Pneumonia Insert PDF - American Pharmacists Association

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Pneumonia Insert PDF - American Pharmacists Association

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Expiration date:

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EMPIRIC ANTIMICROBIALS

IN PNEUMONIA:

BALANCING RISK AGAINST

BENEFIT IN AN ERA

OF RESISTANCE

A supplement to Pharmacy Today

Empiric Antimicrobials in Pneumonia: Balancing Risk Against Benefit in an Era of Resistance 1


TargeT audience

This activity has been designed to meet the educational needs of

pharmacists involved in the management of patients with pneumonia faced with

the increasing trends of antibiotic resistance.

STaTemenT of need/Program overview

The impact of respiratory infections on individuals in society is important

and is growing as the population ages. Lower respiratory tract infections in

particular are major causes of morbidity and mortality. Atypical pathogens are

implicated in up to 40% of community-acquired pneumonia (CAP) cases and

commonly occur as copathogens in mixed-infection CAP, an etiology associated

with particularly high mortality (up to 25%). Staphylococcus aureus continues to

account for nearly 30% of all cases of ventilator-associated pneumonia; however,

the antimicrobial susceptibilities of these organisms have evolved. Specifically,

increasing rates of resistance are now reported for both gram-negative and grampositive

pathogens. For example, in the intensive care unit, approximately 70%

of S aureus species are methicillin resistant. Laboratory methods for detecting

atypical pathogens are slow, and there is significant overlap between atypical

and typical manifestations. For these reasons, accurate prediction of etiology

cannot be made purely on clinical or radiologic grounds. Consequently, empiric

antimicrobial therapy warrants careful consideration. Recently, safety concerns

have subjected empiric antimicrobials to intense scrutiny and further study.

However, in light of the growing number of atypical pathogens, it is critical

clinicians mitigate the adverse event concerns against local resistance patterns,

individual patient risk factors, and distinctive clinical circumstances such as the

severity of illness. For the patient “at risk,” clinician assessment of antimicrobial

risk-to-benefit ratio is warranted.

educaTional objecTiveS

After completing this activity, the participant should be better able to:

• Differentiate the pathogens of significance found in nosocomial,

community-acquired, and health care–associated pneumonia

• Review treatment challenges for pneumonia due to increasing trends of

antibiotic resistance

• Describe the principles of antimicrobial stewardship, empiric therapy, and

de-escalation

• Explain benefit-risk profiles of available empiric antimicrobial agents in

pneumonia

• Identify mitigating clinical factors for assessment, including local resistance

patterns, patient risk factors, and severity of illness, to customize care and

optimize outcomes

faculTy

Robert P. Rapp, PharmD, FCCP

Professor of Pharmacy & Surgery

Colleges of Pharmacy & Medicine

University of Kentucky Medical Center

Lexington, Kentucky

Robert E. Siegel, MD

Chief, Pulmonary and Critical Care Medicine

James J. Peters Veterans Affairs Medical Center

Bronx, New York

Associate Professor of Medicine

Mount Sinai School of Medicine

New York, New York

accrediTaTion STaTemenT

Postgraduate Institute for Medicine is accredited by the

Accreditation Council for Pharmacy Education as a provider of

continuing pharmacy education.

crediT deSignaTion

Postgraduate Institute for Medicine designates this continuing education

activity for 1.25 contact hour(s) (0.125 CEUs) of the Accreditation Council for

Pharmacy Education. (Universal Activity Number - 809-999-09-035-H01-P)

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The faculty reported the following financial relationships or relationships

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name of faculTy

or PreSenTer

Robert P. Rapp, PharmD,

FCCP

Robert E. Siegel, MD

rePorTed financial

relaTionShiP

Speakers’ bureaus: Astellas, Ortho-McNeil,

Wyeth; Consultant: Ortho-McNeil

Speakers’ bureaus: Ortho-McNeil, Pfizer;

Consultant: Ortho-McNeil

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EMPIRIC ANTIMICROBIALS IN PNEUMONIA:

BALANCING RISK AGAINST BENEFIT IN AN ERA OF RESISTANCE

INTRODUCTION

With the advent of antimicrobial therapy, the United States,

in the latter half of the 20th century, witnessed major reductions

in the morbidity and mortality associated with infectious diseases.

Nevertheless, nearly a decade into the 21st century, communityacquired

and hospital-acquired pneumonia persist as major causes

of antimicrobial consumption, morbidity, and mortality. In 2005,

the most recent year for which data are available, pneumonia/

influenza ranked as the eighth leading cause of death, accounting

for 2.6% of all deaths. 1 The syndromes were associated with an

age-adjusted mortality rate of 20.3%, amounting to 63,000 total

deaths. 1,2

Despite the numbers, pneumonia is a treatable and curable

disease, provided that patients receive prompt and appropriate

antimicrobial therapy. For the treatment of community-acquired

pneumonia (CAP), recent guidelines from the American Thoracic

Society (ATS) and Infectious Diseases Society of America (IDSA)

recommend prompt empiric antimicrobial therapy targeted to

suspected underlying pathogens. For hospital-acquired pneumonia

(HAP), ventilator-associated pneumonia (VAP), and health

care–associated pneumonia (HCAP), guidelines recommend

empiric broad-spectrum treatment followed by a switch to

pathogen-specific treatment (de-escalation) based on the results

of microbiologic studies. 3,4 Empiric broad-spectrum strategies

facilitate rapid treatment and provide coverage for the diversity of

typical, atypical, and antimicrobial-resistant pathogens that may

underlie an infection. Subsequent de-escalation strategies minimize

overexposure to broad-spectrum agents, thereby lessening the

probability of the emergence of antimicrobial resistance. 3,4

Empiric therapy, when implemented in accordance with

guideline-recommended treatment strategies, has the potential

to substantially reduce mortality rates in CAP. 5 However, simply

adhering to the guidelines and administering any of the available

broad-spectrum agents is insufficient for providing safe and

effective treatment. Guidelines can be outdated quickly and are

not always current with patterns of antimicrobial resistance. Health

care professionals must consider the local rates of antimicrobial

resistance as well as individual patient risk factors for adverse events

when selecting treatment.

In recent years, empiric broad-spectrum therapy has come

under scrutiny as safety concerns with the commonly reliedupon

agents, ranging from cardiac toxicities to tendinopathy,

have emerged. Simultaneously, the efficacy of the existing

antimicrobial armamentarium has dwindled, along with research

and development of new agents. 6 The confluence of events has

created multiple challenges for health care professionals who treat

pneumonia: promptly selecting empiric therapy with activity

against all potential pathogens while balancing the need for

preserving antimicrobial efficacy and avoiding toxicities. They must

therefore be capable of balancing patients’ need for, and potential

benefits of, empiric antimicrobial therapy with the potential for

adverse events, while judiciously employing existing agents. 7-11

Doing so requires an understanding of pneumonia categories,

treatment strategies, and the risks and benefits of individual classes

of antimicrobial agents.

