Infectious Disease board review - the UNC Department of Medicine

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.
B.
C.
D.
CD4 cell count measurement
Epstein- Barr virus IgM measurement
HIV RNA viral load measurement
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.
 ELISA—99%specific, 98.5 % sensitive
 Western Blot—100% 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.
 Opportunistic
infections, blood transfusions, herpes
outbreaks and immunizations may transiently increase
viral load.
 Check 4 weeks after initiation or changes in therapy.
 Goal <50 copies/ml—should 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, HIVassociated 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 regeneratepathologic 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
sequestra—involucrum
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


Radiograph:



Takes 2 weeks to show acute changes.
Sensitivity 60%, Specificity 60%
MRI




Open vs. CT-guided aspirate
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
levels—abscess 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
intermediate (9.2%)
3
Group 3;
high (22%)
Consider hospital-supervised
treatment (either short-stay inpatient
or hospital-supervised outpatient)
mortality Manage in hospital as severe
pneumonia; consider admission to
intensive care unit, especially with
CURB-65 score of 4 or 5
PSI/PORT
Risk Factors
Demographic factors
Patient Characteristic
Male
Female
Comorbid illnesses
Physical examination
Laboratory
Points
Age* in yrs
Age* in yrs - 10
Nursing home resident
+10
Neoplastic disease[B]
+30
Liver disease[C]
+20
Congestive heart failure[D]
+10
Cerebrovascular disease[E]
+10
Renal disease[F]
+10
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
F) or more
+15
Pulse 125/minute or more
+10
Arterial pH less than 7.35
+30
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
Hematocrit less than 30% (0.30)
+10
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
(Chronic Heart, Lung, Liver, Kidney Dz, DM, Alcoholism, Malignancy,
Asplenia,Immunosuppresion, ABX in past 3 months)
Respiratory Fluoroquinolone
Or
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!!!!!