3/15/2017

Cases in Infectious Diseases NO DISCLOSURES

Richard A. Jacobs, M.D., PhD.

Case Records of the Massachusetts General Hospital Case Presentation

A 22 yr old comes to the office complaining of the acute onset of unilateral • Periventricular heterotopia due to an FLNA of the right side of his face. mutation and congenital alveolar dysplasia. Your diagnosis is Bell’s Palsy.

N Engl J Med 2017; 376:562‐574

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What is Your Therapy? Etiology of Facial Nerve Palsy

100% • 50% are idiopathic (Bell’s Palsy) 1. Prednisolone • Herpes Simplex/Varicella Zoster (Geniculate 2. Acyclovir ganglion) – Direct invasion v. immunologic/inflammatory 3. Prednisolone + • Lyme disease (most common cause of bilateral FN acyclovir palsy) 4. Nothing • Other infections—CMV, EBV,HIV • Non‐infectious—Diabetes, sarcoid, tumors,

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Therapy of Bell’s Palsy Therapy of Bell’s Palsy

• 839 patients enrolled within 72 hours of • Quite controversial onset of symptoms • Because of the association with herpes – Placebo + placebo (206) the use of acyclovir has been felt to be – Prednisilone (60mg X 5 days then reduced beneficial by 10 mg/day) + placebo (210) • – Valacyclovir (1000mg TID X 7 Days) + Two well done prospective, randomized, placebo (207) controlled, blinded studies have been done – Valacyclovir X7 Days + prednisolone X10 Days (206)

Lancet Neurol 2008;7:993‐1000

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Therapy of Bell’s Palsy

Prednisilone Prednisilone • Case closed on therapy??? NO!! + valacyclovir

Placebo • Other less powered studies and subgroup Valacyclovir analyses suggest that acyclovir might be + placebo beneficial in the most severe cases – Minimal or no movement of facial muscles and inability to close the eye

Take Home Points Case Presentation

• 57 yo male with polycystic kidney disease, • Early treatment (within 72 hours of gout, HTN and hyperlipidemia onset) recommended • Underwent bilateral nephrectomies and renal • For most cases prednisolone for 10 days transplant (CMV D +/R‐). Required ATG post‐ is adequate transplant • For severe cases (complete or near • Immunosuppression—mycophenolate 360 mg complete paralysis) prednisolone for 10 BID, tacrolimus 7 mg BID and prednisone 5 mg days + valacyclovir 1000mg TID for 7 days is recommended QD; prophylactic ganciclovir

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Case Presentation (cont) Case Presentation (cont)

• Shortly after transplant sustained an “injury” • P&SH to his (R) ankle resulting in pain and swelling – Lives in Oakland, CA • About 2 months post‐transplant, at a routine – No travel clinic visit his ankle was warm, red, tender and – No unusual food/animal exposures swollen. • BCs X 2 neg • • WBC‐ 12.5 (4.0‐11.0), CRP‐72 (<6.3) and xray Urine culture‐100,000 CFU of MRSA showed an effusion • Aspiration – Bloody fluid with 102,000 WBCs & 96% PMNs • Admitted for evaluation – Negative for crystals

Case Presentation (cont) Case Presentation (cont)

• Cultures/stains from aspiration and OR were • The following day he was taken to the OR for I&D all negative for bacteria, fungus and AFB – Chronic appearing inflammation with friable synovium • About one week later, because of failure to • WORKING DIAGNOSIS—transient S. aureus improve, an MRI‐c/w with intraosseous abscesses bacteremia from septic (R) ankle with S. aureus . • Back to the OR – • Started on vancomycin & ceftriaxone pending No gross purulence cultures – “cystic void” in the calcaneus and talus that were opened

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Case Presentation (cont) What is your diagnosis?

• Cultures for: 1. Gout – Bacteria 2. S. aureus – Fungus 3. Yeast infection (candida) – AFB 4. Mold infection • Additional specialized tests (aspergillus/rhizopus) 5. AFB‐MTb or NTM • 1 week later a diagnosis was made 6. Other

University of Washington Molecular Diagnostic Laboratory Can submit tissue, paraffin blocks or sterile fluid DNA sequencing for: UREAPLASMA UREALYTICUM Bacteria (16S ribosomal RNA) Yeast (26S ribosomal RNA) Moulds (28S ribosomal RNA)

http://depts.washington.edu/molmicdx/mdx/te sts/bctseq.shtml

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Culture Negative Septic Arthritis Culture Negative Septic Arthritis

• Prior • Sensitivity of the test ( ≈90%) • Reactive arthritis • Lyme disease (Borrelia spp.) – Following diarrhea • Fastidious organisms • Salmonella, Shigella, Campylobacter, Yersinia, C. difficile – Brucella – Coxiella (Q ) – Following urogenital infections – Legionella • Chlamydia trachomatis – – Whipple’s disease – Mycoplasma (immunoglobulin deficiency)

Case Presentation Should Prophylaxis Be Given?

