive and
gram-negative aerobes, anaerobes, and atypical pathogens.
Tigecycline is active against S pneumoniae, S aureus
(MRSA),5 and Enterococcus faecalis (including vancomycinresistant enterococcus) and Enterococcus faecium6 as well as
H influenza, Klebsiella pneumoniae, and Morexella catarrhalis. In addition, there is coverage for C pneumoniae, M pneumoniae, Legionella,5 and anaerobes such as Bacteroides fragilis.4
Due to decreased susceptibilities in Pseudomonas aeruginosa
and P mirabilis, tigecycline should not be used to treat these
organisms if they are suspected.7 Tigecycline is able to
overcome the mechanisms of tetracycline resistance, ribosomal
protection, and active efflux from inside the bacteria, by the
addition of a large substituent at position 9 of the tetracycline
molecule. This affords the drug activity against bacteria that
carry these genes. Patients receiving tigecycline should be
given 100 mg iv once, followed by 50 mg every 12 hours for
7 to 14 days. No dosage adjustment is necessary for patients
with renal insufficiency; however, those with severe hepatic
impairment (Child Pugh Score C) require the dose to be
reduced to 25 mg every 12 hours. The most common adverse
effects are nausea (34.5%) and vomiting (19.6%).4

Ceftaroline Fosamil
The FOCUS 1 and FOCUS 2 clinical trials are randomized,
double-blind, multicenter phase III studies evaluating the
safety and efficacy of ceftaroline fosamil when compared to
ceftriaxone for the treatment of hospitalized patients with
CABP. Study participants were randomized (1:1) to receive
treatment for 5 to 7 days of either ceftaroline fosamil 600 mg
every 12 hours or ceftriaxone 1 g every 24 hours if hospitalized
with CABP, requiring iv therapy, and having a Pneumonia Outcomes Research Team (PORT) risk class score of III or IV. The
FOCUS 1 and FOCUS 2 studies were intended as parallel,
methodologically alike (with the exception of 2 doses of
clarithromycin given on day 1 in FOCUS 1 only), comparative
analyses that did not allow switching to oral medications for
treatment completion.8,9

Safety and Tolerability


During the FOCUS 1 and FOCUS 2 phase III studies, all 1228
patients enrolled were monitored for treatment-emergent
adverse events (TEAEs). There were 613 patients followed

