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References
 Pharmacotherapy: A Pathophysiologic Approach. 10th edition 2017.
 Applied Therapeutics: The Clinical Use of Drugs. 10th Edition.2013.
Chapter 64.
 Infectious Diseases Society of America/American Thoracic Society
consensus guidelines on the management of community-acquired
pneumonia in adults. Clin Infect Dis 2007 Mar 1;44 Suppl 2:S27-72.
(IDSA/ATS/CAP)
 Management of Adults With Hospital-acquired and Ventilatorassociated Pneumonia: 2016 Clinical Practice Guidelines by the
Infectious Diseases Society of America and the American Thoracic
Society (IDSA/ATS)
 Guidelines for the management of community acquired pneumonia in
adults: update 2009. British Thoracic Society Community Acquired
Pneumonia in Adults Guideline Group. October 2009 Vol 64 Supplement
III (BTS/CAP)
2
INTRODUCTION
lower respiratory tract: tracheobronchial
tree and lung parenchyma.
 The most common infections involving the lower respiratory
tract include bronchitis, bronchiolitis, and pneumonia.
 Lower respiratory tract infections in children and adults are
most commonly a result of either viral or bacterial invasion of
lung parenchyma.
 The diagnosis of viral infections rests primarily on the
recognition of a characteristic constellation of clinical signs
and symptoms.
 In contrast, because bacterial pneumonia usually necessitates
expedient, effective, and specific antibiotic therapy,
 its management depends, in large part, on isolation of the
etiologic agent by culture from lung tissue or secretions.
3
 Bronchitis and bronchiolitis are inflammatory conditions of
the large and small elements, respectively, of the
tracheobronchial tree.
 The inflammatory process does not extend to the alveoli.
 Bronchitis frequently is classified as acute or chronic.
 Acute bronchitis occurs in all ages,
whereas chronic bronchitis primarily affects adults.
 Bronchiolitis is a disease of infancy.
 Respiratory syncytial virus is the most common cause of acute
bronchiolitis, an infection that mostly affects infants during their first
year of life. In the well infant, bronchiolitis is usually a self-limiting viral
illness, whereas in the child with underlying respiratory or cardiac
disease or both, the child may develop severe respiratory compromise
(failure) necessitating in-hospital treatment, such as rehydration,
oxygen, and in select patients, bronchodilators, ribavirin aerosol, or
both.
4
 Acute bronchitis
 occurs most commonly during the winter months,
following a pattern similar to those of other acute
respiratory tract infections.
 Cold, damp climates, the presence of high
concentrations of irritating substances, such as air
pollution or cigarette smoke, or both

may precipitate attacks.
5
Acute bronchitis usually begins as an upper respiratory infection with
nonspecific complaints. Cough is the hallmark of acute
bronchitis and occurs early. The onset of cough may be insidious
or abrupt, and the symptoms persist despite resolution of nasal or
nasopharyngeal complaints.
6
 Respiratory viruses are by far the most common
infectious agents associated with acute bronchitis.
 Routine use of antibiotics in the treatment of
acute bronchitis should be discouraged;
 however, in patients who exhibit persistent fever or
respiratory symptoms for more than 4 to 6 days, the
possibility of a concurrent bacterial infection should
be suspected. When possible, antibiotic therapy

should be directed toward anticipated respiratory
pathogen(s) (S. pneumoniae, H. influenzae, M.
pneumoniae).
7
Treatment of acute bronchitis
General Approach to Treatment
 Treatment of acute bronchitis is symptomatic and supportive
in nature.
 Reassurance and antipyretics frequently are all that are needed.
 Bed rest for comfort may be instituted as desired.
 Patients should be encouraged to drink fluids to prevent
dehydration and possibly to decrease the viscosity of
respiratory secretions. Mist therapy (use of a vaporizer) may
promote the thinning and loosening of respiratory secretions.
8
Treatment of acute bronchitis
Pharmacologic Therapy
 Mild analgesic–antipyretic therapy : aspirin (not
children?), acetamenophen, ibuprofen.
 Antitussives; although not recommended for routine use, persistent,
mild cough, which may be bothersome, can be treated
with dextromethorphan
 Occasional antibiotics (Routine use, should be
discouraged :
 Erythromycin or its analogues (clarithromycin,
azithromycin).
 Alternatively and empirically, a fluoroquinolone with
activity against the suspected bacterial pathogens (such as
levofloxacin) may be used.
9
PNEUMONIA
 Pneumonia remains the most common cause of severe
sepsis and infectious cause of death in children and adults
in the United States, with a mortality rate of 30% to 40
 where approximately 4 million cases are diagnosed annually at a
cost of $23 billion redundant to the health care system.
 Pneumonia occurs throughout the year, with the relative
prevalence of disease resulting from different etiologic
agents varying with the seasons.
 It occurs in persons of all ages,
 although the clinical manifestations are most severe in the very
young, the elderly, and the chronically ill.
11
Definition
 Acute infiltrate on chest radiograph, or
 Auscultatory findings such as altered breath sounds or
localized rales ‫حشرجة‬
Pneumonia can be generally defined as inflammation of the
lung parenchyma, in which:

