Treating Opportunistic Infections among

HIV-Infected Adults and Adolescents

Bacterial Infections

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 December 2004. The intended audience
is clinicians involved in the care of patients with HIV.
The user is cautioned that due to 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field of HIV care, this information could become out of
date quickly.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
12/04
 Bacterial Infections Contents
 Bacterial respiratory infections
 Bacterial enteric infections
 Syphilis
 Bartonellosis

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 Disease-Specific
Recommendations
For each disease:
 Epidemiology
 Clinical Manifestations
 Diagnosis
 Treatment Recommendations
 Monitoring and Adverse Events
 Management of Treatment Failure
 Prevention of Recurrence
 Special Considerations during Pregnancy

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 Bacterial Respiratory Disease:
Epidemiology
 Common cause of HIV-related morbidity
 Rates much higher than in HIV uninfected

Organisms:
 S pneumoniae
 >150 times more common than in HIV uninfected
 Recurrence in 8-25% within 6 months
 H influenzae
 P aeruginosa
 S aureus
 Atypicals (less common)
 No identified organism in up to 33%
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 Bacterial Respiratory Disease:
Clinical Manifestations

 Presentation similar to that of HIV uninfected,

with acute symptoms
 Subacute illness suggests alternative diagnosis
(PCP, TB, chronic fungal disease, etc)

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 Bacterial Respiratory Disease:
Diagnosis
 History and physical exam
 Chest X ray:
 Commonly shows lobar consolidation, but may show
atypical presentations (multilobar, nodular,
reticulonodular)
 Blood cultures, CBC/differential, Gram stain, and
culture of expectorated sputum
 Evaluation for PCP and TB, if clinically indicated
(PCP may coexist with bacterial pneumonia)
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 Bacterial Respiratory Disease:
Diagnosis
 If no clinical improvement on antibiotics,
consider further testing:
 Urine antigen for L pneumophila and histoplasmosis;
IgM and IgG serology for M pneumoniae and
C pneumoniae, serum cryptococcal antigen
 Chest CT scan
 Bronchoscopy

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 Bacterial Respiratory Infections:

Treatment
 Target most common pathogens, particularly
S pneumoniae and H influenzae
 Treat as for HIV-uninfected patients
 Preferred: extended-spectrum cephalosporin (ceftriaxone
or cefotaxime) or fluoroquinolone with activity against
S pneumoniae (levofloxacin, moxifloxacin, gatifloxacin)
 Select agents according to sensitivity results, if available
 If CD4 count <100 cells/µL, prior history of Pseudomonas,
or neutropenia
 Consider broader coverage for gram-negative bacteria, including
P aeruginosa

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 Bacterial Respiratory Infections:

Treatment Failure

 Clinical improvement expected 48-72

hours after initiation of appropriate therapy
 If worsening symptoms/signs or no
improvement, evaluate further
 Bronchoalveolar lavage or transbronchial
biopsy
 Consider broader spectrum antibiotics
pending additional diagnostic testing

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 Bacterial Respiratory Infections:

Prevention of Recurrence

 Optimize ART
 23-valent pneumococcal vaccine, in adults and
adolescents with CD4 count >200 cells/µL, if not
given in preceding 5 years
 If frequent serious bacterial respiratory infections,
consider prophylactic antibiotics (TMP-SMX,
clarithromycin, or azithromycin, if organism is
sensitive)

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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:
 Avoid clarithromycin (birth defects in rodents)
 Avoid quinolones unless drug-resistant disease with
no other alternatives (arthropathy in animals)
 Pneumococcal and influenza vaccines can be
administered

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 Bacterial Enteric Disease:
Epidemiology

 Higher incidence in HIV-infected patients

 Most common species of bacteria:
 Salmonella
 Campylobacter
 Shigella

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 Bacterial Enteric Disease:
Clinical Manifestations
Salmonellosis
 Source: usually contaminated food
 Three clinical syndromes
 Self-limited gastroenteritis
 Diarrheal disease with fever, bloody diarrhea, weight
loss
 Salmonella septicemia
 Usually nontyphoidal strains (unlike HIV-uninfected patients)
 Bacteremia more likely in advanced HIV
disease, may relapse 12/04
 Bacterial Enteric Disease:
Clinical Manifestations
Campylobacter disease
 Higher incidence in men who have sex with men
 In severe immunodeficiency, more severe disease:
more prolonged diarrhea, invasive disease,
bacteremia, extraintestinal involvement
Shigellosis
 Higher incidence in men who have sex with men
 Acute diarrhea (may be bloody), with fever, upper GI
symptoms

