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February
2008: VOLUME
1, NUMBER 8
Community-Acquired
Pneumonia
In this Issue...
Community-acquired
pneumonia (CAP) is the sixth most common cause of death in the US and
the major cause of death due to an infectious disease. The majority
of patients who die with CAP have major co-morbidities or are elderly;
in fact, most are “elderly, elderly” in reference to those
over 85 years. Nevertheless, there are few infectious diseases that
have spawned such controversy in terms of antibiotic selection and diagnostic
testing: new pathogens are frequently detected, resistance in common
pathogens continues to evolve, and Centers for Medicare & Medicaid Services
(CMS) have made this a target diagnosis so that CAP is now a component
of regular audits of all hospitals that receive Medicare funding.
In this issue, we analyze the
recently released joint guidelines from the Infectious Disease Society
of America (IDSA) and the American Thoracic Society (ATS), and review
some of the practical issues in the clinical management of CAP. |
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Course
Directors
John
G. Bartlett, MD
Professor of Medicine
Department of Medicine
The Johns Hopkins
University
School of Medicine
Baltimore, MD
Paul
G. Auwaerter, MD
Associate Professor
of Medicine
Clinical Director
Division of Infectious
Diseases
The Johns Hopkins
University
School of Medicine
Baltimore, MD
Sara
E. Cosgrove, MD, MS
Assistant Professor
of Medicine
Division of Infectious
Diseases
Director
Antibiotic Management
Program
Associate Hospital
Epidemiologist
The Johns Hopkins
University
School of Medicine
Baltimore, MD |
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GUEST
AUTHOR OF THE MONTH |
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Commentary
& Reviews: |
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John
G. Bartlett, MD
Professor
of Medicine
Department
of Medicine
The Johns
Hopkins University
School
of Medicine
Baltimore,
MD |
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Guest
Faculty Disclosures
John
G. Bartlett, MD has disclosed that he has served on the HIV
Advisory Board for GlaxoSmithKline, Abbott, Bristol-Myers Squibb,
Pfizer and Tibotec. He is also on the Policy Board for Johnson & Johnson.
Unlabeled/Unapproved Uses
The author has indicated
that there will be no reference to unlabeled or unapproved uses of
drugs or products in the presentation.
Program
Directors' Disclosures |
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At
the conclusion of this activity, participants should be able to:
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Discuss
with colleagues the current recommendations regarding antibiotic
selection in the management of pneumonia |
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Describe
to colleagues the current recommendations regarding diagnostic testing
in patients with suspected community-acquired pneumonia |
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Discuss
with colleagues the rationale for early institution of treatment
and the liability of over diagnosis |
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COMPLETE
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Complete the post-test and course
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eInfections
Review is proud to continue its accredited
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In
this audio interview John G Bartlett, MD from the Johns Hopkins University
School of Medicine discusses community-acquired pneumonia.
Participants can now receive
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To learn more about podcasting
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Despite
the controversies surrounding the diagnosis and management of CAP,
there does seem to be an evolving consensus in some areas. Regarding
therapy, while there have been hundreds of comparative trials, to our
knowledge, none have ever shown one antibiotic to be better than another.
Now, however, antibiotic selection has been addressed by the joint
recommendations of the IDSA/ATS, based on an enormous (over 30,000
patients) database from Medicare. With regard to microbiology, studies
over the past 50 years have consistently failed to detect a pathogen
in 30-50% of cases even with the best techniques available at the time.
In the past few years there have been major advances in diagnostic
microbiology, especially with molecular diagnostics. But paradoxically,
there is currently a sharp decrease in the quality of standard microbiology
with respiratory secretions, reflecting issues of cost, need, the Clinical
Laboratory Improvement Amendments (CLIA) requirements that eliminated
ward-based laboratories, the Medicare mandate for rapid evaluation,
the low priority often given to microbiology by laboratory directors,
and outsourcing. The result is that over 80% of patients with CAP are
treated empirically with no microbiology results for guidance.
The papers reviewed herein discuss
practical issues in the management of CAP. Perhaps most important are
the recent guidelines from the IDSA/ATS, which provide guidance regarding
current recommendations for nearly all clinical decisions. There are
few surprises here, since the pathogens are largely the same as they
have been for the past decade, and the empiric antibiotic recommendations
therefore are also quite similar. There are, however, a few observations
that address the more contemporary issues.
