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Transcript
Guidelines for Prevention and Treatment of Opportunistic
Infections in HIV-Infected Adults and Adolescents
Bacterial Respiratory Infections
Slide Set
Prepared by the AETC National Coordinating Resource
Center based on recommendations from the CDC,
National Institutes of Health, and HIV Medicine
Association/Infectious Diseases Society of America
About This Presentation
These slides were developed using recommendations
published in May 2013. The intended audience is
clinicians involved in the care of patients with HIV.
Users are cautioned that, because of the rapidly
changing field of HIV care, this information could
become out of date quickly. Finally, it is intended that
these slides be used as prepared, without changes in
either content or attribution. Users are asked to honor
this intent.
– AETC National Resource Center
http://www.aidsetc.org
www.aidsetc.org
June 2013
2
Bacterial Respiratory Infections
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



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Epidemiology
Clinical Manifestations
Diagnosis
Prevention
Treatment
Considerations in Pregnancy
www.aidsetc.org
June 2013
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Bacterial Respiratory Disease:
Epidemiology
 Bacterial pneumonia is a common cause of HIVrelated morbidity
 In HIV-infected persons:
 Higher rates of bacterial pneumonia
 Higher mortality
 Increased incidence of bacteremia (esp. with S
pneumoniae)
 Can occur at any CD4 count or stage of disease
 Recurrent pneumonia (≥2 episodes in 1 year) is
an AIDS-defining condition
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Bacterial Respiratory Disease:
Epidemiology (2)
 Incidence lower with use of ART
 Risk factors include
 Low CD4 count (<200 cells/µL)
 No or intermittent use of ART
 Cigarette smoking
 Injection drug use
 Chronic viral hepatitis
www.aidsetc.org
June 2013
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Bacterial Respiratory Disease:
Epidemiology (3)
 Organisms:
 S pneumoniae
 Drug-resistant strains are increasingly common
 H influenzae
 P aeruginosa
 S aureus, including MRSA
 Atypicals (infrequent)
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June 2013
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Bacterial Respiratory Disease: Clinical
Manifestations
 Presentation similar to that of HIV uninfected,
with acute symptoms (fevers, chills, rigors, chest
pain, productive cough, dyspnea)
 Subacute illness suggests alternative diagnosis (PCP,
TB, chronic fungal disease, etc)
 Physical exam: evidence of focal consolidation or
pleural effusion
 WBC usually elevated, may see left shift
www.aidsetc.org
June 2013
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Bacterial Respiratory Disease: Clinical
Manifestations (2)
 Assess disease severity (including signs of sepsis) and
arterial oxygenation in all patients
 Pneumonia Severity Index (PSI) appears valid for HIV-infected
patients
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June 2013
8
Bacterial Respiratory Disease:
Diagnosis
 Chest X ray:
Commonly shows
unilateral, focal,
segmental, or lobar
consolidation, but
may show atypical
presentations
(multilobar, nodular,
reticulonodular)
Chest X ray: pneumococcal pneumonia
showing right middle lobe consolidation
Credit: C. Daley, MD; HIV InSite
www.aidsetc.org
June 2013
9
Bacterial Respiratory Disease:
Diagnosis (2)
 CAP diagnosis and management guidelines apply to HIVinfected as well as HIV-uninfected patients
 Chest X ray: PA and lateral, if possible
 Consider the possibility of specific pathogens, eg:
 TB: if compatible clinical and X-ray presentation, manage as
potential TB, pending test results
 PCP: evaluate if clinically indicated (PCP may coexist with
bacterial pneumonia)