PNEUMONIA CATEGORIES

AND ETIOLOGY

Pneumonia is categorized according to suspected acquisition

site. HAP is a pulmonary infection occurring 48 or more hours

after hospital admission in individuals who previously had no

infection. 3 VAP is pneumonia occurring more than 48 hours after

endotracheal intubation (early onset within 48-96 hours; late onset

>96 hours). 3 CAP is defined as pneumonia in a community resident

without risk factors for HCAP. 4 HCAP is a recently differentiated

category that includes patients with an infection developing

Table 1. Risk Factors for Health Care–Associated

Pneumonia (HCAP) 3

Patients meeting any of the following conditions are

considered to have HCAP:

• Infection developing within 90 days of ≥2-day

hospitalization

• Infection in nursing home resident or long-term–care

resident

• Infection within 30 days of receiving intravenous

antimicrobial therapy, chemotherapy, or wound care

• Infection following a hospital or hemodialysis clinic visit

• Contact with a multidrug-resistant pathogen

All patients with HCAP are considered at risk for a

multidrug-resistant infection.

within days or weeks of exposure to health care institutions and/or

procedures (Table 1). 3 Pneumonia guidelines include stratification

strategies for antimicrobial selection based on risk factors for various

causative pathogens.

These categories are distinguished by patient history.

Presentation, symptoms, and disease severity are variable and

cannot be used to determine an underlying etiology. Differentiation

is essential as etiology and, therefore, treatment vary according to

acquisition site. Based on currently available data, HAP, VAP, and

HCAP share similar etiologies, and these etiologies are distinct

from those of CAP.

eTiology of haP/vaP

HAP accounts for 25% of infections occurring in intensive

care units (ICUs), and VAP occurs in 9% to 27% of all intubated

patients. 3 Both are associated with excess morbidity and mortality. 3

Nosocomial tracheobronchitis, the second most common hospitalacquired

lower respiratory tract infection, occurs in nearly 4% of

ICU patients; intubated patients in particular have an increased

risk. 12 The majority of cases—at least two-thirds—of nosocomial

pneumonia and tracheobronchitis are caused by gram-negative

pathogens. 3,13-15 Frequently isolated pathogens include Pseudomonas

aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Acinetobacter

species. 3,13,14 Gram-positive pathogens account for the remaining

cases, with Staphylococcus aureus, including methicillin-resistant

strains (MRSA), being the most frequently isolated. 3,13,14

Empiric Antimicrobials in Pneumonia: Balancing Risk Against Benefit in an Era of Resistance 1


eTiology of caP

CAP is among the leading causes of emergency department

visits and hospitalization in the United States, accounting for up to

1.2 million annual hospitalizations and costing up to $10 billion. 16,17

Multiple pathogens are implicated in CAP, but Streptococcus

pneumoniae remains the most frequently isolated. 4 Other frequently

identified pathogens include Mycoplasma pneumoniae, Haemophilus

infl uenzae, Chlamydophila pneumoniae, and Legionella species. 4

Pathogens of emerging importance are those that were once

primarily confined to hospital environments. 18,19 For example,

gram-negative pathogens, such as P aeruginosa, Enterobacter cloacae,

Klebsiella species, and E coli, and community-acquired (CA) MRSA

are increasingly recognized as causative pathogens among patients

with CAP. 18,19

CAP caused by CA-MRSA is a growing source of concern.

Currently, it is an infrequent cause of CAP, accounting for 2%

or less of all cases, 20 but this rate is expected to increase, and

future iterations of guidelines are expected to specifically address

CA-MRSA CAP. Clear risk factors for CA-MRSA CAP have yet to

be identified, but it may be associated with prior influenza infection

or influenza prodromes, prior CA-MRSA skin and soft tissue

infection, exposure to someone with a CA-MRSA infection, and

recent antimicrobial use. 20,21

eTiology of hcaP

Based on currently available evidence, the etiology of HCAP

resembles that of HAP/VAP and is distinctly different from that

of CAP, making identification of risk factors an essential factor in

the selection of initial empiric antimicrobial therapy. The process

of delineating the definitive etiology of HCAP is ongoing, but

multiple recent studies comparing the microbiology of HCAP and

CAP have, in general, found a higher incidence of drug-resistant

pathogens and gram-negative pathogens among patients with

HCAP (Figure 1). 3,14,22,23 Pathogens such as Pseudomonas species,

Acinetobacter species, and MRSA tend to predominate. 3,14,22-24

ANTIMICROBIAL RESISTANCE

IN PNEUMONIA

Antimicrobial resistance may occur in any pneumonia

category and with any underlying pathogen (Table 2). 3,4 However,

antimicrobial resistance tends to occur more frequently in HAP,

VAP, and HCAP than in CAP infections, and all patients with

HCAP are, by definition, considered at risk for multidrug-resistant

pathogens.

The potential consequences of antimicrobial resistance can

include prolonged hospital stays, increased need for surgical

procedures, increased morbidity and mortality, and higher costs. 25-29

Antimicrobial resistance may also increase the likelihood of

selecting inappropriate empiric antimicrobial therapy (choosing

therapy to which the organism is not sensitive), 26 which, in itself,

increases a patient’s risk of death. 30-35

This has been found to be especially true among patients

with HCAP. A 639-patient retrospective cohort study comparing

patients with HCAP (n=431) and CAP (n=208) at a single center

found that patients with HCAP were more than twice as likely

to receive inappropriate therapy as were those with CAP (28.3%

vs 13.0%, respectively; P


Table 2. Risk Factors for Antimicrobial-Resistant

Pneumonia 3,4

Risk factors for antimicrobial-resistant nosocomial

pneumonia

• Antimicrobial therapy in the preceding 90 days

• Current hospitalization of ≥5 days

• High frequency of antimicrobial resistance in the

community

• High frequency of antimicrobial resistance in the specifi c

hospital unit

• Presence of risk factors for health care–associated

pneumonia (HCAP)

• Immunosuppressive disease and/or therapy

Risk factors for antimicrobial-resistant communityacquired

pneumonia

• Antimicrobial therapy in the preceding 90 days

• Presence of comorbidities

- Chronic heart failure; chronic lung, liver, or renal

disease; diabetes mellitus; alcoholism; malignancies;

asplenia

• Immunosuppressive disease and/or therapy

• Age 65 years

• Presence of risk factors for HCAP

Reprinted with permission from American Thoracic Society,

Infectious Diseases Society of America. Am J Respir Crit Care Med.