consolidation of the affected part
 and a filling of the alveolar air spaces with exudate,
inflammatory cells, and fibrin is characteristic.
12
Acute infection of pulmonary parenchyma (alveoli) with
at least some symptoms of acute infection accompanied
by:
BTS/CAP definition
 The clinical definition of CAP that has been used in community studies has
varied widely but has generally included :
 a complex of symptoms and signs both from the respiratory tract and regarding
the general health of the patient.

Features such as :

fever (>38°C),

pleural pain,

dyspnoea

and tachypnoea

and signs on physical examination of the chest (particularly when new and
localizing) seem most useful when compared with the gold standard of radiologica
diagnosis of CAP
13
Pneumonia is inflammation of the lung with consolidation. The cause of the
inflammation is infection, which can result from a wide range of organisms.
 Community-acquired pneumonia (CAP) Patients who develop pneumonia in the
outpatient setting and have not been in any health care facilities, which include
wound care and hemodialysis clinics. (Pneumonia developing in patients with no contact to a
medical facility)

Aspiration is of either oropharyngeal or gastrointestinal contents.
 Hospital-acquired pneumonia (HAP): pneumonia that occurs 48 hours or more after
admission. (Not changed based on HAP-VAP 2016)
 Ventilator-associated pneumonia (VAP) requires endotracheal intubation for at least
48 to 72 hours before the onset of pneumonia. VAP is defined as a pneumonia
occurring >48 hours after endotracheal intubation(Not changed based on HAP-VAP
2016)
14
 HAP accounts for about 25% of all ICU infections.
15
 Intubation and mechanical ventilation increase the
risk of HAP by 6 to 21-fold.
 Nearly 90% of ICU HAP occurs in mechanically
ventilated patients (VAP).
 50% of VAP occurs within the first four days of
ventilation.
HCAP 2005
 Health care–associated pneumonia (HCAP): HCAP: Pneumonia developing in
patients not in an acute care medical facility but two or more risk factors
for MDR (multidrug resistant) pathogens: ((e.g., P. aeruginosa, Acinetobacter
species, and MRSA]

Recent hospitalization ≥2 days within past 90 days; Nursing home or long-term
care facility resident; Recent (past 30 days) antibiotic use, chemotherapy,
wound care or infusion therapy at either a healthcare facility or home;
Hemodialysis patients; Contact with a family member with infection caused by
MDR pathogen
Risk factors for exposure to MDR bacteria in HCAP include the following:
1.
Hospitalization for 2 or more days in an acute care facility within
90 days of current illness
2. Exposure to antibiotics, chemotherapy, or wound care within 30
days of current illness
3. Residence in a nursing home or long-term care facility
4. Hemodialysis at a hospital or clinic
5. Home nursing care (infusion therapy, wound care)
6. Contact with a family member or other close person with
infection due to MDR bacteria
16
HCAP, 2016 new
 Healthcare-Associated Pneumonia
 The rationale for inclusion of the HCAP designation with the
HAP/VAP guidelines in 2005 was that patients with HCAP were
thought to be at high risk for MDR organisms by virtue of their contact
with the healthcare system. Therefore, due to both the patients’
contact with the healthcare system and the presumed high risk of
MDR pathogens, guidelines for these patients were included with
guidelines for HAP and VAP, the HAPs.
 However, There is increasing evidence that many patients defined as
having HCAP are not at high risk for MDR pathogens . Furthermore,
although interaction with the healthcare system is potentially a risk for
MDR pathogens, underlying patient characteristics are also
important independent determinants of risk for MDR pathogens.
 For these reasons, the panel unanimously decided that HCAP
should not be included in the HAP/VAP guidelines. HAP-VAP 2016
17
EPIDEMIOLOGY AND ETIOLOGY
Most common organisms:
 S. pneumoniae is the predominant bacterial pathogen associated with
CAP. (70 % of all cases)
 Mycoplasma pneumoniae.
 Nontypeable Hemophilus influenzae esp.: COPD patients and those
with cystic fibrosis.
 Moraxella catarrhalis: the very young and the very old. (10-20 % of all
cases)
 Chlamydia pneumoniae and Legionella
 Viruses are a common cause of CAP in children (~65%) and much less
common in adults (~15%).
1. More common: influenza A (adult) and B and adenoviruses,
2. less common causes include rhinoviruses, enteroviruses,
18
cytomegalovirus, varicella-zoster virus, herpes simplex virus, and
others.
18
In children, viral pneumonia is caused more
commonly by:



respiratory syncyntial virus,
influenza A virus,
and parainfluenza virus.
 In elderly patients admitted to the hospital with
severe pneumonia, the mortality rate is up to 40%
 In the outpatient setting (mild to moderate
disease), the mortality rate is less than 5%.
19
19
The term ‘‘atypical pathogens’’ is used to define
pneumonia infections caused by:
Mycoplasma pneumoniae;
Chlamydophila pneumoniae;
Chlamydophila psittaci (psittacosis, parrot fever);
and
Coxiella burnetii. (Q fever; cattle, sheep, goats and
other domestic mammal)
20
21
22
Aspiration Pneumonia
Aspiration of the oropharyngeal or gastric contents may lead to aspiration
pneumonia or chemical (acid) pneumonitis. Aspiration pneumonia refers
specifically to the development of an infectious infiltrate in patients who are
at increased risk of oropharyngeal aspiration.
Risk factors for aspiration include:
 Dysphagia (can be caused by stroke or other neurologic disorders, seizures,
alcoholism, and aging)
 Change in oropharyngeal colonization (altered by oral/dental disease, poor oral
hygiene, tube feedings, or medications)
 Gastroesophageal reflux (Acid suppression is an important factor in the
treatment of GERD, which may allow enteric gram-negative bacilli to colonize the
gastric contents)
 Decreased host defenses like:
1.
2.
3.
impaired mucus production or cilia function,
decreased immunoglobulin in secretions,
altered cough reflex.
The infection can result in a necrotizing pneumonia or lung abscess.
23
23
HAP and VAP
Risk factors for the development of HAP fall into four general
categories:
1. Intubation and mechanical ventilation: increase the risk of
HAP/VAP 6- to 21-fold.
2. Aspiration:
supine positioning of the patient, the presence of the endotracheal tube preventing
closure of the epiglottis over the glottis, enteral feedings, gastroesophageal
reflux, medications.
3. Oropharyngeal colonization: altered by
oral/dental disease, poor oral hygiene, tube feedings, medications. use of
antibiotics, oral antiseptics, poor infection control measures, which may decrease
normal commensal flora and allow pathogenic organisms to colonize the oral
cavity.
4. Hyperglycemia: two proposed mechanisms are:
a.
b.
inhibiting phagocytosis
providing additional nutrients for bacteria.
24
VAP: Colonization of the ventilator circuit.
24
25
DIAGNOSIS
IDSA/ATS
 The diagnosis of CAP is based on:
 the presence of select clinical features (e.g., cough, fever, sputum
production, and pleuritic chest pain)
 and is supported by imaging of the lung, usually by chest radiography.
 Physical examination to detect rales or bronchial breath sounds is
an important component of the evaluation but is less sensitive and
specific than chest radiographs.
 Both clinical features and physical exam findings may be lacking or
altered in elderly patients.
 Pneumonia can be classified as typical or atypical, although the
clinical presentations are often similar.
26
27
28
31
 Physicians should begin their treatment decisions
by assessing the need for hospitalization :
 using a prediction tool for increased mortality, such
as the Pneumonia Severity Index (PSI), combined
with clinical judgment.
 Severity-of-illness scores, such as the CURB-65
criteria (confusion, uremia, respiratory rate, low blood
pressure, age 65 years or greater), or prognostic
models, such as the PSI, can be used to identify
patients with CAP who may be candidates for
outpatient treatment. (Strong recommendation;
level I evidence.)
32
PSI is based on 20 variables.
Based on the score, patients are stratified
into five risk categories based on 30day mortality.
33
PSI categories
34
BTS 2009
35
36
BTS 2007
37
38
GUIDELINES: SITE-OF-CARE DECISIONS (IDSA)

