Open Wide:
Big Bolus of ID
2014 Internal Medicine
Board Review
Friday, July 18th
Jason Parham, MD, MPH
Board
Question
Breakdown
Infectious
Disease (9%)
19–21 Q
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AIDS and HIV infection 2–4
Lower respiratory tract infections 1–5
Enteric infections 1–4
CNS infections 1–3
Infectious arthritis 1–2
Procedure- and device-associated infections 1–2
Specific causative organisms 0–5
Skin and soft tissue infections 0–3
STD, genital tract infections 0–2
Endocarditis and other cardiovascular infections 0–2
Upper respiratory tract infections 0–2
Hepatic infections 0–2
Bacteremia/sepsis syndrome 0–2
Urinary tract infections 0–1
Osteomyelitis 0–1
Rheumatic fever 0–1
Nosocomial infections 0–1
Immunization 0–1
Prevention of infectious disease 0–1
Miscellaneous infectious disease disorders 0–1
Antibiotic Questions
• Options for treating Pseudomonas infection in a patient with a
serious PCN allergy: name 3 classes of antibiotics.
• Antibiotic which can precipitate with calcium and form biliary
stones?
• Class of antibiotics that can precipitate tendinitis and tendon
rupture in adults?
• Name 3 antibiotics used to treat Listeria infections.
• What lab do you need to monitor in patients on daptomycin?
More Antibiotic Questions
• Main side effect of metronidazole?
• Most common side effect of rifampin?
• What two antibiotics (in different classes) that can prolong
the QT interval?
• Adverse events with linezolid?
• Long-term use of this antibiotic can result in peripheral
neuropathy, hepatotoxicity and pulmonary toxicity, most
often seen in the elderly?
Respiratory Infections
• Bacterial Sinusitis
– Acute Bacterial Sinusitis (ABS)
• Often preceded by viral URTI
• Suggests ABS
–
–
–
–
Symptoms past 7-10 d
Unilateral sinus pain/tenderness
Maxillary tooth or face pain
Purulent nasal discharge
• Diagnosis: ultimately clinical and unsatisfying
– Gold: culture of sinus aspirate (not often done)
– Imaging for uncomplicated ABS not recommended
Respiratory Infections
• Bacterial Sinusitis
– Acute Bacterial Sinusitis (ABS)
• Micro: S.pneumonia, H. influenzae, M. catarrhalis
• Treatment
– Most will get better without abx
– If treating, prefer amox-clav
– Complications are rare but include meningitis, brain abscess,
osteomyelitis
HY: 1. Sounds viral/allergic/recent/stable – don’t give abx
2. In acute sinusitis, give abx or don’t– imaging isn’t the answer
Respiratory Infections
• Bacterial Sinusitis
– Chronic Sinusitis
• It’s all about obstruction  use nasal
saline, topical corticosteroids,
antihistamines, decongestants
• Micro
– S.aureus, S. epidermidis, anaerobes
– Targeting them probably doesn’t help
– If acute flare, treat same organisms as
ABS
– CT sinuses may be helpful (polyps),
ENT should evaluate if present
Respiratory Infections
• Otitis Media
– Starts with URI or allergies
– Uncommon in adults
– Most common symptoms: otalgia, fever
– Bulging red TM (insufflation)
– S. pneumonia, H. influenzae common
– Amoxicillin/clavulanate, cefuroxime, azithromycin
(w/ questionable utility)
– Meningitis, mastoiditis, osteomyelitis - rare
Respiratory Infections
• Pharyngitis
– Usually viral (80%) in adults;
group A streptococci in kids
– GABHS or Streptococcus
pyogenes (5-10%)
• Sore throat, exudate, adenopathy,
fever+/• No cough or hoarseness
• Rapid antigen detection test
• Most accurate: culture
• Always susceptible to penicillin
(goal is to prevent rheumatic fever)
HY: 1. In adults, if rapid negative, pass on culture
2. Gram stain of throat is worthless
Acute Rheumatic Fever
• Noninfectious sequelae 2-4 weeks after
GAS infection (usually pharyngitis, not SSTI)
• Most common in kids 5-15
• Clinical diagnosis
• 80-85% have elevated ASO titers
• Treatment: aspirin, eradicate GAS (pcn), treat heart
failure if present
• Strong tendency to recur after reinfection with GAS,
so secondary prophylaxis to prevent (usually 10
years, or until 21, whichever is longer)
Acute rheumatic fever: Jones criteria
GAS & 2 major or 1 major/2 minor
• Major
J : Joints (migratory arthritis, usually
large joints)
: Pancarditis (50-60%) {aschoff bodies}
N: Nodules, subcutaneous (<4%)
E : Erythema marginatum (<10%)
S : Sydenham chorea (20-30%)
• Minor
Fever, arthralgias, elevated
CRP/ESR, prolonged PR
Infectious mononucleosis
Pharyngitis in adults -> consider
other possibilities
IM: primary infection with EBV
– Fever, sore throat, LAD
– Splenomegaly (no contact sports until
resolved)
– Look for increased lymphocytes on
differential and elevated ALT, AST or LDH
– If given amoxicillin diffuse, pruritic, MP
rash (not allergic rxn)
– Heterophile Ab against EBV (90% +)
Back to Respiratory Infections
• Acute Bronchitis
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Most common cause of acute cough in outpatients
In healthy, nonsmokers: 90% viral
Purulent sputum doesn’t mean bacteria
In 50%, cough resolves by 2 weeks; 90% by 3 weeks
If cough is severe, >3 weeks: consider pertussis
No need for cultures if VS normal, chest exam normal
No chest x-ray
No antibiotics needed in healthy patients; self-limited
Symptomatic support
Acute Exacerbation of Chronic Bronchitis
• COPD associated
• Can be viral or bacterial
• Bacterial
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–
–
–
Haemophilus influenzae (22%), especially smokers
Moraxella catarrhalis (9-15%)
Streptococcus pneumoniae (10-12%)
Pseudomonas and other GNR (up to 15%), prior abx use,
hospitalization, frequent flares
• Bronchodilators, corticosteroids helpful
• Antibiotics commonly used, not great data
Question
An 18 year old male presents to your office with mild fever
and cough of several days duration. Negative PMH.
No h/o recent antibiotic use.
PE: O2 sat 99%, crackles left mid-lung.
CXR: infiltrate in the mid-left lung.
What is the most appropriate treatment?
a.
b.
c.
d.
e.
