Infectious Diseases Pearls Randall S Edson MD MACP Professor of Medicine Mayo Clinic College of Medicine Internal Medicine Program Director CPMC San Francisco CA 2011 MFMER slide 1 Disclosures etc ID: 768079
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Infectious Diseases Pearls Randall S. Edson, MD, MACPProfessor of MedicineMayo Clinic College of MedicineInternal Medicine Program Director, CPMCSan Francisco, CA ©2011 MFMER | slide- 1
Disclosures, etcNo financial disclosures or discussion of off-label drugs, etc. ©2011 MFMER | slide-2
Coming clean…………………….. Went through express lane with > 12 itemsForgot to return shopping cart to corral on one occasionDeliberately avoids using the stairs at all costs, despite ubiquitous signage and propaganda
Public Service Announcement
Learning objectives Recognize important travel-acquired infectionsUnderstand the approach to the diagnosis of LTBDiagnose CNS infection based on pattern recognitionReview updated guidelines for UTI managementDiagnose a mystery rash©2011 MFMER | slide-5
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 diarrheaExam: Appears ill; T 38.80; oral ulcers, exudative pharyngitis, post-cervical nodes, rash rashLab: HCT 38%; WBC 12,000(↑lymphs, “atypical”); mild ↑AST; Mono spot neg ; HIV Ab negative
Which of the following would most likely establish diagnosis? EBV serologyCMV serologyDengue serologyPCR for HIV RNARickettsia africae serology
Acute HIV: Don’t miss!!! Occurs in 30-50% of HIV-infected patients“Hyper-transmitters” with formidable viral loadShould be suspected in sexually active patients with prolonged “mono” syndromeNegative HIV antibody common (too early)Order PCR/quantitative HIV testAnn 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
>50,000 new cases of HIV/year in US What’s in your travel kit??
STD in Returning Travelers Casual sex: 5-51% of short term travelers, ↑ among long term travelersMeta 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
Geo Sentinel Surveillance database; Lancet ID 2013;13:205 Distribution of STD’s in ill travelers:1996-2010
Pre-employment evaluation 28 yr. old ♀ respiratory tech about to begin work at your hospital Mild asthma, controlled with occasional albuterol; otherwise healthyImmigrated to US from Philippines 3 years agoCervical cytology, all adult immunizations current; received BCG as a child ©2012 MFMER | 3177424- 14
Your hospital requires screening for LTB Which of the following would be the most appropriate screening test for latent TB?Chest x-rayInterferon-γ release assayPPD(5 TU)PPD(10 TU)©2012 MFMER | 3177424- 15
TB and Latent TB 1/3 of world population infected with TB Latent TB develops in ≈ 30% exposedEstimated cases of LTB in US ≈11 millionLifetime risk of reactivation 5-10%Most clinical TB in US occurs in immigrants from high prevalence countriesHerrera et al.Clin Inf Dis 2011;52(8):1031
Screening options for Latent TB* TST(PPD)Interferon γ release (IGRA) assaysQuantiFERON®-TB Gold (QFT-GIT)T-SPOT®. TB test (T-Spot)Mechanism of actionPatient’s WBC + MTB antigens: ↑ γ-IFN©2012 MFMER | 3177424-17 * Targeted screening only for those at highest risk
IGRA Single visitResults in 24 hoursNot affected by BCGMinimal cross-reactivity with other mycobacteriaCircumvents technical “challenges” of PPD administration, interpretationMust process in 8-30 hrs.Limited data: children < 5, immunosuppression, recent exposure↑ False + in low prevalence* © Pros Cons *Chest 2012 Jul 1;142:55 and 10
When to use IGRA? Most situations where PPD is usedPatients not likely to return at 48-72 hoursForeign born patients who received BCGBoth TST and IGRA may be used:Foreign-born HCW who attribute + PPD to BCGInitial test negative in high risk patients“Tie breaker” in low risk patients with + test©2012 MFMER | 3177424-19 MMWR 2010;59(RR-5):1-25
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
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 HADM2, s/p bariatric surgery, hypertensionSexually active, farms and road maintenanceExam: T 38.50; drowsy; mild neck stiffnessCSF: WBC 165 cells/µL(mostly lymphs) Protein 150 mg/dL; glucose 61mg/dL Gram stain: no organisms seen
Develops significant weakness and cog-wheeling several hours later Which one of the following tests would most likely establish the correct diagnosis?MRI of head with gadoliniumCSF PCR for Herpes simplex virusCSF IgM for West Nile virusCSF serology for enterovirus
4891 cases, 2293(51%) Neuro-invasive, 223 deaths; 70% from 10 states; highest number to date since 2003
Unintended consequence of foreclosure
WNV transmission, life cycle Hi, I’m Culex sp.