The major new pathogen, discussed
herein in a Centers for Disease Control and Prevention (CDC) report,
is the community-acquired methicillin-resistant Staphylococcus aureus (MRSA)
that has received so much notoriety in the past 3-4 years. While this
is a rare cause of CAP, it is devastating when it is seen. Most of the
patients are young and previously healthy, the course is rapid, many
have necrotizing pneumonia with the sepsis syndrome, and the recommendations
for antibiotic selection are quite different than the standard recommendations
for CAP. Of note is the observation that the clinical features of this
infection are sufficiently unique so that the clinician is unlikely
to be fooled. In this setting, diagnostic studies are clearly indicated
and microbiology nearly always yields the putative agent in blood cultures
and/or expectorated sputum. Antibiotic treatments recommended by the
IDSA/ATS guidelines for MRSA pneumonia are vancomycin or linezolid.
Antibiotic recommendations for
other patients have been largely dictated by multiple studies, and from
guidelines and mandates from Medicare and other agencies. However, none
of these have adequately addressed the issue of the duration of treatment.
Thus, the report from The Netherlands by el Moussaoul et al, suggesting
that 3 days duration of treatment is the equivalent of 8 days, is a
start at examining that issue. This paper was highlighted, in part because
it reflects some of the current trends in the field of infectious disease,
which emphasize short duration antibiotics when feasible. This is quite
contrary to standard teaching 10-20 years ago, when we always were instructed
to complete the course to assure eradication of the pathogen. Now there
is increasing emphasis on short duration antibiotics in the effort to
reduce resistance, cost, and side effects. While it is premature to
say that 3 days should be a "standard course" of antibiotics for patients
with CAP, the data shows that the often customary response of treating
for 1 week, 10 days, or 2 weeks for patients with mild or moderate CAP
is probably too long for most of them.
The issue of pathogen-directed
therapy versus empiric treatment (van der Eerden et al, reviewed herein)
is of interest in view of the ongoing debate regarding the merits of
microbiology in CAP. Both sides were winners in this report: while efficacy
was virtually identical in both arms, there was a difference in the
high rate of adverse reactions with standard empiric regimens. It might
be noted that most of the adverse reactions here were GI intolerance
due to erythromycin, and this effect would be unlikely with the macrolides
used most frequently in the US. Nevertheless, despite the adequacy of
outcome with empiric drugs found in this report, there may be some important
benefits for microbiology in terms of detecting epidemics, identifying
shifting resistance patterns, and the detection of pathogens of substantial
importance such as Legionella, MRSA, SARS, Avian influenza,
agents of bioterrorism, etc.
Another controversial issue to
address is the Medicare audits that now include CAP, with the expected
(later in 2008) implementation of public reporting and pay-for-performance
as mandated by Congress. The most controversial component of the auditing
done to date has been the requirement to give antibiotics within 4 hours
of registration. It is worth emphasizing the fact that rapid institution
of antibiotics may be as important as the selection of specific agents
in terms of outcome. However, the need to treat rapidly has also resulted
in antibiotic abuse with additional cost, toxicity, and resistance.
Studies to define these "unintended consequences" have resulted in two
important 11th hour changes: the first is a new category called "diagnostic
uncertainty" of the CAP diagnosis, which eliminates this 4 hour requirement
from the audit because it indicates that there may be congestive failure,
pulmonary embolism, or some other diagnosis that would result in antibiotic
abuse. The second "correction factor" has been to eliminate this measure
as a criterion in the "pay-for-performance" decision. |
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ANALYSIS
OF THE IDSA/ATS CONSENSUS GUIDELINES |
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Mandell
LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD et al. Infectious
Diseases Society of America/American Thoracic Society consensus
guidelines on the management of community-acquired pneumonia
in adults. Clin Infect Dis. 2007;44 Suppl 2:S27-72.
(For non-journal subscribers, an additional fee may apply
for full text articles.) |
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The
2007 Guidelines for the Management of CAP from the IDSA/ATS discuss
nearly all facets of community-acquired pneumonia. Among the key
questions answered:
- What conditions are covered in these guidelines? The
document deals with CAP but excludes aspiration pneumonia, pneumonia
caused by viruses including influenza, pneumonia in the immunocompromised
host, and the recently recognized healthcare-associated pneumonia
which applies to patients in nursing homes and those engaged in
the healthcare system through dialysis, outpatient infusion therapy,
etc.