Amoxicillin
Bactrim
Ceftriaxone
Doxycycline
Levofloxacin
CAP – Microbes/Associations
• Pneumococcus: most common cause among all ages (urine Ag)
• MRSA: cavitary infiltrates (w/o aspiration), sepsis, IVDU, recent
SSTI or influenza
• Legionella – can be epidemics, recent travel (hotel/cruise),
summer; severe CAP, GI sx, CNS sx, hyponatremia (urine Ag)
• Klebsiella: alcoholics
• H. flu and Moraxella more common in patients with chronic
lung disease
• Pseudomonas: CF, bronchiectasis, severe COPD, chronic steroids
• Adolescents and outpatients who are not that ill – consider
Mycoplasma (serology, cold agglutinins) or Chlamydia
pneumoniae (serology) {resp. PCR best for both}
• Anaerobic bacteria – aspiration pneumonia
CAP – Microbes/Associations
• Coxiella burnetti (Q fever) – farm animals, parturient cats
(serology)
• Viral (uncommon in adults): adenovirus, parainfluenza,
respiratory syncytial virus, and human metapneumovirus
• Histoplasma – bat or bird droppings
• Francisella tularensis – rabbits
• Hantavirus - rodent poop/piss
• Coccidioides, hantavirus – Southwest US
• Burkholderia pseudomallei – Southeast Asia and China
CAP Diagnosis in Hospitalized Patients:
2007 IDSA/ATS Guidelines
– Sputum gram stain and culture (expectorated or endotracheal
aspirates) recommended for the following groups of patients:
•
•
•
•
•
•
•
•
Intensive care unit admission
Failure of outpatient antibiotic therapy
Cavitary lesions
Active alcohol abuse
Severe obstructive or structural lung disease
Positive urine antigen test for pneumococcus
Positive urine antigen test for legionella (special culture needed)
Pleural effusion
– Blood cultures: low yield (5-14%) but when positive,
establishes the diagnosis
– Urinary legionella and pneumococcal antigen tests
– CXR
CAP Treatment: 2007 IDSA/ATS Guidelines
Outpatient
General Medical Ward
ICU/Severe
If no significant risks for
DRSP*:
Macrolide or doxycycline
If risks for DRSP*:
Antipneumococcal
fluoroquinolone
OR
High-dose amoxicillin (3
gm/day) or high dose
amoxicillin/clavulanate (4
gm/day) plus macrolide (if
amoxicillin is used and there is
a concern for H. influenzae,
use macrolide active for lactamase producing strains)
Beta-lactam (ceftriaxone,
cefotaxime,
ampicillin/sulbactam,
ertapenem) plus macrolide
(can use doxycycline if
macrolide not tolerated)
OR
Antipneumococcal
fluoroquinolone alone
Beta-lactam (ceftriaxone,
cefotaxime,
ampicillin/sulbactam) plus IV
azithromycin or IV
fluoroquinolone
If concern for Pseudomonas
(eg, presence of structural
lung disease such as
bronchiectasis):
antipseudomonal agent
(piperacillin/tazobactam,
imipenem, meropenem, or
cefepime) plus
antipseudomonal
fluoroquinolone (ciprofloxacin
or high dose levofloxacin);
If concern for MRSA: add
vancomycin or linezolid
*RF for DRSP: >65, exposure to children in day care, alcoholism or other severe underlying disease, or recent antibiotics
Community Acquired Pneumonia
• A few last thoughts
– Elderly
• Present atypically (tachypnea best marker)
• Account for 60% of pneumonia admissions
– F/u CXR unnecessary except in >40, or in smokers
– Smoking cessation, flu and pneumococcal vaccines are
always good answers
– Will likely still have respiratory symptoms 14d out, 1/3 for
as long as 28d
Healthcare-Associated Pneumonia
• Risk Factors:
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–
–
–
IV therapy, wound care, or IV chemo within 30 days
NH, LTAC
Recent hospitalization (last 90d) for 2+ days
Hospital or hemodialysis clinic last 30 days
• Antibiotic choice depends on RF for multi-drug resistant
organisms (MDR):
– No known risk factors for MDR: ceftriaxone 2 g IV daily, ampicillinsulbactam 3 g IV q6h or piperacillin-tazobactam 4.5 g IV q6h,
levofloxacin 750 mg IV daily, moxifloxacin 400 mg IV daily, or
ertapenem 1 g IV qd
– Risk factors for MDR: cefipime 2 g IV q8h or ceftazidime 2 g IV q8h,
imipenem 500 g IV q6h, meropenem/doripenem, piperacillintazobactam 4.5 g IV q6hr, or aztreonam 2 g IV q6-8hr
PLUS levofloxacin 750 mg IV qd or gentamicin 7 mg/kg IV daily
PLUS linezolid or vancomycin (if MRSA suspected)
HAP & VAP
• Pneumonia that occurs 48 hours or more after admission
and did not appear to be incubating at the time of
admission
• Ventilator is the number one RF
• Treatment regimens similar to health-care associated
pneumonia
• Treat early and broadly, then de-escalate based on
clinical improvement and culture results
• A short duration of therapy (eg, 7-8 days) is sufficient for
most patients with uncomplicated infection who have a
good clinical response
Hospital acquired infections
• Not present on admission, develop after 48h
• Hand hygiene is the most important preventative measure
• CAUTI (UTI in patient w/ catheter)
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–
–
–
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Pyuria not reliable
Local or systemic symptoms
D/c foley if possible, or if not possible, change if in place 2+ weeks, then get culture
Usually treat for 7 d, no more than 10-14d
Antiseptic-coated catheters, screening cultures unnecessary
• CLABSI (bloodstream infection w/central line, w/o other source)
– Removal of line most important (Staph aureus, Pseudomonas, Candida)
– For prevention: site selection, HH, full barrier precautions, chlorhexidine
• SSI (within 30d of surgery in local manipulated)
– Staph aureus most common
– Prevent: follow abx prophylaxis guidelines, clipping, chlorhexidine, glucose control
Hospital acquired infections:
Multidrug-resistant organisms
• Risk factors: ICU, transfer from OSH, HD, surgery,
indwelling devices, malignancy, multiple prior abx
• MRSA: vancomycin (unless MIC>=2 and failing therapy)
– Pneumonia : linezolid, clindamycin
– Bloodstream: daptomycin
• VRE: if ampicillin sensitive, use it (alt:linezolid, dapto)
• ESBL: carbapenem; once susceptibilities back, may have
other options (but never pcn or cephalosporins)
Urinary Tract Infections
• Predisposing factors: stricture, stone, obstruction, tumor, foreign
body, DM
• Presentation: all can have dysuria, frequency, urgency
– Cystitis: SP pain, mild/absent fever
– Pyelonephritis: CVA/flank tenderness, fever
– Perinephric abscess: Same as pyelo but persisting despite appropriate
treatment
• Diagnosis
– Urinalysis
• 10+ WBC or +leukocyte esterase on dipstick
• if above present w/ symptoms, then UTI
– Urine culture
• Not needed in uncomplicated cystitis
• >100,000 cfu
– Only image pyleo if cont. fever or flank pain after 72h of abx treatment
– If perinephric abscess, aspirate to guide therapy
Urinary Tract Infections
• Treatment
– Uncomplicated cystitis: empiric, 3 days (TMP-SMX, nitrofurantoin,
fosfomycin); 7 days if complicated
– Pyelonephritis
• 14 days (TMP-SMX, AG or cephalosporin)
• 7 days cipro 500mg po bid
• 5 days levo 750mg po daily
– Perinephric abscess: need culture, antibiotic pressure usually selects
for uncovered gram positive cocci
• Asymptomatic bacteriuria:
– Only screen and treat pregnant women and those undergoing
urologic procedures expected to cause mucosal bleeding
– In all other cases, treatment increases resistance and does not
improve the outcome, including those with indwelling bladder
catheters and no signs systemic disease – change catheter only
Endocarditis Prophylaxis
• 2007 AHA guideline for the prevention of endocarditis made
major revisions, decreasing indications for prophylaxis.
• Cardiac conditions associated with the highest risk of bad
outcome if IE (and thus worthy of prophylaxis):
– Prosthetic cardiac valve or prosthetic material used for cardiac valve
repair
– Previous IE
– Congenital heart disease (CHD):
• Unrepaired cyanotic CHD, including palliative shunts and conduits
• Completely repaired congenital heart defect with prosthetic material or
device, whether placed by surgery or by catheter intervention, during the first
6 months after the procedure
• Repaired CHD with residual defects at the site or adjacent to the site of a
prosthetic patch or prosthetic device (which inhibit endothelialization)
– Cardiac transplants who develop cardiac valvulopathy
Endocarditis Prophylaxis –
Dental Procedures
• Prophylaxis is reasonable for patients with high risk cardiac
conditions AND undergoing dental procedures involving
manipulation of gingival tissues/periapical region of teeth or
perforation of oral mucosa
• Antibiotic regimens:
– Oral:
•
•
•
•
Amoxicillin 2 grams
Clindamycin 600 mg
Cephalexin 2 grams
Clarithromycin 500 mg or azithromycin 500 mg
– IV/IM (cannot take po):
• Ampicillin 2 grams IM or IV
• Cefazolin 1 gram IM or IV
• Clindamycin 600 mg IV
Endocarditis Prophylaxis –
Respiratory Tract Procedures
• Antibiotic prophylaxis is reasonable only for patients with high
risk cardiac conditions who undergo an invasive procedure of
the respiratory tract that involves incision and biopsy of the
respiratory mucosa
• ABX prophylaxis is NOT recommended for bronchoscopy
unless the procedure involves incision of the respiratory tract
mucosa
• ABX Regimens:
• Amoxicillin 2 g PO
• Ampicillin 2 g IV
• Vancomycin 1 g IV (PCN allergic)
Endocarditis Prophylaxis –
GI, Biliary, and GU Procedures
• Antibiotic prophylaxis is reasonable only for patients
with high risk cardiac conditions AND ongoing active
infections in the procedure area
• If they meet that criteria, and aren’t on appropriate
coverage for their existing infection then,
ABX regimens:
– Amoxicillin 2 g PO
– Ampicillin 2 g IV
– Vancomycin 1 g IV (PCN allergic)
Endocarditis Prophylaxis Q&A
• Patient with h/o IE undergoing root canal:
– Prophylaxis or no?
