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

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

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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information could become out of date quickly.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
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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

6
Bacterial Respiratory Disease Epidemiology (2)

• Incidence lower with use of ART
• Risk factors include
• Low CD4 count (lt200 cells/µL)
• No or intermittent use of ART
• Cigarette smoking
• Injection drug use
• Chronic viral hepatitis

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)

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

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

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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
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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

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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

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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

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Bacterial Respiratory Disease Preventing Exposure

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

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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

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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 lt200 cells/µL, PPV23 can be offered 8
  weeks after PCV13 or can await increase of CD4 to
  gt200 cells/µL
• Alternative
• 1 dose PPV23
• Previous PPV23 vaccination
• 1 dose of PCV13, to be given 1 year after last
  receipt of PPV23

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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

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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

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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)

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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

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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
  lt200 cells/µL
• Some offer hospitalization to all CAP patients
  with CD4 lt200 cells/µL and use PSI to guide
  decision in those with CD4 gt200 cells/µL
• Basic principles of treatment are same as those
  for HIV uninfected

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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)

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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

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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

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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

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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

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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

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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

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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 lt37.8C, heart
  rate lt100/minute, respiratory rate lt24/minute,
  SBP 90 mm Hg, room air O2 saturation gt90 or
  PaO2 gt60 mm Hg

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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

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Bacterial Respiratory Infections Monitoring and
Adverse Events

• Clinical response typically seen within 48-72
  hours after start of appropriate antimicrobial
  therapy
• Advanced HIV, CD4 lt100 cells/µL, S pneumoniae
  infection prolonged the time to clinical
  stability (gt7 days)
• Patients on ART had shorter time to clinical
  stability
• IRIS has not been described

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Bacterial Respiratory Infections Treatment
Failure

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

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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)

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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,stainin
  g of fetal teeth and bones)

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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

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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

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Bacterial Infections

• Bacterial Enteric Infections

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Bacterial Enteric Disease Epidemiology

• Higher incidence of gram-negative enteric
  infections among HIV-infected patients
• Risk greatest if CD4 lt200 cells/µL or AIDS
• Risk decreased with ART
• Most commonly cultured bacteria
• Salmonella
• Shigella
• Campylobacter
• E coli
• Clostridium difficile

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Bacterial Enteric Disease Epidemiology (2)

• 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

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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

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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

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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-coli Campylobacter species request special
  testingfor these if initial evaluation is
  unrevealing

43
Bacterial Enteric Disease Diagnosis (2)

• C difficile toxin or PCR
• If recent or current antibiotic exposure, cancer
  chemotherapy, recent hospitalization, residence
  in long-term care facility, CD4 lt200 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)

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
  resultin oral exposure to feces

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)

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

47
Bacterial Enteric Disease Treatment (2)

• Empiric Therapy
• CD4 count and clinical status guide initiation
  and duration of empiric antibiotics, eg
• CD4 count gt500 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 lt200 cells/µL with severe diarrhea,
  bloody stool, or fevers/chills diagnostic
  evaluation and antibiotics

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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
• Travelers diarrhea consider possibility of
  antibiotic resistance

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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
• Levofloxacin 750 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

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 lt200 cells/µL 2-6 weeks
• Gastroenteritis with bacteremia
• CD4 count 200 cells/µL14 days, longer if
  persistent bacteremia or complicated infection
• CD4 count lt200 cells/µL 2-6 weeks
• If bacteremia, monitor closely for recurrence
  (eg, bacteremia or localized infection)

51
Bacterial Enteric Disease Treatment (6)Shigella
spp.

• Treatment recommended, to shorten duration and
  possibly prevent transmission
• Preferred
• Ciprofloxacin 500-750 mg PO or 400 mg IV Q12H
• Alternative (depending on susceptibilities)
• Levofloxacin 750 mg PO or IV Q24H
• Moxifloxacin 400 mg PO or IV Q24H
• TMP-SMX 106/800 mg PO or IV Q12H for 3-7 days
• Azithromycin 500 mg PO QD for 5 days (not
  recommended if bacteremia)
• High rate of TMP-SMX resistance in infections
  acquired outside the United States

52
Bacterial Enteric Disease Treatment (7)
Shigella spp. (cont.)

• Duration of therapy
• Gastroenteritis 7-10 days (5 days for
  azithromycin)
• Bacteremia 14 days
• Recurrent infection up to 6 weeks

