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Prepared by the AETC National Coordinating Resource Center based on recommendations from Prepared by the AETC National Coordinating Resource Center based on recommendations from

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Prepared by the AETC National Coordinating Resource Center based on recommendations from - PPT Presentation

National Institutes of Health and HIV Medicine AssociationInfectious Diseases Society of America Guidelines for Prevention and Treatment of Opportunistic Infections in HIVInfected Adults and Adolescents ID: 731631

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Slide1

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

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

Bacterial Infections Slide SetSlide2

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Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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 Centerhttp://www.aidsetc.org

About This Presentation

June 2013

www.aidsetc.org

2Slide3

Bacterial respiratory infections Bacterial enteric infections

Bartonellosis

Syphilis Bacterial Infections

June 2013

www.aidsetc.org

3Slide4

EpidemiologyClinical Manifestations

Diagnosis

PreventionTreatmentConsiderations in Pregnancy

Bacterial Respiratory Infections

June 2013

www.aidsetc.org

4Slide5

Bacterial pneumonia is a common cause of HIV-related morbidityIn HIV-infected persons:Higher rates of bacterial pneumoniaHigher mortality

Increased incidence of bacteremia (esp. with S pneumoniae)

Can occur at any CD4 count or stage of diseaseRecurrent pneumonia (≥2 episodes in 1 year) is an AIDS-defining conditionBacterial Respiratory Disease: EpidemiologyJune 2013

www.aidsetc.org

5Slide6

Incidence lower with use of ARTRisk factors include Low CD4 count (<200 cells/µL)No or intermittent use of ARTCigarette smokingInjection drug use

Chronic viral hepatitis

Bacterial Respiratory Disease: Epidemiology (2)June 2013

www.aidsetc.org

6Slide7

Organisms:S pneumoniaeDrug-resistant strains are increasingly commonH influenzaeP aeruginosaS aureus, including MRSAAtypicals (infrequent)

Bacterial Respiratory Disease: Epidemiology (3)

June 2013www.aidsetc.org

7Slide8

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 effusionWBC usually elevated, may see left shift

Bacterial Respiratory Disease: Clinical Manifestations

June 2013www.aidsetc.org

8Slide9

Assess disease severity (including signs of sepsis) and arterial oxygenation in all patientsPneumonia Severity Index (PSI) appears valid for HIV-infected patientsBacterial Respiratory Disease: Clinical Manifestations (2)

June 2013

www.aidsetc.org

9Slide10

June 2013www.aidsetc.org

10

Chest X ray: pneumococcal pneumonia showing right middle lobe consolidation

Credit: C. Daley, MD; HIV InSite

Chest X ray:

Commonly shows unilateral, focal, segmental, or lobar consolidation, but may show atypical presentations (

multilobar

, nodular,

reticulonodular

)

Bacterial Respiratory Disease: DiagnosisSlide11

CAP diagnosis and management guidelines apply to HIV-infected as well as HIV-uninfected patientsChest X ray: PA and lateral, if possibleConsider 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 facilityS aureus: if recent influenza or other viral infection, history of injection drug use, or severe bilateral necrotizing pneumoniaBacterial Respiratory Disease: Diagnosis (2)

June 2013

www.aidsetc.org

11Slide12

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 suspectedFor 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 measuresEndotracheal aspirate sample for intubated patientsConsider bronchoscopy with BAL lavage if differential includes pathogens such as P jiroveciBacterial Respiratory Disease: Diagnosis (3)

June 2013

www.aidsetc.org

12Slide13

Microbiologic diagnosisConsider blood cultures for all: Higher rate of bacteremia in HIV-infected patients with CAPHigher risk of drug-resistant pneumococcal infectionBlood culture has high specificity but low sensitivity

Consider urinary antigen tests for L pneumophila and S pneumoniae

Consider diagnostic thoracentesis if pleural effusionBacterial Respiratory Disease: Diagnosis (4)June 2013

www.aidsetc.org

13Slide14

No effective means of reducing exposure to S pneumoniae and H influenzaeBacterial Respiratory Disease: Preventing Exposure

June 2013

www.aidsetc.org14Slide15

Pneumococcal vaccine:Recommended for all with HIV infection, regardless of CD4 count23-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 conditions7-valent PCV High efficacy against vaccine-type invasive pneumococcal disease in one studyBacterial Respiratory Disease: Preventing Disease

June 2013

www.aidsetc.org

15Slide16

Pneumococcal vaccination recommendations No previous pneumococcal vaccinationPreferred: 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/µLAlternative:1 dose PPV23Previous PPV23 vaccination1 dose of PCV13, to be given ≥1 year after last receipt of PPV23 Bacterial Respiratory Disease: Preventing Disease (2)

June 2013

www.aidsetc.org

16Slide17

Pneumococcal vaccination recommendations (2)RevaccinationIndividuals who previously received PPV23Duration 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 PPV23Single dose of PCV13 should be given if ≥1 year since previous PPV23Subsequent doses of PPV23 as aboveNo more than 3 lifetime doses of PPV23Bacterial Respiratory Disease: Preventing Disease (3)