100% • The dentist of your 45 year old female patient with MVP and moderate mitral 1.Yes regurgitation calls wanting to know if she needs prophylaxis for a root 2.No canal and which one.

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Prophylaxis for Endocarditis Prophylaxis for Endocarditis

• Paradigm shift in recommendations – Lack of published data showing benefit • Original AHA Guidelines in 1997 – Transient bacteremia occurs commonly as a result of normal daily activities • Major revision by AHA in 2007 with several • Brushing and flossing—20%‐68% updates, the most recent in 2014 (J Am Coll • Toothpick—20%‐40% Cardiol. 2014;63(22):e57) • Chewing food—7%‐51% – Endocarditis is more likely to occur from frequent bacteremias associated with daily activities than from bacteremias caused by dental, GI or GU procedures

Prophylaxis for Endocarditis High Risk Procedures

DENTAL PROCEDURES • Prophylaxis recommended ONLY for: Manipulation of the gingivial tissue: HIGH RISK PROCEDURES ROUTINE DENTAL CLEANING In TOOTH EXTRACTION HIGH RISK INDIVIDUALS Manipulation of the periapical region of the tooth: ROOT CANAL

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High Risk Procedures High Risk Procedures

RESPIRATORY PROCEDURES SKIN & MUSCULOSKELETAL PROCEDURES

Violation of the respiratory mucosa Drainage of an abscess TONSILLECTOMY/ADNOIDECTOMY antibiotics directed at S. aureus and Group A BRONCHOSCOPY WITH BIOPSY Drainage of infected material DRAINAGE OF AN EMPYEMA

Procedures for Which Endocarditis Conditions of Highest Risk Prophylaxis is NOT Recommended • Included • Not included • GI PROCEDURES – Prosthetic heart valves – Bicuspid aortic valve – Risk of bacteremia low even with biopsy (2%‐5%) – Prior endocarditis – Acquired aortic or mitral valve disease and organisms involved rarely cause endocarditis – Cyanotic heart disease • Unrepaired • MVP with regurgitation • GU PROCEDURES • Partially repaired • Prior valve repair – Risk of bacteremia high with bacteriuria • Repaired within last 6 – Hypertrophic months cardiomyopathy with – TREAT BACTERIURIA BEFORE PROCEDURE – Heart transplant with latent or resting “valvulopathy” obstruction

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Back to the Patient Recommended Regimens ( Single Dose 30‐60 min Before Procedure) • She had a high risk procedure—root canal Situation Agent Adult Dose • BUT did NOT have a high risk heart Oral regimen Amoxicillin 2 g Allergic to Cephalexin or 2 g condition—MVP with regurgitation penicillin or Clindamycin 600 mg ampicillin or (minor allergy) Azithromycin/ 500 mg Clarithromycin NO PROHYLAXIS INDICATED Allergic to Clindamycin 600 mg penicillin or or ampicillin Azithromycin/ 500 mg (anaphylaxis, Clarithromycin angioedema or urticaria

Case Presentation Should Prophylaxis Be Given?

100%

• The dentist of your 65 year old patient who is 9 months s/p total hip 1. Yes arthroplasty calls wanting to know if prophylaxis should be given for a root 2. No canal

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Dental Prophylaxis for Prosthetic Dental Prophylaxis for Prosthetic Joints Joints—2013 Guidelines • GOOD NEWS • Area of controversy for years between the ADA, AAOS and IDSA – 2004 AAOS & ADA recommendation prophylaxis if joint placed within past 2 years – 2009 AAOS recommends prophylaxis for all prosthetic joints regardless of when placed – Promise of collaboration with joint guidelines – 2013 AAOS & ADA propose new guidelines