Hospital Admission Decision

Severity-of-illness scores, such as the CURB-65 criteria (confusion, uremia, respiratory
rate, low blood pressure, age 65 years or greater), or prognostic models, such as the
Pneumonia Severity Index (PSI), can be used to identify patients with CAP who may be
candidates for outpatient treatment. (Strong recommendation; level I evidence)
 Objective criteria or scores should always be supplemented with physician
determination of subjective factors, including the ability to safely and reliably take oral
medication and the availability of outpatient support resources. (Strong
recommendation; level II evidence)
 For patients with CURB-65 scores >2, more-intensive treatment—that is,
hospitalization or, where appropriate and available, intensive in-home health care
services—is usually warranted. (Moderate recommendation; level III evidence)

Intensive Care Unit (ICU) Admission Decision

Direct admission to an ICU is required for patients with septic shock requiring
vasopressors or with acute respiratory failure requiring intubation and mechanical
ventilation. (Strong recommendation; level II evidence)
 Direct admission to an ICU or high-level monitoring unit is recommended for patients
with 3 of the minor criteria for severe CAP listed in the Table below. (Moderate
39
recommendation; level II evidence)
IDSA/ATS CAP criteria
PaO2 to
fraction of
inspired
oxygen
The presence of 3 of the following
minor criteria indicates severe CAP
and suggests the likely need for ICUlevel care
Direct admission to an ICU is mandated
40
Desired Outcomes
The goal of antibiotic therapy is to:
eliminate the patient’s symptoms,
2. minimize or prevent complications,
3. and decrease mortality.
1.
Potential complications secondary to pneumonia include
1. further decline in pulmonary function in patients with underlying
pulmonary disease,
2. prolonged mechanical ventilation,
3. bacteremia/sepsis/septic shock, and death.
In addition, using an agent with the narrowest spectrum of activity that
covers the suspected pathogen without having activity against organisms
not involved in the infection is preferred. This is to minimize the
41
development of resistance.
General Approach to Treatment
Designing a therapeutic regimen for any patient with any type of
pneumonia begins with three general categories of consideration:
1. Patient-specific factors that will affect therapy:
a. age,
b. renal function,
c.
drug allergies and/or drug intolerances,
d. immune status (e.g., diabetes, neutropenia, or
immunocompromised host),
e. cardiopulmonary disease,
f.
pregnancy,
g. medical insurance and prescription coverage,
h. prior antibiotic exposure(s) (what agents and when).
42
42
General Approach to Treatment
2. The top one to three organisms likely causing the
infection and resistance issues associated with
each organism.
 Treating patients with HCAP?, HAP, or VAP is more
complex than treating patients with CAP.
3. What antimicrobials:
Will cover these organisms
b. Will not be too broad or narrow in spectrum,
c. Will penetrate into the site of infection,
d. What they cost.
a.
43
43
Factors influencing infection from
a resistant organism:
Antimicrobial therapy in preceding 90 days
Current hospitalization of at least 5 days
High occurrence of antibiotic resistance in the community or in the
specific hospital unit
4) Presence of risk factors for HCAP:
1)
2)
3)
1)
2)
3)
4)
5)
6)
5)
Hospitalization for 2 days or more in the preceding 90 days
Residence in a nursing home or extended-care facility
Home infusion therapy (including antibiotics)
Peritoneal or hemodialysis within 30 days
Home wound care
Close contact family member with MDR pathogen
Immunosuppressive disease and/or therapy.
Once these issues are addressed, antimicrobial therapy can be selected44
and
initiated.
44
General Approach to Treatment
 The first priority in assessing the patient with pneumonia is to:
 evaluate the adequacy of respiratory function and
 to determine the presence of signs of systemic illness, specifically dehydration or
sepsis with resulting circulatory collapse.
 Oxygen or, in severe cases, mechanical ventilation and fluid resuscitation should be
provided as necessary.
 Further supportive care of the patient with pneumonia includes humidified oxygen
for hypoxemia, administration of bronchodilators (albuterol) when bronchospasm
is present,
 Additional therapeutic adjuncts include adequate hydration (IV if necessary),
optimal nutritional support, and control of fever.
 Selection of an appropriate antimicrobial must be made based on the
patient’s probable or documented microbiology, distribution in the respiratory
tract, side effects, and cost.
 Respiratory tract infection diagnosis and treatment guideline reports have been
published by authoritative professional organizations (BTS and ATS)
45
General Approach to Treatment
 Delayed antibiotic therapy has been associated with an increased length of
stay and decreased survival in CAP; therefore, a rapid and correct diagnosis is
imperative.
 The most recent IDSA/ATS CAP treatment guidelines recommend the first dose