June 2013

www.aidsetc.org

17Slide18

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

Bacterial Respiratory Disease: Preventing Disease (4)

June 2013www.aidsetc.org

18Slide19

H influenzae type B vaccine: Not usually recommended for adults, unless anatomic or functional asplenia (low incidence of infection) Bacterial Respiratory Disease: Preventing Disease (5)

June 2013

www.aidsetc.org

19Slide20

Antiretroviral therapy: reduces risk of bacterial pneumoniaTMP-SMX and macrolides: reduce frequency of bacterial respiratory infections when given as prophylaxis for PCP or MAC, respectivelyThese should not be prescribed solely to prevent bacterial respiratory infectionsBehavioral interventions:

Cessation of smoking, injection drug use, alcohol use

Bacterial Respiratory Disease: Preventing Disease (6)June 2013

www.aidsetc.org

20Slide21

Outpatient versus inpatient treatment: Severity of disease and CD4 count may both be importantMortality higher with higher PSI class, with CD4 <200 cells/µLSome 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

Bacterial Respiratory Infections: TreatmentJune 2013

www.aidsetc.org

21Slide22

Target most common pathogens, particularly S pneumoniae and H influenzaeEmpiric treatment should be started promptlySpecimens for diagnosis should be collected before antibiotics are givenModify 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)Bacterial Respiratory Infections: Treatment (2)

June 2013

www.aidsetc.org

22Slide23

Outpatient treatment (empiric)Preferred: Oral beta-lactam + macrolide (azithromycin, clarithromycin)Preferred beta-lactams: high-dose amoxicillin or amoxicillin-clavulanateAlternative beta-lactams: cefpodoxime, cefuroxime

Fluoroquinolone, especially if penicillin allergy

Levofloxacin 750 mg PO QDMoxifloxacin 400 mg PO QDAlternative: beta-lactam + doxycyclineDuration of therapy: 7-10 days for most; minimum 5 daysShould be afebrile for 48-72 hours, clinically stable

Bacterial Respiratory Infections: Treatment (3)

June 2013

www.aidsetc.org

23Slide24

Hospitalized, non-ICU treatment (empiric)Preferred: IV beta-lactam + macrolide (azithromycin, clarithromycin)Preferred beta-lactams: ceftriaxone, cefotaxime, ampicillin-sulbactamIV fluoroquinolone, especially if penicillin allergy

Levofloxacin 750 mg IV QD

Moxifloxacin 400 mg IV QDAlternative: IV beta-lactam + doxycyclineIV penicillin for confirmed pneumococcal pneumoniaBacterial Respiratory Infections: Treatment (4)

June 2013

www.aidsetc.org

24Slide25

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 aboveBacterial Respiratory Infections: Treatment (5)June 2013

www.aidsetc.org

25Slide26

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 suspectedDiagnostic tests (sputum Gram stain and culture) likely to be of high yield

Bacterial Respiratory Infections:

Treatment (6)June 2013www.aidsetc.org

26Slide27

Empiric Pseudomonas treatmentPreferred: antipneumococcal antipseudomonal beta-lactam + (ciprofloxacin 400 mg IV Q8-12H or levofloxacin 750 mg IV QD)Preferred beta-lactams: piperacillin-tazobactam, cefepime, imipenem, meropenemAlternative: 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 aztreonamBacterial Respiratory Infections: Treatment (7)June 2013

www.aidsetc.org

27Slide28

Empiric S aureus (including community-acquired MRSA) treatment:Add vancomycin (IV) or linezolid (IV or PO) alone to the antibiotic regimenFor severe necrotizing pneumonia, consider addition of clindamycin to vancomycin (not to linezolid), to minimize bacterial toxin production

Bacterial Respiratory Infections:

Treatment (8)June 2013www.aidsetc.org

28Slide29

When etiology of the pneumonia is identified, modify antimicrobial therapy to target that pathogenConsider switch from IV to PO therapy: when improved clinically, able to tolerate PO medications, have intact GI functionClinical 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

Bacterial Respiratory Infections:

Treatment (9)June 2013

www.aidsetc.org

29Slide30

Initiate ART early in course of bacterial pneumoniaIn one randomized study, early ART in setting of OIs (including bacterial infections) decreased AIDS progression and deathBacterial Respiratory Infections:

Starting ART

June 2013www.aidsetc.org

30Slide31

Clinical response typically seen within 48-72 hours after start of appropriate antimicrobial therapyAdvanced HIV, CD4 <100 cells/µL, S pneumoniae infection prolonged the time to clinical stability (>7 days)Patients on ART had shorter time to clinical stabilityIRIS has not been described

Bacterial Respiratory Infections:

Monitoring and Adverse EventsJune 2013www.aidsetc.org

31Slide32

If worsening symptoms/signs or no improvement, evaluate further for other infectious and noninfectious causesConsider possibility of TB

Bacterial Respiratory Infections:

Treatment FailureJune 2013www.aidsetc.org

32Slide33

23-valent pneumococcal vaccine, as aboveInfluenza vaccine during influenza seasonAntibiotic prophylaxis generally not recommended to prevent bacterial respiratory infections (potential for drug resistance and toxicity)

Bacterial Respiratory Infections:

Preventing RecurrenceJune 2013www.aidsetc.org

33Slide34

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 indicatedQuinolones 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)Bacterial Respiratory Infections: Considerations in Pregnancy June 2013

www.aidsetc.org

34Slide35

Management:Beta-lactams: no known teratogenicity or increased toxicityAminoglycosides: theoretical risk of fetal renal or eighth nerve damage, but not documented in humans except with streptomycin, kanamycinLinezolid: limited data; not teratogenic in animal studies

Bacterial Respiratory Infections: Considerations in Pregnancy (2)

June 2013www.aidsetc.org

35Slide36

Increased risk of preterm labor and deliveryIf pneumonia after 20 weeks of gestation, monitor for contractionsPneumococcal and influenza vaccines can be administeredInfluenza vaccine recommended for all pregnant women during influenza seasonDuring pregnancy, vaccines should be administered after ART has been initiated, to minimize transient HIV RNA increases that may be caused by vaccine

Bacterial Respiratory Infections: Considerations in Pregnancy (3)

June 2013

www.aidsetc.org

36Slide37

EpidemiologyClinical Manifestations

Diagnosis

PreventionTreatmentConsiderations in Pregnancy

Bacterial Enteric Infections

June 2013

www.aidsetc.org

37Slide38

Higher incidence of gram-negative enteric infections among HIV-infected patientsRisk greatest if CD4 <200 cells/µL or AIDSRisk decreased with ARTMost commonly cultured bacteria:Salmonella

Shigella

CampylobacterE coliClostridium difficileBacterial Enteric Disease: EpidemiologyJune 2013

www.aidsetc.org

38Slide39

Source usually ingestion of contaminated food or water Other risks: Oral-fecal exposure through sexual activity (especially Shigella and Campylobacter)HIV-related alterations in mucosal immunity or intestinal integrity, gastric acid-blocking medications

Bacterial Enteric Disease: Epidemiology (2)

June 2013www.aidsetc.org

39Slide40

Three major clinical syndromesSelf-limited gastroenteritisDiarrheal disease +/- fever, bloody diarrhea, weight loss, possible bacteremiaBacteremia associated with extraintestinal involvement, with or without GI illness

Bacterial Enteric Disease:

Clinical ManifestationsJune 2013www.aidsetc.org

40Slide41

Severe diarrhea: ≥6 loose stools per day, with our without other signs/symptomsIn HIV infection:Greater risk of more serious illness with greater immunosuppressionRelapses may occur after treatmentRecurrent Salmonella bacteremia is an AIDS-defining illness

Bacterial Enteric Disease:

Clinical Manifestations (2)June 2013

www.aidsetc.org

41Slide42

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

Bacterial Enteric Disease: Diagnosis

June 2013www.aidsetc.org

42Slide43

Stool and blood culturesObtain blood cultures in patients with diarrhea and feverRoutine stool culture may not identify non-jejuni

non-coli Campylobacter species; request special testing

for these if initial evaluation is unrevealingAntibiotic susceptibility should be performed on all stool samples Increased rates of resistant and multidrug-resistant Enterobacteriaceae, especially outside the U.S.Consider possible resistance when prescribing empiric treatment for persons who develop diarrhea or systemic infection while traveling or returning to the U.S.

Bacterial Enteric Disease: Diagnosis (2)

June 2013

www.aidsetc.org

43Slide44

C difficile toxin or PCRIf 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 diarrheaEndoscopyIf 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)Bacterial Enteric Disease: Diagnosis (3)

June 2013

www.aidsetc.org

44Slide45

Advice to patients:Handwashing: After potential contact with feces, pets or other animals, gardening or contact with soil; before preparing food, eating; before and after sexFor 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 resultin oral exposure to feces Bacterial Enteric Disease: Preventing Exposure

June 2013

www.aidsetc.org

45Slide46

Antimicrobial prophylaxis usually not recommended, including for travellersRisk of adverse reactions, resistant organisms, C difficile infectionCan be considered in rare cases, depending on level of immunosuppression and the region and duration of travelFluoroquinolone (FQ) or rifaximin

TMP-SMX may give limited protection (eg, if pregnant or already taking for PCP prophylaxis)

Bacterial Enteric Disease: Preventing DiseaseJune 2013

www.aidsetc.org

46Slide47

Treatments usually the same as in HIV-uninfected patientsGive oral or IV rehydration if indicatedAdvise bland diet and avoidance of fat, dairy, and complex carbohydratesEffectiveness and safety of probiotics or antimotility agents not adequately studied in HIV-infected patients

Avoid antimotility agents if concern about inflammatory diarrhea

Bacterial Enteric Disease: TreatmentJune 2013www.aidsetc.org

47Slide48

Empiric TherapyCD4 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; empiric treatment with ciprofloxacin is reasonableBacterial Enteric Disease: Treatment (2)