- What
tests should be done? Routine diagnostic testing should
include a history, physical exam, imaging (generally chest x-ray),
pulse oximetry, and highly selective use of the microbiology
laboratory. The chest x-ray is necessary to show pneumonia and
distinguish it from bronchitis. High resolution CT scan will
show more pulmonary infiltrates, compared to plain chest x-rays,
but the clinical significance of these false-negative x-rays
is unclear.1 Previously,
routine blood cultures were performed prior to antibiotics for
all patients who are hospitalized with pneumonia; this routine
blood culture is now recognized as “optional” except
in patients who are sufficiently ill to require hospitalization
in the intensive care unit (ICU). The reason is that positive
blood cultures usually yield S. pneumoniae, which is
covered with the standard empiric antibiotics. Further, many
patients have blood cultures contaminated with coagulase-negative Staphylococcus,
which has often prompted treatment with vancomycin for suspected S.
aureus before the gram-positive cocci (GPC) are identified.
With regard to sputum cultures and gram stains, these are now
regarded as “optional” for hospitalized patients
and recommended primarily for those patients who have a suspected
pathogen that is not treatable with the empiric antibiotics that
are listed in the table below.
- What antibiotics should be given? Antibiotic
selection is largely empiric and based on site of care and severity
of illness. The table above summarizes the current antibiotic recommendations
for outpatients, patients hospitalized in the general medical service,
and patient hospitalized in the intensive care unit. In general,
the recommendations provide optimal coverage for the major categories
of pathogens, including S. pneumoniae, Haemophilus
influenzae and the atypical agents such as Chlamydia pneumoniae, Mycoplasma
pneumoniae and Legionella. For patients hospitalized
in the intensive care unit, the major target of the empiric selection
is S. pneumoniae and Legionella, both of which
are the most common and the most likely to cause devastating infection.
Recommendations are also provided for pathogen-specific treatment
for infections involving methicillin-resistant-S. aureus (USA
300 strains) using vancomycin or linezolid, and for Pseudomonas
aeruginosa with regimens that will also cover S. pneumoniae and Legionella,
since these are much more common.
The rationale
for this selection of drugs is largely based on in vitro activity
against the major pulmonary pathogens and excellent performance
in clinical trials. An analysis of a very large database from Medicare,
with over 30,000 patients, that stratified them according to severity
of illness, antibiotic regimen, time to start therapy, length-of-stay
(LOS), and outcome supported the same conclusions. These data showed
that the regimens advocated are superior to others in terms of
mortality.2,3 The
initial analysis, in 1999, compared a β-lactam to over 30
other regimens and noted that the combination of a β-lactam
plus macrolide reduced mortality by 26%, and the use of a fluoroquinolone,
alone, reduced mortality by 36%.
- What
accounts for the failure to improve? The list includes:
a resistant pathogen (rare), undrained pus (empyema or metastatic
infection), erroneous diagnosis (pulmonary embolism, aspiration,
adult respiratory distress syndrome (ARDS), congestive heart
failure, bronchiolitis obliterans organizing pneumonia (BOOP),
etc), severity of illness, complication of treatment (drug fever, Clostridium
difficile infection, line sepsis), or pulmonary superinfection.
In practice, the most common cause is simply persistent infection
with severe illness, nosocomial infection, or a non-infectious
disease cause of the pulmonary infiltrate.4 A
resistant or neglected pathogen is uncommon, although the physician
must be alert to the possibility of tuberculosis or Pneumocystis pneumonia
as well as other resistant pathogens.
- How can we prevent pneumonia? Among the most
important findings are smoking cessation, appropriate use of influenza
vaccine, and the use of the protein-conjugated pneumococcal vaccine
for children.5 Pneumococcal
vaccine polyvalent is advocated for patients at risk for pneumococcal
infections, but actually shows a relatively modest effect on the
frequency of pneumonia or pneumococcal pneumonia; its major effect
appears to be a 40-50% reduction in the frequency of pneumococcal
bacteremia.6,7 The
most impressive result has been with the pediatric vaccine given
to children under two years of age, which has resulted in an 80%
reduction in the frequency of invasive pneumococcal infections
in elderly5;
the implication is that young children are the major vectors of
pneumococcal infections.
