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Prevention and Treatment of Bacterial Infections in HIV-Infected Adults

This slide set provides guidelines for preventing and treating bacterial infections in HIV-infected adults, including information on epidemiology, clinical manifestations, diagnosis, and preventing exposure.

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Prevention and Treatment of Bacterial Infections in HIV-Infected Adults

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  1. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and AdolescentsBacterial Infections 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

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 • Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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

  3. Bacterial Infections • Bacterial respiratory infections • Bacterial enteric infections • Bartonellosis • Syphilis

  4. Bacterial Infections Bacterial Respiratory Infections

  5. 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 www.aidsetc.org

  6. 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

  7. Bacterial Respiratory Disease:Epidemiology (3) Organisms: • S pneumoniae • Drug-resistant strains are increasingly common • H influenzae • P aeruginosa • S aureus, including MRSA • Atypicals (infrequent) www.aidsetc.org

  8. 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

  9. 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 www.aidsetc.org

  10. 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

  11. 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 www.aidsetc.org

  12. 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

  13. 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

  14. Bacterial Respiratory Disease:Preventing Exposure • No effective means of reducing exposure to S pneumoniae and H influenzae www.aidsetc.org

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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 TBsuspected but not being treated (risk of TB monotherapy) • Empiric macrolide monotherapy cannot be routinely recommended (risk of macrolide-resistantS pneumoniae) www.aidsetc.org

  23. 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

  24. Bacterial Respiratory Infections:Treatment (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 www.aidsetc.org

  25. 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, ampicillin-sulbactam • Alternative: • Penicillin allergy: aztreonam IV + IV levofloxacin or moxifloxacin as above www.aidsetc.org

  26. 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

  27. Bacterial Respiratory Infections:Treatment (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 www.aidsetc.org

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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

  37. Bacterial Infections Bacterial Enteric Infections

  38. Bacterial Enteric Disease:Epidemiology • Higher incidence of gram-negative enteric infections among HIV-infected patients • Risk greatest if CD4 <200 cells/µL or AIDS • Risk decreased with ART • Most commonly cultured bacteria: • Salmonella • Shigella • Campylobacter • E coli • Clostridium difficile www.aidsetc.org

  39. Bacterial Enteric Disease:Epidemiology (2) • Source usually ingestion of contaminated food or water • Other risks: • Oral-fecal exposure through sexual activity (especially Shigellaand Campylobacter) • HIV-related alterations in mucosal immunity or intestinal integrity, gastric acid-blocking medications www.aidsetc.org

  40. Bacterial Enteric Disease:Clinical Manifestations • Three major clinical syndromes • Self-limited gastroenteritis • Diarrheal disease +/- fever, bloody diarrhea, weight loss, possible bacteremia • Bacteremia associated with extraintestinal involvement, with or without GI illness www.aidsetc.org

  41. Bacterial Enteric Disease:Clinical Manifestations (2) • Severe diarrhea: ≥6 loose stools per day, with our without other signs/symptoms • In HIV infection: • Greater risk of more serious illness with greater immunosuppression • Relapses may occur after treatment • Recurrent Salmonella bacteremia is an AIDS-defining illness www.aidsetc.org

  42. Bacterial Enteric Disease: Diagnosis • History: exposures; medication review; diarrhea frequency, volume, presence of blood; associated signs/symptoms (eg, fever) • Physical exam including temperature, assessment of hydration and nutritional status • Stool and blood cultures • Obtain blood cultures in patients with diarrhea and fever • Routine stool culture may not identify non-jejuni non-coliCampylobacter species; request special testingfor these if initial evaluation is unrevealing www.aidsetc.org

  43. Bacterial Enteric Disease: Diagnosis (2) • C difficiletoxin or PCR • If recent or current antibiotic exposure, cancer chemotherapy, recent hospitalization, residence in long-term care facility, CD4 <200 cells/µL, acid-suppressive medications, moderate-severe community-acquired diarrhea • Endoscopy • If stool studies and blood culture are nondiagnostic, or if treatment for an established diagnosis fails • May diagnose nonbacterial causes (eg, parasites, CMV, MAC, noninfectious causes) • Consider STDs (eg, rectal infections caused by lymphogranuloma venereum or N gonorrhoeae) www.aidsetc.org

  44. Bacterial Enteric Disease: Preventing Exposure Advice to patients: • Handwashing: • After potential contact with feces, pets or other animals, gardening/ contact with soil; before preparing food, eating; before and after sex • For prevention of enteric infection, soap and water preferred over alcohol-based cleansers (these do not kill C difficile spores, are partly active against norovirus and Cryptosporidium) • Sex: • Avoid unprotected sexual practices that might result in oral exposure to feces www.aidsetc.org

  45. Bacterial Enteric Disease: Preventing Disease • Antimicrobial prophylaxis usually not recommended, including for travellers • Risk of adverse reactions, resistant organisms, C difficile infection • Can be considered in rare cases, depending on level of immunosuppression and the region and duration of travel • Fluoroquinolone (FQ) or rifaximin • TMP-SMX may give limited protection (eg, if pregnant or already taking for PCP prophylaxis) www.aidsetc.org

  46. Bacterial Enteric Disease: Treatment • Treatments usually the same as in HIV-uninfected patients • Give oral or IV rehydration if indicated • Advise bland diet and avoidance of fat, dairy, and complex carbohydrates • Effectiveness and safety of probiotics or antimotility agents not adequately studied in HIV-infected patients • Avoid antimotility agents if concern about inflammatory diarrhea www.aidsetc.org

  47. Bacterial Enteric Disease: Treatment (2) Empiric Therapy • CD4 count and clinical status guide initiation and duration of empiric antibiotics, eg: • CD4 count >500 cells/µL with mild symptoms: only rehydration may be needed • CD4 count 200-500 cells/µL and symptoms that compromise quality of life: consider short course of antibiotics • CD4 count <200 cells/µL with severe diarrhea, bloody stool, or fevers/chills: diagnostic evaluation and antibiotics www.aidsetc.org

  48. Bacterial Enteric Disease: Treatment (3) Empiric Therapy (cont.) • Preferred: ciprofloxacin 500-750 mg PO (or 400 mg IV) Q12H • Alternative: ceftriaxone 1 g IV Q24H or cefotaxime 1 g IV Q8H • Adjust therapy based on study results • Traveler’s diarrhea: consider possibility of antibiotic resistance www.aidsetc.org

  49. Bacterial Enteric Disease: Treatment (4)Salmonella spp. • In HIV infection, treatment recommended, because of high risk of bacteremia and mortality in HIV-infected patients • Preferred: • Ciprofloxacin 500-750 mg PO (or 400 mg IV) Q12H • Alternative: • Levofloxacin750 mg PO or IV Q24H • Moxifloxacin 400 mg PO or IV Q24H • TMP-SMX PO or IV, if susceptible • Ceftriaxone (IV) or cefotaxime (IV), if susceptible www.aidsetc.org

  50. Bacterial Enteric Disease: Treatment (5)Salmonella spp. (cont.) • Optimal duration of therapy not defined • Gastroenteritis without bacteremia • CD4 count ≥200 cells/µL: 7-14 days • CD4 count <200 cells/µL: 2-6 weeks • Gastroenteritis with bacteremia • CD4 count ≥200 cells/µL:14 days, longer if persistent bacteremia or complicated infection • CD4 count <200 cells/µL: 2-6 weeks • If bacteremia, monitor closely for recurrence (eg, bacteremia or localized infection) www.aidsetc.org

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