53
Bacterial Enteric Disease Treatment
(8)Campylobacter spp.

• Optimal treatment in HIV poorly defined
• Culture and susceptibility recommended
  (increasing resistance to FQ)
• Mild disease and CD4 gt200 copies/µL may withhold
  antibiotics unless symptoms persist beyond
  several days
• Mild-moderate disease
• Preferred
• Ciprofloxacin 500-750 mg PO or 400 mg IV Q12H
• Azithromycin 500 mg PO QD for 5 days (avoid if
  bacteremia)
• Alternative (depending on susceptibilities)
• Levofloxacin 750 mg PO or IV Q24H
• Moxifloxacin 400 mg PO or IV Q24H
• Bacteremia ciprofloxacin 500-750 mg PO or 400
  mgIV Q12H aminoglycoside

54
Bacterial Enteric Disease Treatment (9)
Campylobacter spp. (cont.)

• Duration of therapy
• Gastroenteritis 7-10 days (5 days for
  azithromycin)
• Bacteremia gt14 days
• Recurrent bacteremic disease 2-6 weeks

55
Bacterial Enteric Disease Treatment (10) C
difficile

• Treatment as in HIV-uninfected patients

56
Bacterial Enteric Disease Initiating ART

• ART expected to decrease risk of recurrent
  Salmonella, Shigella, and Campylobacter
  infections
• Follow standard guidelines
• Consider patients ability to ingest and absorb
  ARV medications
• Consider prompt ART initiation if Salmonella
  bacteremia, regardless of CD4 count (should not
  be delayed)

57
Bacterial Enteric Disease Monitoring and Adverse
Effects

• Monitor closely for treatment response
• Follow-up stool culture not required if clinical
  symptoms and diarrhea resolve
• May be required if public health considerations
  and state law dictate
• IRIS has not been described

58
Bacterial Enteric Disease Treatment Failure

• Consider follow-up stool culture if lack of
  response to appropriate antibiotic therapy
• Look for other enteric pathogens including C
  difficile antibiotic resistance
• Consider malabsorption of antibiotics use IV
  antibiotics if patient is clinically unstable

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Bacterial Enteric Disease Preventing Recurrence

• Salmonella
• Secondary prophylaxis should be considered for
  patients with recurrent Salmonella bacteremia
  also might be considered for those with recurrent
  gastroenteritis (with or without bacteremia) and
  in those with CD4 count lt200 cells/µL and severe
  diarrhea
• This approach is not well established weigh
  benefits and risks
• Consider stopping secondary prophylaxis if
  Salmonella infection is resolved, patient is on
  ART with virologic suppression and CD4 count gt200
  cells/µL

60
Bacterial Enteric Disease Preventing Recurrence
(2)

• Shigella
• Chronic suppressive therapy not recommended for
  first-time infections
• Recurrent infections extend antibiotic treatment
  for up to 6 weeks
• ART expected to decrease recurrence
• Campylobacter
• Chronic suppressive therapy not recommended for
  first-time infections
• Recurrent infections extend antibiotic treatment
  for 2-6 weeks
• ART expected to decrease recurrence

61
Bacterial Enteric Disease Considerations in
Pregnancy

• Diagnosis as with nonpregnant women
• Management 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 (increased risk of
  birth defects)
• Sulfa therapy near delivery may increase risk to
  newborn of hyperbilirubinemia and kernicterus

62
Bacterial Infections

• Bartonellosis

63
Bartonellosis Epidemiology

• 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 lt50 cells/µL
• B henselae linked to cat scratches from cats
  infested with fleas, cat fleas
• B quintana associated with louse infestation

64
Bartonellosis Clinical Manifestations

• 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

65
Bartonellosis Clinical Manifestations (2)
Skin lesions of Bartonella
Credits Left P. Volberding, MD, UCSF Center
for HIV Information Image Library Right G.
Beatty, MD A. Lukusa, MD, HIV InSite
66
Bartonellosis Diagnosis

• Tissue biopsy histopathologic examination
• Serologic 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 antibodies
• Antibody levels can indicate resolution and
  recrudescence of infection
• Blood culture
• PCR not widely available

67
Bartonellosis Preventing Exposure

• If CD4 count lt100 cells/µL, high risk of severe
  disease if infected by B quintana or B henselae
• Advice to patients
• B quintana
• Consider risks of contact with cats
• If acquiring a cat cat should be gt1 year of age,
  in good health, free of fleas
• Avoid cats with fleas, stray cats
• Avoid cat scratches
• Avoid contact with flea feces
• Control fleas
• B henselae
• Eradicate body lice, if present

