Download Treating Opportunistic Infections Among HIV

Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected Adults
and Adolescents
Bacterial 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
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become out of date quickly.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
Bacterial Infections
Bacterial Respiratory Infections
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
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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
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Bacterial Respiratory Disease:
Epidemiology (3)
Organisms:
 S pneumoniae
 Drug-resistant strains are increasingly
common
 H influenzae
 P aeruginosa
 S aureus, including MRSA
 Atypicals (infrequent)
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Bacterial Respiratory Disease:
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
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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 <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
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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 <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
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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 TB
suspected but not being treated (risk of TB monotherapy)
 Empiric macrolide monotherapy cannot be routinely
recommended (risk of macrolide-resistant
S 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 amoxicillinclavulanate
 Alternative beta-lactams: cefpodoxime, cefuroxime
 Fluoroquinolone, especially if penicillin allergy
 Levofloxacin 750 mg PO QD
 Moxifloxacin 400 mg PO QD
 Alternative: beta-lactam + doxycycline
 Duration of therapy: 7-10 days for most; minimum 5 days
 Should be afebrile for 48-72 hours, clinically stable
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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, ampicillinsulbactam
 IV fluoroquinolone, especially if penicillin allergy
 Levofloxacin 750 mg IV QD
 Moxifloxacin 400 mg IV QD
 Alternative:
 IV beta-lactam + doxycycline
 IV penicillin for confirmed pneumococcal pneumonia
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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, ampicillinsulbactam
 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 betalactam + (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 communityacquired 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 <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
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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 <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
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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,
staining 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
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
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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 AIDSdefining 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 noncoli Campylobacter species; request special testing
for these if initial evaluation is unrevealing
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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 <200 cells/µL, acidsuppressive 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)
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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
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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)
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Bacterial Enteric Disease: Treatment
 Treatments usually the same as in HIVuninfected 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 HIVinfected patients
 Avoid antimotility agents if concern about
inflammatory diarrhea
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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
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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
 Traveler’s 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
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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)
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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):




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Levofloxacin 750 mg PO or IV Q24H
Moxifloxacin 400 mg PO or IV Q24H
TMP-SMX 106/800 mg PO or IV Q12H
Azithromycin 500 mg PO QD for 5 days (not
recommended if bacteremia)
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Bacterial Enteric Disease: Treatment (7)
Shigella spp. (cont.)
 High rate of TMP-SMX resistance in infections
acquired outside the U.S.; reports of azithromycin
resistance in HIV-infected MSM
 Duration of therapy
 Gastroenteritis: 7-10 days (5 days for
azithromycin)
 Bacteremia: ≥14 days
 Recurrent infection: up to 6 weeks
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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 >200 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
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Bacterial Enteric Disease: Treatment (9)
Campylobacter spp. (cont.)
 Bacteremia: ciprofloxacin 500-750 mg PO or 400
mg IV Q12H + aminoglycoside
 Duration of therapy
 Gastroenteritis: 7-10 days (5 days for azithromycin)
 Bacteremia: >14 days
 Recurrent bacteremic disease: 2-6 weeks
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Bacterial Enteric Disease: Treatment (10)
C difficile
 Treatment as in HIV-uninfected patients
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Bacterial Enteric Disease: Initiating ART
 ART expected to decrease risk of recurrent
Salmonella, Shigella, and Campylobacter
infections
 Follow standard guidelines
 Consider patient’s ability to ingest and absorb
ARV medications
 Consider prompt ART initiation if Salmonella
bacteremia, regardless of CD4 count (should not
be delayed)
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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
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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 <200 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 >200 cells/µL
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Bacterial Enteric Disease:
Preventing Recurrence (2)
 Shigella
 Chronic suppressive therapy not recommended for firsttime infections
 Recurrent infections: extend antibiotic treatment for up to
6 weeks
 ART expected to decrease recurrence
 Campylobacter
 Chronic suppressive therapy not recommended for firsttime infections
 Recurrent infections: extend antibiotic treatment for 2-6
weeks
 ART expected to decrease recurrence
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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
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Bacterial Infections
Bartonellosis
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 <50 cells/µL
 B henselae linked to cat scratches from cats infested
with fleas, cat fleas
 B quintana associated with louse infestation
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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
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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
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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
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Bartonellosis: Preventing Exposure
 If CD4 count <100 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 >1 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
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Bartonellosis: Preventing Disease
 Primary chemoprophylaxis not
recommended
 Macrolide or rifamycin was protective in a
retrospective case-control study
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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
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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
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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
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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
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Bartonellosis: Treatment Failure
 Consider alternative second-line
regimens (above)
 If positive or increasing Ab titer, treat
until a 4-fold decrease
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Bartonellosis: Preventing Recurrence
 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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Bartonellosis:
Considerations in Pregnancy
 No data on Bartonella infections during
pregnancy in HIV-infected women; in HIVnegative 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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Bacterial Infections
Syphilis
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
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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
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Syphilis: Clinical Manifestations (2)
Chancres of primary syphilis
Credit: Centers for Disease Control and Prevention
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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
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Syphilis: Clinical Manifestations (4)
Rash of secondary syphilis
Credit: Centers for Disease Control and Prevention
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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
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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
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Syphilis: Diagnosis
 Direct detection of T pallidum
 Darkfield microscopy of mucocutaneous lesion, DFATP, biopsy with silver stain
 Presumptive serologic diagnosis tests
 Nontreponemal serologic tests (VDRL, RPR)
 Treponemal tests (eg, FTA-ABS, TP-PA, EIAs,
chemiluminescence immunoassays)
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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
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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 HIVuninfected 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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Syphilis: Diagnosis (4)
 Latent syphilis:
 Serologic tests positive but no clinical
manifestations
 Early latent: evidence of infection <1 year
 Late latent: evidence of infection >1 year or
duration is not known
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Syphilis: Diagnosis (5)
 Late-stage disease:
 Cardiovascular and gummatous: same
as for HIV-uninfected patients
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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
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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
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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
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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
>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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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
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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 >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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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)
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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)
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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
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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
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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
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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
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Syphilis: Monitoring and Adverse Events (2)
 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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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
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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
 >15% of early syphilis patients (HIV infected and
uninfected) do not have 4-fold decline in titer after
treatment
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Syphilis: Treatment Failure (2)
Early stage
 Retreatment: benzathine penicillin G, 2.4 million
units weekly for 3 weeks (if neurosyphilis present,
treat for that)
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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)
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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
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Syphilis: Preventing Recurrence
 Secondary prevention and
maintenance therapy not indicated
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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
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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
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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
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Websites to Access the Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov
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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
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