 P aeruginosa: if CD4 ≤50 cells/µL, preexisting lung disease,
neutropenia, on corticosteroids, recent hospitalization, or
residence in a health care facility
 S aureus: if recent influenza or other viral infection, history of
injection drug use, or severe bilateral necrotizing pneumonia
www.aidsetc.org
June 2013
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Bacterial Respiratory Disease:
Diagnosis (3)
 Microbiologic diagnosis allows targeted treatment of
specific pathogen(s)
 Test to identify specific pathogens that would significantly
alter standard (empirical) management decisions, if their
presence is suspected
 For patients well enough to be treated as outpatient: routine
testing for etiology is optional
 For hospitalized patients with suspected CAP: Gram stain
and culture of expectorated sputum specimen, 2 blood
cultures
 Gram stain and culture of expectorated sputum only if good quality
specimen as well as good lab performance measures
 Endotracheal aspirate sample for intubated patients
 Consider bronchoscopy with BAL lavage if differential includes
pathogens such as P jiroveci
www.aidsetc.org
June 2013
11
Bacterial Respiratory Disease:
Diagnosis (4)
 Microbiologic diagnosis
 Consider blood cultures for all:
 Higher rate of bacteremia in HIV-infected patients with CAP
 Higher risk of drug-resistant pneumococcal infection
 Blood culture has high specificity but low sensitivity
 Consider urinary antigen tests for L pneumophila and S
pneumoniae
 Consider diagnostic thoracentesis if pleural effusion
www.aidsetc.org
June 2013
12
Bacterial Respiratory Disease:
Preventing Exposure
 No effective means of reducing exposure to S
pneumoniae and H influenzae
www.aidsetc.org
June 2013
13
Bacterial Respiratory Disease:
Preventing Disease
 Pneumococcal vaccine:
 Recommended for all with HIV infection, regardless of CD4
count
 23-valent pneumococcal polysaccharide vaccine (PPV23)
 Multiple observational studies reported benefits including reduced
risk of pneumococcal bacteremia
 13-valent pneumococcal conjugate vaccine (PCV13)
 Recommended for use in adults with HIV or other
immunocompromising conditions
 7-valent PCV
 High efficacy against vaccine-type invasive pneumococcal disease
in one study
www.aidsetc.org
June 2013
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Bacterial Respiratory Disease:
Preventing Disease (2)
 Pneumococcal vaccination recommendations
 No previous pneumococcal vaccination
 Preferred:
 1 dose PCV13 followed by:
 If CD4 ≥200 cells/µL: PPV23 should be given ≥8 weeks after
PCV13
 If CD4 <200 cells/µL, PPV23 can be offered ≥8 weeks after
PCV13 or can await increase of CD4 to >200 cells/µL
 Alternative:
 1 dose PPV23
 Previous PPV23 vaccination
 1 dose of PCV13, to be given ≥1 year after last receipt of
PPV23
www.aidsetc.org
June 2013
15
Bacterial Respiratory Disease:
Preventing Disease (3)
 Pneumococcal vaccination recommendations (2)
 Revaccination
 Individuals who previously received PPV23
 Duration of protective effect of PPV23 is not known
 1 dose PPV23 recommended for age 19-64 years if ≥5 years since
1st dose of PPV
 Another dose of PPV23 for age ≥65 if ≥5 years since previous
PPV23
 Single dose of PCV13 should be given if ≥1 year since
previous PPV23
 Subsequent doses of PPV23 as above
 No more than 3 lifetime doses of PPV23
www.aidsetc.org
June 2013
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Bacterial Respiratory Disease:
Preventing Disease (4)
 Influenza vaccine:
 Recommended annually during influenza season
(bacterial pneumonia may occur as complication of
influenza)
 Live attenuated vaccine is contraindicated and is not
recommended for HIV-infected persons
www.aidsetc.org
June 2013
17
Bacterial Respiratory Disease:
Preventing Disease (5)
 H influenzae type B vaccine:
 Not usually recommended for adults, unless anatomic
or functional asplenia (low incidence of infection)