June 2013

www.aidsetc.org

48Slide49

Empiric Therapy (cont.)Preferred: ciprofloxacin 500-750 mg PO (or 400 mg IV) Q12HAlternative: ceftriaxone 1 g IV Q24H or cefotaxime 1 g IV Q8HAdjust therapy based on study results

Traveler

’s diarrhea: antibiotic resistance is common outside the U.S.Consider this when prescribing enteric antibiotics (esp. in travelers to South and Southeast Asia)Bacterial Enteric Disease: Treatment (3)

June 2013

www.aidsetc.org

49Slide50

In HIV infection, treatment recommended, because of high risk of bacteremia and mortality Preferred: Ciprofloxacin 500-750 mg PO (or 400 mg IV) Q12HAlternative: Levofloxacin 750 mg PO or IV Q24H

Moxifloxacin 400 mg PO or IV Q24H

TMP-SMX 160/800 mg PO or IV Q12H, if susceptibleCeftriaxone 1 g IV Q24H or cefotaxime 1 g IV Q8H, if susceptibleBacterial Enteric Disease: Treatment (4) Salmonella spp.June 2013

www.aidsetc.org

50Slide51

Optimal duration of therapy not definedGastroenteritis without bacteremiaCD4 count ≥200 cells/µL: 7-14 daysCD4 count <200 cells/µL: 2-6 weeks

Gastroenteritis with bacteremia

CD4 count ≥200 cells/µL:14 days, longer if persistent bacteremia or complicated infectionCD4 count <200 cells/µL: 2-6 weeksIf bacteremia, monitor closely for recurrence (eg, bacteremia or localized infection) Bacterial Enteric Disease: Treatment (5) Salmonella spp. (cont.)

June 2013

www.aidsetc.org

51Slide52

Treatment recommended, to shorten duration and possibly prevent transmissionPreferred: Ciprofloxacin 500-750 mg PO or 400 mg IV Q12HAlternative (depending on susceptibilities):

Levofloxacin 750 mg PO or IV Q24H

Moxifloxacin 400 mg PO or IV Q24HTMP-SMX 160/800 mg PO or IV Q12H Azithromycin 500 mg PO QD for 5 days (not recommended if bacteremia)Cipro resistance reported, associated with MSM, homelessness, international travel; azithro resistance reported in HIV-infected MSM; high rate of TMP-SMX resistance in infections acquired outside the U.S.

Bacterial Enteric Disease: Treatment (6) Shigella

spp.June 2013

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52Slide53

Duration of therapyGastroenteritis: 7-10 days (5 days for azithromycin)Bacteremia: ≥14 days is reasonableRecurrent infection: up to 6 weeks

Bacterial Enteric Disease: Treatment (7)

Shigella spp. (cont.)June 2013www.aidsetc.org

53Slide54

Optimal treatment in HIV poorly definedCulture and susceptibility recommended Rates of resistance to FQs and azithromycin differ by Campylobacter species

Bacterial Enteric Disease: Treatment (8) Campylobacter spp.

June 2013www.aidsetc.org

54Slide55

Mild disease and CD4 >200 copies/µL: some clinicians withhold antibiotics unless symptoms persist > several daysMild-moderate disease (if susceptible)Preferred Ciprofloxacin 500-750 mg PO or 400 mg IV Q12H

Azithromycin 500 mg PO QD (not recommended if bacteremia)

Alternative (depending on susceptibilities):Levofloxacin 750 mg PO or IV Q24HMoxifloxacin 400 mg PO or IV Q24HBacteremia: ciprofloxacin 500-750 mg PO or 400 mg IV Q12H + aminoglycosideBacterial Enteric Disease: Treatment (9) Campylobacter spp.

June 2013

www.aidsetc.org

55Slide56

Duration of therapyGastroenteritis: 7-10 days (5 days for azithromycin)Bacteremia: ≥14 daysRecurrent bacteremic disease: 2-6 weeks

Bacterial Enteric Disease: Treatment (10) Campylobacter spp. (cont.)

June 2013www.aidsetc.org

56Slide57

Treatment as in HIV-uninfected patientsVancomycin recommended over metronidazole, with possible exception of mild C difficile infectionBacterial Enteric Disease: Treatment (11) C difficile

June 2013

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57Slide58

ART expected to decrease risk of recurrent Salmonella, Shigella, and Campylobacter infectionsFollow standard guidelinesConsider patient’s ability to ingest and absorb ARV medicationsConsider prompt ART initiation if Salmonella bacteremia, regardless of CD4 count (should not be delayed)

Bacterial Enteric Disease: Initiating ART

June 2013

www.aidsetc.org

58Slide59

Monitor closely for treatment responseFollow-up stool culture not required if clinical symptoms and diarrhea resolveMay be required if public health considerations and state law dictateIRIS has not been described

