Transcript Randall S. Edson, MD, MACP Professor of Medicine Mayo Clinic College of Medicine Internal Medicine Program Director, CPMC San Francisco, CA Division of INFECTIOUS DISEASES ©2011 MFMER | slide-1

Randall S. Edson, MD, MACP
Professor of Medicine
Mayo Clinic College of Medicine
Internal Medicine Program Director, CPMC
San Francisco, CA
Division of
INFECTIOUS DISEASES
©2011
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Disclosures, etc
 No financial disclosures or discussion of off-label
drugs, etc.
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Coming clean……………………..
 Went through express lane with > 12 items
 Forgot to return shopping cart to corral on
one occasion
 Deliberately avoids using the stairs at all
costs, despite ubiquitous signage and
propaganda
Public Service Announcement
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Learning objectives
 Recognize important travel-acquired infections
 Understand the approach to the diagnosis of
LTB
 Diagnose CNS infection based on pattern
recognition
 Review updated guidelines for UTI
management
 Diagnose a mystery rash
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25 yr old ♂ with three week history: fever,
sore throat, fatigue, sweats.
Grad student; just returned from 3 week trip to
Southern Africa. Ate local food, swam in fresh
water, took brief course of ciprofloxacin for
traveler’s diarrhea
Exam: Appears ill; T 38.80; oral ulcers, exudative
pharyngitis, post-cervical nodes, rash rash
Lab: HCT 38%; WBC 12,000(↑lymphs, “atypical”);
mild ↑AST; Mono spot neg; HIV Ab negative
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Which of the following would most likely
establish diagnosis?
a.
b.
c.
d.
e.
EBV serology
CMV serology
Dengue serology
PCR for HIV RNA
Rickettsia africae serology
Acute HIV: Don’t miss!!!
 Occurs in 30-50% of HIV-infected patients
 “Hyper-transmitters” with formidable viral load
 Should be suspected in sexually active patients with
prolonged “mono” syndrome
 Negative HIV antibody common (too early)
 Order PCR/quantitative HIV test
Ann Int Med 1996;125:257 NEJM 1998;339:33
•Symptom onset within 2 weeks of acquisition
•Peak viremia
•10 fold + ↑ risk of transmission
JID 2010:202(Suppl 2):S270
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What’s in your travel kit??
>50,000 new cases of HIV/year in US
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STD in Returning Travelers
Casual sex: 5-51% of short term travelers, ↑ among
long term travelers
Meta analysis: 20% have casual sex abroad;50%
unprotected*
Not usually addressed in pre-travel consults
* Intern J of Inf. Dis 2010;14(10):e842-51
CID 2001;32:1063
J Travel Med 2009;16:79
Distribution of STD’s in ill travelers:1996-2010
Geo Sentinel Surveillance database; Lancet ID 2013;13:205
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Pre-employment evaluation
 28 yr. old ♀ respiratory tech about to begin work at
your hospital
 Mild asthma, controlled with occasional albuterol;
otherwise healthy
 Immigrated to US from Philippines 3 years ago
 Cervical cytology, all adult immunizations current;
received BCG as a child
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Your hospital requires screening for LTB
Which of the following would be the most
appropriate screening test for latent TB?
a) Chest x-ray
b) Interferon-γ release assay
c) PPD(5 TU)
d) PPD(10 TU)
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TB and Latent TB
 1/3 of world population infected with TB
 Latent TB develops in ≈ 30% exposed
 Estimated cases of LTB in US ≈11 million
 Lifetime risk of reactivation 5-10%
 Most clinical TB in US occurs in immigrants from
high prevalence countries
Herrera et al.Clin Inf Dis 2011;52(8):1031
Screening options for Latent TB*
TST(PPD)
Interferon γ release (IGRA) assays
 QuantiFERON®-TB Gold (QFT-GIT)
 T-SPOT®. TB test (T-Spot)
 Mechanism of action
 Patient’s WBC + MTB antigens: ↑ γ-IFN
* Targeted
screening only for those at highest risk
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IGRA
Pros
 Single visit
 Results in 24 hours
 Not affected by BCG
 Minimal cross-reactivity
with other mycobacteria
 Circumvents technical
“challenges” of PPD
administration,
interpretation
Cons
 Must process in 8-30 hrs.