- What is the most contentious issue? Unquestionably,
the most controversial issue is the “4-Hour Rule”.
Medicare audited charts in selected categories to determine the
quality of care. For CAP, they require compliance with the antibiotic
recommendations previously discussed for hospitalized patients,
and, further, also require that antibiotics be given within 4 hours
of the time of registration in a hospital or emergency room. This
latter requirement is based on audits which show further delays
in the initiation of antibiotics are associated with significant
increases in mortality.2,3 The
plan was to use hospital audits for compliance with the "4-Hour
Rule" for public reporting and pay-for-performance when these mandates
are implemented later in 2008. The concern about this measure is
that it has forced antibiotic decisions leading to antibiotic abuse.
In one report there were actually several deaths due to C.
difficile infections that resulted from fluoroquinolones given
for CAP that, on review, was never established based on chest x-ray
review.8 The
result is that Medicare has now recognized this “unintended
consequence” of the “4-Hour Rule” and has consequently
implemented a new category designated “diagnostic uncertainty”9 that
eliminates the case from audit; more recently they have eliminated
the “4-Hour Rule” completely from the pay-for-performance
category.
References
| 1. |
Syrjälä H,
Broas M, Suranamo I, Ojala A, Lähde S. High-resolution
computed tomography for the diagnosis of community-acquired pneumonia. Clin
Infect Dis. 1998;27:358-363. |
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| 2. |
Gleason
PP, Meehan TP, Fine JM, Galusha DH, Fine MJ. Associations
between initial antimicrobial therapy and medical outcomes for
hospitalized elderly patients with pneumonia. Arch Intern
Med. 1999;159:2562-2572. |
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| 3. |
Houck
PM, Bratzler DW, Nsa W, Ma A, Bartlett JG. Timing
of antibiotic administration and outcomes for Medicare patients
hospitalized with community-acquired pneumonia. Arch
Intern Med. 2004;164:637-644. |
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| 4. |
Arancibia
F, Ewig S, Martinez JA, Ruiz M, Bauer T et al. Antimicrobial
treatment failures in patients with community-acquired pneumonia:
causes and prognostic implications. Am J Respir Crit
Care Med. 2000;162:154-160. |
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| 5. |
Kyaw
MH, Lynfield R, Schaffner W, Craig AS, Hadler J, et al. Effect
of introduction of the pneumococcal conjugate vaccine on drug-resistant
Streptococcus pneumoniae. N Engl J Med. 2006;354:1455-1463. |
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| 6. |
Butler
JC, Breiman RF, Campbell JF, Lipman HB, Broome CV, Facklam RR. Pneumococcal
polysaccharide vaccine efficacy. An evaluation of current recommendations. JAMA. 1993;270:1826-1831. |
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| 7. |
Shapiro
ED, Berg AT, Austrian R, Schroeder D, Parcells V, et al. The
protective efficacy of polyvalent pneumococcal polysaccharide
vaccine. N Engl J Med. 1991;325:1453-1460. |
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| 8. |
Polgreen
PM, Chen YY, Cavanaugh JE, Ward M, Coffman S. An
outbreak of severe Clostridium difficile-associated disease possibly
inappropriate antimicrobial therapy for community-acquired pneumonia. Infect
Control Hosp Epidemiol. 2007;28:212-214. |
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| 9. |
Metersky
ML, Sweeney TA, Getzow MB, Siddiqui F, Nsa W, Bratzler DW. Antibiotic
timing and diagnostic uncertainty in Medicare patients with pneumonia:
is it reasonable to expect all patients to receive antibiotics
within 4 hours? Chest. 2006;130:16-21. |
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Centers
for Disease Control and Prevention (CDC). Severe methicillin-resistant Staphylococcus
aureus community-acquired pneumonia associated with influenza — Louisiana
and Georgia, December 2006-January 2007. CDC:MMWR Morb
Mortal Wkly Rep. 2007;56:325-329.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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This
2007 CDC paper reports on CAP associated with influenza and MRSA superinfection
in 10 cases reported from Louisiana and Georgia. The patients were previously
healthy and generally young (median age 18 years). They presented with
severe pneumonia that was associated with pulmonary necrosis, severe
pulmonary symptoms, and a mortality rate of 60%. The median duration
of symptoms from onset to death was only 3.5 days. The infective agent
is the relatively recently recognized “community-acquired-MRSA” that
is generally designated as the “USA 300 strain”. A widely
quoted report from the CDC has called attention to the two distinct
forms of MRSA1,
noting that the USA 300 strains have recently become far more prevalent
in the community than the USA 100 strains that have been predominant
in hospital-acquired infections over the past 3 decades.