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 Bacterial Enteric Disease:
Diagnosis

 Stool and blood cultures

 Stool culture may not identify nonjejuni
Campylobacter species
 Endoscopy

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 Bacterial Enteric Disease:
Treatment

Salmonellosis
 Treatment recommended, because of high risk
of bacteremia in HIV-infected patients
 Preferred: ciprofloxacin 500-750 mg PO BID
(or 400 mg IV BID) for 7-14 days
 For advanced HIV (CD4 count <200 cells/µL) and/or
bacteremia, treat 4-6 weeks
 Alternative: TMP-SMX PO or IV; or ceftriaxone
(IV) or cefotaxime (IV)

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 Bacterial Enteric Disease:
Treatment
Campylobacter jejuni
 Mild disease: may withhold antibiotics unless
symptoms persist for several days
 Preferred therapy (not well defined)
 Ciprofloxacin 500-750 mg PO BID for 7 days
 If severe disease or bacteremia, treat at least 2 weeks
or
 Azithromycin 500 mg PO QD
 If bacteremia, consider adding aminoglycoside
 Increasing resistance to fluoroquinolones: check
drug susceptibility 12/04
 Bacterial Enteric Disease:
Treatment
Shigellosis
 Treatment recommended, to shorten disease
course and prevent transmission
 Preferred: fluoroquinolone PO or IV for 3-7 days
 If severe disease or bacteremia, treat at least 2
weeks
 Alternative: TMP-SMX DS 1 tablet PO for 3-7
days; or azithromycin 500 mg PO day 1, then
250 mg PO QD for 4 days
 High rate of TMP-SMX resistance in infections
acquired outside the United States
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 Bacterial Enteric Disease:
Treatment Failure

 Lack of clinical response and persistence of

organisms after completion of appropriate
antibiotic therapy
 Possible causes:
 Wrong antibiotic: treatment should be guided by drug
susceptibility testing of pathogen
 Consider malabsorption of oral antibiotics, sequestered
focus of infection (eg, abscess), inadequate antibiotic
levels

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 Bacterial Enteric Disease:
Prevention of Recurrence

 HIV-infected patients with Salmonella

bacteremia: long-term secondary
prophylaxis (ciprofloxacin or other FQ)
 Chronic maintenance therapy not
indicated for Campylobacter or Shigella
infections

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 Bacterial Enteric Disease:
Considerations in Pregnancy
 Diagnosis as in nonpregnant women
 Management as in nonpregnant adults,
except:
 Avoid quinolones unless drug-resistant disease
with no other alternatives (arthropathy in
animals)
 Caution with sulfa therapy near delivery
because of theoretical increased risk to the
newborn of hyperbilirubinemia and kernicterus
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 Bartonellosis: Epidemiology
 Bacillary angiomatosis (BA): usually
caused by B henselae and B quintana;
have been linked to cat exposure
 B quintana associated with louse infestation
 Typically occurs late in HIV infection; CD4
count usually <50 cells/µL

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 Bartonellosis: Clinical Manifestations
 Symptoms often chronic (months-years)
 May involve any organ system
 BA of the skin: papular red vascular lesions,
subcutaneous nodules; resembles Kaposi
sarcoma
 Osteomyelitis (lytic lesions)
 Peliosis hepatica
 Systemic symptoms of fever, sweats, fatigue,
malaise, weight loss

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 Bartonellosis: Diagnosis

 Tissue biopsy
 Serologic tests (available through the
CDC)
 Blood culture

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 Bartonellosis: Treatment
 Non-CNS infections
Preferred:
 Erythromycin 500 mg PO (or IV) QID;

or
 Doxycycline 100 mg PO or IV Q 12 hours
Alternative: azithromycin 600 mg PO QD or
clarithromycin 500 mg PO BID; fluoroquinolones
 CNS infections
Preferred: doxycycline 100 mg PO or IV Q 12 hours
Alternative: azithromycin or clarithromycin
 Duration of treatment: at least 3 months
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 Bartonellosis: Treatment Failure