– What if he’s allergic to penicillin?
• Patient with prosthetic AV
– Undergoing screening colonoscopy with expected biopsy of polyp?
– Getting transbronchial biopsy of mediastinal node?
• Patient with mitral valve prolapse with regurgitation getting
cystoscopy?
• Given the dramatic reduction in indications for prophylaxis,
if you have to guess, “no prophylaxis indicated”
Endocarditis
• Presentation:
– Fever & new/changed murmur
– Hands/feet
• Janeway lesions: flat & painless
• Osler nodes: raised & painful
• Splinter hemorrhages in nail beds
– Retina: Roth spots
– Hematuria
• Emboli to kidneys
• Post-infectious glomerulonephritis with immune complexes in glomeruli
– Mycotic aneurysms
Endocarditis
• Diagnostic tests:
– Blood cultures
• Best initial test: 95-99% sensitive
– If positive, then transthoracic echo
• If both positive, you’ve got endocarditis
(but organism needs to be a typical microbe for endocarditis)
– If negative transthoracic echo, then TEE
– TTE and TEE equally specific (95%)
– Sensitivity: TTE (60%); TEE (90-95%)
Endocarditis
• Diagnostic tests (cont.)
– Normocytic anemia in 90%
– Elevated ESR (& CRP)
– UA with proteinuria, hematuria, red cell casts
• Culture negative endocarditis
– In the 1-5% with negative blood cultures, vegetation on
ECHO also needs any 3 minor criteria
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•
•
•
•
Fever
Risk factor (PV, IV drug use)
Vascular phenomena (infarcts, hemorrhages, Janeway)
Immunologic phenomena (GN, Osler, Roth)
Atypical organisms
Endocarditis Treatment
• Best initial empiric if acutely ill: vancomycin
• Strep Viridans group
• Penicillin or ampicillin or ceftriaxone x 4 weeks
• If partial resistance, pen or amp x 4 weeks,
with gentamicin added for first 2 weeks
– Enterococcus
• Ampicillin and gentamicin x 6 weeks
– MSSA
• Oxacillin or Nafcillin x 6 weeks (+/- gent for 3-5 days)
– MRSA
• Vancomycin x 6 weeks
– HACEK (Haemophilus,Aggregatibacter/Actinobacillus,Cardiobacterium,Eikenella,Kingella)
• Ceftriaxone or ampicillin/sulbactam x 4 weeks
Endocarditis: Micro Pearls
• Streptococcus gallolyticus (formerly bovis): colonoscopy, r/o CA
• Q fever: parturient cats, livestock, chronic fibrosis on histopath; if
positive culture and serology for Coxiella burnetii = major criteria
• Staphylococcus lugdunensis – coag negative staph, NVE, bad
infection
• Gram negative rods: healthcare associated >> IVDU
• Bartonella: homeless, alcoholic, body lice, cats
• Whipple’s: histopath: “foamy macrophages”; indolent infection
with arthralgias, CHF, murmur, emboli; no fever; diarrhea and GI
symptoms may be mild/absent
• Culture negative:
– prior antibiotics #1 cause (usually masking a typical strep)
– also think about HACEK, Bartonella sp., Coxiella burnetii, Brucella, and
Tropheryma whipplei
Endocarditis
• Indications for surgery
– Acute rupture of valve or chordae tendinae
– Acute congestive heart failure
– Abscess
– Fungal endocarditis
– AV block
– Recurrent major embolic events on antimicrobials
Endocarditis Treatment Questions
• Right-sided due to MSSA (IVDU)?
Nafcillin/Oxacillin (x4w) + Gent (x2w)
• Prosthetic valve due to MSSA?
Nafcillin/Oxacillin + Rifampin (x6w), + Gent (x2w)
• Prosthetic valve due to MRSA?
Vanco + Rifampin (x6w), + Gent (x2w)
Central Nervous System Infections
• “Most likely diagnosis”
– All present with fever and headache
• Also could see N/V, seizures
– Some overlap sx, but if alone
• Focal neurologic findings (abscess)
• Altered mental status and confusion (encephalitis)
• Neck stiffness (meningitis)
– If multiple overlap sx, then you need CT or LP for
diagnosis
Meningitis
• Most commonly present with mix of fever, HA, stiff
neck, photophobia
• Diagnostics
– Best initial test: CSF cell count (sens: 95-98%)
– Most accurate test: CSF culture (spec: ~100%)
– GS: if positive, specific (sens: 60-70%);
narrow Rx accordingly
– Protein: normal protein excludes meningitis
– Glucose: poor sens/spec
– Cell count: if very high neutrophil count, fairly specific
– Bacterial antigen (latex agglutination) doesn’t usually add
to treatment, so ACP advising not to order
CSF in Meningitis
Bacterial
Viral
TB
Cryptococcus
20-50 cm H20
< 25
18-30
>20
1000-5000 wbc
50-1000 wbc
50-300 wbc
20-500 wbc
Neutrophils
Lymphocytes
Lymphocytes
Lymphocytes
Glu < 40 mg/dl
>45 (nl-50% of
(less than 18 strongly serum glu)
predictive)
< 45
< 40
Protein 100-500
mg/dl (nl 20-40
1mg/1000 rbcs)
< 200 (slightly
elevated)
50-300
>45
Gram stain (+6090%)
Stains – (add fungal,
VDRL, AFB, India
Ink, HSV PCR)
(repeat at 3 days if
suspicion remains)
AFB (25%+) – (add
fungal studies,VDRL,
India Ink, etc.)
India ink + > 60%) –
(obtain crypto Ag
CSF)
Meningitis
• CT head before LP if
–
–
–
–
–
Papilledema
Focal neurologic deficits
Seizure or severe confusion
Immunocompromised
H/o CNS disease
• If a CT is needed, answer “antibiotics prior to CT”
• Regardless, there is always time for STAT blood
cultures before antibiotics and/or LP
Meningitis
• Etiology
– Pneumococcus (GPC): common (60-70%), OM/sinusitis/pna,
immunocompromised, csf leak
– Neisseria meningitidis (GN diplococcus): young, healthy,
military, college (young adult w/ petechial rash, 1000’s neutrophils on CSF)
– Haemophilus influenzae (GN coccobacilli): rare since vaccine
– Listeria monocytogenes (GP rod): immunocompromised, >50
– Staphylococcus aureus (GPC): NSG, penetrating trauma
Meningitis Associations
• Cranial nerve involvement
• TB, sarcoid, Lyme disease (especially 7th: Bell’s palsy - also may
have foot drop), carcinomatosis
• Exposures
• TB – prisoner, immigrant, abnormal CXR
• Cryptococcus- HIV, alcoholics, chronic steroids, AIDS, ALL,
Hodgkins lymphoma
• Listeria – elderly, alcoholics, pregnant, immunosuppressed
• Coccidioides – Southwest US
• Meningococcal – crowded living conditions
• Recurrent meningitis
• Aseptic – NSAIDs, Mollaret’s (herpes simplex), tumor
• Pneumococcal – CSF leak, asplenia
• Meningococcal – properdin & C5-9 deficiency, asplenia
Empiric Therapy for Meningitis
Based on Age or Underlying Condition
Age 2-50
S. pneumo/N.meningitidis
Vanc + third generation ceph
(cefotaxime, ceftriaxone)
Age > 50
S. pneumo/N.meningitidis/
Listeria
Vanc + 3rd ceph + Amp
Basilar skull FX
S. pneumo/H. flu/ gr A strep
Vanc + 3rd ceph
Post
neurosurg/trauma
S. aureus, Coag-neg
staph/gram negative bacilli
(including pseudomonas)
Vanc + Ceftazidime or
Cefepime or meropenem
CSF Shunt
S. Aureus, coag-neg staph/
gram negative bacilli
(including
pseudomonas)/diptheroids
Vanc + Ceftazidime or
Cefepime or meropenem
Meningitis
• Treatment
– If positive gram stain (or culture) should narrow Rx
• Meningococcus, Haemophilus – 3rd gen cephalosporin
• Pneumococcus – vanco, 3rd gen cephalosporin,
dexamethasone
• Listeria – ampicillin or PCN G
– If meningococcus
• Suspected - needs droplet isolation (for 24 hours after abx)
• Confirmed: close contacts
– Get cipro, rifampin or ceftriaxone within 24h of ID
– CC are day care, household contacts, salivary contacts, or HCW in
direct contact with oral or respiratory secretions
– If random HCW, classroom/office contact, “reassurance only”
CSF lymphocytosis (aseptic meningitis)
Tuberculosis
• Immigrant, lung lesions, very high
protein