2005;171(4):388-416.

eTiology of anTimicrobial reSiSTance

Of the estimated 2 million nosocomial infections that occur

each year in the United States, at least 70% are caused by an

antimicrobial-resistant organism. 6,13,37 Gram-negative pathogens

tend to predominate among such infections, except for skin and

soft tissue infections, which are more often caused by gram-positive

organisms. Currently important antimicrobial-resistant nosocomial

pathogens include Acinetobacter species, P aeruginosa, MRSA, and

extended-spectrum beta-lactamase–producing organisms such as

E coli and K pneumoniae. More recently, K pneumoniae

carbapenemase–producing gram-negative bacteria appear to be

spreading rapidly throughout the United States.

Among patients with CAP, resistant strains of S pneumoniae are

of particular importance. Resistance to a variety of agents including

Table 3. New Antibacterial Agents Approved in

the United States, 1983-2002, per 5-Year Period 36

Period

No. of New

Antibacterial Agents

1983-1987 16

1988-1992 14

1993-1997 10

1998-2002 7

penicillin, macrolides, tetracycline, trimethoprim-sulfamethoxazole,

and clindamycin has been reported, but such trends may be

stabilizing or receding. 4,38-41 However, macrolide resistance remains

widespread, and this class of agents is currently recommended only

for patients with uncomplicated CAP (otherwise healthy patients

without major comorbidities or risks for an antimicrobial-resistant

infection) and in combination with beta-lactams in patients with

comorbidities to target atypical pathogens. 4 In 2007, the Clinical

and Laboratory Standards Institute adopted revised breakpoints

for penicillin in pneumonia infections caused by S pneumoniae. The

change in the susceptibility breakpoint from ≤0.06 mcg/mL to

≤2 mcg/mL has also reduced the proportion of isolates considered

resistant.

Fluoroquinolone-resistant S pneumoniae remains relatively

uncommon, 42,43 and, to preserve the effectiveness of the class,

CAP guidelines discourage use in ambulatory patients with

uncomplicated CAP. 4 Rather, these agents are recommended

for patients requiring hospitalization, those with risk factors for

multidrug-resistant S pneumoniae, and those with macrolide-resistant

infections.

STRATEGIES FOR PREVENTING

AND CONTROLLING

ANTIMICROBIAL RESISTANCE

The spread of antimicrobial-resistant pathogens may be

controlled with stringent infection control measures (Table 4), 44

but the emergence of antimicrobial-resistant organisms requires

re-evaluation and re-implementation of the overall use of and

reliance on antimicrobial agents. Although there are many causes

of antimicrobial resistance, the volume of antimicrobials used and

Table 4. Strategies for Preventing/Controlling

Antimicrobial Resistance 44

• Hand hygiene

• De-escalation of broad-spectrum antimicrobial therapy

• Short-course antimicrobial therapy

• Tenets of antimicrobial use

- Never treat a single positive blood culture for

coagulase-negative Staphylococcus

- Never treat acute bronchitis with an antimicrobial unless

the patient has pertussis

• Avoid double coverage—it is a myth for virtually every

pathogen

• Vaccinate patients and health care workers

• Use diagnostics wisely

• Use care when interpreting culture results

• Remember that the pathogens currently considered the

most important (eg, MRSA, Clostridium diffi cile, resistant

gram-negative bacilli) are all the product of antimicrobial

use and abuse

MRSA, methicillin-resistant Staphylococcus aureus.

Reprinted with permission from Rapp RP. http://www.medcme.org/

infectious-disease/132:best-practices-in-community-acquiredpneumonia-improving-quality-a-patient-outcomes.

Accessed January

22, 2009.

Empiric Antimicrobials in Pneumonia: Balancing Risk Against Benefit in an Era of Resistance 3


the ways in which they are used are frequently cited as primary and

reversible causes. 45 These factors may be tempered and controlled

with the implementation of antimicrobial stewardship programs

(ASPs). ASPs are designed to ensure that patients receive optimal

antimicrobial therapy—the correct dose of the correct agent

given via the appropriate route of administration for the needed

duration of time. 29 In so doing, ASPs aim to prevent inappropriate

antimicrobial use and overuse, preserve the effectiveness of existing

agents, and improve the safety and effectiveness of antimicrobial

therapy.

aSP STraTEgiES

The first guidelines for developing an ASP were published in

2007 by the IDSA and the Society for Healthcare Epidemiology

of America 29 and outline 2 broad approaches to antimicrobial

stewardship: prior authorization strategies and prospective audit

and feedback strategies. 29 In the former strategy, prescriptions

are submitted to, and jointly reviewed by, an ASP team (often a

pharmacist or infectious disease specialist or interdisciplinary team)

and the physician before the requested agent is dispensed. Prior

authorization is a quick and effective means to reduce the volume

of antimicrobial use and to reduce costs. 29 Determining the degree

to which such strategies reduce antimicrobial resistance has been

difficult to measure; however, it is reasonable to infer that less

antimicrobial use ultimately results in less antimicrobial resistance.

These strategies are resource intensive and may be most appropriate

for tertiary care and academic medical centers.

In audit and feedback systems, antimicrobial use is audited

and interventions suggested by the ASP team when needed. 29 The

ASP team should include an infectious disease physician and a

clinical pharmacist with infectious disease training. Ideally, the ASP

team would also include a clinical microbiologist, an information

system specialist, an infection control professional, and a hospital

epidemiologist. Such systems are less cumbersome than are prior

authorization strategies because an on-call authorizing individual

or team is not required and audits may be conducted as resources

permit. Audit and feedback strategies are well suited to community

hospitals, particularly as an initial step to establishing an ASP.

Importantly, the audit process also provides an opportunity for

education. Carling et al 46 evaluated parenteral antibiotic use, cost

per 1000 patient-days, and Medicare Case Mix Index (MCCMI)

trends for a 7-year period following implementation of an

interventional multidisciplinary antibiotic management program in

a hospital setting. Results from this study indicated that an ongoing

antibiotic management program has a sustained benefit reducing

both expenditures for and use of antimicrobials while decreasing

the incidence of infections with resistant bacterial pathogens

even as both the MCCMI and intensive care unit patient-days

increased over this period. These programs, too, are associated with

reductions in inappropriate prescribing and incidence of nosocomial

Clostridium diffi cile infections. 29,46,47

These ASP strategies are not mutually exclusive—audit

and feedback systems may be combined with prior authorization

strategies. The overarching strategies may also be combined with a

variety of supplemental strategies that optimize if, when, and how

patients receive treatment. Of recent interest are dose-optimization

strategies based on pharmacokinetic and pharmacodynamic

(PK/PD) principles, short-course antimicrobial therapy, and deescalation.