The relevance of these observations
to CAP is the recognition of MRSA as a rare but very important cause.
It is usually a complication of influenza, the host is often young and
previously healthy, the course is rapid, progressive and often lethal,
and the common presentation is rapidly progressive sepsis with pulmonary
necrosis and/or empyema. The virulence factors responsible for this
devastating complication are not clear. Some have opined that the critical
virulence factor for pulmonary necrosis has been the Panton-Valentine
leukocidin toxin2,
but more recent studies suggest that virulence is defined by high concentrations
of cytolytic peptides that recruit, activate, and then lyse neutrophils.3 With
regard to treatment, the current ISDA/ATS recommendation is for vancomycin
or linezolid.
References
| 1. |
Labandeira-Rey
M, Couzon F, Boisset S, Brown EL, Bes M. Staphylococcus
aureus Panton-Valentine leukocidin causes necrotizing pneumonia. Science. 2007;315:1130-1133. |
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| 2. |
Labandeira-Rey
M, Couzon F, Boisset S, Brown EL, Bes M. Staphylococcus
aureus Panton-Valentine leukocidin causes necrotizing pneumonia. Science. 2007;315:1130-1133. |
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| 3. |
Wang
R, Braughton KR, Kretschmer D, Bach TH, Queck SY. Identification
of novel cytolytic peptides as key virulence determinants for community-associated
MRSA. Nat Med. 2007 Nov 11 [Epub ahead of print]. |
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DISCONTINUING
ANTIBIOTIC TREATMENT AFTER 3 DAYS VERSUS 8 DAYS |
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el
Moussaoui R, de Borgie CA, van den Broek P, Hustinx WN, Bresser
P, et al. Effectiveness of discontinuing antibiotic treatment
after three days versus eight days in mild to moderate-severe community-acquired
pneumonia: randomized, double blind study. BMJ. 2006;332(7554):1355.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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The
duration of antibiotic treatment for CAP is not supported by scientific
evidence and there is increasing concern that prolonged antibiotic abuse
is contributing to resistance, cost, and toxicity. This report by el
Moussaoui et al from The Netherlands directly addresses this issue.
Patients judged to have mild
or moderate-severe CAP were randomized to receive intravenous amoxicillin
and evaluated for response at 3 days. Those who were judged to have
substantial improvement at 3 days were randomized for either oral amoxicillin
or placebo for 5 days. The primary outcome measure was the clinical
evaluation at day 10, with secondary outcome measured at day 28. Results
were evaluated by follow-up cultures, x-rays, and description of clinical
symptoms at 10 and 28 days.
The results, summarized below,
showed no difference with treatment for 3 versus 8 days in terms of
clinical cure, bacteriologic cure, and radiologic cure at the evaluation
at 10 days as well as the evaluation at 28 days.
The authors conclude that discontinuing
amoxicillin treatment after 3 days is comparable to continued amoxicillin
in patients with mild to moderately severe CAP if there is clinical
improvement at day 3. |
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PATHOGEN
DIRECTED vs EMPIRIC ANTIBIOTIC TREATMENT |
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van
der Eerden MM, Vlaspolder F, de Graaff CS, Groot T, Bronsveld W. Comparison
between pathogen directed antibiotic treatment and empirical broad
spectrum antibiotic treatment in patients with community acquired
pneumonia: a prospective randomized study. Thorax. 2005;60:672-678.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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The
authors address the value of microbiology studies in patients with CAP
in one of the rare clinical trials comparing pathogen-directed treatment
versus empiric treatment using standard CAP guidelines for empiric treatment.
Participants were hospitalized
patients with CAP, and were randomized for treatment based on microbiology
results or empiric treatment. The former group underwent extensive diagnostic
testing including sputum gram stain and culture of sputum or bronchoscopic
aspirates with serology for viruses (influenza, parainfluenza virus,
respiratory syncytial virus (RSV) adenovirus and atypicals), and urinary
antigen assay for S. pneumoniae and Legionella serology
for atypicals. This arm received penicillin for pneumococcal pneumonia,
erythromycin for atypical pathogens, and amoxicillin-clavulanate for
most other bacteria. Those given empiric treatment received a β-lactam/β-lactamase
inhibitor plus erythromycin; for ICU admissions, the empiric treatment
was ceftazidime plus erythromycin.