Bacterial Enteric Disease: Monitoring and Adverse Effects

June 2013www.aidsetc.org

59Slide60

Consider follow-up stool culture if lack of response to appropriate antibiotic therapyLook for other enteric pathogens including C difficile; antibiotic resistanceConsider malabsorption of antibiotics: Avoid coadministration of FQs with Mg- or Al-containing antacids, or with calcium, zinc, or iron (they interfere with FQ absorption

Use IV antibiotics if patient is clinically unstable

Bacterial Enteric Disease: Treatment FailureJune 2013

www.aidsetc.org

60Slide61

Salmonella Consider secondary prophylaxis for patients with recurrent Salmonella bacteremia; also might consider for those with recurrent gastroenteritis (with or without bacteremia) and in those with CD4 count <200 cells/µL and severe diarrheaThis approach is not well established; weigh benefits and risks

ART appears to reduce risk of recurrence

Consider stopping secondary prophylaxis if Salmonella infection is resolved, patient is on ART with viral suppression and CD4 count >200 cells/µLBacterial Enteric Disease: Preventing RecurrenceJune 2013

www.aidsetc.org

61Slide62

ShigellaChronic suppressive therapy not recommended for first-time infectionsRecurrent infections: extend antibiotic treatment for up to 6 weeksART expected to decrease recurrenceCampylobacter

Chronic suppressive therapy not recommended for first-time infections

Recurrent infections: extend antibiotic treatment for 2-6 weeksART expected to decrease recurrenceBacterial Enteric Disease: Preventing Recurrence (2)June 2013

www.aidsetc.org

62Slide63

Diagnosis as with nonpregnant womenManagement as with nonpregnant

adults, except:

Expanded-spectrum cephalosporins or azithromycin should be first-line therapy for bacterial enteric infections (depending on organism and susceptibility testing)FQs can be used if indicated by susceptibility testing or failure of first-line therapy (arthropathy in animals; no increased risk of arthropathy or birth defects in humans after in utero exposure)Avoid TMP-SMX in 1st trimester (associated with increased risk of birth defects, but recent review supports use if indicated)

Sulfa therapy near delivery may increase risk to newborn of hyperbilirubinemia and kernicterusRifaximin

can be used as with nonpregnant women

Bacterial Enteric Disease: Considerations in Pregnancy

June 2013

www.aidsetc.org

63Slide64

EpidemiologyClinical Manifestations

Diagnosis

PreventionTreatmentConsiderations in Pregnancy

Bartonellosis

June 2013

www.aidsetc.org

64Slide65

June 2013

www.aidsetc.org

65

Bartonella spp. cause variety of infections, including cat-scratch disease, retinitis, trench fever, relapsing bacteremia, endocarditis

In immunocompromised: also bacillary angiomatosis (BA) and peliosis hepatis

BA usually caused by B henselae or B quintana

Typically occurs late in HIV infection; median CD4 count <50 cells/µL

B henselae linked to cat scratches from cats infested with fleas, cat fleas

B quintana associated with louse infestation

Bartonellosis: EpidemiologySlide66

June 2013

www.aidsetc.org

66

In HIV-infected persons, symptoms often chronic (months-years)

May involve nearly any organ system

BA of the skin: papular red vascular lesions, subcutaneous nodules; may resemble Kaposi sarcoma or pyogenic granuloma

Osteomyelitis (lytic lesions)

Peliosis hepatica (B henselae)

Endocarditis

Systemic symptoms of fever, sweats, weight loss, fatigue, malaise

Bartonellosis: Clinical ManifestationsSlide67

June 2013www.aidsetc.org

67

Skin lesions of

Bartonella

Credit: P

. Volberding, MD, UCSF Center for HIV Information Image Library

Skin lesions of

Bartonella

(2)

Credit: G

. Beatty, MD; A.

Lukusa

, MD, HIV

InSite

Bartonellosis

: Clinical Manifestations (2)Slide68

Tissue biopsy: histopathologic examinationSerologic tests (available through the CDC and some state health labs)Up to 25% of patients with advanced HIV infection and positive blood cultures for Bartonella may not develop antibodiesAntibody levels can indicate resolution and recrudescence of infection

Blood culture

PCR not widely availableBartonellosis: DiagnosisJune 2013

www.aidsetc.org

68Slide69

If CD4 count <100 cells/µL, high risk of severe disease if infected by B quintana or B henselaeAdvice to patients:

B

quintanaConsider risks of contact with cats If acquiring a cat: cat should be >1 year of age, in good health, free of fleasAvoid cats with fleas, stray catsAvoid cat scratchesAvoid contact with flea feces Control fleasB henselae

Eradicate body lice, if present

Bartonellosis: Preventing Exposure

June 2013

www.aidsetc.org

69Slide70

Primary chemoprophylaxis not recommendedMacrolide or rifamycin was protective in a retrospective case-control studyBartonellosis: Preventing Disease

June 2013

www.aidsetc.org70Slide71

No randomized controlled trials in HIV-infected patientsBA, peliosis hepatica, bacteremia, osteomyelitisPreferred: Doxycycline 100 mg PO or IV Q12H

