Transcript Treating Opportunistic Infections Among HIV

Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected Adults
and Adolescents
Bacterial Respiratory Disease Slide Set
Prepared by the AETC National 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become out of date quickly.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
2
May 2013
www.aidsetc.org
Bacterial Respiratory Disease:
Epidemiology
 Bacterial pneumonia is a common cause of
HIV-related 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
3
May 2013
www.aidsetc.org
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
4
May 2013
www.aidsetc.org
Bacterial Respiratory Disease:
Epidemiology (3)
Organisms:
 S pneumoniae
 Drug-resistant strains are increasingly
common
 H influenzae
 P aeruginosa
 S aureus, including MRSA
 Atypicals (infrequent)
5
May 2013
www.aidsetc.org
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
6
May 2013
www.aidsetc.org
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
7
May 2013
www.aidsetc.org
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
8
May 2013
www.aidsetc.org
Bacterial Respiratory Disease:
Diagnosis (2)
 CAP diagnosis and management guidelines apply to
HIV-infected 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
9
May 2013
www.aidsetc.org
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
10
May 2013
www.aidsetc.org
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
11
May 2013
www.aidsetc.org
Bacterial Respiratory Disease:
Preventing Exposure
 No effective means of reducing exposure
to S pneumoniae and H influenzae
12
May 2013
www.aidsetc.org
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
13
May 2013
www.aidsetc.org
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
14
May 2013
www.aidsetc.org
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
15
May 2013
www.aidsetc.org
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
16
May 2013
www.aidsetc.org
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)
17
May 2013
www.aidsetc.org
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
18
May 2013
www.aidsetc.org
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
19
May 2013
www.aidsetc.org
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)
20
May 2013
www.aidsetc.org
Bacterial Respiratory Infections:
Treatment (3)
 Outpatient treatment (empiric)
 Preferred:
 Oral beta-lactam + macrolide (azithromycin, clarithromycin)
 Preferred beta-lactams: high-dose amoxicillin or amoxicillinclavulanate
 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
21
May 2013
www.aidsetc.org
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
22
May 2013
www.aidsetc.org
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
23
May 2013
www.aidsetc.org
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
24
May 2013
www.aidsetc.org
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
25
May 2013
www.aidsetc.org
Bacterial Respiratory Infections:
Treatment (8)
 Empiric S aureus (including communityacquired 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
26
May 2013
www.aidsetc.org
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
27
May 2013
www.aidsetc.org
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
28
May 2013
www.aidsetc.org
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
29
May 2013
www.aidsetc.org
Bacterial Respiratory Infections:
Treatment Failure
 If worsening symptoms/signs or no
improvement, evaluate further for other
infectious and noninfectious causes
 Consider possibility of TB
30
May 2013
www.aidsetc.org
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)
31
May 2013
www.aidsetc.org
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)
32
May 2013
www.aidsetc.org
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
33
May 2013
www.aidsetc.org
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
34
May 2013
www.aidsetc.org
Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
35
May 2013
www.aidsetc.org
About This Slide Set
 This presentation was prepared by Susa Coffey,
MD, for the AETC National Resource Center in
May 2013.
 See the AETC NRC website for the most current
version of this presentation:
http://www.aidsetc.org
36
May 2013
www.aidsetc.org