• high volume serial lp for AFB; also PCR
• 4 drug rx + steroids
RMSF
• Camper/hiker w/ rash moving to trunk
• Serology, biopsy
• Doxycycline
Lyme
• Tick bite, rash, joint pain, carditis
• Serology
• IV ceftriaxone/cefotaxime
Enteroviral
•
•
PCR for diagnosis
Treatment is supportive
Drug-induced
•
•
NSAIDs, IVIG, trim-sulfa
Stop the offender
Cryptococcus
•
•
•
AIDS, cd4 <50
India ink, Ag
Ampho, then fluconazole
Encephalitis Associations
• West Nile: flu-like symptoms followed by flaccid paralysis,
seizures
• Rabies – presume exposure if bat in room and patient not at
100% awareness (Sx: hydrophobia, pharyngeal spasms,
hyperactivity)
• Mumps – parotitis present
• VZV - Grouped vesicles - (but can have without vesicles)
• HSV - Temporal lobe changes on imaging studies - *clinically
most important to r/o since treatment changes mortality*
HSV & CNS
• Type I traditionally non-genital
• Type II predominantly genital (see STD section)
• Common infection in the general population
(Type I 80%, Type II 20% adults positive)
• Acute treatment reduces duration of symptoms
• Chronic treatment reduces symptomatic episodes,
asymptomatic shedding and transmission
• Two neurological syndromes:
– Aseptic meningitis – Type II, benign but may be recurrent
– Encephalitis – Type I, needs IV acyclovir, high
morbidity/mortality if untreated
HSV Infections – Ophthalmologic &
Neurologic Syndromes
• Dendritic keratitis – usually caused by Type I, reactivation of the virus in
the trigeminal ganglion, ulcers seen on fluorescein staining, most
frequent cause of corneal blindness in US
• Encephalitis – usually caused by Type I
– CSF with lymphocytic pleocytosis, increased number of erythrocytes, and
elevated protein
• Unilateral temporal lobe lesions on imaging with associated mass effect
– Diagnose with HSV PCR CSF (98% sensitive, 94-100% specific)
– Treat with IV acyclovir 10 mg/kg q8h; give early if clinical picture is suspicious
for this infection; early therapy prevents mortality and limits the severity of
chronic post-encephalitic behavioral and cognitive impairments
– 70% mortality if untreated
– Duration of therapy 14-21 days
• Aseptic meningitis – Type II, benign but may be recurrent (Mollaret’s)
VZV Infection (shingles)
•
•
Characteristic clinical presentation: rash in a
dermatomal distribution with acute neuritis
Complications in immunocompetent patients:
– Post herpetic neuralgia
– Bacterial skin infections
– Ocular complications, including uveitis and
keratitis
– Motor neuropathy
– Meningitis
– Ramsay Hunt Syndrome
(Bell's palsy, deafness, vertigo, and pain)
•
Cause of herpes zoster ophthalmicus:
– Linked to VZV reactivation in the trigeminal
ganglion; sight-threatening disease
– Vesicular lesions on the nose: Hutchinson’s
sign: involvement of nasociliary branch of CN V:
conveys high risk of zoster opthalmicus
•
Cause of acute retinal necrosis (ARN)
Varicella Zoster Virus
• Treatment:
– Acyclovir, valacyclovir, famciclovir (high dose)
– Analgesia for acute neuritis
– Prednisone – role uncertain – may be useful in acute
neuritis that is not controlled by opioid analgesics
– Immunocompromised – IV acyclovir
– Varicella zoster immune globulin for high risk patients
(exposed immunocompromised or seronegative pregnant)
– Herpes zoster vaccine for prevention of shingles if >60;
reduces incidence, decreases postherpetic neuralgia
Influenza
• Influenza A
– Subtypes based on surface proteins (hemagglutinin, neuraminidase)
– Drifts: minor mutations, local outbreaks
– Shifts: major mutations, epidemics/pandemics (if human illness, efficient human
to human transfer, and little preexisting immunity)
• Influenza B
– Less severe outbreaks, can’t differentiate clinically
•
•
•
•
•
•
Illness in winter months, most serious <2, >65, comorbidities
1-4d incubation
Symptoms: fever, HA, myalgia, nonproductive cough, sore throat, nasal d/c
Rapid test helpful if positive, doesn’t exclude if negative
If influenza in community, diagnose w/ signs/symptoms only
Treat (oseltamivir, zanamivir) hospitalized, severely infected, severely at
risk; try to start in first 2 days of illness
• Vaccinate all above 6 months of age
Malignant Otitis Externa
•
•
•
•
Invasive infection of the external auditory canal and temporal bone
Elderly patients with diabetes mellitus
Pseudomonas always the responsible organism
Patients present with exquisite otalgia and otorrhea, which are not
responsive to topical measures used to treat simple external otitis;
also can have a cranial neuropathy (usually CN 7) and intracranial
complications (meningitis, brain abscess, dural sinus thrombosis)
• Diagnosis: culture and sensitivity of drainage from ear, imaging
studies (CT, MRI, bone scan)
• Treatment: anti-pseudomonal antimicrobial; duration 6 weeks due to
associated osteomyelitis
• Surgery reserved for local debridement, removal of bony sequestrum,
or abscess drainage
Soft Tissue Infections from Cat or Dog Bites
• Microbes
• Pasteurella species: 50% dog wounds, 75% cat wounds
• Capnocytophaga canimorsus: fastidious GNR, bacteremia and fatal sepsis,
especially in asplenic, hepatic disease
• Anaerobes
• Staph and strep from human skin
• Wound care, antibiotics, and tetanus vaccination
• Amoxicillin/clavulanate, or if severe ampicillin-sulbactam IV
• Antibiotic prophylaxis X 3-5 days w/ amox-clav if :
–
–
–
–
–
–
Deep puncture wounds (especially due to cat bites)
Moderate to severe wounds with associated crush injury
Wounds in areas of underlying venous and/or lymphatic compromise
Wounds on the hand(s) or in close proximity to a bone or joint
Wounds requiring surgical repair
Wounds in immunocompromised hosts
Human Bites
• Human mouths are nasty
• Microbes
– Oral flora, polymicrobial
– Staph, strep, Haemophilus, Eikenella,
anaerobes
• Consider evaluation other potential pathogens
– HIV, Hep B, Hep C, HSV
• Prophylaxis for all wounds w/ amoxicillin-clavulanate
for 3-5 days
• Closed-fist injuries deserve radiography, hand consult,
possibly admission
MRSA Infections
• Altered penicillin binding proteins – resistant to all
beta-lactam antibiotics
• Causes skin/soft tissue infections, bacteremia, and pneumonia
• Hospital and community strains differ:
– CA-MRSA associated with Panton-Valentine leukocidin (PVL) virulence factor
– HA-MRSA strains more resistant to other antibiotics
• CA-MRSA associated with crowding (prisons), athletes, hot tubs,
body shaving, etc.
• CA-MRSA now dominant clone of community isolates, and
increasingly in hospital
MRSA – Outpatient Treatment
Local Drainage Most Important for Skin/Soft Tissue Infections
Drug
Issues
Doxycycline
15% resistance
Trimethoprim/sulfa
Not good for group A strep
Fluoroquinolone
Resistance frequent HAMRSA
15% resistance, inducible
resistance, positive D test
High cost, marrow
suppression
Clindamycin
Linezolid
MRSA – Treatment for
Pneumonia/Bacteremia
Drug
Issues
Vancomycin
Time tested, slow clearance of
bacteremia, MIC creep (2+)
Daptomycin
Poor pulmonary activity, high
cost
Linezolid
IV/PO, BMT, high cost
Tigecycline
Low blood levels / not for BSI,
high cost
Necrotizing fasciitis
• Severe infection of SC soft tissues;
erythema, swelling  bullae,
cutaneous gangrene (rapid).