West Nile Virus 101 FlavivirusSt Louis Encephalitis; Yellow fever; JEAcquisition: mosquito, transfusion, transplantPeak incidence: Late August, early SeptemberIncubation: 2 to 14 days80% asymptomatic20% WN fever; < 1% Neuro-invasive
When to suspect West Nile infection Mosquito season(especially August)West Nile fever is nonspecific: fever and HACharacteristic features of neuro-invasive diseaseAcute flaccid paralysisParkinson-like symptoms10% mortality with neuro-invasive diseaseProfound, prolonged fatigue may persist for a yearJAMA 2003;290:511 and Lancet Inf. Dis 2002;2:519Am 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 testIgM antibodies may persist for a year www.mayomedicallaboratories.com/articles/communique/2008
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?Obtain urine for gram stain and culturePrescribe trimethoprim-sulfa for 3 daysPrescribe amoxicillin for 3 daysPrescribe nitrofurantoin 5 daysPrescribe ciprofloxacin for 3 days
When words fail……………
NEJM 2012;366:1028-37 and Clin Inf Dis 2011;52(5):e103-e120
Key facts in UTI management E.coli increasingly resistant to TMP/SMX, FQAvoid TMP/SMX if local resistance is ≥ 20% or used w/n last 3 monthsAvoid 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 transplantPrior to urologic instrumentationUnintended consequences of AB Rx↑ frequency of subsequent symptomatic UTI1 Asymptomatic bacteriuria may be “protective”Alarming increase in community-acquired multidrug resistant E. coli 2 1 Clin Infect Dis 2012;55:771 2 Mayo Clin Proc 2012;87(8):753
Antimicrobial Cost Considerations Nitrofurantoin100 mg BID x 5 days$30-35TMP/SMX DS BID x 3 days $9.62 1 Ciprofloxacin 500 mg BID x 3 days $13 1 Fosfomycin 3 gram packet once $54-60 $4 for TMP/SMX and Cipro 1
Bottom line in UTI management Alarming increase in antimicrobial resistance among community-acquired E. coliTreatment guidelines reflect this resistanceNitrofurantoin, TMP/SMX, Fosfomycin are top 3 choicesDO NOT screen for and/or treat AB©2011 MFMER | slide-35
67 yr old man with a rash Developed painless nodular, pustular rash 2 weeks agoDid not respond to several oral antibiotics and five infusions of vancomycinSwab culture: rare Pseudomonas fluorescenceTreated with ciprofloxacin without improvementExaminationVital signs normal, afebrileRash on dorsum of left forearm
What would you do next?Begin anti-mycobacterial Rx Start trimethoprim-sulfa for suspected NocardiaStart antifungal RxSend to Derm for biopsy
Most likely diagnosis?Squamous cell carcinoma BlastomycosisNocardiosisNon-tuberculous mycobacterial infectionDermatophyte
Additional history5 days before rash onset cleared brush, had exposure to mud, thorns; recalls many scratches, wearing short-sleeve shirt Has cattle, dogs, cats
Results of biopsy/cultureLab reports growth of Trichophyton verrucosumMajocchi’s granulomaDeep folliculitis due to dermatophyte infectionCan be transmitted from cows, horses to humans
Trichophyton verrucosum
Clinical bottom lineThe 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 coursesPMH: MS, COPDSH: divorced, disabled miner; 50 pack year smoking history; former daily marijuana smoker, now using marijuana “chocolates.” Lives in wooded area of Michigan’s UPRecently moved into old house with obvious mold; spent several weeks using leaf blower; several local dogs ill with respiratory symptoms
MBF
Malignancy suspected; second opinion sought Physical examinationAppears cachectic(“hunter-gatherer diet”)AfebrileMany missing teeth and periodontal diseaseFew rales at right lung baseCBC, electrolytes, etc. all normal
CT chest, 2/20/2013
Bronchoscopy done on 2/20/13Mucopurulent secretions noted in right lower lung. A diagnostic result was received……..
Direct smear from BAL fluid
What is the most likely diagnosis? Bronchogenic CA with post-obstructive pneumoniaMixed aerobic/anaerobic pneumonitisPulmonary blastomycosisPulmonary nocardiosis
Etiologic agent Blastomyces dermatitidis Natural habitat Boggy soil, wood Location River valleys: Ohio, Miss, Mo Pathogenesis Inhalation Blastomycosis
Blastomyces dermatitidis:dimorphic fungus52 Mycelial phase in culture Yeast phase in tissue
NEJM 1986;314(9):529-34 “Leave it to Beaver”
Looking for Blastomyces dermatitidis Several regional beaver dams were neutralized with dynamite
56 SKIN BONE PROSTATE Tissue tropism of Blastomycosis Am J Med 2011;124(12):1132 Clin Inf Dis 2008;46:1801(PG) Infect Dis Clin of NA 2006;20:645 NEJM 1993;329:1231
Cutaneous manifestation of disseminated Blastomycosis
Blastomycosis: making the diagnosis Direct smear from clinical specimenCultureSerologyPrevious CF test had poor sensitivity, specificityNewly approved EIA has excellent sensitivity, specificityUrine antigen: high sensitivity, poor specificity
Don’t forget to do your part ©2011 MFMER | slide-59