from the initial iv administration of ceftaroline fosamil until the


test-of-cure (TOC) visit, and 615 patients similarly followed in
the ceftriaxone group. Patients receiving any amount of drug
were included in the safety analysis. Additionally, serious
adverse events (SAEs) including deaths that transpired within
30 days of the last study drug dose administered and/or up to
the late follow-up (LFU) visit were documented. Study drug
mean exposure was 6.5 + 1.1 days for both study groups.
Patients participated in scheduled laboratory visits from initiation until the TOC visit, while unscheduled laboratory visits
were conducted until the LFU visit.810
The following safety results reported are from the integrated
summary of the FOCUS 1 and FOCUS 2 clinical trials. The
most frequently documented TEAEs in the ceftaroline fosamil
treatment group were diarrhea (4.2%), headache (3.4%), and
insomnia (3.1%). About 75% of patients experienced none or
only mild TEAEs in either treatment group. Therefore, the
severity-based distribution of TEAEs was similar between the
2 treatment groups. The overall incidence rates of adverse
events (AEs) were consistent between the ceftaroline fosamil
group and the ceftriaxone group, respectively, as follows:
patients experiencing at least 1 TEAE (47.0% vs 45.7%), SAE
(11.3% vs 11.7%), discontinuation due to an AE (4.4% vs
4.1%), or who died (2.4% vs 2.0%).10
A total of 27 deaths occurred during the FOCUS trials; 15
occurred in the ceftaroline fosamil group and 12 in the ceftriaxone group. Two deaths (1 from each group) could have been
related to study drug when reviewed by the investigator. Of the
deaths reported, the investigator categorized them by type or
organ system. Deaths related to cardiac disorders (2 vs 7), infections and infestations (3 vs 1), neoplasms (4 vs 0), respiratory
disorders (4 vs 3), and general disorders such as sudden death
and multiple organ disorder (2 vs 1) occurred in the ceftaroline
fosamil and ceftriaxone treatment groups, respectively.10
There were 7 SAEs reported in more than 2 patients in the
ceftaroline fosamil group, which include pneumonia (as
defined by worsening or relapse of CABP or nosocomial pneumonia, 9 patients), pleural effusion (5 patients), pulmonary
embolism (5 patients), chronic obstructive pulmonary disease
(4 patients), pyothorax (4 patients), respiratory failure
(4 patients), and malignant lung neoplasm (3 patients). The
investigator reviewed the SAEs, and the majority of the SAEs
(95.7% in the ceftaroline fosamil group and 91.7% in the ceftriaxone group) were regarded as not related to study drug.
As a result, there were no safety concerns discovered. There
was not a TEAE occurring in more than 2 patients in the ceftaroline fosamil group that led to discontinuation of study drug
or withdrawal from study. However, pneumonia (as defined
above), pulmonary embolism, respiratory failure, septic shock,
and sudden death each occurred in 2 patients in the ceftaroline
fosamil group which led to discontinuation of the study drug or
withdrawal from the study for those patients. A total of 10
patients in the ceftaroline fosamil group and 9 patients in the
ceftriaxone group either discontinued the study drug or withdrew from the study. The majority of the SAEs and the TEAEs
leading to discontinuation of the study drug reflected an

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571

Table 1. Clinical Cure Rates in Clinically Evaluable Patients

FOCUS 1
FOCUS 2
Integrated efficacy analysis

Ceftaroline
fosamil group

Ceftriaxone
group

Difference

95% Confidence interval


[CI] for difference

86.6%
82.1%
84.3%

78.2%
77.2%
77.7%

8.4%
4.9%
6.7%

1.4%-15.4%
2.5%-12.5%
1.6%-11.8%

Table 2. Clinical Cure Rates in Modified Intent-to-Treat Efficacy Patients

FOCUS 1
FOCUS 2
Integrated efficacy analysis

Ceftaroline
fosamil group

Ceftriaxone
group

Difference

95% Confidence interval


[CI] for difference

83.8%
81.3%
82.6%

77.7%
75.5%
76.6%

6.2%
5.9%
6.0%

0.2%-12.6%
1.0%-12.7%
1.4%-10.7%

insufficient therapeutic response, which resulted in a prolonged


hospitalization (meets criteria of the SAE definition) or reflects
AEs which result in death (withdrawal from the study).10
Overall, ceftaroline fosamil is well tolerated and does not
possess any unforeseen safety concerns. Ceftaroline fosamil
is classified as pregnancy category B. Caution should be used
in patients previously experiencing an allergic skin reaction
to any other beta-lactam antibiotic, and ceftaroline fosamil
should be immediately discontinued if a reaction develops.
Ceftaroline fosamil has a consistent safety and tolerability profile as seen with ceftriaxone and the cephalosporin class as a
whole.10,11