• Often LE, abdomen, perineum
• Type I: polymicrobial
(anaerobes/strept/enterobacter)
• Type II: group A strep
• Also can see w/ CA-MRSA
• RF: DM, PVD, surgery, trauma
• Surgical exploration stat
• Empiric antibiotics (vancomycin plus
clindamycin plus beta-lactam/bl-inhibitor
or carbapenem)
Gas Gangrene
– Clostridial myonecrosis: lifethreatening muscle infection that
develops from contiguous area of
superficial trauma
– Diagnosis: severe pain at site of injury,
systemic toxicity,
swelling/crepitance/gas in the soft
tissues, large gram variable rods in
tissue
– Treat with surgical debridement, PCN +
clindamycin
Streptococcal Toxic Shock Syndrome
• Group A streptococcal infection (usually SSTI), fever,
hypotension MOF
• Mediated by toxins, cause release of inflammatory cytokines
 capillary leak and tissue damage
• Risk factors: minor trauma, liposuction, vaginal delivery or csection, minor and major surgeries, viral infections, NSAIDs
• Complications include bacteremia (usually), ARDS, DIC, MSOF
• Usually no rash or desquamation
• Treat with IV fluids, penicillin, clindamycin
Staphylococcal Toxic Shock Syndrome
• Fever, sunburn rash, hypotension  MOF
• Associated with colonization of wound or vagina with toxinproducing S. aureus w/o invasive disease
• Not usually bacteremic
• Desquamation occurs late
• Most commonly associated with menstruation
• Support with IV fluids, removal of source (tampon, sponge) are
most important treatments
• ABX may help; vanco and clinda empiric; if cultured + for MSSA
can do naf/ox and clinda
Vibrio vulnificus
• Present w/ sepsis, hemorrhagic bullae,
necrotizing fasciitis
• H/o exposure
– Warm brackish/salt water, Gulf of Mexico, summer
– Inoculation through skin trauma
– (Can also see as septicemia after ingestion of raw
or undercooked shellfish)
• RF: hemachromatosis, liver disease
• Rx: Doxycycline + ceftriaxone
Infectious Arthritis
• Nongonococcal arthritis
–
–
–
–
–
Acute onset, monoarticular joint pain, swelling
Knee most common, then hip
Staph aureus, Strept most common
Ecoli, Pseudomonas less common
RF: age >80, DM, IVDU, endocarditis, recent joint surgery,
joint prosthesis, skin infection, RA
– Fever, chills, NWB, pain w/ motion, large effusion, hot and
tender joint
– Diagnosis:
• Blood cultures + in <50%
• Typical arthrocentesis: >50k wbc, >90% neutrophils
Infectious Arthritis
• Gonococcal arthritis
– Most common < 40 yo
– Women > men
– Migratory polyarthralgias, tenosynovitis,
papulopustular rash, fever
– Arthrocentesis
• Can see >50k wbc
• 10% w/ positive gram stain
• <50% are culture positive
– Treat with ceftriaxone, include doxy or azithro to
cover chlamydia
Osteomyelitis
Osteomyelitis
• Contiguous or hematogenous
• Predisposing conditions: PAD, DM, Skin ulcer with local
infection
• Presents with
– pain, tenderness, erythema, warmth
– severe osteomyelitis can lead to sinus tract
– fever and systemic signs rare (10%)
• Staphylococcus aureus most common, but many others
• Diagnostic tests
Osteomyelitis
– X-ray best initial
• If positive no need for further imaging
• 2-3 weeks to see changes (periosteal elevation, destroyed bone)
– MRI if X-ray negative; don’t f/u MRI for resolution
– Nuclear bone scan: only if MRI contraindicated (PM)
– To guide therapy you need:
• Most accurate: bone biopsy with culture
• Positive blood cultures (10%)
– Sterile metal probe to bone gives diagnosis, but biopsy for culture
needed to get organism
• Treatment
–
–
–
–
Empiric therapy shouldn’t be an answer
MSSA: ox/naf/cefaz
MRSA: vanco
GNR: oral FQ
Anyone out there still awake?
Sexually Transmitted Diseases
•
•
•
•
•
Gonorrhea
Chlamydia
PID
Trichomonas
Genital Ulcerative Disease
–
–
–
–
Syphilis
Herpes
Chancroid
LGV
• Genital Warts /HPV
Gonorrhea
• Urethritis in males; cervicitis and PID in females
• GS of urethral discharge showing PMNs
with intracellular gram-negative diplococci,
but not sensitive enough to exclude, so NAAT
• Treatment options:
– Ceftriaxone 250 mg IM X 1
– Cefixime 400 mg po X 1
– Alternatives:
• Spectinomycin 2 g IM X 1 (not readily available)
• Azithromycin 2 g po X 1 (GI tract symptoms in 35% patients, expensive)
– Pregnant:
• Either of the above cephalosporins or spectinomycin or azithromycin
– Note: Fluoroquinolones not recommended anymore
– Always treat for Chlamydia infection as well as co-infection rates are high
– Always treat partners
Disseminated Gonococcal Infection
•
•
•
•
•
Fever, migratory polyarthralgias, tenosynovitis, and skin lesions
(maculopapular, vesicular, or necrotic)
Asymmetric joint involvement common
If untreated, patient can later present with a monoarticular septic arthritis
Diagnosis: send specimen to be plated on Thayer-Martin media:
– Arthrocentesis diagnostic procedure of choice:
• Synovial fluid cultures positive in only 25-30% patients
– 80% patients have a positive test for gonorrhea from cervix, urethra,
rectum, blood, or pharynx
Treatment options:
– Ceftriaxone 1 g IV qd
– Cefotaxime 1 g IV q8
– After improvement, can do Cefixime 400 mg po bid
for at least a week
Chlamydia
• Non-gonococcal urethritis (NGU)
in males; cervicitis and PID in
females
• Intracellular organism
• Diagnosed with NAAT
• Treatment options:
– Azithromycin 1 gram po X 1
– Doxycycline 100 mg po bid X 7 days
– Pregnant women:
• Amoxicillin 500 mg po tid X 7 days
• Zithromax 1 gram po X 1
• Need test for cure in 3-4 weeks
– Treat all partners of infected
patients
Pelvic Inflammatory Disease
• PID is considered polymicrobial, GC and CT cause most of it
• Highest risk in young, sexually active females
• Can be mild, have to have high index of suspicion due to
complications (FT scarring, TOA, infertility)
• Consider if sexually active woman w/ low abd or pelvic pain,
plus cervical motion, uterine or adnexal tenderness
• Mucopurulent cervicitis increases likelihood
• Can also see fever, +GC/CT on NAAT
• Rx
– Parenteral: cefotetan/cefoxitin + doxycycline
– Outpatient (PO + IM) ceftriaxone + doxy, +/-metronidazole
Trichomoniasis
• Intense pruritis with a malodorous, frothy, yellow
discharge
• Pelvic exam demonstrates diffuse erythema of vaginal
walls and cervical inflammation (strawberry cervix)
• Typically asymptomatic in men
• Diagnosis made by observing motile trichomonads on wet
prep; vaginal pH > 4.5
• Treatment options:
– Metronidazole 2 grams po X 1
– Tinidazole 2 grams po X 1
– Failure: Metronidazole 500 mg po bid X 7 days
– Pregnant: Clotrimazole 100 mg vaginal suppository or
cream qd for 7 days: may relieve symptoms
– Treat all partners of infected patients
Genital Ulcer Diseases
•
•
•
•
Syphilis – painless ulcer
Genital herpes – painful ulcer
Chancroid – painful ulcer, tender nodes
Lymphogranuloma venereum – painless ulcer,
tender nodes
STD Question 1
• A 26 year old sexually active male comes to the STD clinic
for routine screening. He has no complaints and physical
exam is normal. Review of the chart shows that he had a
nonreactive RPR at his last visit 8 months ago. A repeat RPR
today is reactive at 1:1024. What is your diagnosis?
– A) Early latent syphilis
– B) Late latent syphilis
– C) Tertiary syphilis
– D) False positive reaction
STD Question 2
• What is the treatment of choice for this
patient?