PK/Pd doSing STraTegieS

Antimicrobial agents are broadly categorized into those with

either time-dependent or concentration-dependent activity. Agents

with time-dependent bacteriocidal activity (macrolides and betalactams)

exert bacteriocidal activity when a pathogen is exposed to

a specific minimum inhibitory concentration for a specific duration

of time. With concentration-dependent agents (fluoroquinolones

and aminoglycosides), it is the total amount of drug administered

that determines efficacy. Dosing strategies based on PK/PD

principles are designed to maximize these properties and maintain

adequate drug concentrations at infection sites for sufficient periods

of time. 48

Figure 2. Comparison of Pharmacokinetic/

Pharmacodynamic (PK/PD)-Based High-Dose,

Short-Course Levofloxacin (750 mg once daily

for 5 days) With Standard Therapy (500 mg once

daily for 10 days) in Patients With Community-

Acquired Pneumonia 49

% of Patients

100

Several examples of the efficacy of such strategies are available

in the literature. For example, a randomized, double-blind trial

compared a 500-mg/day, 10-day course of levofloxacin with a

PK/PD-based, high-dose, short-course strategy of 750 mg/day for

5 days in patients with CAP. 49 The strategies produced comparable

rates of clinical success and microbiologic eradication regardless of

the infectious pathogen, disease severity, and patient age, but the

overall duration of treatment and total amount of drug exposure

Figure 3. Clinical Cure Rates for Ventilator-

Associated Pneumonia in Different Study

Populations 53

Clinical Cure Rate (%)

80

60

40

20

0

80

60

40

20

0

92.4 91.1 93.2 92.4

59.0 57.8

PK/PD strategy

68.3

69.0

64.8 64.5

57.9 58.7

cMITT CE mMITT ME

Study Population

Standard therapy

Doripenem

Imipenem

cMITT, clinical modifi ed intent-to-treat; mMITT, microbiologic modifi ed

intent-to-treat; CE, clinically evaluable; ME, microbiologically evaluable.

Doripenem was noninferior to imipenem in all populations.

Adapted with permission from Chastre J et al. Crit Care Med.

2008;36(4):1089-1096.

57.8

59.6

Clinical Success Microbiologic Eradication Adverse Events

4

Empiric Antimicrobials in Pneumonia: Balancing Risk Against Benefit in an Era of Resistance


was less with the high-concentration strategy, minimizing patient

exposure and reducing the risk of emergent resistance (Figure 2). 49-51

Symptom resolution was also faster with this strategy, which may

be attributable to the higher antimicrobial concentrations, taking

advantage of the concentration-dependent killing. The dosing

strategy is approved by the FDA. 52

Similarly, a recent phase 3 trial compared a PK/PD-based

dosing strategy of doripenem with that of 2 pharmacodynamically

equivalent standard dosing regimens of imipenem in patients

with VAP. 53 Doripenem is a new carbapenem that has been

FDA approved for complicated intra-abdominal infections and

urinary tract infections, and it is under investigation for treating

pneumonia. Like other drugs of its class, doripenem’s bacteriocidal

activity is time dependent, and a prolonged infusion time could

maximize the agent’s bacteriocidal activity while minimizing

overall patient exposure. The study compared a prolonged,

4-hour infusion of doripenem (500 mg every 8 hours) with 30- or

60-minute infusions of imipenem (500 mg every 6 hours and 1000

mg every 8 hours, respectively) in 531 randomized patients. The

prolonged infusion, despite its lower total dose, produced clinical

cure rates that were noninferior to those obtainable with the higherdose,

shorter infusions, demonstrating that antimicrobial therapy

can be optimized based on PK/PD principles (Figure 3). 53

de-eScalaTion and ShorT-courSe TheraPy

De-escalation is a strategy of switching from broad-spectrum

antimicrobial therapy to pathogen-specific therapy based on the

results of microbiologic studies, discontinuing therapy when an

infection appears unlikely, or reducing drug dosages. 3 The approach

minimizes patient exposure to broad-spectrum therapy, helping

prevent the emergence of resistance and preserving the efficacy of

the existing armamentarium. A recent study of 143 patients with

VAP diagnosed by culture of tracheal aspirate and bronchoalveolar

lavage compared outcomes of patients who underwent de-escalation

(n=58) with those who did not (n=85). 54 De-escalation was

associated with significantly shorter ICU stays (17.2 vs 22.7 days,

Table 5. Recommended Empiric Antimicrobials for Community-Acquired Pneumonia 4

Outpatient treatment

1. Previously healthy and no use of antimicrobials within the previous 3 months

• A macrolide (strong recommendation; level I evidence)

• Doxycycline (weak recommendation; level III evidence)

2. Presence of comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies;

asplenia; immunosuppressing conditions or use of immunosuppressing drugs; or use of antimicrobials within the previous

3 months (in which case an alternative from a different class should be selected)

• A respiratory fl uoroquinolone (moxifl oxacin, gemifl oxacin, or levofl oxacin [750 mg]) (strong recommendation; level I evidence)

• A beta-lactam plus a macrolide (strong recommendation; level I evidence)

3. In regions with a high rate (>25%) of infection with high-level (MIC ≥16 mg/mL) macrolide-resistant Streptococcus pneumoniae,

consider use of alternative agents listed above in (2) for patients without comorbidities (moderate recommendation; level III

evidence)

Inpatients, non-ICU treatment

• A respiratory fl uoroquinolone (strong recommendation; level I evidence)

• A beta-lactam plus a macrolide (strong recommendation; level I evidence)

Inpatients, ICU treatment

• A beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin (level II evidence) or a respiratory

fl uoroquinolone (level I evidence) (strong recommendation) (for penicillin-allergic patients, a respiratory fl uoroquinolone and

aztreonam are recommended)

Special concerns

1. If Pseudomonas is a consideration

• An antipneumococcal, antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either

ciprofl oxacin or levofl oxacin (750 mg)

or

• The above beta-lactam plus an aminoglycoside and azithromycin

or

• The above beta-lactam plus an aminoglycoside and an antipneumococcal fl uoroquinolone (for penicillin-allergic patients,

substitute aztreonam for above beta-lactam) (moderate recommendation; level III evidence)

2. If CA-MRSA is a consideration, add vancomycin or linezolid (moderate recommendation; level III evidence)

MIC, minimum inhibitory concentration; CA-MRSA, community-acquired methicillin-resistant Staphylococcus aureus.