 Consider second-line regimens

 If relapse, consider lifelong therapy

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 Bartonellosis:
Prevention of Recurrence

 In case of relapse or reinfection, consider

chronic maintenance therapy
(erythromycin or doxycycline)

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 Bartonellosis:
Considerations in Pregnancy
 No data on Bartonella infections in pregnancy in HIV-
infected women; in HIV-negative women,
B bacilliformis associated with more severe course
 B bacilliformis may increase risk of spontaneous
abortion and stillbirth, and may be transmitted to fetus
 No data on other Bartonella species in pregnancy
 Diagnosis as in nonpregnant adults
 Treatment: avoid tetracyclines (hepatotoxicity and
staining of fetal teeth and tones); use erythromycin

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 Syphilis: Epidemiology
 Caused by Treponema pallidum
 Increased incidence in men who have sex
with men
 HIV infection alters diagnosis, natural
history, management, and outcome of
syphilis
 These guidelines refer specifically to
management of syphilis in HIV-infected
patients
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 Syphilis: Clinical Manifestations
 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
 Secondary syphilis (2-8 weeks after primary inoculation)
 Protean symptoms, may include:
 Rash (macular, maculopapular, 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
 Latent syphilis: no overt signs/symptoms, though relapse
of manifestations of secondary syphilis may occur
 Late syphilis: neurosyphilis, cardiovascular syphilis,
gummatous syphilis; or slowly progressive disease in
any organ system
 Neurologic complications or neurosyphilis may occur
earlier or progress more rapidly in HIV-positive patients
 Meningitis, meningovascular, or parenchymatous disease
similar in HIV-uninfected patients
 Concomitant uveitis and meningitis more common in HIV-
positive patients
 Asymptomatic neurosyphilis (CSF with elevated protein,
lymphocytosis, or positive serologic test, in absence of
symptoms): not a late complication or manifestation

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 Syphilis: Diagnosis
 As in HIV-uninfected patients
 Direct tests
 Darkfield microscopy of mucocutaneous
lesion
 Serologic tests: DFA-TP, FTA-ABS, TP-TA
 Indirect tests
 Nontreponemal serologic tests (VDRL, RPR)

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 Syphilis: Diagnosis
 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

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 Syphilis: Diagnosis
 Late-stage disease:
 Cardiovascular and gummatous: same as for
HIV-uninfected patients
 Neurosyphilis: CSF examination
 Mild mononuclear pleocytosis (10-200 cells/µL)
 CSF VDRL
 Specific; not sensitive (reactive test confirms
neurosyphilis; nonreactive test does not exclude it)
 CSF treponemal tests
 Sensitive; not specific (reactive test does not establish
the diagnosis; nonreactive test excludes neurosyphilis)
 CSF may show normal or mildly elevated protein
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 Syphilis: Diagnosis

 Neurosyphilis testing, considerations:

 Reactive CSF VDRL plus CSF WBC ≥10 cells/µL
supports diagnosis of neurosyphilis
 Mild mononuclear CSF pleocytosis (5-15 cells/µL)
may be associated with HIV infection itself and may
complicate diagnosis of neurosyphilis
 Elevated CSF protein concentration alone is not
sufficient to establish diagnosis
 If neurosyphilis cannot be excluded by nonreactive
CSF treponemal test, patient should be treated for
neurosyphilis

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 Syphilis: Treatment
 Special considerations in HIV-infected patients:
 Closer follow-up is recommended to detect treatment
failure or disease progression
 All should be evaluated for clinical evidence of CNS
or ocular involvement
 CSF exam should be done in any patient with:
 Neurologic or ocular symptoms or signs
 Late-latent (or unknown duration) syphilis
 Tertiary syphilis
 Failure of treatment for nonneurologic syphilis
 Some recommend CSF exam for all HIV-infected patients,
regardless of stage
 If CSF abnormalities consistent with neurosyphilis,
treat for neurosyphilis
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 Syphilis: Treatment

Early stage (primary, secondary, early-latent)