A) Benzathine penicillin G 2.4 million units IM in
a single dose
B) Benzathine penicillin G 2.4 million units IM in
three consecutive doses once a week for three
weeks
C) Aqueous crystalline penicillin G 4 million
units IV q4hrs for 14 days
D) Doxycycline 100 mg po bid X 14 days
Syphilis
• Primary syphilis
– Painless chancre; resolves in 3-6 weeks
– Regional LAD
• Secondary syphilis
– MP rash, condylomata lata, alopecia, mucous patch
– LG fever, malaise, pharyngitis, laryngitis, LAD, anorexia,
weight loss, arthralgias, HA, meningismus
– Usually 2-8 weeks after chancre
• Latent syphilis
– Positive serology, no symptoms
– Early latent: less than a year
– Late latent: > 1 year or unknown
Syphilis
• Tertiary syphilis
– Can have aortitis, gummas
– Neurosyphilis
• CSF: wbc>5, increased protein,
low glucose, positive VDRL
• Usually asymptomatic
• Some signs
Tabes dorsalis – wide-base gait, foot slap
Argyll Robertson pupil (small, does not react to light,
contracts normally to accommodation)
Meningovascular disease
Syphilis serology
• Non-treponemal tests (Screening test)
– Relies on reactivity of serum antibodies against a cardiolipin-lecithincholesterol antigen (RPR, VDRL)
– Not highly specific; can have false positives
– Insensitive in primary and late syphilis: check a treponemal test
– Titers of 1:8 or higher are unusual for false positives
– 4-fold decline in titer is considered an adequate response
• Treponemal tests: antibody to T. pallidum (TPPA, FTA-Abs)
– Confirmatory test
– May remain positive for extended periods, possibly for life, even after
adequate treatment of syphilis
– A persistently reactive treponemal test does NOT indicate inadequate
treatment, relapse, or re-infection
Syphilis Treatment
• Primary, secondary, early latent (test and treat contacts):
– Benzathine penicillin G 2.4 million units IM X 1
– Alternative:
• Doxycycline 100 mg po bid X 14 days
• Tertiary (not neurosyphilis) and late latent:
– Benzathine penicillin G 2.4 million units IM q week X 3 weeks
– Alternative:
• Doxycycline 100 mg po bid X 28 days
• Neurosyphilis:
– Penicillin G IV x 10-14 days
– Alternative:
• Ceftriaxone 2 g IV qd x 10-14 days
• If pregnant + penicillin allergic: desensitize to penicillin
• If neurosyphilis + penicillin allergic: desensitize to penicillin
Genital Herpes
• Caused by HSV-1 or HSV-2 infection
• 45 million Americans with positive HSV-2 serology
• Spread by direct contact – abraded skin or mucous membranes are
more susceptible than intact skin
• Characterized by small, painful, grouped vesicles in the anogenital
region that rapidly ulcerate and form shallow, tender lesions:
– Initial episode most severe and may present with fever, myalgias,
inguinal adenopathy, headache, and aseptic meningitis
– Recurrent episodes may be proceeded by a prodromal period
associated with pain
– Diagnosis by viral culture or PCR (more sensitive)
– Serologic studies useful for counseling couples
– Serodiscordant considerations: avoid sex during prodrome/outbreak,
condoms, daily suppressive medication
Genital Herpes
Anogenital Herpes
Treatment of Genital Herpes
• Initial episode
– Acyclovir 400 mg po tid x 7-10 days
– Famciclovir 250 mg po tid x 7-10 days
– Valacyclovir 1 g po bid x 7-10 days
• Recurrent episode
– Same meds, slight changes in dosing
– Most effective if initiated during the prodrome or within
one day of recurrence of vesicles
• Daily suppressive therapy
– If the patient is having 6 or more episodes per year, or
serodiscordant couple
– Asymptomatic viral shedding can still occur on treatment
Chancroid
• Common worldwide, uncommon in U.S., usually related to sex
for drugs
• Caused by Haemophilus ducreyi
• Painful genital ulcers with tender suppurative inguinal
lymphadenopathy
• Consider only after syphilis and HSV excluded
• Diagnosis made by inguinal LN biopsy
• Re-examine in one week to evaluate for ulcer improvement
• Treatment options:
–
–
–
–
Zithromax 1 g po X 1
Ceftriaxone 250 mg IM X 1
Ciprofloxacin 500 mg po bid X 3 days
Erythromycin base 500 mg po tid X 7 days
Chancroid
Lymphogranuloma Venereum (LGV)
• Caused by Chlamydia trachomatis serovars L1-L3
• Painless ulcer at inoculation, resolves, followed by unilateral
tender inguinal lymphadenopathy which may suppurate, drain
• Diagnosis made by type-specific Chlamydia serology
• Treatment of choice:
– Doxycycline 100 mg po bid X 21 days
• Alternative treatments:
– Zithromax 1g po qweek X 3 weeks
– Ciprofloxacin 750 mg po bid X 3 weeks
– Erythromycin base 500 mg po qid X 3 weeks
– Bactrim DS bid X 3 weeks
LGV
Genital Warts
• Usually due to HPV serotypes 6 and 11 (16 and 18 associated
with cervical CA)
• Perianal warts common in MSM, associated w/ CA
• Usually asymptomatic
• Clinical diagnosis
• Treatment only if symptomatic, or cosmetic concerns
• HPV vaccine recommended for 11-12 yo males x 3 doses;
protects against HPV, related CA, and likely will protect
females by reducing transmission of cervical CA causing
serotypes
Antifungal Questions
• Antifungal known to cause electrolyte disturbances, especially
hypokalemia and hypomagnesemia?
• Name 3 antifungals that are active against aspergillus infection.
• Name 2 antifungals that needs an acidic environment for
absorption.
• What is standard of care treatment for cryptococcal meningitis?
In pregnancy?
• What species of Candida is intrinsically resistant to fluconazole?
Invasive Fungal Infections
• Dimorphic fungi
–
–
–
–
–
Histoplasma capsulatum
Blastomyces dermatitidis
Coccidioides immitis
Penicillium marneffei
Sporothrix schenckii
• Opportunistic Yeasts
and Molds
–
–
–
–
–
Candida
Cryptococcus
Aspergillus
Pneumocystis
Zygomycetes
Sporotrichosis
•
•
•
•
•
•
Soil fungus that causes a subacute to
chronic infections (Sporothrix schenckii)
Suppurating multiple subcutaneous
nodules that progress proximally along
lymphatic channels (lymphocutaneous
sporotrichosis)
Initial reddish, necrotic, nodular papule
of cutaneous sporotrichosis generally
appears 1-10 weeks after a penetrating
skin injury: usually from a splinter, thorn,
or woody fragments of plants
Associated with: gardening,
landscaping, farming, berry-picking,
horticulture, and carpentry
Definitive diagnosis requires isolation of
the organism in a specimen culture or
visualization (cigar-shaped yeast) in a
tissue biopsy
Itraconazole is the drug of choice for
treatment, continue until 2-4 weeks after
all lesions have resolved
Candidemia
• Candida in blood is not a contaminant, it’s an emergency
• Start empiric antifungal therapy
– Echinocandin
• If previous exposure to fluconazole
• If institution has high % of resistant species (C. glabrata & krusei)
• If severe sepsis
– After speciation, change to fluconazole if possible
• Cheaper
• Oral fine if stable
• Remove lines
• Dilated ophthalmologic exam to r/o candidal endophthalmitis
• Treat at least 2 weeks after clearance of blood cultures
Mucormycosis
– Rare OI (rhino-orbital-cerebral
most common, rapidly fatal)
– RF: diabetes, iron overload, burn
patients, immunocompromised
state
– HA, fever, visual changes, sinusitis,
& eventually proptosis
– Black necrotic tissue on nose or
palate is pathognomonic
– Diagnose with imaging studies,
FNA of material in sinuses with
histopathology: non-septate
hyphae with broad right angle
branching
– Treat with Amphotericin B,
aggressive, surgical excision
Fungal Question 1
A 26 year old man underwent
alloBMT for relapsed Hodgkin’s;
complicated by GVHD. He is on
prednisone and tacrolimus.
Admitted with fever, headache,
and ataxia
MRI shows cerebellar mass and
brain biopsy shows septate
hyphae with branching at acute
angles
What is your diagnosis?
A.) Mucormycosis
B.) Cryptococcus
C.) Aspergillus
D.) Blastomycosis
Fungal Question 2
48 year old man from Chicago
went on an archaeological dig in
the caves of Costa Rica. Three
weeks later he developed fever,
chills, sweats, diarrhea, and 10
pound weight loss
Exam: T 103, + cervical and
axillary LAD, and splenomegaly
WBC 2000, Hgb 8, Plts 75K
His peripheral smear is shown.
What is your diagnosis?
A) Blastomycosis
B) Histoplasmosis
C) Coccidioidomycosis
D) Disseminated tuberculosis
Fungal Question 3
39 year old woman from Chicago
presents with 3 weeks of fever, dry
cough, and pleurisy
CXR shows LLL infiltrate, treated
with azithromycin without relief
Over the next month, she develops
raised, painless skin lesions on her
face and cough persists
A skin biopsy is performed
What is your diagnosis?
