Guidelines for Prevention and Treatment of Opportunistic Infections

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 Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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 CD 4 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 CD 4 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 In. Site 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 CD 4 ≤ 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 CD 4 count § 23 -valent pneumococcal polysaccharide vaccine (PPV 23) § Multiple observational studies reported benefits including reduced risk of pneumococcal bacteremia § 13 -valent pneumococcal conjugate vaccine (PCV 13) § 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 PCV 13 followed by: § If CD 4 ≥ 200 cells/µL: PPV 23 should be given ≥ 8 weeks after PCV 13 § If CD 4 <200 cells/µL, PPV 23 can be offered ≥ 8 weeks after PCV 13 or can await increase of CD 4 to >200 cells/µL § Alternative: § 1 dose PPV 23 § Previous PPV 23 vaccination § 1 dose of PCV 13, to be given ≥ 1 year after last receipt of PPV 23 14 May 2013 www. aidsetc. org

Bacterial Respiratory Disease: Preventing Disease (3) Pneumococcal vaccination recommendations (2) § Revaccination § Individuals who previously received PPV 23 § Duration of protective effect of PPV 23 is not known § 1 dose PPV 23 recommended for age 19 -64 years if ≥ 5 years since 1 st dose of PPV § Another dose of PPV 23 for age ≥ 65 if ≥ 5 years since previous PPV 23 § Single dose of PCV 13 should be given if ≥ 1 year since previous PPV 23 § Subsequent doses of PPV 23 as above § No more than 3 lifetime doses of PPV 23 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 CD 4 count may both be important § Mortality higher with higher PSI class, with CD 4 <200 cells/µL § Some offer hospitalization to all CAP patients with CD 4 <200 cells/µL and use PSI to guide decision in those with CD 4 >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 Q 8 -12 H 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 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 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 O 2 saturation >90% or Pa. O 2 >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, CD 4 <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