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INFECTIOUS DISEASE

BOARD REVIEW

Patricia D. Jones, MD
Question 11
A 28 yo man is evaluated at a community health center for a 10-day history of sore
throat, HA, fever, anorexia, and muscle aches. Two days ago, a rash developed on
his trunk and abdomen. He had been previously healthy and has not had any
contact with ill persons. He has had multiple male and female sexual partners and
infrequently uses condoms. He has been tested for HIV infection several times, most
recently 8 months ago; all results were negative.
On physical examination, temperature is 38.6 C There are several small ulcers on
the tongue and buccal mucosa and cervical and supraclavicular lymphadenopathy.
A faint maculopapular rash is present on the trunk and abdomen. A rapid plasma
reagin test is ordered.

Which of the following diagnostic studies should also be done at this time?
A. CD4 cell count measurement
B. Epstein- Barr virus IgM measurement
C. HIV RNA viral load measurement
D. Skin biopsy
CDC: Diagnosis of AIDS
Definitive AIDS Diagnosis (w/ or w/o laboratory evidence of HIV infection:

Candidiasis of esophagus, trachea, bronchi or lungs.


Cryptococcosis, extrapulmonary
Cryptosporidiosis w/ diarrhea >1 month
CMV infection of organ other than liver, spleen or lymph nodes
HSV infection causing a mucocutaneous ulcer that persists >1 month, or bronchitis,
PNA or esophagitis of any duration
Kaposi sarcoma in patient < 60 yo
Lymphoma of the brain (primary) in patient <60 yo
Mycobacterium avium complex or Mycobacterium kansasii infection, disseminated ( at
a site other than or in addition to the lungs, skin, or cervical or hilar lymph nodes)
Pneumocystis jirovecii pneumonia
Progressive multifocal leukoencephalopathy
Toxoplasmosis of the brain.
CDC: Diagnosis of AIDS
Definitive AIDS Diagnosis (with laboratory evidence of HIV infection)

Coccidioidomycosis, disseminated (at a site other than or in addition to the lungs or cervical or hilar lymph
nodes)
HIV encephalopathy
Histoplasmosis, disseminated (at a site other than or in addition to the lungs or cervical or hilar lymph nodes)
Isosporiasis with diarrhea persisting > 1month
Kaposi sarcoma at any age
Lymphoma of the brain (primary) at any age
Other non-Hodgkin lymphoma of B-cell or unknown immunologic phenotype
Any mycobacterial disease caused by mycobacteria other than or in addition to the lungs, skin, or cervical or
hilar lymph nodes.
Disease caused by extrapulmonary M. tuberculosis
Salmonella (nontyphoid) septicemia, recurrent
HIV wasting syndrome
CD4 count <200/ul or a CD4 lymphocyte percentage below 14%
Pulmonary tuberculosis
Recurrent pneumonia
Invasive cervical cancer
CDC: Diagnosis of AIDS
Presumptive AIDS Diagnosis (with laboratory evidence of HIV infection)

Candidiasis of esophagus: (a) recent onset of retrosternal pain on swallowing and


(b) oral candidiasis
CMV retinitis
Mycobacteriosis: specimen from stool or normally sterile body fluids or tissue from
site other than lungs, skin, or cervical or hilar lymph nodes showing acid-fast bacilli of
a species not identified by culture
Kaposi sarcoma: erythematous or violaceous plaque-like lesion on skin or mucous
membrane
Pneumocystis jirovecii pneumonia
Toxoplasmosis of the brain
Recurrent pneumonia
Pulmonary tuberculosis
Pathophysiology of HIV Infection

http://www.nwabr.org/education/pdfs/hiv_lifecycle.jpg
Acute Retroviral Syndrome
2-6 weeks post infection
Check HIV RNA Viral Load and HIV antibody
Fever (96%)
Lymphadenopathy (74%)
Exudative Pharyngitis (70%)
Rash (70%)
Myalgia or arthralgia (54%)
Diarrhea (32%)
Headache (32%)
N/V (27%)
Hepatosplenomegaly (14%))
Weight Loss (13%)
Thrush (12%)
Neurologic Symptoms (12%)
Screening and Diagnosis
Screening: Routine HIV testing in all patients aged 13-64, those
beginning treatment for TB, those being treated for STDs, those who
engage in high-risk behaviors.