Clinical Efficacy
The primary end point of the FOCUS program was to determine noninferiority of ceftaroline fosamil in clinical cure rates
when compared with ceftriaxone in the clinically evaluable
(CE) and modified intent-to-treat efficacy (MITTE) populations at the TOC visit (Tables 1 and 2). A clinical cure was
defined as resolution of all signs and symptoms of pneumonia
or improvement to that point that no further antimicrobial treatment was needed. Patients had to demonstrate total resolution
of CABP signs and symptoms in addition to being afebrile for
24 consecutive hours for clinical cure to be established. If a
patient previously established a clinical cure at the TOC visit,
but later displayed returning symptoms involving additional
antimicrobial treatment during the LFU visit then relapse was
confirmed. The TOC visit occurred 8 to 15 days from the last
dose of study drug administered, and the LFU occurred 21 to
35 days from the last dose of study drug.12
FOCUS 1 clinical cure rates in CE patients were 86.6% in
the ceftaroline fosamil group versus 78.2% in the ceftriaxone
group (difference, 8.4%; 95% confidence interval [CI], 1.4%15.4%). During FOCUS 2, the clinical cure rates in the CE population were 82.1% in the ceftaroline fosamil group versus
77.2% in the ceftriaxone group (difference, 4.9%; 95% CI,
2.5%-12.5%). In the integrated efficacy analysis of the 2

trials, the clinical cure rates in the CE population were 84.3%


in the ceftaroline fosamil group versus 77.7% in the ceftriaxone
group (difference, 6.7%; 95% CI, 1.6%-11.8%).8,9,12
FOCUS 1 clinical cure rates in MITTE patients were 83.8%
in the ceftaroline fosamil group versus 77.7% in the ceftriaxone
group (difference, 6.2%; 95% confidence interval [CI], 0.2%12.6%). During FOCUS 2, the clinical cure rates in the MITTE
population were 81.3% in the ceftaroline fosamil group versus
75.5% in the ceftriaxone group (difference, 5.9%; 95% CI,
1.0%-12.7%). The integrated summary reports clinical cure
rates in MITTE patients as 82.6% versus 76.6% for ceftaroline
fosamil and ceftriaxone, respectively (difference, 6.0%; 95%
CI, 1.4%-10.7%).8,9,12
Clinical cure rates for ceftaroline fosamil were noninferior
to those of ceftriaxone across all predefined study populations
during the FOCUS program. Additionally, clinical relapse rates
at LFU were consistent between the 2 study groups for the CE
and MITTE populations as reported in the integrated analysis.
Therefore, ceftaroline fosamil 600 mg administered iv every 12
hours was determined efficacious and noninferior to ceftriaxone 1 g administered iv every 24 hours in hospitalized patients
with CABP, requiring iv therapy, and having a PORT risk class
score of III or IV.8,9,12

Tigecycline
Currently, there are results from 2 phase III, multicenter,
double-blind, randomized clinical trials evaluating the safety
and efficacy of tigecycline for the treatment of CABP when
compared to levofloxacin in hospitalized patients requiring iv
therapy.1315 Bergallo et al investigated a comparison study
featuring an initial dose of tigecycline 100 mg administered
iv followed by 50 mg every 12 hours versus levofloxacin 500
mg administered iv every 24 hours for creatinine clearance
rates 50 mL/min. Patients in the levofloxacin group with
creatinine clearance rates <50 mL/min received a dose appropriate for their degree of renal impairment per the approved
package insert. Patients were randomized (1:1) to receive either

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Journal of Pharmacy Practice 25(6)

study drug for a minimum of 3 days. The total duration of therapy was 7 to 14 days. After receiving 6 or more doses of study
drug iv, patients could be changed to oral levofloxacin for the
remaining treatment duration.13
Tanaseanu et al conducted a prospective, noninferiority
study testing an initial dose of tigecycline 100 mg administered
iv over 1 hour followed by 50 mg every 12 hours versus levofloxacin 500 mg administered iv over 1 hour every 12 or 24
hours for creatinine clearance rates 50 mL/min. Patients in
the levofloxacin group with creatinine clearance rates of 20
to 49 mL/min received an initial dose of levofloxacin 500 mg
followed by 250 mg every 12 or 24 hours administered iv.
Patients were randomized (1:1) to receive either study drug for
a minimum of 7 days. The total duration of therapy was 7 to 14
days.14