The evaluation included 134 patients
in the pathogen-directed group and 128 in the empiric treatment group.
The clinical outcome was essentially the same in the two groups in terms
of mortality, rate of clinical failure, length of stay, duration of
antibiotics, and time to defervescence (results detailed in the table
below). However, there was a very significant difference in terms of
adverse events: 17% in the pathogen-directed group compared to 60% in
those receiving empiric treatment. The main difference was in the frequency
of GI intolerance, and less commonly, phlebitis and reversible hearing
loss.
The authors conclude that empiric
treatment with broad spectrum antibiotics for the management of hospitalized
patients with CAP shows efficacy that is comparable to pathogen-directed
treatment, although the rate of side effects is much greater with empiric
treatment. |
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REDUCTION
IN MORTALITY ASSOCIATED WITH INFLUENZA TREATMENT IN HOSPITALIZED ADULTS |
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McGeer
A, Green K, Plevneshi A, et al. for the Toronto Invasive Bacterial
Diseases Network. Antiviral therapy and outcome of influenza
requiring hospitalization in Ontario, Canada. Clin
Infect Dis. 2007;45(12):1568-1575.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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Influenza
remains a common cause of morbidity and mortality among older adults.
Influenza can be a primary cause of pneumonia or can place an individual
at risk for post-influenza bacterial pneumonia. While early therapy
with neuraminidase inhibitors has been shown to reduce the risk of complications
associated with influenza, the trials demonstrating this effect involved
relatively young, healthy adult outpatients treated within 48 hours
after the onset of symptoms. The investigators performed a prospective,
cohort study of elderly patients with confirmed influenza infection
randomized to receive oseltamivir or no antiviral treatment. The median
age was 77 years, 75% had chronic associated conditions, and 71% had
been vaccinated against influenza. Of 327 patients enrolled, 16% required
intensive care unit admission. The overall mortality rate was 8.3% within
15 days of onset of symptoms. Some of the patients received amantadine,
but this was inactive against influenza during the study period of 2005
and 2006, so these patients were considered in the non-treatment group.
The overall result showed that
patients given oseltamivir had a 80% reduction in mortality rate compared
to those that did not receive an effective antiviral (odds ratio 0.21,
p=0.03), thus suggesting the benefit of neuraminidase inhibitor antiviral
therapy in reducing influenza-associated CAP in elderly patients. |
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At
the conclusion of this activity, participants should be able to:
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Discuss
with colleagues the current recommendations regarding antibiotic
selection in the management of pneumonia |
|
|
|
Describe
to colleagues the current recommendations regarding diagnostic
testing in patients with suspected community-acquired pneumonia |
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|
|
Discuss
with colleagues the rationale for early institution of treatment
and the liability of over diagnosis |
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John
G. Bartlett, MD has disclosed that he has served on
the HIV Advisory Board for GlaxoSmithKline, Abbott, Bristol-Myers
Squibb, Pfizer and Tibotec. He is also on the Policy Board for
Johnson & Johnson. |
|
|
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Paul
G. Auwaerter, MD has disclosed that he has served as
a consultant for Novartis, Pfizer, Ortho-McNeil, Schering-Plough,
and Genzyme. He is on the Speakers' Bureau for Schering-Plough
and has also disclosed that he is a Stock Shareholder for Johnson &
Johnson. |
|
|
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Sara
E. Cosgrove, MD, MS has disclosed that she has received
grants or research support from Merck and served on the Advisory
Boards for Ortho-McNeil, Cadence Pharmaceuticals, and Theravance/Astellas. |
Guest
Author Disclosures |
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| Disclaimer
Statement — back
to top |
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| The
opinions and recommendations expressed by faculty and other experts
whose input is included in this program are their own. Use of The
Johns Hopkins University School of Medicine name implies review
of educational format design and approach. Please review the complete
prescribing information of specific drugs or combination of drugs,
including indications, contraindications, warnings and adverse effects
before administering pharmacologic therapy to patients. |
|
©
2008 JHUSOM and eInfections Review
Created by DKBmed. |
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