Erythromycin 500 mg PO or IV Q6H

Alternative: Azithromycin 500 mg PO QD Clarithromycin 500 mg PO BIDDuration: at least 3 monthsBartonella Infection: Treatment

June 2013

www.aidsetc.org

71Slide72

CNS infectionsPreferred: doxycycline 100 mg PO or IV Q12H +/− rifampin 300 mg PO or IV Q12HEndocarditis (confirmed Bartonella)Doxycycline 100 mg IV Q12H + gentamicin 1 mg/kg IV Q8H x 2 weeks, then doxycycline 100 mg IV or PO Q12H

If renal insufficiency: doxycycline 100 mg IV Q12H + rifampin 300 mg IV or PO Q12H x 2 weeks, then doxycycline 100 mg PO Q12H

Other severe infectionsDoxycycline 100 mg PO or IV Q12H + rifampin 300 mg PO or IV Q12HErythromycin 500 mg PO or IV Q6H + rifampin 300 mg PO or IV Q12H

Bartonella Infection: Treatment (2)

June 2013

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72Slide73

Bartonella CNS or ophthalmic lesions: if not on ART, probably should treat with doxycycline + a rifamycin for 2-4 weeks before initiating ART Bartonellosis: Starting ART

June 2013

www.aidsetc.org73Slide74

Check Bartonella IgG titer at diagnosis and (if positive) every 6-8 weeks until 4-fold decreaseOral doxycycline: risk of pill-associated ulcerative esophagitisRifamycins have significant interactions with many ARVs; some combinations must be avoidedIRIS has not been described

Bartonellosis

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Consider alternative second-line regimens (above)

If positive or increasing Ab titer, treat until a 4-fold decrease

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Secondary prophylaxis:

In case of relapse after ≥3 months of treatment, long-term suppression is recommended while CD4 count <200 cells/µL: doxycycline or macrolide

Discontinuing suppressive therapy:

After 3-4 months of therapy and CD4 count >200 cells/µL for ≥6 months; some also require a 4-fold decrease in Bartonella titers

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No data on Bartonella infections during pregnancy in HIV-infected women; in HIV-negative women, B bacilliformis associated with increased complications and risk of death

Diagnosis as in nonpregnant women

Treatment: erythromycin recommended; avoid tetracyclines (hepatotoxicity and staining of fetal teeth)

Alternative: 3rd-generation cephalosporins (1st- and 2nd-generation cephalosporins not effective against Bartonella)

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EpidemiologyClinical Manifestations

Diagnosis

PreventionTreatmentConsiderations in Pregnancy

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Caused by Treponema pallidumAssociated with increased risk of HIV sexual acquisition and transmissionIncreased incidence in men who have sex with menHIV infection may somewhat alter diagnosis, natural history, and management of syphilis, but principles of management are the same with or without HIV infection

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HIV may make clinical lesions more apparent and accelerate progression of syphilisPrimary syphilis Painless nodule at site of contact, rapidly ulcerates (chancre) In HIV-infected patients, may see multiple or atypical chancres, or no primary lesion

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Primary syphilis chancres

Credit: Centers for Disease Control and

Prevention

Primary syphilis chancres

Credit: Centers for Disease Control and

Prevention

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Secondary syphilis (2-8 weeks after primary inoculation)Protean symptoms, may involve almost any organ system and include: Rash (macular, maculopapular, papulosquamous, or pustular); or condyloma lata Generalized lymphadenopathy

Constitutional symptoms (fever, malaise, anorexia, arthralgias, headache)

CNS symptoms Symptoms last days-weeksIn advanced HIV infection, may be more severe or progress more rapidlyDistinguish from primary HIV infectionSyphilis: Clinical Manifestations (3)

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Rash of secondary

syphilis

Credit: Centers for Disease Control and PreventionSyphilis: Clinical Manifestations (4)June 2013

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Latent syphilis: no overt signs/symptoms (but serologic evidence of syphilis), though relapse of manifestations of secondary syphilis may occurLate syphilis: cardiovascular syphilis, gummatous syphilis; or slowly progressive disease in any organ system

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Neurosyphilis: May occur at any stage of syphilis, with various symptomsCranial nerve dysfunction, stroke, meningitis, acute or chronic mental status change, loss of vibration sense, auditory or ophthalmic abnormalities, similar in HIV-uninfected patientsConcomitant uveitis and meningitis more common in HIV-positive patients

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Direct detection of T pallidumDarkfield microscopy of mucocutaneous lesion, DFA-TP, biopsy with silver stainPresumptive serologic diagnosis tests Nontreponemal serologic tests (VDRL, RPR)Treponemal tests (eg, FTA-ABS, TP-PA, EIAs, chemiluminescence immunoassays)