Safety and Tolerability


The safety evaluation conducted by Bergallo et al occurred at
baseline and day 3 (consisting of laboratory tests and 12-lead
electrocardiogram) which additionally monitored for AEs. This
evaluation included all patients receiving any amount of study
drug in the modified intent-to-treat (mITT) population (n
208 tigecycline, n 210 levofloxacin). The AEs and SAEs
were documented up to and including the TOC visit that
occurred between 7 and 23 days after administering the last
dose of study drug or 14 days after the last dose of study drug,
whichever was greater. The mITT population for the 2 treatment groups received study drug for a median of 4 days followed by a median of 6 days of oral levofloxacin therapy.13
Almost half of the patients (48.6%, 203 of 418) from the
mITT population of both study groups reported at least 1
drug-related AE (DRAE). The most frequently documented
DRAEs in the tigecycline group were nausea (16.3%) and
vomiting (12.0%), but they were categorized as mild to moderate in severity with few patients discontinuing tigecycline as a
result. Discontinuation rates due to any type of AEs were consistent between the 2 study groups. In all, 5 tigecycline-treated
patients and 6 levofloxacin-treated patients died during the
clinical study, but the investigators reviewed the deaths finding
them to be unrelated to the study drugs. There were no significant findings between the 2 treatment groups in hospital length
of stay or hospital readmissions. Overall, the investigators concluded that tigecycline was well tolerated and safe.13
The safety assessment reported by Tanaseanu et al included
medical history, physical examination, laboratory tests, and a
12-lead electrocardiogram that occurred at baseline (within
24 hours of study drug dose), during treatment, 2 to 4 days post
therapy (early follow-up), and during the TOC visit. The
assessment of AEs included all patients receiving any amount
of study drug in the mITT population (n 216 tigecycline and
n 212 levofloxacin). The AEs and SAEs were documented
up to and including the TOC visit which occurred between
10 and 21 days after administering the last dose of study drug
or 14 days after the last dose of study drug, whichever was
greater.14

More than half of the tigecycline-treated patients (62.5%,


135/216) reported at least 1 TEAE which is statistically significant when compared to the levofloxacin-treated patients
(47.2%, 100 of 212; P .002). The most frequently documented AEs in the tigecycline group were nausea (26.9%) and
vomiting (16.7%), but they were categorized as mild to moderate in severity. However, when compared to nausea (8.5%) and
vomiting (6.6%) in levofloxacin-treated patients this was statistically significant (nausea, P < .001 and vomiting, P .001).
The investigator also reported significantly more DRAEs in the
tigecycline-treated patients compared to the levofloxacintreated patients (44.4% vs 29.2%, P < .001). Discontinuation
rates due to any type of AEs, including nausea and vomiting,
were consistent between the 2 study groups. In all, 7
tigecycline-treated patients and 5 levofloxacin-treated patients
died during the clinical study, but the investigators reviewed
the deaths finding them to be unrelated to the study drugs. This
study summarized tigecyclines safety profile and states it is
generally well tolerated.14
For patients with severe hepatic impairment (Child Pugh
Score C), the initial tigecycline dose is 100 mg followed by a
reduced maintenance dose of 25 mg every 12 hours. These
patients should be cautiously treated and monitored for treatment response. Tigecycline is classified as pregnancy category
D due to possible teratogenic effects, and it should not be administered to a pregnant patient since it may cause fetal harm. On
September 1, 2010, the FDA issued a Drug Safety Communication concerning the increased risk of all-cause mortality associated with tigecycline compared to other antimicrobials used
to treat serious infections. To date, the cause for this increased
risk of death has not been identified. Therefore, health care providers should be cautioned to fully weigh the potential risk versus benefit before initiating tigecycline in patients with severe
infections.15,16