68
Bartonellosis Preventing Disease

• Primary chemoprophylaxis not recommended
• Macrolide or rifamycin was protective in a
  retrospective case-control study

69
Bartonella Infection Treatment

• No randomized controlled trials in HIV-infected
  patients
• BA, peliosis hepatica, bacteremia, osteomyelitis
• Preferred
• Doxycycline 100 mg PO or IV Q12H
• Erythromycin 500 mg PO or IV Q6H
• Alternative
• Azithromycin 500 mg PO QD
• Clarithromycin 500 mg PO BID
• Duration at least 3 months

70
Bartonella Infection Treatment (2)

• CNS infections
• Preferred doxycycline 100 mg PO or IV Q12H /-
  rifampin 300 mg PO or IV Q12H
• Endocarditis (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 infections
• Doxycycline 100 mg PO or IV Q12H rifampin 300
  mg PO or IV Q12H
• Erythromycin 500 mg PO or IV Q6H rifampin 300
  mg PO or IV Q12H

71
Bartonellosis Starting ART

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

72
Bartonellosis Monitoring and Adverse Effects

• Check Bartonella IgG titer at diagnosis and (if
  positive) every 6-8 weeks until 4-fold decrease
• Oral doxycycline risk of pill-associated
  ulcerative esophagitis
• Rifamycins have significant interactions with
  many ARVs some combinations must be avoided
• IRIS has not been described

73
Bartonellosis Treatment Failure

• Consider alternative second-line regimens (above)
• If positive or increasing Ab titer, treat until a
  4-fold decrease

74
Bartonellosis Preventing Recurrence

• Secondary prophylaxis
• In case of relapse after 3 months of treatment,
  long-term suppression is recommended while CD4
  count lt200 cells/µL doxycycline or macrolide
• Discontinuing suppressive therapy
• After 3-4 months of therapy and CD4 count gt200
  cells/µL for 6 months some also require a
  4-fold decrease in Bartonella titers

75
Bartonellosis Considerations in Pregnancy

• 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)

76
Bacterial Infections

• Syphilis

77
Syphilis Epidemiology

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

78
Syphilis Clinical Manifestations

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

79
Syphilis Clinical Manifestations (2)
Chancres of primary syphilis
Credit Centers for Disease Control and Prevention
80
Syphilis Clinical Manifestations (3)

• 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-weeks
• In advanced HIV infection, may be more severe or
  progress more rapidly
• Distinguish from primary HIV infection

81
Syphilis Clinical Manifestations (4)
Rash of secondary syphilis
Credit Centers for Disease Control and Prevention
82
Syphilis Clinical Manifestations (5)

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

83
Syphilis Clinical Manifestations (6)

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

84
Syphilis Diagnosis

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

85
Syphilis Diagnosis (2)

• Testing algorithms
• Traditional screening for nontreponemal
  antibodies confirmation of reactive tests by
  treponemal assay
• Newer screening with treponemal test (EIA or
  CIA), with reflex nontreponemal test if positive
• May identify previously treated syphilis
  infection more often than untreated infection
• If 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 treatment
• If suspected primary syphilis treat empirically,
  retest with nontreponemal test in several weeks
  to confirm diagnosis
• If 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

86
Syphilis Diagnosis (3)

• Early-stage disease
• Nontreponemal serologic tests (VDRL, RPR) may
  show atypical responses (higher, lower, or
  delayed) in HIV-infected patients
• False-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)

87
Syphilis Diagnosis (4)

• Latent syphilis
• Serologic tests positive but no clinical
  manifestations
• Early latent evidence of infection lt1 year
• Late latent evidence of infection gt1 year or
  duration is not known

88
Syphilis Diagnosis (5)

• Late-stage disease
• Cardiovascular and gummatous same as for
  HIV-uninfected patients

89
Syphilis Diagnosis (6)

• Neurosyphilis
• All with syphilis (regardless of stage) should be
  evaluated for clinical evidence of CNS or ocular
  involvement
• CSF 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
  syphilis

90
Syphilis Diagnosis (7)

• 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

91
Syphilis Diagnosis (8)

• Neurosyphilis
• CSF examination
• Mild mononuclear pleocytosis (6-200 cells/µL),
  normal or mildly elevated protein
• CSF VDRL
• Specific 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 recommended

92
Syphilis Diagnosis (9)

• 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 gt20 cells/µL may improve specificity of
  neurosyphilis diagnosis in HIV-infected patients
• Elevated CSF protein concentration should not be
  used as sole diagnostic criterion