Empiric Antimicrobials in Pneumonia: Balancing Risk Against Benefit in an Era of Resistance 5


Table 6. Guideline-Recommended Antimicrobials for Initial Empiric Treatment of HAP/VAP/HCAP 3

Treatments for Patients With HAP or VAP, With No MDR Risk Factors, Early Onset, Any Severity

Potential Pathogen

Recommended Antimicrobial

Streptococcus pneumoniae

Haemophilus influenzae

MSSA

Antimicrobial-sensitive enteric gram-negative bacilli

(Escherichia coli, Klebsiella pneumoniae, Enterobacter

species, Proteus species, Serratia marcescens)

Ceftriaxone

Or

Levofl oxacin, moxifl oxacin, or ciprofl oxacin

Or

Ampicillin-sulbactam

Or

Ertapenem

Treatments for Patients With HAP, VAP, or HCAP, Late Onset, or With MDR Risk Factors, All Severities

Above pathogens and MDR pathogens (Pseudomonas

aeruginosa, K pneumoniae [ESBL + ], a Acinetobacter species)

MRSA

Legionella pneumophila a

Antipseudomonal cephalosporin (cefepime, ceftazidime)

Or

Antipseudomonal carbapenem (imipenem or meropenem) b

Or

Beta-lactam/beta-lactamase inhibitor

(piperacillin/tazobactam)

+

Antipseudomonal fl uoroquinolone a

(ciprofl oxacin or levofl oxacin)

Or

Aminoglycoside

(amikacin, gentamicin, or tobramycin)

+

Linezolid or vancomycin c

HAP, hospital-associated pneumonia; VAP, ventilator-associated pneumonia; HCAP, health care–associated pneumonia; MDR, multidrug-resistant;

MSSA, methicillin-sensitive Staphylococcus aureus; ESBL, extended-spectrum beta-lactamases; MRSA, methicillin-resistant S aureus.

a

If an ESBL + strain, such as K pneumoniae, or an Acinetobacter species is suspected, a carbapenem is a reliable choice. If L pneumophila is suspected,

the combination antimicrobial regimen should include a macrolide (eg, azithromycin), or a fl uoroquinolone (eg, ciprofl oxacin, levofl oxacin) should be used

rather than an aminoglycoside.

b

Doripenem, a newly marketed carbapenem, may also be used. This agent was not approved at the time the guidelines were written.

c

If MRSA risk factors are present or there is a high incidence locally.

Adapted with permission from American Thoracic Society, Infectious Diseases Society of America. Am J Respir Crit Care Med. 2005;171(4):388-416.

respectively; P


Table 7. Risk Factors for QT-Interval Prolongation and Torsade de Pointes, Resulting in Reduced

Repolarization Reserve 61

Drug-Related Risk Factors

Intrinsic QT-prolonging potential

(eg, I Kr

antagonism)

Effects on cardiac ion currents other than the I Kr

Comedications associated with signifi cant QT-interval prolongation:

class IA antiarrhythmics (quinidine, disopyramide, procainamide) and

class III antiarrhythmics (sotalol, amiodarone, ibutilide, dofetilide,

almokalant)

Metabolic drug interactions

(eg, inhibition of CYP isoenzymes, especially CYP3A4, which results

in supratherapeutic concentrations of a second coadministered drug

known to cause QT-interval prolongation)

High dose of drug

Route of drug (IV vs PO)

(eg, erythromycin IV and PO)

Arsenic, organophosphates

Alcoholism, cocaine use

Potassium-wasting diuretics (eg, furosemide), resulting in depletion of

potassium

Host-Related Risk Factors

Electrolyte derangements (hypokalemia, hypomagnesemia,

hypocalcemia)

Increased age

Gender (female > male)

Structural heart disease (congestive heart failure, myocardial

ischemia)

Bradycardia

Organ dysfunction with failure to adjust dosage accordingly for

drugs known to prolong the QT interval

Hypothyroidism

CNS infection or tumor

Obesity

Genetics (known and unknown gene variants encoding

mutations in cardiac ion currents)

I Kr

, rapid component of the delayed rectifi er potassium current; CYP, cytochrome P450; IV, intravenous; PO, oral; CNS, central nervous system.

Adapted with permission from Owens RC Jr. Drugs. 2004;64(10):1091-1124.

• Patient history (comorbidities, current medications including

recent antimicrobial use)

• Disease severity (need for hospitalization/ICU admission)

• Knowledge of local pathogens

• Local patterns of antimicrobial resistance

• Safety profile of individual antimicrobial agents and patients’

risk for adverse events

Antimicrobial therapy is mostly likely to be appropriate when

treatment is based on guideline-recommended agents (Table 5,

page 5 and Table 6), 3,4 and adherence to guidelines is associated

with lower mortality rates than is nonadherence. 5 However,

using empiric broad-spectrum therapy always carries with it the

responsibility to de-escalate when culture and susceptibly results

are known. Therefore, in addition to avoiding overuse of broadspectrum

agents, health care professionals must weigh the safety

risks associated with individual agents and agent classes with the

potential for adverse events in individual patients. Understanding

these risks and identifying patients who are at increased risk for

treatment-related complications is an essential component of

selecting empiric antimicrobial therapy.

albeit rarely, may lead to life-threatening ventricular arrhythmias

such as torsade de pointes (TdP). 59,60 Risk factors for TdP include

combining antimicrobials with other drugs that prolong the

QT interval (polypharmacy), increased age, female sex, and

comorbidities (bradycardia, congestive heart failure, hypokalemia,

hypomagnesia) (Table 7). 60-63 The accumulation of these risk factors

also increases TdP risk.

Of the available classes of antimicrobials, macrolides are

associated with the highest risk of QT-interval prolongation

and TdP, accounting for approximately 77% of reported TdP

cases. 61,62 Macrolides induce metabolic liability by inhibiting

the cytochrome P-450 3A4 (CYP3A4) metabolic pathway and

antagonizing the rapid component of the delayed rectifier potassium

current (I Kr

), possibly resulting in QT-interval prolongation. The

risk is increased when macrolides are given with other drugs

also metabolized by the CYP3A4 pathway and those which alter

electrolyte balance. 61 The degree of prolongation varies by agent

(eg, erythromycin > clarithromycin > azithromycin). 62 Other

antimicrobial drugs that may prolong the QT interval include

ketoconazole, itraconazole, fluconazole, and voriconazole. 61

QT-interval prolongation is also considered a class effect of

fluoroquinolones. 60 Like macrolides, these agents inhibit I Kr

but have

no metabolic liability. The risk of TdP is similar with moxifloxacin

and levofloxacin, but the risk with gemifloxacin is unknown.