Dental Prophylaxis for Prosthetic Dental Prophylaxis for Prosthetic Joints—2013 Guidelines Joints—2013 Guidelines • GOOD NEWS • GOOD NEWS – The practitioner might consider discontinuing the – The practitioner might consider discontinuing the practice of routinely prescribing prophylactic practice of routinely prescribing prophylactic antibiotics for patients with hip and knee antibiotics for patients with hip and knee prosthetic joint implants undergoing dental prosthetic joint implants undergoing dental procedures. procedures. • BAD NEWS

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Dental Prophylaxis for Prosthetic Dental Prophylaxis for Prosthetic Joints—2013 Guidelines Joints—2013 Guidelines • GOOD NEWS • GOOD NEWS – The practitioner might consider discontinuing the – The practitioner might consider discontinuing the practice of routinely prescribing prophylactic practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic antibiotics for patients with hip and knee joint implants undergoing dental procedures. prosthetic joint implants undergoing dental • BAD NEWS—> Grade of Recommendation is procedures. Limited • BAD NEWS—> Grade of Recommendation is • Practitioners should be cautious in deciding Limited whether to follow a recommendation classified as Limited

What TO DO?? ADA Recommendations

• In 2014 the ADA Council on Scientific Affairs • Disconnect between organisms causing PJIs convened an expert panel to clarify the 2013 and mouth flora ADA/AAOS confusing recommendations – Late infections almost always due to skin flora (S. epi, P. acnes, corynebacterium spp) not streptococci found in the mouth • Bacteremias common as a result of everyday activities • Best study cited in the recommendations: (Clin Infect Dis 2010;50:8-16) • Dental procedures do NOT increase the risk of PJI

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ADA Recommendations Take Home Points

• In 2014 the ADA Council on Scientific Affairs convened an expert panel to clarify the 2013 ADA/AAOS confusing recommendations • Prophylaxis NOT indicated for pins, • CLINICAL RECOMMENDATION: plates, fixation devices, THA or TKA – In general, for patients with prosthetic joint regardless of when the implant was implants, prophylactic antibiotics are NOT placed recommended to dental procedures to prevent prosthetic joint infections

JADA 2015:146(1):11‐16

Drug Allergies Types of Hypersensitivity Reactions

• Important to use DOC to maximize outcomes • TYPE I‐IgE‐mediated immediate‐type • Use of alternative drugs hypersensitivity – Within 1 hour – Worse outcomes – Anaphylaxis, angioedema, bronchospasm, urticaria – More adverse drug reactions (hives) – More readmissions • TYPE IV‐cell‐mediated delayed‐type – Often more costly hypersensitivity – Greater than 72 hours – Maculopapular rash

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History Very Important Cross‐Reactivity among β‐lactams

• Timing (early v delayed) and nature of the 2-3% reaction ??? • Is the reaction a true allergy or is it just an adverse drug reaction?—nausea, diarrhea, Penicillin ??? abdominal pain, HA, yeast vaginitis —>No Cephalosporin concern ??? <1% 0% 0% • Has the patient received cephalosporins before – If previously tolerated OK to administer

0% Carbapenem Monobactam (Imipenem/meropenem (aztreonam) Ertapenem) Slide courtesy Kathy Yang

What Would You Do At This Point? Skin Testing: Clinical Pearls

• Skin tests for cephalosporin not standardized 1. Prescribe vancomycin • Only useful for detecting IgE mediated 2. Skin test with hypersensitivity reactions to PCN cephalosporins • A negative skin test has a high NPV—>OK to give a 3. Skin test with penicillin cephalosporin 4. Give cefazolin • A positive skin test—>2‐3% chance of cross reactivity with cephalosporins some of which are Type I • 80% with IgE‐mediated PCN allergy have lost the sensitivity after 10 Years

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cephalosporin administration to patients What Would You Do At This Point? with a history of penicillin allergy

1. Prescribe vancomycin 2. Skin test with PCN Skin testing cephalosporins 3. Skin test with penicillin Negative Positive 4. Give cefazolin

Give Options cephalosporin 1. Give alt drug 2. Give cephalosporin with graded challenge 3. Desensitize to cephalosporin

Take Home Points Case Presentation

• Of individuals with a H/O PCN allergy very few • A 36 y/o F underwent a reduction mammoplasty are truly allergic (5%‐10%) • Per protocol she was on Keflex® 500 mg TID for 7 • A careful history can usually determine days – Allergic from adverse drug reactions • Post‐op day #5 she developed wound breakdown – IgE‐mediated reactions from delayed reactions with serous drainage • When in doubt, PCN skin testing is very useful • Antibiotics were changed to Avelox® with a high NPV —> if negative OK to give • Despite this her wound worsened and she was penicillins, cephalosporins, carbapenems. admitted to the hospital for IV antibiotics and debridement