Diagnosis: Antibodies appear in the circulation 2-12 weeks following


initial infection.
ELISA99%specific, 98.5 % sensitive
Western Blot100% sensitive, 100% specific
Detects antibodies to core (p17, p24, p55), polymerase (p31, p51, p66) and
envelope (gp41, gp120, gp160) proteins
Positive: Reactive to gp120 and either gp41 or p24
Negative: Nonreactive
Indeterminate: Other band pattern that is not clearly positive.
Exposed persons with negative initial ELISA should have repeat testing
at 6 weeks and 3 months.
Laboratory Testing
HIV RNA Viral Load: predicts prognosis and the
rate of decline of CD4 lymphocytes.

Opportunisticinfections, blood transfusions, herpes


outbreaks and immunizations may transiently increase
viral load.
Check 4 weeks after initiation or changes in therapy.
Goal <50 copies/mlshould be achieved within 6
months of beginning effective therapy.
Monitor every 3-4 months
Preventative Care
Routine Immunizations
Routine Breast, Colon Cancer and Hyperlipidemia
Screening
Cervical Cancer/Anal Cancer Screening
Opportunistic Disease Prophylaxis
Pneumovax every 5 years
Influenza annually
Hep B, A unless documented immunity
PPD annually
Prophylaxis for Opportunistic Infections:

Pneumocystic jirovecii (PCP):


Indications: CD4<200, CD4<14%, Recurrent Candidiasis, Persistent
Fevere, Previous PCP
Treatment: TMP-SMX, Dapsone, Atovaquone, Pentamidine-aerosolized

Toxoplasmosis:
Indications: CD4<100, positive Toxoplasma IgG antibody titer
Treatment: TMP-SMX, Dapsone, Pyrimethamine, Leucovorin,

Mycobacterium avium complex infection:


Indications: CD4 <50
Treatment: Azithromycin, Clarithromycin, Rifabutin
Treatment of HIV Infection
When: AIDS-defining illness, CD4 <350, HIV-
associated nephropathy, Co-infection with chronic
Hepatitis B, Pregnancy.
2 NRTIs + NNRTI or PI

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors


(NRTIs)
Abacavir, Didanosine, Emtricitabine, Lamivudine,
Stavudine, Tenofovir, Zalcitabine, Zidovudine
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Delavirdine, Efavirenz, Etravirine, Nevirapine

Protease Inhibitors
Atazanavir, Darunavir, Fosaprenavir, Indinavir,
Lopinavir/Ritonavir, Nelfinavir, Ritonavir, Saquinavir
HGC, Saquinavir SGC, Tipranavir
Fusion Inhibitors
Enfuvirtide
Co-receptor Antagonists
Araviroc

Integrase Inhibitors
Raltegravir

http://img.thebody.com/thebody/2008/virus_life_cycle.gif
Efavirenz contraindicated in women of child-bearing
age.
Complications of HIV Infection/Therapy

Cardiovascular:
Increased exposure to protease inhibitors increases dyslipidemia and
increased risk of MI.

Immune Reconstitution Inflammatory Syndrome:


Suppression of viral replication allows the immune system to regenerate-
pathologic inflammatory state that tends to occur in patient with
advanced HIV just starting HAART. Occurs 3 days-5years after initiation:
Unmasking: Occult subclinical infection-HAART improves immune function and the
ability to mount an effective response against pathogens.
Paradoxical: Recurrence of a previously successfully treated infection. Primarily
due to the presence of persistent antigens.
Management-Conservative and Steroids in severe reactions.
Opportunistic Infections
Cryptococcal Infection:
Induction: Amphotericin B+/- Flucytosine for 14 days
Consolidation: Fluconazole for 8 weeks

CMV Infection: Retina, GI tract, Nervous system


Induction/Maintenance: Ganciclovir
Alternatives: Foscarnet/Cidofovir

Mycobacterium avium complex Infection:


Fever, weight loss, HSM, Malaise, Abdominal pain
Treatment: Macrolide and Ethambutol +/-Rifampin

Pneumocystis jirovecii Pneumonia


Fever, dry cough, dyspnea, bilateral interstitial infiltrates
Diagnose by silver stain of induced sputum or bronchoscopic sample showing cysts
3 week TMP/SMX
Steroids for PaO2 <70 mm Hg, A-a gradient >35 mm Hg