Ciprofloxacin is considered to have the lowest risk. 60

When selecting agents from these classes for empiric therapy,

Empiric Antimicrobials in Pneumonia: Balancing Risk Against Benefit in an Era of Resistance 7

carDiac TOxiciTiES:

qT-inTErval PrOlOngaTiOn

Antimicrobial agents, along with many other drugs, may induce

prolongation of the QT interval of the electrocardiogram, which,


Figure 4. Relative Risk of Mortality With Short-Course Versus Extended-Course Antibiotic Regimens 55

Study, Year

Risk Ratio

(95% CI) a

% Weight

Bohte et al, 1995

Brion et al, 1990

Dunbar et al, 2003

Kinasewitz et al, 1991

Leophonte et al, 2004

Leophonte et al, 2002

Siegal et al, 1999

Tellier et al, 2004

Kobayashi et al, 1995

O’Doherty et al, 1998

Rahav et al, 2004

Rizzato et al, 1995

Schonwald et al, 1994

Schonwald et al, 1990

Sopena et al, 2004

1.10 (0.07; 16.45)

0.93 (0.20; 4.38)

0.58 (0.20; 1.69)

0.62 (0.06; 6.68)

1.22 (0.28; 5.37)

0.76 (0.21; 2.77)

2.79 (0.12; 65.38)

0.72 (0.12; 4.29)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

(Excluded)

3.6

11.9

33.8

6.8

12.0

19.6

2.0

10.3

0.0

0.0

0.0

0.0

0.0

0.0

0.0

Overall (95% CI)

0.81 (0.46; 1.43)

.015294 1

Favors Short-Course

65.3844

Favors Extended-Course

CI, confi dence interval.

a

The relative risk of mortality could not be calculated in 7 studies (those indicated by Excluded) because of the lack of deaths in both arms.

Adapted with permission from Li JZ et al. Am J Med. 2007;120(9):783-790.

health care professionals should consider patient risk factors such

as age, gender, and comorbidities and take a thorough history,

checking for concomitant medications that might alter the QT

interval, such as class I antiarrhythmics, diuretics, antidepressants,

and calcium channel blockers. The need for treatment must be

balanced with the risk of TdP.

dySglycemia

Fluoroquinolones are associated with dysglycemia—

hypoglycemia and hyperglycemia. 64 These are uncommon

complications occurring in approximately 1% to 2% of treated

patients. 64 Drugs of this class affect the activity of the K + –adenosine

triphosphate channels in the pancreatic beta-cell membrane,

stimulating the release of insulin, thereby inducing hypoglycemia. 65

It remains unclear how these agents cause hyperglycemia, which is

more common than is hypoglycemia. 65,66

Dysglycemia is considered a class effect and may occur with

any fluoroquinolone, but it is more common with gatifloxacin than

with the other fluoroquinolones, and, as a result, gatifloxacin was

withdrawn from US markets in 2006. 67-69 Elderly patients with type

2 diabetes receiving a sulfonylurea or insulin and any patients with

glucose abnormalities have the highest risk for dysglycemias with

the use of this class of antimicrobial. 64-66,68

Although dysglycemia is a rare complication of antimicrobial

therapy, health care professionals, when selecting treatment, should

consider a patient’s glucose status and medications, as well as other

risk factors. When prescribing treatments that may disrupt glucose

status, they must consider the consequences of dysglycemia and the

potential benefits of therapy.

C DIFFICILE infecTion (cdi)

C dif fi cile can be part of the normal human intestinal flora.

CDI results from antimicrobial-induced changes in the normal flora

of the colon and infection with the toxin-producing opportunistic

strain of C dif fi cile. CDI may occur with any antimicrobial therapy,

and 20% of hospitalized patients acquire C dif fi cile, 30% of whom

develop CDI. 70 Up to 3 million cases are reported annually in the

United States. 70 Disease severity ranges from self-limiting diarrhea

to sepsis, colonic perforation, and toxic megacolon. 71 Colonization

occurs via the oral-fecal transmission route.

All antimicrobial agents, including those used to treat CDI

(metronidazole and vancomycin), can lead to CDI; however,

the risk appears to be greatest with cephalosporins. 70,71 The risk

of fluoroquinolone-associated CDI, once thought to be low or

moderate, has increased over time, as drugs of this class became

more widely used to treat infections. 71 The risk may be greater

with moxifloxacin because of its anti-anaerobic activity. The risk

with clindamycin, aminoglycosides, macrolides, and carbapenems

is variable. Risk factors for CDI include antimicrobial therapy

(risk increases with duration of treatment), treatment with ≥2

antimicrobials, hospitalization, age >60 years, immunosuppression,

and gastric acid suppression (eg, use of proton pump inhibitors). 70,71

Environmental factors also contribute to disease risk and may be

mitigated by preventing ingestion (environmental cleaning, hand

8

Empiric Antimicrobials in Pneumonia: Balancing Risk Against Benefit in an Era of Resistance


hygiene, barriers) and preventing infection by reducing unnecessary

antimicrobial exposure. 71,72

Recently, a particularly virulent strain of C diffi cile has

emerged and, as of October 2008, was reported in 40 US states.

The strain, known as the BI/NAP1 (ribotype 027) strain, contains

a binary toxin and, in one Canadian study, was highly resistant

to fluoroquinolones but susceptible to clindamycin. 73,74 In the

Canadian study, BI/NAP1 was associated with a 2-fold increase in

30-day mortality as compared to other ribotypes (adjusted odds

ratio, 2.06; 95% confidence interval, 1.00; 4.22). 74

Also of note is the emergence of CA-CDI. 75-77 CA-CDI is not

nationally reportable, but statewide surveillance in Connecticut

(2006) and other US states reported CA-CDI in otherwise healthy

persons and, at least in Connecticut, an incidence of 6.9 cases per

100,000 population. 76,77 A substantial proportion of these patients

did not have traditional risk factors for CDI, such as long-term–care

residency, recent hospitalization, older age, or recent antimicrobial

exposure. 75-77 The findings suggest a changing epidemiology.

Treatment of CDI is dependent on disease severity. 71 For

colonized but asymptomatic patients, treatment is unnecessary,

but the need for antimicrobial therapy should be reconsidered and

discontinued if deemed unnecessary. Symptomatic patients may

require treatment with metronidazole or vancomycin, and surgery

should be considered for patients with ileus or toxic megacolon.

CDI is a common complication of antimicrobial therapy. When

suspected, the continued need for antimicrobial therapy must be

reconsidered and discontinued if unnecessary. To minimize risk,

unnecessary and overly long courses of antimicrobial treatment

should be avoided, and, of course, infection control strategies should

be maintained.

immune-mediaTed adverSe evenTS

Immune-mediated adverse events are relatively common side

effects of antimicrobial therapy. Hypersensitivity reactions, such as

rash, pruritus, and/or urticaria, are the most frequently reported,

occurring in up to 8% of penicillin-treated patients and 3% of

cephalosporin-treated patients. 78 More serious events, such as

thrombocytopenia, leukopenia, acute hepatitis, and hepatotoxicity,

are possible but occur infrequently. 65,78

Beta-lactams, fluoroquinolones, glycopeptides, and sulfa

drugs have all been associated with immune-mediated adverse

events. 65,78,79 Amoxicillin/clavulanate and oxacillin are associated

with hepatotoxicity, and beta-lactams, linezolid, and glycopeptides

with various forms of bone marrow suppression. 78

Immune-mediated events are difficult to predict. A health care

professional’s best defense against such complications is a thorough

patient history that includes potential allergies, although this

provides no guarantee.

cenTral nervouS SySTem (cnS)

adverSe evenTS

Antimicrobial agents may induce CNS complications, such as

seizures, confusional states, and myoclonic activity. Beta-lactams,

fluoroquinolones, and isoniazid are associated with seizure. Betalactam–induced

seizures occur in a dose-dependent manner.

