Guidelines for Prevention and Treatment of Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults Opportunistic Infections in HIV-Infected Adults and Adolescentsand Adolescents

Bacterial Respiratory Disease Slide SetBacterial 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

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About This PresentationAbout 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Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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

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May 20132

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: EpidemiologyEpidemiology

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

May 20133

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Epidemiology Epidemiology (2)(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

May 20134

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Epidemiology Epidemiology (3)(3)

Organisms:

S pneumoniae Drug-resistant strains are increasingly

common

H influenzae

P aeruginosa

S aureus, including MRSA

Atypicals (infrequent)

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Clinical ManifestationsClinical 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

May 20136

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Clinical ManifestationsClinical Manifestations (2) (2)

Assess disease severity (including signs of sepsis) and arterial oxygenation in all patients Pneumonia Severity Index (PSI) appears valid for

HIV-infected patients

May 20137

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: DiagnosisDiagnosis

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

May 20138

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Diagnosis Diagnosis (2)(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

May 20139

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Diagnosis Diagnosis (3)(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

May 201310

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Diagnosis Diagnosis (4)(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

May 201311

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Preventing ExposurePreventing Exposure

No effective means of reducing exposure to S pneumoniae and H influenzae

May 201312

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Preventing DiseasePreventing 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

May 201313

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Preventing Disease Preventing Disease (2)(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

May 201314

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Preventing Disease Preventing Disease (3)(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

May 201315

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Preventing Disease Preventing Disease (4)(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

May 201316

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Preventing Disease Preventing Disease (5)(5)

H influenzae type B vaccine: Not usually recommended for adults, unless

anatomic or functional asplenia (low incidence of infection)

May 201317

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Bacterial Respiratory Disease:Bacterial Respiratory Disease: Preventing Disease Preventing Disease (6)(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

May 201318

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Bacterial Respiratory Infections:Bacterial Respiratory Infections: TreatmentTreatment

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

May 201319

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Bacterial Respiratory Infections:Bacterial Respiratory Infections: Treatment Treatment (2)(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-resistantS pneumoniae)

May 201320

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Bacterial Respiratory Infections:Bacterial Respiratory Infections:

Treatment Treatment (3)(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

May 201321

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Bacterial Respiratory Infections:Bacterial Respiratory Infections:

Treatment Treatment (4)(4) Hospitalized, non-ICU treatment (empiric) Preferred:

IV beta-lactam + macrolide (azithromycin, clarithromycin) Preferred beta-lactams: ceftriaxone, cefotaxime, ampicillin-

sulbactam 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

May 201322

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Bacterial Respiratory Infections:Bacterial Respiratory Infections: Treatment Treatment (5)(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, ampicillin-

sulbactam

Alternative: Penicillin allergy: aztreonam IV + IV levofloxacin or

moxifloxacin as above

May 201323

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Bacterial Respiratory Infections:Bacterial Respiratory Infections:

Treatment Treatment (6)(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

May 201324

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Bacterial Respiratory Infections:Bacterial Respiratory Infections:

Treatment Treatment (7)(7) Empiric Pseudomonas treatment Preferred: antipneumococcal antipseudomonal beta-

lactam + (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

May 201325

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Bacterial Respiratory Infections:Bacterial Respiratory Infections:

Treatment Treatment (8)(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

May 201326

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Bacterial Respiratory Infections:Bacterial Respiratory Infections:

Treatment Treatment (9)(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

May 201327

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Bacterial Respiratory Infections:Bacterial Respiratory Infections: Starting ARTStarting 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

May 201328

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Bacterial Respiratory Infections:Bacterial Respiratory Infections: Monitoring and Adverse EventsMonitoring 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

May 201329

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Bacterial Respiratory Infections:Bacterial Respiratory Infections:

Treatment FailureTreatment Failure If worsening symptoms/signs or no

improvement, evaluate further for other infectious and noninfectious causes Consider possibility of TB

May 201330

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Bacterial Respiratory Infections:Bacterial Respiratory Infections: Preventing RecurrencePreventing 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)

May 201331

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Bacterial Respiratory Infections:Bacterial Respiratory Infections: Considerations in PregnancyConsiderations 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)

May 201332

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Bacterial Respiratory Infections:Bacterial Respiratory Infections: Considerations in PregnancyConsiderations in Pregnancy (2)(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

May 201333

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Bacterial Respiratory Infections:Bacterial Respiratory Infections: Considerations in PregnancyConsiderations in Pregnancy (3)(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

May 201334

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Websites to Access the GuidelinesWebsites to Access the Guidelines

http://www.aidsetc.org

http://aidsinfo.nih.gov

May 201335

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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

About This Slide SetAbout This Slide Set

May 201336