www.aidsetc.org
June 2013
18
Bacterial Respiratory Disease:
Preventing Disease (6)
 Antiretroviral therapy: reduces risk of bacterial
pneumonia
 TMP-SMX and macrolides: reduce frequency of
bacterial respiratory infections when given as
prophylaxis for PCP or MAC, respectively
 These should not be prescribed solely to prevent
bacterial respiratory infections
 Behavioral interventions:
 Cessation of smoking, injection drug use, alcohol use
www.aidsetc.org
June 2013
19
Bacterial Respiratory Infections:
Treatment
 Outpatient versus inpatient treatment:
 Severity of disease and CD4 count may both be
important
 Mortality higher with higher PSI class, with CD4 <200
cells/µL
 Some offer hospitalization to all CAP patients with CD4
<200 cells/µL and use PSI to guide decision in those
with CD4 >200 cells/µL
 Basic principles of treatment are same as those
for HIV uninfected
www.aidsetc.org
June 2013
20
Bacterial Respiratory Infections:
Treatment (2)
 Target most common pathogens, particularly S
pneumoniae and H influenzae
 Empiric treatment should be started promptly
 Specimens for diagnosis should be collected before
antibiotics are given
 Modify treatment, if indicated, based on microbiologic and
drug susceptibility results
 Fluoroquinolones should be used cautiously if TB
suspected but not being treated (risk of TB monotherapy)
 Empiric macrolide monotherapy cannot be routinely
recommended (risk of macrolide-resistant
S pneumoniae)
www.aidsetc.org
June 2013
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Bacterial Respiratory Infections:
Treatment (3)
 Outpatient treatment (empiric)
 Preferred:
 Oral beta-lactam + macrolide (azithromycin, clarithromycin)
 Preferred beta-lactams: high-dose amoxicillin or amoxicillin-clavulanate
 Alternative beta-lactams: cefpodoxime, cefuroxime
 Fluoroquinolone, especially if penicillin allergy
 Levofloxacin 750 mg PO QD
 Moxifloxacin 400 mg PO QD
 Alternative: beta-lactam + doxycycline
 Duration of therapy: 7-10 days for most; minimum 5 days
 Should be afebrile for 48-72 hours, clinically stable
www.aidsetc.org
June 2013
22
Bacterial Respiratory Infections:
Treatment (4)
 Hospitalized, non-ICU treatment (empiric)
 Preferred:
 IV beta-lactam + macrolide (azithromycin, clarithromycin)
 Preferred beta-lactams: ceftriaxone, cefotaxime, ampicillinsulbactam
 IV fluoroquinolone, especially if penicillin allergy
 Levofloxacin 750 mg IV QD
 Moxifloxacin 400 mg IV QD
 Alternative:
 IV beta-lactam + doxycycline
 IV penicillin for confirmed pneumococcal pneumonia
www.aidsetc.org
June 2013
23
Bacterial Respiratory Infections:
Treatment (5)
 Inpatient, ICU (empiric)
 Preferred:
 IV beta-lactam + IV azithromycin
 IV beta-lactam + (levofloxacin 750 mg IV QD or moxifloxacin
400 mg IV QD)
 Preferred beta-lactams: ceftriaxone, cefotaxime, ampicillinsulbactam
 Alternative:
 Penicillin allergy: aztreonam IV + IV levofloxacin or
moxifloxacin as above
www.aidsetc.org
June 2013
24
Bacterial Respiratory Infections:
Treatment (6)
 Most CAP pathogens can be treated with the
recommended regimens
 Exceptions: P aeruginosa and S aureus
(including community-acquired MRSA)
 Empiric coverage may be warranted, if either is
suspected
 Diagnostic tests (sputum Gram stain and culture) likely
to be of high yield
www.aidsetc.org
June 2013
25
Bacterial Respiratory Infections:
Treatment (7)
 Empiric Pseudomonas treatment
 Preferred: antipneumococcal antipseudomonal betalactam + (ciprofloxacin 400 mg IV Q8-12H or
levofloxacin 750 mg IV QD)
 Preferred beta-lactams: piperacillin-tazobactam, cefepime,
imipenem, meropenem
 Alternative:
 Beta-lactam as above + IV aminoglycoside + IV azithromycin
 Beta-lactam as above + IV aminoglycoside + (moxifloxacin 400
mg IV QD or levofloxacin 750 mg IV QD)
 Penicillin allergy: replace beta-lactam with aztreonam
www.aidsetc.org
June 2013
26