Aminoglycosides are associated with auditory, vestibular, and

muscular derangements, and imipenem with confusional states,

myoclonic activity, and seizures. CNS complications are infrequent

with meropenem (seizure rate ≤0.7%), and doripenem has not been

associated with seizure in 4 registration trials. 78,80-83

TendinoPaThy

Tendinopathy—tendinitis and/or rupture—is an uncommon

complication of fluoroquinolone therapy, with an estimated

incidence of 0.14% to 0.4%. 10 Although the incidence is low, given

the large numbers of patients receiving drugs of this class, in 2008

the FDA instructed manufacturers to add a Boxed Warning to

the prescribing information for ciprofloxacin, extended-release

ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin,

and ofloxacin advising of this potential complication. 11

Tendinitis (the most common) or rupture usually occurs

within several weeks of treatment and preferentially targets

the Achilles tendon. Risk factors for tendinopathy include age,

comorbidities, and rheumatic disease, among others (Table

8), and those individuals with such risks may have the highest

risk of fluoroquinolone-associated tendinopathy. 8,10 As with

other antimicrobial agents, health care professionals must assess

individual patient risk and balance the need for treatment with the

potential benefits of therapy.

Table 8. Risk Factors for Tendinopathy 8,10

• Renal transplantation

• Renal failure

• Hemodialysis

• Age >50 years

• Use of corticosteroids

• Diabetes mellitus

• Gout

• Hyperparathyroidism

• Peripheral vascular disease

• Sports participation

• Rheumatic disease

• COPD treated with corticosteroids

COPD, chronic obstructive pulmonary disease.

CONCLUSION

Empiric broad-spectrum antimicrobial therapy is essential for

the treatment of pneumonia and guidelines stress the stratification

of care based on likely organisms. Broad-spectrum therapy provides

coverage for all potential pathogens, and targets resistant pathogens

in patients with risk factors for antimicrobial resistance, but carries

the responsibility of de-escalation. All antimicrobial agents are

associated with some degree of risk, and although most adverse

reactions are uncommon, some patients may be more susceptible

than others. Health care professionals must carefully assess the

risk-to-benefit ratio in individual patients to determine the need for

therapy and the most appropriate agents.

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ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290(19):2588-

2598.

57. Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course empiric antibiotic

therapy for patients with pulmonary infiltrates in the intensive care unit: a proposed

solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med. 2000;162(2 pt

1):505-511.

58. Joint Commission on Pneumonia. NQF-endorsed voluntary consensus standards for

hospital care. http://www.jointcommission.org/NR/rdonlyres/304A9AA7-0C23-46F8-

A94C-A14C25744690/0/NHQM_v25b_pdf_add76513.zip. Accessed December 15, 2008.

59. Fermini B, Fossa AA. The impact of drug-induced QT interval prolongation on drug

discovery and development. Nat Rev Drug Discov. 2003;2(6):439-447.

60. Owens RC Jr, Nolin TD. Antimicrobial-associated QT interval prolongation: pointes of

interest. Clin Infect Dis. 2006;43(12):1603-1611.

61. Owens RC Jr. QT prolongation with antimicrobial agents: understanding the significance.

Drugs. 2004;64(10):1091-1124.

62. Shaffer D, Singer S, Korvick J, Honig P. Concomitant risk factors in reports of torsades

de pointes associated with macrolide use: review of the United States Food and Drug

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63. Zeltser D, Justo D, Halkin A, Prokhorov V, Heller K, Viskin S. Torsade de pointes due to

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64. Owens RC Jr. Fluoroquinolone-associated dysglycemias: a tale of two toxicities.

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65. Owens RC Jr, Ambrose PG. Antimicrobial safety: focus on fluoroquinolones. Clin Infect

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66. Mohr JF, McKinnon PS, Peymann PJ, Kenton I, Septimus E, Okhuysen PC. A

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Empiric Antimicrobials in Pneumonia: Balancing Risk Against Benefit in an Era of Resistance


EMPIRIC ANTIMICROBIALS IN PNEUMONIA:

BALANCING RISK AGAINST BENEFIT IN AN ERA OF RESISTANCE

POST-TEST

Participation should take approximately 1.25 hours. To complete

this activity and receive credit, the participant should:

1. Read the learning objectives and faculty disclosures

2. Study the educational activity

3. Complete the post-test by recording the best answer to each

question in the “Post-Test Answers” box on the evaluation form

4. Complete the evaluation form

5. Mail or fax the evaluation form with the post-test answers to

Postgraduate Institute for Medicine

6. You may also complete the post-test online at

www.cmeuniversity.com. Click on “Find Post-Test/Evaluation by

Course” on the navigation menu, and search by project ID 6368.

mailing addreSS:

Attn: Records Department

Postgraduate Institute for Medicine

367 Inverness Parkway, Suite 215

Englewood, CO 80112

Fax number: (303) 790-4876

A statement of credit will be issued only upon receipt of a

completed activity evaluation form and a completed post-test with

a score of 70% or better. Your statement of credit will be mailed to

you within 3 weeks.

1. Which of the following best differentiates pneumonia

category

a. Specific findings on chest films

b. Etiology

c. Duration of symptoms

d. Patient history

2. Which of the following describes guideline-recommended

initiation of treatment for CAP

a. Delay until the results of laboratory microbiology studies

are available

b. Start empiric targeted therapy based on suspected

underlying pathogen

c. Always start with a macrolide

d. Always include coverage for CA-MRSA

3. Which of the following is the recommended time-frame

for initiation of antimicrobial therapy in hospitalized

patients with CAP

a. Within 2 hours

b. Within 4 hours

c. Within 6 hours

d. Within 8 hours

4. The causative organisms of HAP and VAP infections are

predominantly:

a. Gram-positive

b. Gram-negative

c. MRSA

d. Polymicrobial

5. The etiology of HCAP:

a. Most closely resembles that for HAP/VAP infections

b. Most closely resembles that for CAP infections

c. Is similar to that for nosocomial tracheobronchitis

d. Is distinct from other upper respiratory tract infections

6. Which of the following classes of antimicrobial agents

have time-dependent bacteriocidal activity

a. Macrolides only

b. Fluoroquinolones only

c. Beta-lactams and macrolides

d. Fluoroquinolones and aminoglycosides

7. Which antimicrobial agent class poses the highest risk of

QT-interval prolongation

a. Fluoroquinolones

b. Beta-lactams

c. Aminoglycosides

d. Macrolides

8. Which antimicrobial agent class may result in Clostridium

difficile infection in patients treated for pneumonia

a. Fluoroquinolones

b. Aminoglycosides

c. Macrolides

d. Any antimicrobial agent

9. Which of the following carbapenems is not associated

with seizures in phase 3 trials

a. Doripenem

b. Imipenem

c. Meropenem

d. Ertapenem

10. In patients who develop Clostridium difficile infection,

antimicrobial therapy should be:

a. Immediately discontinued, regardless of the status of the

infection

b. Immediately switched to empiric broad-spectrum therapy

c. Re-evaluated and discontinued if unnecessary

d. Continued with originally prescribed agent until the first

infection resolves

Empiric Antimicrobials in Pneumonia: Balancing Risk Against Benefit in an Era of Resistance 11


EMPIRIC ANTIMICROBIALS IN PNEUMONIA:

BALANCING RISK AGAINST BENEFIT IN AN ERA OF RESISTANCE

EvaluaTiOn FOrm • PrOjEcT iD: 6368 ES 29/6509 OS 29

To assist us in evaluating the effectiveness of this activity and to make recommendations for future educational offerings, please take a few

minutes to complete this evaluation form. You must complete this evaluation form to receive acknowledgment for completing this activity.

Please answer the questions that follow. (Please check one box.)

What is your practice type Pharmacist MD/DO Pharmacy technician Other_______________

What is the setting for your practice

Acute Care/Hospital Managed care Retail Government

Research Industry Other________________________________________

How many years have you been in practice 15

To what extent do you agree with the following statements

(Please circle the appropriate number on the scale.)

1 = Strongly Disagree 2 = Disagree 3 = Somewhat Disagree 4 = Somewhat Agree 5 = Agree 6 = Strongly Agree

Recent studies indicate a higher incidence of drug-resistant pathogens among patients with health care–associated pneumonia.

Strongly Disagree 1 2 3 4 5 6 Strongly Agree

Antimicrobial stewardship programs (ASPs) are an effective strategy for preventing and controlling antimicrobial resistance.

Strongly Disagree 1 2 3 4 5 6 Strongly Agree

Employing a de-escalation strategy in the use of antimicrobial-based microbiologic studies has been shown to improve outcomes

in patients with ventilator-associated pneumonia.

Strongly Disagree 1 2 3 4 5 6 Strongly Agree

Use of macrolides and fluoroquinolones should be avoided if possible in patients who may be at risk for ventricular arrhythmias

such as torsade de pointes.

Strongly Disagree 1 2 3 4 5 6 Strongly Agree

While the symptoms and presentation may be similar, the microbial etiology of community-acquired pneumonia differs from

that of health care–associated pneumonia.

Strongly Disagree 1 2 3 4 5 6 Strongly Agree

Antimicrobial dosing methods that take into account both the pharmacodynamics and the pharmacokinetics of the drugs being

given are strategies for preventing and controlling antimicrobial resistance.

Strongly Disagree 1 2 3 4 5 6 Strongly Agree

Please answer the following questions by circling the appropriate rating:

1 = Strongly Disagree 2 = Disagree 3 = Neutral 4 = Agree 5 = Strongly Agree

ExTEnT TO Which PrOgram acTiviTiES mET ThE iDEnTiFiED ObjEcTivES

After completing this activity, I am now better able to:

• Differentiate the pathogens of significance found in nosocomial, community-acquired, and health care–associated pneumonia

1 2 3 4 5

12

• Review treatment challenges for pneumonia due to increasing trends of antibiotic resistance

1 2 3 4 5

• Describe the principles of antimicrobial stewardship, empiric therapy, and de-escalation

1 2 3 4 5

• Explain benefit-risk profiles of available empiric antimicrobial agents in pneumonia

1 2 3 4 5

• Identify mitigating clinical factors for assessment, including local resistance patterns, patient risk factors, and severity of illness, to

customize care and optimize outcomes

1 2 3 4 5

Empiric Antimicrobials in Pneumonia: Balancing Risk Against Benefit in an Era of Resistance


EMPIRIC ANTIMICROBIALS IN PNEUMONIA:

BALANCING RISK AGAINST BENEFIT IN AN ERA OF RESISTANCE

OvErall EFFEcTivEnESS OF ThE acTiviTy

The content presented:

Was timely and will influence how I practice 1 2 3 4 5

Enhanced my current knowledge base 1 2 3 4 5

Addressed my most pressing questions 1 2 3 4 5

Provided new ideas or information I expect to use 1 2 3 4 5

Addressed competencies identified by my specialty 1 2 3 4 5

Avoided commercial bias or influence 1 2 3 4 5

imPacT OF ThE acTiviTy

Name one thing you intend to change in your practice as a result of completing this activity:

__________________________________________________________________________________________________________

__________________________________________________________________________________________________________

Please list any topics you would like to see addressed in future educational activities:

__________________________________________________________________________________________________________

__________________________________________________________________________________________________________

Additional comments about this activity:

__________________________________________________________________________________________________________

__________________________________________________________________________________________________________

EvaluaTiOn FOrm • PrOjEcT iD: 6368 ES 29

FOllOW-uP

As part of our continuous quality improvement effort, we conduct post-activity follow-up surveys to assess the impact of our educational

interventions on professional practice. Please indicate if you would be willing to participate in such a survey:

Yes, I would be interested in participating in a follow-up survey.

No, I’m not interested in participating in a follow-up survey.

If you wish to receive acknowledgment for completing this activity, please complete the post-test by selecting the best answer

to each question, complete this evaluation verification of participation, and fax to: (303) 790-4876. You may also complete

the post-test online at www.cmeuniversity.com. Click on “Find Post-Test/Evaluation by Course” on the navigation menu, and

search by project ID 6368. Upon successfully completing the post-test and evaluation, your certificate will be made available

immediately.

POST-TEST anSWEr KEy

1 2 3 4 5 6 7 8 9 10

rEquEST FOr crEDiT

Name ____________________________________________ Degree ___________________________________________________

Organization ______________________________________ Specialty _________________________________________________

Address ___________________________________________________________________________________________________

City, State, ZIP ______________________________________________________________________________________________

Telephone _________________________________________ Fax _____________________________________________________

E-mail ____________________________________________________________________________________________________

Signature _________________________________________ Date ____________________________________________________

Empiric Antimicrobials in Pneumonia: Balancing Risk Against Benefit in an Era of Resistance 13


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