 Preferred: benzathine penicillin 2.4 million units
IM, single dose
 Alternative (not thoroughly evaluated in HIV-
infected patients; monitor closely):
 Doxycycline 100 mg PO BID for 14 days
 Ceftriaxone 1 g IM or IV QD for 8-10 days
 Azithromycin 2 g PO for 1 dose (note case reports of
treatment failure and resistance)

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 Syphilis: Treatment

Late-latent (no CNS involvement)

 Preferred: benzathine penicillin 2.4 million units
IM, weekly for 3 weeks
 Alternative (not thoroughly evaluated in HIV-
infected patients; monitor closely): doxycycline
100 mg PO BID for 28 days
Late-stage (cardiovascular or gummatous)
 Consult infectious disease specialist

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 Syphilis: Treatment

Neurosyphilis
 Preferred: aqueous crystalline penicillin G, 3-4 million units
IV every 4 hours or continuous infusion for 10-14 days*
 Alternative: procaine penicillin 2.4 million units IM QD plus
probenecid 500 mg PO QID for 10-14 days;* or ceftriaxone
2 g IM or IV QD for 10-14 days*
 *Some specialists recommend benzathine penicillin 2.4 million
units IM weekly for 3 weeks after completion of IV or IM therapy
indicated above
 For patients allergic to penicillin, consider penicillin
desensitization, as penicillin is preferred treatment

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 Syphilis: Monitoring

 Treatment failure: ≤4-fold decrease in nontreponemal

test titer 6-12 months after therapy
 Monitor clinical and serologic response to treatment:
 Early stage: at 3, 6, 9, 12, 24 months
 Late-latent: at 3, 6, 12, 18, 24 months
 Neurosyphilis: repeat CSF exam at 3 and 6 months, then every 6
months until SCF WBC is normal and CSF VDRL is nonreactive
 After successful treatment, nontreponemal tests may
continue to be reactive, at low (≤1:8) and stable titer
 ≥4-fold increase in titer indicates reinfection

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 Syphilis: Treatment Failure
 Early stage
Re-treat if:
 ≤4-fold decrease in serum nontreponemal test titer 6-12
months after therapy, or
 4-fold increase in titer after initial reduction after
treatment, or
 persistent or recurring clinical signs or symptoms of
syphilis
 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
 Late-latent stage
Repeat CSF exam
Re-treat if:
 Clinical signs or symptoms of syphilis, or
 4-fold increase in titer after initial reduction after
treatment, or
 ≤4-fold decrease in serum nontreponemal test titer
12-24 months after therapy
 Treatment: repeat benzathine penicillin G, 2.4
million units weekly for 3 weeks (if neurosyphilis
present, treat for that)
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 Syphilis: Treatment Failure

Neurosyphilis
Re-treat if:
 CSF WBC count has not decreased 6 months
after completion of treatment, or
 CSF-VDRL remains reactive 2 years after
treatment

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 Syphilis: Prevention of Recurrence
 Secondary prevention and
maintenance therapy not indicated

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 Syphilis:
Considerations in Pregnancy

 Pregnancy does not alter the course of syphilis in

adults
 Transmission and adverse outcomes highest with
early syphilis
 Syphilis may increase risk of perinatal HIV
transmission to infants
 Screening:
 At first prenatal visit in all women; in high-prevalence
areas or high-risk women, repeat at 28 weeks and at
delivery
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 Syphilis:
Considerations in Pregnancy
 Diagnosis: as in nonpregnant adults
 Treatment:
 Benzathine penicillin, as in nonpregnant HIV-infected adults
(for early syphilis, consider injection 1 week after initial injection)
 No proven effective and safe alternatives to penicillin;
for penicillin allergy, refer for desensitization
 Jarisch-Herxheimer reaction in second half of pregnancy
may precipitate preterm labor or fetal distress: monitor
 Monitoring: for women treated during pregnancy, repeat
serologic titers in third trimester and at delivery

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 Web Sites to Access the
Guidelines
 http://www.aidsetc.org
 http://aidsinfo.nih.gov

12/04
 About this Slide Set
 This presentation was prepared by Susa
Coffey, MD for the AETC National
Resource Center in June 2005.
 See the AETC NRC Web Site for the
most current version of this presentation.
http://www.aidsetc.org

12/04