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Testing algorithms:Traditional: screening for nontreponemal antibodies + confirmation of reactive tests by

treponemal

assayNewer: screening with treponemal test (EIA or CIA), with reflex nontreponemal test if positiveMay identify previously treated syphilis infection more often than untreated infectionIf positive treponemal screening test and negative reflex nontreponemal test: second

treponemal test should be done (using different antigens) to confirm If second

treponemal test is positive: assess risk factors and prior syphilis treatmentIf suspected primary syphilis: treat empirically, retest with

nontreponemal test in several weeks to confirm diagnosisIf no evidence of primary syphilis: treat for late-latent syphilis (unless past treatment can be confirmed)

If second

treponemal

test is negative: no treatment indicated

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Early-stage disease:Nontreponemal serologic tests (VDRL, RPR) may show atypical responses (higher, lower, or delayed) in HIV-infected patientsFalse-negative tests possible (as in HIV-uninfected patients); pursue other diagnostic tests if high suspicion of syphilis (eg, repeat serology, biopsy, DFA of lesion material; exclude prozone phenomenon)

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Latent syphilis:Serologic tests positive but no clinical manifestationsEarly latent: evidence of infection <1 yearLate latent: evidence of infection >1 year or duration is not known

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Late-stage disease:Cardiovascular and gummatous: same as for HIV-uninfected patientsSyphilis: Diagnosis (5)

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Neurosyphilis: All with syphilis (regardless of stage) should be evaluated for clinical evidence of CNS or ocular involvementCSF exam should be done for any patient with:Neurologic, auditory, or ophthalmic symptoms or signs

Tertiary syphilis

Treatment failure (on basis of serologic tests)CSF abnormalities (elevated protein, mononuclear pleocytosis) common in early syphilis and in HIV, without neurologic symptoms: no evidence that clinical and prognostic significance is different in HIV-infected and HIV-uninfected with early syphilisSyphilis: Diagnosis (6)June 2013

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Neurosyphilis: No single test used to diagnose; instead, various combinations of reactive serologic tests, CSF cell count and protein, and reactive CSF-VDRL with or without clinical manifestations support the diagnosis

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Neurosyphilis: CSF examination Mild mononuclear pleocytosis (6-200 cells/µL), normal or mildly elevated proteinCSF VDRLSpecific; not sensitive (reactive test establishes neurosyphilis; nonreactive test does not exclude it)

CSF FTA-ABS

Highly sensitive; less specific (reactive test does not establish the diagnosis; nonreactive test excludes neurosyphilis)PCR-based methods not recommendedSyphilis: Diagnosis (8)June 2013

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Neurosyphilis testing, considerations:Reactive CSF VDRL plus CSF WBC ≥10 cells/µL supports diagnosis of neurosyphilis Mild mononuclear CSF pleocytosis (6-15 cells/µL) may be associated with HIV infection itself and may complicate diagnosis of neurosyphilis; using cutoff of >20 cells/µL may improve specificity of neurosyphilis diagnosis in HIV-infected patients

Elevated CSF protein concentration should not be used as sole diagnostic criterion

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Risk screening should be routineClient-centered risk-reduction messages; give specific actions to reduce risk of acquiring STIs and for transmitting HIVRoutine serologic testing for syphilis at least annually; Q 3-6 months if multiple partners, unprotected intercourse, injection drug or methamphetamine use, or partners with risksConsider referral for behavioral intervention

Evaluate for other STIs

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For persons exposed sexually to someone with syphilis: evaluate clinically and serologically and treat presumptivelyPersons exposed within the 90 days preceding diagnosis of primary, secondary, or early-latent syphilis in a sex partner may be infected even if tests are seronegative: treat presumptivelyPersons exposed >90 days before diagnosis of primary, secondary, or early-latent syphilis in a sex partner: treat presumptively if serologic test results are not available immediately and follow-up is uncertain

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Management similar to that for HIV-uninfected persons, but rates of serologic treatment failure and neurologic complications may be higher in HIV infection; closer follow-up is recommended Penicillin is treatment of choicePatients with penicillin allergy whose compliance or follow-up cannot be ensured: desensitize and treat with penicillin

Use alternatives to penicillin only with close clinical and serologic monitoring

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Early stage (primary, secondary, early-latent)Preferred: Benzathine penicillin G 2.4 million units IM, single doseAlternative (for penicillin-allergic patients; monitor closely): Doxycycline 100 mg PO BID for 14 days

Ceftriaxone 1 g IM or IV QD for 10-14 days

Azithromycin 2 g PO for 1 dose (note: reports of treatment failure and resistance; should not be used in MSM or pregnant women)Syphilis: Treatment (2)June 2013

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Late-latent (no signs of neurosyphilis)Preferred: Benzathine penicillin G 2.4 million units IM weekly for 3 weeksAlternative (for penicillin-allergic patients):Doxycycline 100 mg PO BID for 28 days (not thoroughly evaluated in HIV-infected patients; monitor closely)

Late-stage (cardiovascular or gummatous)

CSF examination; consult ID specialistPreferred: Benzathine penicillin G 2.4 million units IM weekly for 3 weeksSyphilis: Treatment (3)June 2013