of antibiotic be given in the ED in effort to avoid treatment delays associated
with the hospital admission process.
 Initial antimicrobial treatment is empirical because of the limited turnaround
time, sensitivity, and specificity of currently available microbiological tests.
 All patients should be empirically treated for pneumococcus and atypical
pathogens. In addition, the choice of the initial regimen should be based on
medical comorbidities or epidemiological factors.
 In addition, an assessment of likelihood for infection caused by an antibiotic-
resistant pathogen should take place.
 The most important consideration in the selection of empiric therapy is to
determine risk for infection with DRSP (Table 64-6).
46
Approach to empiric antibiotic
therapy in patients with communityacquired pneumonia
FQ for PNC
allergic
FQ + aztreonam
for for PNC
allergic
47
48
Doses can be increased for more severe
disease and may require modification in
patients with organ
dysfunction.
a- Tetracyclines are rarely used in pediatric
patients, particularly in those younger than
8 years because
of tetracycline-induced permanent tooth
discoloration.
b- Higher-dose amoxicillin, amoxicillin–
clavulanate (e.g., 90 mg/kg/day) is used for
penicillin-resistant S. pneumoniae.
c- Fluoroquinolones are avoided in
pediatric patients because of the potential
for cartilage damage; however, their use in
pediatrics is emerging.
Doses shown are extrapolated from adults
and require further study.
49
ATS 2007
erythromycin is not often used now, because of gastrointestinal intolerance and
lack of activity against H. influenzae.
50
51
52
53
ertapenem, as
an acceptable
b-lactam
alternative for
hospitalized
patients with
risk factors
for infection with
gram-negative
pathogens other
than
Pseudomonas
Aeruginosa.
•
•
•
•
The severity of illness generally is increased (caused either by the organism itself or by
underlying comorbidities in the patient).
The pathogens are essentially the same as in the outpatient setting.
Therapy should be initiated within the 4 hours of presentation to the emergency room
or hospital.
Conversion to oral therapy should occur within 48 to 72 hours for most patients, and
discharge from the hospital should be within 5 days if there are no complications.
54
the majority
of ICU
patients
would still
require
combinatio
n therapy
 Patients admitted to the intensive-care unit (ICU) have severe
pneumonia, and the etiology includes S. pneumoniae and H.
influenzae as in the other categories; however, the incidence of
Legionella pneumophila increases in this setting and should be
included in the organism differential.
 In addition, enteric gram negative bacilli and S. aureus are more
frequently the cause of the pneumonia.
 This combination therapy minimizes the risk of treatment failure owing
to a resistant pathogen and also provides coverage against all the
potential pathogens.
55
combination
A consistent
Gram stain of
tracheal
aspirate, sputum,
or blood is the
best indication for
Pseudomonas
Coverage
Alternative regimens are
provided for patients who may have recently received an oral
fluoroquinolone, in whom the aminoglycoside-containing regimen
would be preferred
structural lung
diseases, such
as
bronchiectasis,
or repeated
exacerbations of
severe COPD
MRSA
56
Special concerns
If P. aeruginosa is suspected: Recommended regimens double-cover the
Pseudomonas and S.pneumonia, include the use of:
 An antipneumococcal, antipseudomonal b-lactam (piperacillin-
tazobactam, cefepime, imipenem, or meropenem) + either ciprofloxacin
or levofloxacin (750 mg)
or
 The above b-lactam + an aminoglycoside and azithromycin
or
 The above b-lactam + an aminoglycoside and an antipneumococcal
fluoroquinolone (for penicillin-allergic patients, substitute aztreonam for
above b-lactam) (moderate recommendation; level III evidence)
 If comminity-acquired MRSA (CA-MRSA ) is a consideration, add
vancomycin or linezolid (moderate recommendation; level III evidence)
57
57
58
Switch from Intravenous to Oral Therapy
 Patients should be switched from
intravenous to oral therapy when
they are: IDSA/ATS 2007, table 10
 hemodynamically stable
 improving clinically,
 are able to ingest medications,
 have a normally functioning
gastrointestinal tract.
 Patients should be discharged as
soon as they are :
 clinically stable,
 have no other active medical
problems, and
 have a safe environment for
continued care.
 Inpatient observation while receiving
oral therapy is not necessary.
59
60
Duration of Therapy
 The duration of therapy for pneumonia should be kept as
short as possible and depends on several factors:
1.
2.
3.
4.
5.
type of pneumonia,
inpatient or outpatient status,
patient comorbidities,
bacteremia/sepsis,
the antibiotic chosen.
 If the duration of therapy is too prolonged, then it can have a
negative impact on the patient’s normal flora
in the respiratory and gastrointestinal tracts, vaginal tract of
women, and the skin.
 This can result in colonization with resistant pathogens,
Clostridium difficile colitis, or overgrowth of yeast.