Clinical Efficacy
The primary efficacy end points analyzed by Bergallo et al
were clinical responses (categorized as cure, failure, or indeterminate) in the CE and clinical mITT (c-mITT) populations at
the TOC visit (Tables 3 and 4). A clinical cure response means
all signs and symptoms of CABP improved or resolved, chest
radiographs were improved or not worse, no further antibiotic
therapy was required, and there were no new signs and symptoms of CABP at the TOC visit. Noninferiority was confirmed
since the lower limit of the 2-sided 95% CI was greater than or
equal to 15%. The clinical cure rates in CE patients were
90.6% in the tigecycline group versus 87.2% in the levofloxacin group (difference, 3.4%; 95% CI, 4.4%-11.2%). Clinical
cure rates were also consistent with the c-mITT patients, 78%
in the tigecycline group versus 77.8% in the levofloxacin group
(difference, 0.2%; 95% CI, 8.5%-8.9%). Since there were no
statistically significant differences found at TOC, the efficacy
of tigecycline was determined to be statistically noninferior
to levofloxacin. This comparison study confirmed tigecycline
to be efficacious and noninferior to levofloxacin for the

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573

Table 3. Clinical Cure Rates in Clinically Evaluable Patients

Bergallo et al13
Tanaseanu et al14

Tigecycline
group

Levofloxacin
group

Adjusted
difference

95% Confidence interval


[CI] for difference

90.6%
88.9%

87.2%
85.3%

3.4%
3.6%

4.4%-11.2%
4.5%-11.8%

Table 4. Clinical Cure Rates in Clinical Modified Intent-to-Treat Patients

Bergallo et al13
Tanaseanu et al14

Tigecycline
group

Levofloxacin
group

Adjusted
difference

95% Confidence interval


[CI] for difference

78.0%
83.7%

77.8%
81.5%

0.2%
2.0%

8.5%-8.9%
5.5%-9.6%

treatment of CABP in hospitalized patients requiring iv antimicrobial treatment.13


The primary efficacy end points examined by Tanaseanu
et al were clinical responses (cure, failure, or indeterminate)
in the CE and c-mITT populations at the TOC visit (Tables 3
and 4). Noninferiority was confirmed since the lower limit of
the 2-sided 95% CI was greater than or equal to 15%.
Between both CE groups, 88.9% in the tigecycline group
versus 85.3% in the levofloxacin group (adjusted difference,
3.6%; 95% CI, 4.5%-11.8%), clinical cure rates were consistent without statistically significant differences at the TOC
visit. Clinical cure rates in c-mITT patients were 83.7% in the
tigecycline group versus 81.5% in the levofloxacin group
(adjusted difference, 2.0%; 95% CI, 5.5%-9.6%), therefore,
concluding tigecyclines efficacy to be statistically noninferior
to levofloxacin. Differences were adjusted for the Fine
Pneumonia Severity Index Score. This severity index is a clinical prediction that calculates the probability of morbidity and
mortality in patients with CABP. Adjustments were made to
account for differences between the groups with regard to the
severity index score. This prospective study supports noninferiority and efficacy of tigecycline versus levofloxacin for the
treatment of CABP in hospitalized patients requiring iv
therapy.14
During the integrated analysis, Tanaseanu et al evaluated
tigecyclines efficacy and safety results from these 2 phase III
trials. According to the safety observations, there were no
significant differences in discontinuation rates due to AEs, the
frequency of SAEs, or death despite significantly more DRAEs
in the tigecycline-treated patients. It was also noted that in
severely compromised patients with comorbid diseases such
as congestive heart failure, diabetes, and chronic obstructive
pulmonary disease, tigecycline achieved cure rates of 100%,
97.1%, and 81.3%, respectively, as well as 90.9% in patients
with bacteremia. These rates were shown to be noninferior to
the levofloxacin group as there were no statistically significant
differences in the percentages between groups. Ultimately, the
investigators concluded tigecycline appeared to be safe with
noninferior clinical cure rates when compared to levofloxacin
in hospitalized patients with CABP. Overall, clinicians should

exercise caution when weighing the potential risk versus


benefit of using tigecycline in patients with severe infections
due to the increased mortality risk.15,17