Bacterial Respiratory Infections:
Treatment (8)
 Empiric S aureus (including community-acquired
MRSA) treatment:
 Add vancomycin (IV) or linezolid (IV or PO) alone to the
antibiotic regimen
 For severe necrotizing pneumonia, consider addition of
clindamycin to vancomycin (not to linezolid), to
minimize bacterial toxin production
www.aidsetc.org
June 2013
27
Bacterial Respiratory Infections:
Treatment (9)
 When etiology of the pneumonia is identified,
modify antimicrobial therapy to target that
pathogen
 Consider switch from IV to PO therapy: when
improved clinically, able to tolerate PO
medications, have intact GI function
 Clinical stability: temperature <37.8°C, heart rate
<100/minute, respiratory rate <24/minute, SBP ≥90 mm
Hg, room air O2 saturation >90% or PaO2 >60 mm Hg
www.aidsetc.org
June 2013
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Bacterial Respiratory Infections:
Starting ART
 Initiate ART early in course of bacterial
pneumonia
 In one randomized study, early ART in setting of
OIs (including bacterial infections) decreased
AIDS progression and death
www.aidsetc.org
June 2013
29
Bacterial Respiratory Infections:
Monitoring and Adverse Events
 Clinical response typically seen within 48-72
hours after start of appropriate antimicrobial
therapy
 Advanced HIV, CD4 <100 cells/µL, S pneumoniae
infection prolonged the time to clinical stability (>7
days)
 Patients on ART had shorter time to clinical stability
 IRIS has not been described
www.aidsetc.org
June 2013
30
Bacterial Respiratory Infections:
Treatment Failure
 If worsening symptoms/signs or no improvement,
evaluate further for other infectious and
noninfectious causes
 Consider possibility of TB
www.aidsetc.org
June 2013
31
Bacterial Respiratory Infections:
Preventing Recurrence
 23-valent pneumococcal vaccine, as above
 Influenza vaccine during influenza season
 Antibiotic prophylaxis generally not
recommended to prevent bacterial respiratory
infections (potential for drug resistance and
toxicity)
www.aidsetc.org
June 2013
32
Bacterial Respiratory Infections:
Considerations in Pregnancy
 Diagnosis as in nonpregnant adults (abdominal
shielding during radiographic procedures)
 Management as in nonpregnant adults, except:
 Clarithromycin not recommended as first-line agent
(birth defects in animals); azithromycin recommended
when macrolide is indicated
 Quinolones may be used for serious infections when
indicated (no arthropathy or birth defects reported in
exposed human fetuses)
 Doxycycline not recommended (hepatoxicity,
staining of fetal teeth and bones)
www.aidsetc.org
June 2013
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Bacterial Respiratory Infections:
Considerations in Pregnancy (2)
 Management:
 Beta-lactams: no known teratogenicity or increased
toxicity
 Aminoglycosides: theoretical risk of fetal renal or eighth
nerve damage, but not documented in humans except
with streptomycin, kanamycin
 Linezolid: limited data; not teratogenic in animal studies
www.aidsetc.org
June 2013
34
Bacterial Respiratory Infections:
Considerations in Pregnancy (3)
 Increased risk of preterm labor and delivery
 If pneumonia after 20 weeks of gestation, monitor for
contractions
 Pneumococcal and influenza vaccines can be
administered
 Influenza vaccine recommended for all pregnant
women during influenza season
 During pregnancy, vaccines should be administered
after ART has been initiated, to minimize transient HIV
RNA increases that may be caused by vaccine
www.aidsetc.org
June 2013
35
Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
www.aidsetc.org
June 2013
36
About This Slide Set
 This presentation was prepared by Susa Coffey, MD,
for the AETC National Resource Center in June 2013
 See the AETC NRC website for the most current
version of this presentation: http://www.aidsetc.org
www.aidsetc.org
June 2013
37