 The longer antibiotics are administered, the greater is the
chance for toxicity from the agent as well as an increase cost.
61
61
Duration of Therapy for CAP
 For treating outpatient CAP:
 two antibiotics are approved for a 5-day duration of
therapy, levofloxacin (the 750-mg dose) and
azithromycin.
 The duration of therapy for all other therapies is 7 to 10
days.
 For treatment of CAP in patients admitted to the
hospital, the duration depends on whether or not
blood cultures were positive.
 In negative blood cultures, the duration of therapy is 7 to 10
days.
 If blood cultures were positive, then the duration of therapy
should be 2 weeks from the day blood cultures first
became negative.
62
62
63
Transitioning inpatients with community-acquired pneumonia from IV to oral antibiotics
64
Pathogen-Directed Therapy
Once the etiology of CAP has been
identified on the basis of reliable
microbiological methods, antimicrobial,
therapy should be directed at that
pathogen. (Moderate recommendation; level
III evidence.)
66
Aspiration
 If a patient aspirates his or her oral contents and
pneumonia develops, then anaerobes and
Streptococcus spp. are the primary pathogens.

 Antibiotics active against these organisms
include:
1. penicillin G,
2. ampicillin/sulbactam,
3. clindamycin,
4. metronidazole.
67
67
HAP and VAP
• HAP: pneumonia not incubating at the time of
admission and occurring 48 hours or more after
admission
• VAP: pneumonia occurring more than 48 hours
after endotracheal intubation
68
Major Differences in
New Guidelines
• Removal of the concept of healthcare-associated
pneumonia (HCAP)….CAP???
• Recommendation that each hospital generate antibiograms
to base antimicrobial choice upon
• Shorter duration of therapy independent of microbial
etiology, as well as antibiotic de-escalation.
Antibiograms
• Empiric treatment regimens based on antibiograms
• Minimize patient harm and exposure
• Reduce the development of antibiotic resistance
• Decrease the unnecessary use of dual gram-negative
and empiric MRSA treatment
• Specific to VAP populations (ICU)
• Specific to HAP populations
Table 2
72
Risk Factors for MDR
Pathogens (table 2)
MRSA or
VAP
HAP
P. aeruginosa
Prior IV antibiotic use within 90 day
Septic shock at time of VAP
ARDS prior to the occurrence of
VAP
5 or more days of hospitalization
prior to the occurrence of VAP
Acute renal replacement therapy
prior to the occurrence of VAP
74
Empiric Therapy for VAP
• S. aureus, P. aeruginosa and other gram-negative bacilli
• MRSA coverage if
o
Risk factors for antimicrobial resistance (table 2)
o
Units where >10%-20% of S. aureus isolates are methicillin resistant
o
Units where the prevalence of MRSA is not known
o
Vancomycin or linezolid.
• MSSA coverage only, if
o
Without risk factors for antimicrobial resistance
o
ICUs where <10%-20% of S. aureus isolates are methicillin resistant
o
If MSSA empiric coverage is indicated the guidelines suggest using
pippercillin-tazobactam, cefepime. Levofloxacin, imipenem, or
meropenem.
o
If MSSA is proven the use of oxacillin, nafcillin, or cefazolin is
recommended. - but not for empiric treatment
Empiric Antipseudomonal
Coverage VAP
•
Double Coverage
o
o
o
•
Risk factors for resistance
Units where >10% of gram-negative isolates are resistant to an
agent being considered for monotherapy
Susceptibility rates for ICU not available
Monotherapy
o
o
o
No risk factors for resistance
ICU’s where ≤ 10% of gram-negative isolates are resistant to the
agent being considered for monotherapy
Avoid aminoglycosides or colistin when possible
77
Empiric Therapy for
HAP
• S. aureus, P. aeruginosa and other gram-negative bacilli
• MRSA coverage if
o
o
o
o
IV antibiotics in last 90 days
Unit where >20% of S. aureus isolates are methicillin resistant
Prevalence of MRSA is not known
High risk for mortality
• MSSA coverage if
o Empiric treatment and have no risk factors for MRSA
o Not at high risk of mortality
Empiric Antipseudomonal
Coverage HAP
•
•
Double Coverage
o
Risk factors for Pseudomonas or other gram-negative infection
o
IV antibiotics in the last 90 days
o
Structural lung disease
o
High risk of mortality
Monotherapy
o
All other patients with HAP who are being treated empirically
o
Do not use aminoglycoside as sole antipseudomonal agent
80
Definitive
Treatment
Monotherapy vs. Combination
therapy for P. aeruginosa
•
•
Monotherapy
o
Not in septic shock or at high risk of death
o
Susceptibility results are known
Combination therapy
o
Septic shock
o
High risk of death when the results of antibiotic susceptibility
testing are known
•
Recommend against aminoglycoside monotherapy
Duration of Therapy for
HAP and VAP
•
7 day course of antimicrobial therapy
•
Discontinue based on PCT levels + clinical
criteria vs. clinical criteria alone
•
De-escalation of therapy recommended rather
than fixed therapy
DOUBLE COVERAGE FOR PSEUDOMONAS?
Debate over whether or not double coverage for
Pseudomonas is required.
In vitro studies have shown that aminoglycosides exhibit
synergistic killing against gram negative bacilli when
combined with β-lactams.
Dosing of the aminoglycosides depends on the patient’s
renal function.
A high-dose once-daily regimen (e.g., 4–7 mg/kg gentamicin
or tobramycin or 15–20 mg/kg amikacin) can be used in
patients with good renal function.
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Advantages of double coverage when treating VAP, HAP, or :
1. synergistic effect,
2. broaden the coverage empirically to increase the likelihood of
covering the majority of resistant pathogens.
 VAP is the most studied of these types of pneumonias and is often
the most severe.