Toxoplasmosis:
Fever, Neurologic deficits, Ring-enhancing lesions on MRI
Sulfadiazine + Pyrimethamine + Folinic Acid
F/U MRI after 14 days. If no improvement, biopsy to rule out CNS lymphoma.
Question 8
A 75 yo man with type 2 DM is evaluated in the ED for a draining chronic ulcer on the
left foot, erythema, and fever. Drainage initially began 3 weeks ago. Current
medications include metformin and glyburide.
On physical examination, he is not ill appearing. Temperature is 37.9 C; other vital
signs are normal. The left foot is slightly warm and erythematous. A plantar ulcer
that is draining purulent material is present over the 4th metatarsal joint. A metal
probe makes contact with the bone. The remainder of the examination is normal.
The leukocyte count is normal , and ESR is 70 mm/h. A plain radiograph of the foot is
normal.
Gram stain of the purulent drainage at the ulcer base shows numerous leukocytes,
gram-positive cocci in clusters, and gram-negative rods.
Which of the following is the most appropriate management now?
A. Begin Imipenem
B. Begin Vancomycin and Ceftazidime
C. Begin Vancomycin and Metronidazole
D. Perform bone biopsy.
Osteomyelitis
Intense suppurative reaction in bone
associated with edema and thrombosis
which can compromise vascular supply
leading to areas of dead bone
sequestra

New bone reforms around the


sequestrainvolucrum

20% Hematogenous
Most common site intervertebral disk
space and two adjacent vertebrae
Patients on HD, sickle cell, bacteremia
and endocarditis
40-60% cases S. aureus
80% Contiguous
Most infections are polymicrobial

http://www.eorthopod.com/images/ContentImages/child/child_back_pain/child_back_pain_osteomyelitis.jpg
Diagnosis of Osteomyelitis
Bone Biopsy: Gold Standard
Open vs. CT-guided aspirate
Radiograph:
Takes 2 weeks to show acute changes.
Sensitivity 60%, Specificity 60%
MRI
Acute changes noted within days
Sensitivity 90%, Specificity 80%
False-positives: Fractures, Tumors, Healed Osteomyelitis
Nuclear Studies
Diabetes Mellitus-Associated Osteomyelitis

Superficial foot infections lead to cellulitis and disseminate to cause abscess,


necrotizing fasciitis and osteomyelitis.
Physical Exam:
Visible bone in ulcer base or contact with bone upon insertion of metal probe at the
ulcer base (PPV 90%, NPV 60%)
Ulcers > 2x2 cm and present for >2 weeks and ESR >70 associated with underlying
osteomyelitis.
Cultures obtained from a sinus tract or ulcer base usually do not correlate with
deep pathogens causing bone infection.
Treatment
Zosyn, Unasyn, Timentin
3rd/4th generation Cephalosporin + Flagyl
PCN-allergic: Clindamycin + Fluoroquinolone
IV Antibiotics for 4-6 weeks
Debridement
Vertebral Osteomyelitis
S. aureus-most common organism, CONS, GNR and Candida
Gradually worsening back/neck pain, fever (50% pts),
point tenderness.
Blood cultures positive in up to 75% pts
If blood cultures negative, CT-guided biospy to guide
therapy
Treatment:
Vanc + Antipseudomonal cephalosporin or extended-spectrum
beta-lactam antibiotic.
6-8 weeks duration
Question 43
A 70 yo man is evaluated in the ED for the acute onset of fever, cough productive of yellow sputum, right-sided pleuritic chest pain,
and dizziness. He has a history of DM, HTN treated with HCTZ, lisinopril, glyburide, and metformin.
On physical examination, temperature is 35C, BP 110/70, P 120, RR 36. He appears to be in acute respiratory distress. Pulmonary
examination reveals dullness to percussion, increased fremitus, and crackles at the right lung base. He is oriented only to
person.
Laboratory Studies: ABG: (Ambient Air)
Hct 42% pO2 50 mm Hg
WBC 23,000 pCO2 30 mm Hg
Platelet 150,000 pH 7.48
BUN 46
Creatinine 1.4

CXR shows a right lower lobe infiltrate.

Which of the following is the most appropriate management of this patient?