Discussion
As the identification of resistant organisms continues to rise
and the lack of new antimicrobials with novel mechanisms
of action persists, it becomes more evident every day that
antimicrobial stewardship and judicious use of antimicrobials
is the new necessity. Antimicrobials such as ceftaroline fosamil and tigecycline are some new options that have gained an
indication in the treatment of CABP. The data show that these
agents are considered noninferior but there have yet to be
adequate studies to support the preferred use of these antimicrobials. As bacteria adapt to the selective pressure that we
place on them, it is unknown what will be the next reaction
after significant use of these antimicrobials. The approach
to antimicrobial research and practice has shifted more toward
preservation than development due to the lack of novel agents
in the pipeline. This is one reason why antimicrobial
stewardship programs are becoming increasingly important
in all hospital settings and the use of new agents should be
subjected to educated skepticism.
When we step back and take a look at the niche that has been
created for these medications we must consider the relevance
of each individual patients history and their risk for MDROs.
These agents were specifically designed to cover MDROs and
according to the current guidelines the patients at risk for
MDROs would not necessarily meet the criteria for a simple
CABP. Many, if not all of these patients, would be classified
as a health careassociated pneumonia (HCAP). According to
the IDSA guidelines, this classification would justify a more
broad therapy than the currently recommended therapy for
CABP.18 Thus, the utility of these agents in patients who are
actual CABP patients becomes greatly reduced. Empiric
therapy should be driven by evidence-based medicine
(ie, guidelines) and the resistance patterns seen in the community where they reside. Local antibiograms should provide an
appropriate source of guidance when choosing empiric therapy

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Journal of Pharmacy Practice 25(6)

in this patient population. In patients who are identified as


being MRSA colonized or have had past episodes with
multidrug-resistant Streptococcus pneumonia (MDRSP),
these agents may have found their ideal population for CABP
treatment. Along with a small niche for these antimicrobials
there are concerns regarding the efficacy in patients who are
more severely ill. Questions have been raised regarding the
efficacy of tigecycline in the severely ill due to its bacteriostatic nature and also the low serum concentrations that it
exhibits due to its large volume of distribution.19 These characteristics reduce tigecyclines utility in patients who are
severely ill or have documented or presumed bacteremia.
Thus, tigecycline should not be used in patients who are
severely ill (ie, septic, bacteremic, etc) when there are other
options available or until there is more data to support the
safety and efficacy in these patient populations.19 The
utilization of these medications should be reserved for
patients who are at a higher risk for MDROs such as those
classified as HCAP patients.
Along with the clinical relevance of selecting these
antimicrobials comes the question of pharmacoeconomic
efficiency. Given the equivalent efficacy of these antimicrobials
in CABP, they appear to be a potential option for selected patient
populations, however, the cost of use should be evaluated on a
case-by-case basis to determine the most appropriate allocation
of funds.

Recommendations
Ceftaroline fosamil and tigecycline are both agents with
great potential for use in selected patient populations. Nonetheless, true CABP patients who do not exhibit the appropriate risk factors should receive more intensive evaluation by
trained infectious disease practitioners prior to initiating
therapy, whether it is empiric or targeted, with ceftaroline
or tigecycline. There may be a greater utility for deescalation therapy to one of these agents when Pseudomonas aeruginosa, which neither agent has efficacy against,
has been ruled out.
Novel antimicrobials agents are of a dying breed and
MDROs are continuing to adapt to the selective pressure
of the antimicrobial era. Agents such as ceftaroline fosamil
and tigecycline should be used judiciously. Practitioners
should be reserving these antimicrobials for patients who
have risk factors that justify their use or for identified
pathogens with specific resistance to other antimicrobials
that are more cost effective. Given their noninferiority,
more research is warranted to determine whether there is
a significant clinical and pharmacoeconomic benefit to supplant other traditional less-expensive antimicrobials.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.

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