Studies have demonstrated an increase in mortality when inadequate
therapy is initiated for VAP.

Crude mortality ranges from 35% to 92% with inadequate therapy
compared with 25% to 47% with adequate therapy.
 Once a pathogen or pathogens have been identified, therapy
should be narrowed to cover only those pathogens.

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Use of broad-spectrum antibiotics for prolonged durations increases
the risk of colonization with MDR pathogens.
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Prevention
 http://www.cdc.gov/vaccines/hcp/acip-recs/vacc-
specific/pneumo.html
 Pneumonia kills more children than any other illness;
 among approximately 9 million children aged <5 years who die each
year worldwide, 1.6 million die from pneumonia.
 Through the Global Action Plan for Prevention and Control of
Pneumonia, the World Health Organization and international
partners recommend that the global health burden of pneumonia
be reduced by:
 using vaccines against organisms that cause pneumonia.
 providing appropriate care and treatment for persons who contract
pneumonia, and
 promoting preventive measures such as exclusive breastfeeding of
infants during their first 6 months of life
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Transmission
Pneumococcus is in many people's noses and
throats and is spread by coughing, sneezing, or
contact with respiratory secretions.
 Why it suddenly invades the body and causes disease is
unknown.
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 Streptococcus pneumoniae (pneumococcus) and Haemophilus
influenzae type b (Hib) account for approximately 60% of
pneumonia deaths worldwide of children aged 1 month–5 years
 in countries that do not use pneumococcal or Hib conjugate
vaccines.
 In the United States, pneumococcal and Hib conjugate vaccines are
recommended for infants and children aged <2 years as part of the
routine infant immunization schedule and have reduced morbidity and
mortality from pneumococcal disease by 76% and from Hib disease by
>99% among children aged <5 years
 In 2010, a 13-valent pneumococcal conjugate vaccine was licensed
and recommended in the United States. Collaborative international
efforts are expanding use of these vaccines in developing countries.
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Who should receive PPSV23
 All adults 65 years of age and older.
 Anyone 2 through 64 years of age who has a long-term health