A) Cryptococcal infection
B) Histoplasmosis
C) Blastomycosis
D) Coccidioidomycosis
Fungal Question 4
A 48 year old man with no PMHx
presents with a non-pruritic rash on
his neck and finger. He denies fevers
or other symptoms
Camped in AZ one month ago
WBC 7000 with 12% eosinophils,
CXR is clear. HIV Ab is negative
A skin biopsy is performed
What is your diagnosis?
A) Histoplasmosis
B) Coccidioidomycosis
C) Blastomycosis
D) Paracoccidioidomycosis
Tuberculosis Skin Testing (TST)
> 5 mm
– HIV positive
– Persons on steroids (15mg/day)/immunosuppressive drugs
– Transplant patients
– Close contact of an active case
– Fibrotic CXR lesions c/w prior TB
> 10 mm
– Healthcare workers
– Recent immigrants
– IVDU
– Homeless, prisoners, longterm care facilities
– Some chronic health conditions
> 15 mm
– No increased risk
TB screening: IGRA vs. TST
• IGRA
•
•
•
•
as sensitive but more specific
BCG vaccine or chemotherapy does not cross-react
one blood draw, no need for return, multi-step
used in place of (and not in addition to) the TST
• TST
• preferred in children < 5
• cheaper
• reaction influenced by BCG, atypical mycobacteria
Latent Tuberculosis Infection (LTBI)
• Treatment
• Isoniazid (INH) x 9 months
(remember to add pyridoxine [B6])
or
• Rifampin x 4 months
• TB Natural History
– In Normal Host:
• If TB infected:
5% risk of disease in first 2 years
+ 5% risk of disease throughout life
= 10% overall risk of active disease
– In HIV infected:
• 5-10% risk/year of active disease
Tuberculosis
• Extremely rare in U.S. outside certain groups
– Recent immigrants, homeless alcoholics, prisoners, HIV/AIDS, HCW,
transplant recipients, folks on dialysis or w/ silicosis, close contacts
of TB infected
• Presents like other chronic lung infections
– Fever, cough, sputum, weight loss, signs of consolidation on exam
• Diagnostics
–
–
–
–
CXR can show apical infiltrates, cavity formation
Acid-fast stain, mycobacterial culture
Pleural biopsy in presence of effusion is single most accurate test
Direct probes are help in smear positive patients
Treatment summary:
>Start 4 drug therapy w/
isoniazid, rifampin,
pyrazinamide and
ethambutol (+B6)
>At 2 months, sensitivities
known, can usually
drop to INH and
rifampin
>Treat for 6 months total if
no cavitation
>Add steroids for TB pericarditis,
meningitis (9-12m)
>Cavitation calls for 9m total
>Pregnant? Can’t take PZA,
therefore 9 m total
>SE: all hepatotoxic; also
PZA=>hyperuricemia
EMB=>optic neuritis
INH=>neurotoxicity
MMWR 2003
Nocardia vs. Actinomyces
• Both are gram positive branching rods
• Nocardia is acid fast (weak);
Actino is not
• Nocardia: abscesses;
Actino: sulfur granules, sinus tracts
• Nocardia:immunocompromised;
Actino: normal, or maybe poor dentition, IVDU
• Both get lung, but Nocardia CNS;
Actino mandible
• Nocardia treat with TMP-SMX;
Actino with PCN
Tick Borne Diseases
•
•
•
•
•
•
•
RMSF
Lyme
Ehrlichiosis
Southern Tick Associated Rash Illness
Babesiosis
Tularemia
Relapsing Fever
Rocky Mountain Spotted Fever
•
•
•
•
•
Caused by Rickettsia rickettsii
Dermacentor variabilis
Ticks need to attach for 6-10 hours
Seasonal variation: spring and early summer most likely times
Incubation period ~ 7 days (3-12 days), followed by fever (94%),
headache(88%), myalgia (85%), and vomiting (60%)
• 2-6 days later: petechial rash (83%), cough, electrolyte abnormalities,
thrombocytopenia, elevated transaminases
• Initial diagnosis clinical (+/- skin biopsy – not useful after 48 hrs doxycycline);
confirmed by convalescent antibody titer at 14-21 days
• Treatment: doxycycline
– Death in 1-3% of those treated compared with 30% in untreated patients
(death due to ARDS, mycocarditis, ARF, encephalopathy)
Lyme Disease
• Borrelia burgdorferi transmitted by nymph of
deer tick (Ixodes sp.)
• Tick has to feed for 1-2 days for transmission
• Reservoir: white-footed mouse
• Most common in Northeast, MN, WI
• Stage I: erythema migrans (target rash) – occurs
in 80% patients – erythematous rash with
central clearing (bull’s eye appearance),
myalgias, arthralgias, headaches,
lymphadenopathy
• Stage II: early disseminated disease: neurologic
disease including meningitis and cranial nerve
palsies, myocarditis (heart block)
• Stage III: late or chronic disease: arthritis (large
joints), chronic subtle neurologic manifestations
(encephalopathy, peripheral neuropathy)
Lyme Disease – Diagnosis and Treatment
• Diagnosis:
– Stage I: clinical – based on characteristic rash and compatible
history; serology usually NEGATIVE at this time
– Stage II, III: ELISA, Western blot
• High false positive rate
• Treatment:
– Stage I, Bell’s palsy: amoxicillin or doxycycline for 14-21 days
– Arthritis: amoxicillin or doxycycline for 28 days
– Cardiac, neurological manifestations: ceftriaxone IV for 21 days
Ehrlichiosis
• Due to rickettsia-like bacteria
• Two forms:
– Monocytic – South Central USA (HME)
– Granulocytic – Upper Midwest,
Northeast (HGE)
• S&S: fever, HA, cytopenias,
elevated AST, +/- rash in HME
• Diagnosis:
– Serology, PCR
– Inclusions in WBC (morula) – low
sensitivity
• Treatment: doxycycline
• Has been called “spotless RMSF”
Other Zoonoses
•
•
•
•
•
•
Q Fever
Brucellosis
Leptospirosis
Malaria
Leishmaniasis
Cysticercosis
Q Fever – Coxiella burnetii
• Reservoir: livestock
• Exposures: aerosols from infected animals, esp. slaughter
house, after birthing; drinking contaminated birthing
products
• S&S: fever, headache, myalgia, cough, N/V, abdominal pain
• Clinical manifestations: granulomatous hepatitis, culture
negative endocarditis, pneumonia
• Diagnosis: serology: seroconversion usually detected 7-15
days after onset of illness
• Treatment: doxycycline, long duration for endocarditis:
minimum of 18 months!
Brucellosis – Brucella sp.
• Brucella sp.: B. abortus (cow), B. suis (pig), B. melitensis
(goat), B. canis (dog)
• Risk factor: consumption of unpasteurized dairy products,
especially Mexican goat cheese
• Clinical manifestations: non-specific febrile illness; enteric
fever (fever + abdominal pain), septic arthritis, sacroiliitis,
hepatitis, splenitis, meningitis, endocarditis, orchitis,
hematologic disorders
• Diagnosis: blood/marrow cultures (slow-growing); serology
• Treatment: doxycycline + (rifampin or streptomycin)
Leptospirosis – Leptospira interrogans
• Infects many domestic and wild animals
• Human infection after exposure to environmental sources, such as animal
urine, contaminated water or soil, or infected animal tissue. Portals of
entry include cuts or abraded skin, mucous membranes or conjunctiva.