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Neurosyphilis, otic syphilis, ocular syphilisPreferred: Aqueous crystalline penicillin G, 18-24 million units daily, as 3-4 million units IV Q4H or continuous infusion for 10-14 days Consider addition of benzathine penicillin 2.4 million units IM weekly for 3 weeks after completion of IV therapy

Alternative:

Procaine penicillin G 2.4 million units IM QD + probenecid 500 mg PO QID for 10-14 days Consider addition of benzathine penicillin 2.4 million units IM weekly for 3 weeks after completion of abovePatients with sulfa allergy should not receive probenecid, so this regimen is not recommended for themPenicillin allergy: Desensitization to penicillin is preferred; if not feasible, ceftriaxone 2 g IM or IV QD for 10-14 days

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No special considerations, no evidence that ART should be delayed until after treatment for syphilisIRIS is uncommonUse of ART associated with:Decreased risk of serologic failure of syphilis treatmentLower risk of neurosyphilis

Normalization of CSF parameters after treatment

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Monitor clinical and serologic response to treatment; assure at least 4-fold decline from titer done at time of treatment:Early stage: at 3, 6, 9, 12, 24 months Late-latent: at 6, 12, 18, 24 monthsConsider treatment failure: persistence or recurrence in clinical signs and symptoms or sustained 4-fold increase in nontreponemal test titer

Neurosyphilis: if CSF pleocytosis present initially, repeat CSF exam at 6 months; also repeat if symptoms recur or nontreponemal titer increases by 4-fold

Consider retreatment if no decrease in CSF WBC by 6 months or if WBC not normal by 2 yearsSyphilis: Monitoring and Adverse EventsJune 2013

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After successful treatment, nontreponemal tests may remain “serofast,” ie, reactive at stable titer, usually low (≤1:8)

Sustained ≥4-fold increase in titer indicates reinfection

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Jarisch-Herxheimer reaction may occur in the first 24 hours after start of syphilis treatmentFever, headache, myalgiaManage symptoms with antipyreticsMost frequent in those with early syphilis, high nontreponemal titers, and prior penicillin treatment

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Early stage Consider CSF evaluation and retreatment if:≤4-fold decrease in serum nontreponemal test titer 6-12 months after therapy, orSustained 4-fold increase in titer after initial 4-fold reduction after treatment, or

Persistent or recurring signs or symptoms of syphilis

Reinfection is difficult to document and treatment failure is difficult to rule outIf no appropriate titer response after CSF evaluation and retreatment, management is unclear >15% of early syphilis patients (HIV infected and uninfected) do not have 4-fold decline in titer after treatmentSyphilis: Treatment Failure

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Early stage Retreatment: benzathine penicillin G, 2.4 million units weekly for 3 weeks (if neurosyphilis present, treat for that)Syphilis: Treatment Failure (2)

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Late-latent stageRepeat CSF exam and retreat if:Clinical signs or symptoms of syphilis, orSustained 4-fold increase in titer after initial reduction after treatment, or

≤4-fold decrease in serum nontreponemal test titer within 12-24 months after therapy

Treatment: benzathine penicillin G, 2.4 million units weekly for 3 weeks (if neurosyphilis present, treat for that)Syphilis: Treatment Failure (3)June 2013

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NeurosyphilisConsider retreatment if: CSF WBC count has not decreased 6 months after completion of treatment, orCSF WBC count is not normal 2 years after treatment

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Secondary prevention and maintenance therapy not indicatedSyphilis: Preventing

Recurrence

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Screening:At 1st prenatal visit in all women; in high-prevalence areas or high-risk women, repeat early in 3rd trimester and at delivery Transmission to the fetus and adverse pregnancy outcomes highest with early-stage syphilisPregnancy does not alter the clinical course or diagnostic test results of syphilis in adults

Syphilis associated with increased risk of perinatal HIV transmission to infants

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Use penicillin, if possible, as in nonpregnant HIV-infected adultsPenicillin is effective for preventing syphilis transmission to the fetus and for treatment of fetal infectionOptimal penicillin regimen is not clearIn early syphilis, consider second injection of benzathine penicillin G 1 week after first dose

No alternatives to penicillin proven effective and safe for treatment of syphilis during pregnancy or prevention of fetal infection

Pregnant women with syphilis and history of penicillin allergy should undergo desensitization and treatment with penicillinSyphilis: Considerations in Pregnancy (2)June 2013

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Jarisch-Herxheimer reaction in 2nd half of pregnancy may precipitate preterm labor or fetal distressIn 2nd half of pregnancy, sonographic evaluation for fetal or placental syphilisConsult with OB specialistsAfter treatment, repeat serologic titers in 3rd trimester and at delivery

Insufficient data on serologic responses after therapy

Treatment likely inadequate if delivery ≤30 days of treatment, if woman has sign of infection at delivery, or if maternal titer is 4-fold higher than pretreatment titerSyphilis: Considerations in Pregnancy (3) June 2013

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http://www.aidsetc.orghttp://aidsinfo.nih.govWebsites to Access the Guidelines

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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.orgAbout This Slide SetJune 2013

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