A. Admit to general medical floor
B. Admit to the ICU
C. Observe in the ED for 12 hours
D. Treat as an outpatient.
Community-Acquired Pneumonia
Definition: Infectious PNA in patient living independently in
the community of hospitalized for less than 48 hours.
Typical:
Rapid onset of high fever, productive cough, pleuritic chest pain
Usual microorganisms: S. pneumo, H. influenzae, M. catarrhalis
Atypical:
Low grade fever, nonproductive cough, no chest pain
M. pneumonia, Chlamydophila pneumoniae, Legionella pneumophila
Diagnosis
CXR
Cavitary lesions w/ air-fluid
levelsabscess due to
staphylococci, anaerobes or
GNR
Cavitary lesions w/o air-fluid
levels suggest TB or fungal
infection
Blood cultures and sputum gram
stain/culture are particularly
useful in severely ill patients
Urine Legionella antigen-only
positive in cases caused by
serogroup I.
Influenza

http://biomarker.cdc.go.kr:8080/diseaseimg/pneumonia-Community_acquired.jpg
CURB-65
Clinical Feature Points
Confusion (defined as a Mental Test Score of 8, or disorientation in person, place, or time) 1
Uremia: blood urea 7 mmol/L (~19 mg/dL) 1
Respiratory rate: 30 breaths/minute 1
Blood pressure: systolic 90 mm Hg or diastolic 60 mm Hg 1
Age 65 years 1

Score Group Treatment Options


0 or 1 Group 1; mortality Low risk; consider home treatment
low (1.5%)
2 Group 2; mortality Consider hospital-supervised
intermediate (9.2%) treatment (either short-stay inpatient
or hospital-supervised outpatient)
3 Group 3; mortality Manage in hospital as severe
high (22%) pneumonia; consider admission to
intensive care unit, especially with
CURB-65 score of 4 or 5
PSI/PORT
Risk Factors Patient Characteristic Points

Demographic factors Male Age* in yrs

Female Age* in yrs - 10

Nursing home resident +10

Comorbid illnesses Neoplastic disease[B] +30

Liver disease[C] +20

Congestive heart failure[D] +10

Cerebrovascular disease[E] +10

Renal disease[F] +10

Physical examination Altered mental status[G] +20

Respiratory rate 30/min or more +20

Systolic blood pressure less than 90 mm Hg +20

Temperature 35 degrees C (95 degrees F) or less, or 40 degrees C (104 degrees +15


F) or more

Pulse 125/minute or more +10

Laboratory +30
Arterial pH less than 7.35

BUN 30 mg/dL (10.7 mmol/L) or more +20

Sodium less than 130 mEq/L (mmol/L) +20

Glucose greater than 250 mg/dL (13.88 mmol/L) +10

+10
Hematocrit less than 30% (0.30)

Arterial PO2 less than 60 mm Hg (8.0 kPa) or SaO2 less than 90 percent +10

Pleural effusion +10


PSI/PORT
Total PSI Points Risk Class Mortality at 30 days (%)

Absence of predictors I 0.1-0.4

70 or less II 0.6-0.7

71-90 III 0.9-2.8

91-130 IV 8.2-9.3

130 or more V 27-31.1


Treatment
Outpatient Treatment

Previously Healthy/No ABX in past 3 months Marolide or Doxycyline

Comorbid Conditions Respiratory Fluoroquinolone


(Chronic Heart, Lung, Liver, Kidney Dz, DM, Alcoholism, Malignancy, Or
Asplenia,Immunosuppresion, ABX in past 3 months) Beta-Lactam plus a macrolide

Inpatient Treatment

Non-ICU Patient Respiratory Fluoroquinolone


Or
Beta-Lactam plus a macrolide

ICU Patient Beta-Lactam pus either azithromycin or a respiratory fluoroquinolone


PCN Allergic: Respiratory fluoroquinolone and aztreonam

Special Concerns

Pseudomonas Aeruginosa Anti-pneumococcal, antipseudomonoal beta-lactam (Zosyn, Cefepime, Imipenem, or


Meropenem) + either Ciprofloxacin or Levofloxacin
Or
The above beta-lactam + Aminoglycoside + Azithromycin
Or
The above beta-lactam + Aminoglycoside + an antipneumococcal fluoroquinolone
PCN Allergic: Substitute Aztreonam for beta-lactam

MRSA Add Vancomycin or Linezolid

Administer ASAP-preferably while patient still in ED.


Duration of therapy: 7-10 days
THANKS!!!!!

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