INFECTIOUS DISEASEBOARD 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 measurementB. Epstein- Barr virus IgM measurementC. HIV RNA viral load measurementD. 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, 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

Efavirenz contraindicated in women of child-bearing age.

http://img.thebody.com/thebody/2008/virus_life_cycle.gif

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 ImipenemB. Begin Vancomycin and CeftazidimeC. Begin Vancomycin and MetronidazoleD. 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 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 floorB. Admit to the ICUC. Observe in the ED for 12 hoursD. 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.

Influenzahttp://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 Options0 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/PORTRisk 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

F) or more+15

  Pulse 125/minute or more +10

Laboratory   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

TreatmentOutpatient 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 fluoroquinolonePCN Allergic: Respiratory fluoroquinolone and aztreonam

Special Concerns

Pseudomonas Aeruginosa Anti-pneumococcal, antipseudomonoal beta-lactam (Zosyn, Cefepime, Imipenem, or Meropenem) + either Ciprofloxacin or Levofloxacin

OrThe above beta-lactam + Aminoglycoside + Azithromycin OrThe above beta-lactam + Aminoglycoside + an antipneumococcal fluoroquinolonePCN 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!!!!!