• Think of if flu-like illness and environmental exposure (eco-challenge,
adventure racing, triathalon, whitewater rafting)
• Usually contamination arises from infected rat and dog urine
• S&S: fever, myalgias, headache, N/V, conjunctival suffusion, meningitis,
nephritis/ATN, hepatitis (high bilirubin, minimal increase in transaminases);
pneumonia
• **Weil’s syndrome: more severe hepatitis, renal involvement
• Diagnosis: clinical, serology (IgG ELISA, MAT: microscopic agglutination),
blood, urine, and CSF cultures
• Treatment: PCN G, doxycycline
Malaria
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•
•
•
Common cause of fever in returned travelers
Presents w/ fever, chills, malaise, HA, myalgias, GI symptoms
Symptoms cyclical, due to w/ rupture of parasitized RBC (48-72h)
Signs: hemolytic anemia, splenomegaly, hypoglycemia,
thrombocytopenia, transaminitis, indirect hyperbilirubinemia,
hemoglobinuria
• For P. falciparum, 1-2 weeks after infection; longer for others
• Order thick and thin blood smears on all febrile travelers from
endemic areas
Malaria
• P. falciparum
– widespread, drug-resistant, lethal
– high parasitemia (>1%), can have >1
parasite per RBC, banana-shaped
gametocytes, paucity of mature
schizonts
• P. vivax
– widespread, less virulent
– often see gametocytes and schizonts
• P. ovale
– much less common
– often see gametocytes and schizonts
• P. malariae
– much less common
– often see gametocytes and schizonts
• P. vivax and ovale can relapse
(dormant liver stages/hypnozoites)
Malaria - Treatment
• P. falciparum
– Preferred
-Quinine + doxycycline
-Quinine + suladoxinepyrimethamine
– Alternative
-Quinine + clindamycin
-Mefloquine
-Atovaquone/proguanil
• P. vivax, ovale
– Blood stage treatment
• Chloroquine
– Eradication of the
hypnozoite stage is
necessary to prevent
relapses
• Primaquine
Bioterrorism Agents: Anthrax
• Other forms, but pneumonic/inhalational for BT
• Fever, chills, malaise, fatigue, N/V, cough, respiratory
disease, shock, and death within 24-36 hours of severe
symptoms
• Inhalational  mediastinal widening
• Incubation period: range 2-50 days; 4-6 days if inhaled
• Diagnosis: gram stain, culture, ELISA, blood, skin,
pleural fluid, CSF
• Standard isolation precautions
• Chemoprophylaxis: cipro 500 bid x 60d; alt: doxy,
amoxicillin
Anthrax: Cutaneous and Inhalational
Boxcar-shaped gram positive rod
Mediastinal widening
Bioterrorism: Botulism –
Clostridium botulinum
• Neurotoxin of spore-forming Clostridium botulinum
• Inhalational: Incubation period 12 hours to several days
• Key clinical features:
– cranial nerve palsies (ptosis, diplopia, dysphagia)
– followed by symmetrical descending flaccid paralysis
– patients are afebrile, alert, and oriented
• Death usually due to respiratory failure
• Standard isolation precautions
Bioterrorism: Plague – Yersinia pestis
• Primary pneumonic plague – rare, think aerosolized, BT
– Incubation 1-3 days
– Fulminant pneumonia- watery, bloody sputum in previously
healthy persons
– Septic shock, DIC
– Diagnosis: gram stain of blood or sputum (small gram
negative coccobacillus) – bipolar staining (“safety-pin”); DFA
at Public Health lab
– Infection control: transmissible person-to-person by
respiratory droplets – gown, glove, and droplet precautions
(also need eye protection if aerosols anticipated)
Bioterrorism: Tularemia –
Francisella tularensis
• Humans are accidental hosts, following contact with infected
animals (especially rabbits and other rodents)
• Some occupations confer risk for tularemia; they include
laboratory workers, landscapers, farmers, veterinarians,
hunters, trappers, cooks, and meat handlers.
• If bioterrorism event, probably airborne delivery
• Symptoms after 3-5 days or as long as 2 weeks
– Fever, chills, HA, myalgias, arthralgias, diarrhea, dry cough
– Can progress to pneumonia w/ pleuritic CP, hemoptysis, respiratory
failure
• Not spread person to person, so no need for isolation
Bioterrorism: Smallpox
Contact and Airborne Precautions Necessary
CDC Major Criteria
• Febrile prodrome occurring 1-4 days before rash onset: fever and
at least one of the following: prostration, HA, backache, chills,
vomiting, or severe abdominal pain
• Classic smallpox lesions: deep, firm/hard, round, wellcircumscribed; may be umbilicated or confluent
• Lesions are in the same stage of development on any one part of
the body (i.e. face or arm)
CDC Minor Criteria
• Centrifugal distribution: greatest concentration of lesions on face
and distal extremities
• First lesions on oral mucosa or palate, face, forearms
• Patient appears toxic
• Slow evolution: lesions evolve from macules to papules to pustules
over days
• Lesions on palms and soles (majority of cases)
Appearance of Smallpox Lesions
Hemorrhagic-type variola major lesions. Death
usually ensued before typical pustules developed.
Food-borne Illness
•
•
•
•
Secondary to bacteria, viruses, parasites or ingestion of bacterial toxins
Remember to report to Department of Health
Often nausea, vomiting, diarrhea and/or abdominal pain
Timing can be helpful
– 1-6 hours: Staph aureus, Bacillus cereus (preformed enterotoxins)
– 8-16 hours: Clostridium perfringens, B. cereus
– 16-72 hours: Campylobacter, Salmonella, Shigella, E. coli, Yersinia, Vibrio
• Associations
• Rice – Bacillus cereus
• Potato salad, cream pastries, poultry – Staph
• Home-canned foods – Clostridium perfringens
• Honey – Clostridium botulinum
• Apple cider, undercooked hamburgers - STEC
Infectious Diarrhea
• Classified
– Community-acquired
– Healthcare-associated
– Persistent (>7d)
• If healthy
– Bacteria/viral infection self-limited regardless of treatment
– Greater than 7 days duration suggestive of parasitic infection or
noninfectious etiology
• Who gets stool culture?
– Yes, if diarrhea present for >72h (esp. if fever, bloody or mucoid stools)
– No, if present > 1 week, or if starts more than 3d after admission
• What grows?
– Salmonella, Shigella, Campylobacter, (EHEC if ordered)
Infectious Diarrhea Associations
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•
•
•
•
•
•
•
•
•
•
•
Bloody stools (EHEC, Shigella, Salmonella, Campylobacter, Entamoeba)
Raw eggs and reptiles (Salmonella)
Recent abx or hospitalization (C diff)
Seafood/seawater (Vibrio)
Travel (ETEC, EAEC, parasites)
Cruise ship (norovirus)
Hikers (Giardia)
Freshwater (Aeromonas, Plesiomonas)
Pork chitterlings or pseudoappendicitis (Yersinia)
Puppy/kitten w/ diarrhea, chicken salad (Campylobacter)
Daycare centers (Shigella, Giardia, rotavirus, norovirus)
Guillain-Barre Syndrome (Campylobacter)
Pathogens
Treatment
S. Aureus, B. Cereus
None
Non-typhoid Salmonella spp.
None
(Treat if severe illness, elderly, bacteremic, prosthetics, valvular
disease, atherosclerotic disease, IC, malignancy)
Shigella
Oral quinolone
(Always treat, 3 days, or 7 days if IC)
Campylobacter
Azithromycin X 1-3 days
(Treat only if severe illness, high fever, gross blood, elderly,
pregnant or IC)
Yersinia
Oral quinolone X 3 days
(Treat only if IC, bacteremic or pseudoappendicitis syndrome)
ETEC (traveler’s diarrhea)
Oral quinolone X 1-3 days
EHEC: Shiga toxin-producing E. coli
(including O157:H7)
None – avoid, as can precipitate HUS
Entamoeba histolytica
Metronidazole 750 mg tid X 7-10 d
Then paromomycin 500 mg tid X 7 d
Giardia spp.
Metronidazole 250-500 mg tid X 7-10 d
Clostridium difficile infection
• Most commonly presents after extended antibiotic use (any kind)
– Clindamycin, FQ, cephalosporins most common offenders
• Increasingly severe secondary to more virulent strain
(NAP1/BI/O27)
• Signs and symptoms include
– Foul-smelling, watery diarrhea w/ mucous, cramping, tenesmus, abd.
tenderness
– Fever in 15%; if present, severe
• Complications: toxic megacolon, perforation, sepsis
Clostridium difficile infection
• Diagnosis toxins in stool
– EIA up to 30% false negative (so x3); PCR more sensitive and specific (x1)
– Don’t test formed stools, don’t test for clearance
• Treatment
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–
–
–
–
Wash hands with soap and water (not ETOH)
Stop inciting antibiotics if possible
Oral metronidazole for mild-mod disease, repeat same if relapse (20%)
Severe (wbc>15, colitis on CT, low albumin, fever) =>PO vancomycin
Severe w/ MOF, ileus or toxic megacolon =>PO vanco, IV metro, surgery
consult
Have you had more than enough?
The End.