 Limited data: children < 5,
immunosuppression, recent
exposure
 ↑ False + in low prevalence*
*Chest 2012 Jul 1;142:55 and ©10
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When to use IGRA?
 Most situations where PPD is used
 Patients not likely to return at 48-72 hours
 Foreign born patients who received BCG
Both TST and IGRA may be used:
 Foreign-born HCW who attribute + PPD to BCG
 Initial test negative in high risk patients
 “Tie breaker” in low risk patients with + test
MMWR 2010;59(RR-5):1-25
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Game changer in the treatment of latent TB
900mg INH plus 900mg of Rifapentine once weekly for three months
Equally effective as 9 months of daily INH ≈ $40 total
Perfect situation for Directly Observed Therapy (DOT)
Rifapentine is expensive: ≈ $325 for 3 month course
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55 yr. old ♂ farmer with fever and
confusion
 8/2012: difficulty with concentration, spatial
perception; co-workers noted distraction and trouble
with word finding. Day 2: severe HA
 DM2, s/p bariatric surgery, hypertension
 Sexually active, farms and road maintenance
Exam: T 38.50; drowsy; mild neck stiffness
CSF: WBC 165 cells/µL(mostly lymphs)
Protein 150 mg/dL; glucose 61mg/dL
Gram stain: no organisms seen
Develops significant weakness and cogwheeling several hours later
Which one of the following tests would most
likely establish the correct diagnosis?
a.
b.
c.
d.
MRI of head with gadolinium
CSF PCR for Herpes simplex virus
CSF IgM for West Nile virus
CSF serology for enterovirus
4891 cases, 2293(51%) Neuro-invasive, 223 deaths;
70% from 10 states; highest number to date since 2003
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Unintended consequence of
foreclosure
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WNV transmission, life cycle
Hi, I’m Culex sp.
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Flavivirus
West Nile Virus 101
St Louis Encephalitis; Yellow fever; JE
Acquisition: mosquito, transfusion, transplant
Peak incidence: Late August, early September
Incubation: 2 to 14 days
80% asymptomatic
 20% WN fever; < 1% Neuro-invasive
When to suspect West Nile infection
 Mosquito season(especially August)
 West Nile fever is nonspecific: fever and HA
 Characteristic features of neuro-invasive disease
 Acute flaccid paralysis
 Parkinson-like symptoms
 10% mortality with neuro-invasive disease
 Profound, prolonged fatigue may persist for a year
JAMA 2003;290:511 and Lancet Inf. Dis 2002;2:519
Am J Trop Med Hyg 2012:87:179
Annals of Int Med 2008;149:232
Diagnostic time course of West
Nile Virus
Serum or CSF IgM best diagnostic test
IgM antibodies may persist for a year
www.mayomedicallaboratories.com/articles/communique/2008
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A 20 yr old female college student with a 2 day history
of dysuria, urgency and frequency in the absence of
fever, chills, vaginal irritation or discharge; she has had
two previous UTI’s this year, most recently 3 months
ago and received three days of TMP/SMX with
resolution.
What would you do next?
a.
b.
c.
d.
e.