problem such as: heart disease, lung disease, sickle cell disease,
diabetes, alcoholism, cirrhosis, leaks of cerebrospinal fluid or
cochlear implant.
Anyone 2 through 64 years of age who has a disease or condition
that lowers the body’s resistance to infection, such as:
Hodgkin’s disease; lymphoma or leukemia; kidney failure; multiple
myeloma; nephrotic syndrome; HIV infection or AIDS; damaged
spleen, or no spleen; organ transplant.
Anyone 2 through 64 years of age who is taking a drug or
treatment that lowers the body’s resistance to infection, such
as: long-term steroids, certain cancer drugs, radiation therapy.
Any adult 19 through 64 years of age who is a smoker or has asthma.
Residents of nursing homes or long-term care facilities.
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Influenza
Influenza viruses A and B can cause pneumonia in pediatric and
adult patients.
Amantidine and rimantidine are available oral agents with activity
against influenza virus type A.
If started within 48 hours of the onset of the first symptoms, they
reduce the duration of the illness by about 1.3 days.
Oseltamivir (Tamiflu) and zanamivir also reduce the duration of the
illness by about 1.3 days if initiated within 40 to 48 hours of the first
symptoms.
For active infection beyond the first 48 hours, none of these agents is
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effective in treating the infection, and supportive care is the best
treatment for these patients.
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PREVENTION
The influenza vaccine
 The influenza vaccine is available in two forms, injectable and nasal
inhalation.
 The injectable is an inactivated vaccine (containing killed virus).
 The flu shot is approved for use in people older than 6 months of
age, including healthy people and people with chronic medical
conditions.
 The nasal-spray flu vaccine is made with live, weakened flu viruses that
do not cause the flu (live attenuated influenza vaccine).
 This formulation is approved for use in healthy people 5 to 49 years of
age who are not pregnant.
 The ability of the flu vaccine to protect a person depends on two key
factors:
1. the age and health status of the person getting the vaccine
2. and the similarity or “match” between the virus strains in the
vaccine and those in circulation.
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Persons for Whom Annual Vaccination is
Recommended (2012/2013)
 All persons aged 6 months and older should be vaccinated annually.
 Protection of persons at higher risk for influenza-related complications should continue to
be a focus of vaccination efforts.
 When vaccine supply is limited, vaccination efforts should focus on delivering
vaccination to persons who:
 are aged 6 months--4 years (59 months);
 are aged 50 years and older;
 have chronic pulmonary (including asthma), cardiovascular (except hypertension), renal,
hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus);
 are immunosuppressed (including immunosuppression caused by medications or by human
immunodeficiency virus);
 are or will be pregnant during the influenza season;
 are aged 6 months--18 years and receiving long-term aspirin therapy and who therefore
might be at risk for experiencing Reye syndrome after influenza virus infection;
 are residents of nursing homes and other chronic-care facilities;
 are American Indians/Alaska Natives;
 are morbidly obese (body-mass index is 40 or greater);
 are health-care personnel;
 are household contacts and caregivers of children aged younger than 5 years and adults aged
50 years and older, with particular emphasis on vaccinating contacts of children aged younger
than 6 months; and
 are household contacts and caregivers of persons with medical conditions that put them at
higher risk for severe complications from influenza.
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Case
A.T., a 58-year-old man, is admitted to the hospital from home with fever,
increased sputum production, tachypnea, and complaints of a knifelike chest pain that is
made worse by coughing and breathing. Pertinent medical history includes a 12-year
history of CB and chronic renal insufficiency. A.T. regularly produces two cups of sputum
per day and continues to smoke two and one-half packs of cigarettes per day. He has been
taking amoxicillin 250 mg BID prophylactically for the past 14 months.
Physical examination reveals an elderly man lying restlessly in bed, awake, and oriented to
person but not place or time; temperature, 101.5°F (38.6°C), blood pressure (BP), 145/88
mmHg; heart rate (HR), 105 beats/minute; and respiratory rate (RR), 33 breaths/minute.
Chest examination reveals slight splinting on the right side with inspiration and fine
crackling rales in the lower base of the right lung. Examination of the left lung is normal.
Significant laboratory results include the following: WBC count, 16,200 cells/mm3
(normal, 5,000–10,000 cells/mm3); differential polymorphonuclear neutrophils (PMNs),
82% (normal, 45%–79%); bands, 9% (normal, 0%–5%); lymphocytes, 8% (normal, 16%–
47%); hematocrit (Hct), 40% (normal, 37%–47%); sodium, 141; potassium, 4.8; blood urea
nitrogen (BUN), 32; creatinine, 3.8 mg/dL; glucose 148, mg/dL; arterial blood gases
(ABGs), pH 7.46 (normal, 7.38–7.45), PO2, 68 mmHg (normal, 80–100 mmHg), PCO2, 36
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mmHg (normal, 38–45 mmHg), HCO3, 24 mEq/L (normal, 22–26 mEq/L); and Gram stain
reveals <10 epithelial cells, 20 to 25 PMNs, and predominance of Gram-negative rods.
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Case Questions
 What are the normal respiratory defenses against infection?
 What factors present in A.T. make him susceptible to pulmonary
infection?
 What clinical signs, symptoms, and laboratory tests are consistent with
pneumonia in A.T.?
 How can the etiologic organism be determined?
 How should A.T. be treated?
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