93
Syphilis Preventing Exposure

• Risk screening should be routine
• Client-centered risk-reduction messages give
  specific actions to reduce risk of acquiring STIs
  and for transmitting HIV
• Routine serologic testing for syphilis at least
  annually Q 3-6 months if multiple partners,
  unprotected intercourse, injection drug or
  methamphetamine use, or partners with risks
• Consider referral for behavioral intervention
• Evaluate for other STIs

94
Syphilis Preventing Disease

• For persons exposed sexually to someone with
  syphilis evaluate clinically and serologically
  and treat presumptively
• Persons 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 presumptively
• Persons exposed gt90 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

95
Syphilis Treatment

• 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 choice
• Patients 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
• Azithromycin resistance and treatment failure
  especially in men who have sex with men (MSM)

96
Syphilis Treatment (2)

• Early stage (primary, secondary, early-latent)
• Preferred
• Benzathine penicillin G 2.4 million units IM,
  single dose
• Alternative (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)

97
Syphilis Treatment (3)

• Late-latent (no signs of neurosyphilis)
• Preferred
• Benzathine penicillin G 2.4 million units IM
  weekly for 3 weeks
• Alternative (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 specialist
• Preferred Benzathine penicillin G 2.4 million
  units IM weekly for 3 weeks

98
Syphilis Treatment (4)

• Neurosyphilis, otic syphilis, ocular syphilis
• Preferred
• 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 above
• Patients with sulfa allergy should not receive
  probenecid, so this regimen is not recommended
  for them
• Penicillin allergy
• Desensitization to penicillin is preferred if
  not feasible, ceftriaxone 2 g IM or IV QD for
  10-14 days

99
Syphilis Starting ART

• No special considerations, no evidence that ART
  should be delayed until after treatment for
  syphilis
• IRIS is uncommon
• Use of ART associated with
• Decreased risk of serologic failure of syphilis
  treatment
• Lower risk of neurosyphilis
• Normalization of CSF parameters after treatment

100
Syphilis Monitoring and Adverse Events

• 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 months
• Consider 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 years

101
Syphilis Monitoring and Adverse Events (2)

• After successful treatment, nontreponemal tests
  may remain serofast, ie, reactive at stable
  titer, usually low (18)
• Sustained 4-fold increase in titer indicates
  reinfection

102
Syphilis Monitoring and Adverse Events (3)

• Jarisch-Herxheimer reaction may occur in the
  first 24 hours after start of syphilis treatment
• Fever, headache, myalgia
• Manage symptoms with antipyretics
• Most frequent in those with early syphilis, high
  nontreponemal titers, and prior penicillin
  treatment

103
Syphilis Treatment Failure

• Early stage
• Consider CSF evaluation and retreatment if
• 4-fold decrease in serum nontreponemal test
  titer 6-12 months after therapy, or
• Sustained 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 out
• If no appropriate titer response after CSF
  evaluation and retreatment, management is unclear
  
• gt15 of early syphilis patients (HIV infected and
  uninfected) do not have 4-fold decline in titer
  after treatment

104
Syphilis Treatment Failure (2)

• Early stage
• Retreatment benzathine penicillin G, 2.4 million
  units weekly for 3 weeks (if neurosyphilis
  present, treat for that)

105
Syphilis Treatment Failure (3)

• Late-latent stage
• Repeat CSF exam and retreat if
• Clinical signs or symptoms of syphilis, or
• Sustained 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)

106
Syphilis Treatment Failure (4)

• Neurosyphilis
• Consider retreatment if
• CSF WBC count has not decreased 6 months after
  completion of treatment, or
• CSF WBC count is not normal 2 years after
  treatment

107
Syphilis Preventing Recurrence

• Secondary prevention and maintenance therapy not
  indicated

108
Syphilis Considerations in Pregnancy

• 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 syphilis
• Pregnancy 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

109
Syphilis Considerations in Pregnancy (2)

• Use penicillin, if possible, as in nonpregnant
  HIV-infected adults
• Penicillin is effective for preventing syphilis
  transmission to the fetus and for treatment of
  fetal infection
• Optimal penicillin regimen is not clear
• In 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 penicillin

110
Syphilis Considerations in Pregnancy (3)

• Jarisch-Herxheimer reaction in 2nd half of
  pregnancy may precipitate preterm labor or fetal
  distress
• In 2nd half of pregnancy, sonographic evaluation
  for fetal or placental syphilis
• Consult with OB specialists
• After 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 titer

111
Websites to Access the Guidelines

• http//www.aidsetc.org
• http//aidsinfo.nih.gov

112
About This Slide Set

• 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.org