Obtain urine for gram stain and culture
Prescribe trimethoprim-sulfa for 3 days
Prescribe amoxicillin for 3 days
Prescribe nitrofurantoin 5 days
Prescribe ciprofloxacin for 3 days
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When words fail……………
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NEJM 2012;366:1028-37 and Clin Inf Dis 2011;52(5):e103-e120
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Key facts in UTI management
 E.coli increasingly resistant to TMP/SMX, FQ
 Avoid TMP/SMX if local resistance is ≥ 20% or used
w/n last 3 months
 Avoid FQ if local resistance is ≥ 10%
Mayo Antibiogram 2011
More key facts in UTI management
Do not treat asymptomatic bacteriuria(AB) even with
pyuria except:
Pregnancy; post renal transplant
Prior to urologic instrumentation
Unintended consequences of AB Rx
↑ frequency of subsequent symptomatic UTI1
Asymptomatic bacteriuria may be “protective”
Alarming increase in community-acquired multidrug
resistant E. coli 2
1Clin
Infect Dis 2012;55:771
2Mayo
Clin Proc 2012;87(8):753
Antimicrobial Cost Considerations
Nitrofurantoin
TMP/SMX DS
Ciprofloxacin
Fosfomycin
100 mg BID x 5
days
BID x 3 days
500 mg BID x 3
days
3 gram packet
once
$30-35
$9.621
$131
$54-60
$4 for TMP/SMX and Cipro1
Bottom line in UTI management
 Alarming increase in antimicrobial resistance
among community-acquired E. coli
 Treatment guidelines reflect this resistance
 Nitrofurantoin, TMP/SMX, Fosfomycin are top 3
choices
 DO NOT screen for and/or treat AB
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67 yr old man with a rash
 Developed painless nodular, pustular rash 2 weeks ago
 Did not respond to several oral antibiotics and five
infusions of vancomycin
 Swab culture: rare Pseudomonas fluorescence
 Treated with ciprofloxacin without improvement
Examination
 Vital signs normal, afebrile
 Rash on dorsum of left forearm
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What would you do next?
a. Begin anti-mycobacterial Rx
b. Start trimethoprim-sulfa for suspected Nocardia
c. Start antifungal Rx
d. Send to Derm for biopsy
Most likely diagnosis?
a. Squamous cell carcinoma
b. Blastomycosis
c. Nocardiosis
d. Non-tuberculous mycobacterial infection
e. Dermatophyte
Additional history
 5 days before rash onset cleared brush, had exposure
to mud, thorns; recalls many scratches, wearing shortsleeve shirt
 Has cattle, dogs, cats
Results of biopsy/culture
Lab reports growth of
Trichophyton verrucosum
Majocchi’s granuloma
Deep folliculitis due to
dermatophyte infection
Can be transmitted from
cows, horses to humans
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Trichophyton verrucosum
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Clinical bottom line
 The occupational and exposure history can
be critical in broadening the differential
diagnosis
56 year old ♂ with chronic cough,
sweats
 3 month history of productive cough, sweats, weight
loss. No response to several AB courses
 PMH: MS, COPD
 SH: divorced, disabled miner; 50 pack year smoking
history; former daily marijuana smoker, now using
marijuana “chocolates.” Lives in wooded area of
Michigan’s UP
 Recently moved into old house with obvious mold;
spent several weeks using leaf blower; several local
dogs ill with respiratory symptoms
MBF
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Malignancy suspected; second
opinion sought
Physical examination
 Appears cachectic(“hunter-gatherer diet”)
 Afebrile
 Many missing teeth and periodontal disease
 Few rales at right lung base
CBC, electrolytes, etc. all normal
CT chest, 2/20/2013
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Bronchoscopy done on 2/20/13
 Mucopurulent secretions noted in right lower lung.
 A diagnostic result was received……..
Direct smear from BAL fluid
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What is the most likely diagnosis?
a. Bronchogenic CA with post-obstructive pneumonia
b. Mixed aerobic/anaerobic pneumonitis
c. Pulmonary blastomycosis
d. Pulmonary nocardiosis
Blastomycosis
Etiologic agent
Blastomyces
dermatitidis
Natural habitat
Boggy soil,
wood
Location
River valleys:
Ohio, Miss, Mo
Pathogenesis
Inhalation
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Blastomyces
dermatitidis:dimorphic fungus
Mycelial phase in culture
Yeast phase in tissue
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NEJM 1986;314(9):529-34
“Leave it to Beaver”
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Looking for Blastomyces
dermatitidis
Several regional beaver dams were neutralized with dynamite
Tissue tropism of Blastomycosis
SKIN
BONE
Am J Med 2011;124(12):1132
Clin Inf Dis 2008;46:1801(PG)
PROSTATE
Infect Dis Clin of NA 2006;20:645
NEJM 1993;329:1231
56
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Cutaneous manifestation of disseminated Blastomycosis
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Blastomycosis: making the
diagnosis
 Direct smear from clinical specimen
 Culture
 Serology
 Previous CF test had poor sensitivity, specificity
 Newly approved EIA has excellent sensitivity,
specificity
 Urine antigen: high sensitivity, poor specificity
Don’t forget to do your part
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