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Case Presentation Case Presentation

• A 36 y/o F underwent a reduction mammoplasty and abdominoplasty • Per protocol she was on Keflex® 500 mg TID for 7 days • Post‐op day #5 she developed wound breakdown with serous drainage • Antibiotics were changed to Avelox® • Despite several days of Avelox® her wound worsened and she was admitted to the hospital for IV antibiotics and debridement

Case Presentation Case Presentation

• She was taken to surgery where she had an I&D BEFORE systemic antibiotics (vanco & Zosyn®) were started • Her cellulitis progressed despite broadening coverage (vanco/meropenem/caspofungin) and she was taken to surgery 3 more times over the next week • All intra‐operative cultures were negative and she was eventually transferred to UCSF

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Case Presentation What Is The Diagnosis?

1. Fungal infection 2. NTM (M. abscessus/chelonae) • An Infectious Disease Consult was called and a 3. Hydradenitis suppurativa diagnosis was made 4. Sweet’s syndrome 5. Pyoderma gangrenosum

Case Presentation Pyoderma Gangrenosum

• Neutrophilic dermatosis • Occurrence – IBD • Review of the pathology slides revealed soft – After trauma tissue necrosis with abscess formation c/w – Cosmetic surgery PYODERMA GANGRENOSUM • Pathergy • Clue to diagnosis – Worsening disease with negative cultures

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Take Home Point Masqueraders of Cellulitis (Fallagas ME et al. Ann Intern Med 2005;142:47)

• If it looks like a typical case of cellulitis but • Superficial and deep venous thrombosis does does not respond to what should be • Contact dermatitis appropriate therapy • Insect stings/tick bites • Fixed drug eruptions – Get a Dermatology Consult for biopsy to R/O • Hydradenitis suppurativa mimickers of cellulitis • Erythema nodosum • Panniculitis • Sweet’s syndrome • Pyoderma gangrenosum

CASE PRESENTATION What Would You Do At This Point?

• A 45 year old man awoke the day prior to 1. Rapid strep test presentation with a . Throughout the 2. Antibiotics without day the sore throat worsened, and he had testing difficulty eating dinner because of pain. The next 3. Observe without morning he awoke with an even worse sore antibiotics (send home) throat and an elevated temperature of 103.5˚ F. 4. Send to ENT In the office he complained of a severe sore 5. Order head/ CT throat, his temperature was 98˚ F and his had mild erythema without .

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SORE THROAT DIAGNOSIS NOT TO MISS

• • Uvulitis • Para and • Angioedema/anaphylaxis • Diphtheria • Foreign Body • HIV

Uvulitis SORE THROAT DIAGNOSIS NOT TO MISS

• Epiglottitis • Uvulitis • Para and retropharyngeal abscess • Angioedema/anaphylaxis • Diphtheria • Foreign Body • HIV

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SORE THROAT DIAGNOSIS NOT TO Diphtheria MISS

• Epiglottitis • Uvulitis • Para and retropharyngeal abscess • Angioedema/anaphylaxis • Diphtheria • Foreign Body • HIV

When To Suspect Epiglottitis Adult Epiglottitis

• Increasing incidence in adults (decreasing in children • “Worst sore throat of my life” due to Hib vaccination) • Adults ‐‐more indolent (days vhours) and less toxic –With minimal findings on exam appearing • Dx made by direct visualization –Hoarse/muffled voice – fiberoptic laryngoscopy less likely to provoke spasm than mirror exam –Severe odynophagia – Lateral neck films less sensitive than laryngoscopy, but still good in adults – 77% ‐ 88% sensitive (“thumb sign”)

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“Thumb Sign” Adult Epiglottitis

• Bacteriology – H. influenzae/parainfluenzae; S. pneumoniae; Gp A strep; S. aureus (MSSA & MRSA) • Therapy – Antibiotics –3rd generation cephalosporin +/‐ vancomycin (severe sepsis or require intubation) – Airway maintenance—not standard as it is in children – Steroids—Controversial—generally not given as no clear benefit demonstrated

Diagnosis of Gp A Streptococcal Case Presentation

• 20 year old previously healthy male • Day 1 • Onset of sore throat with fever • IDSA (Infectious Disease Society of America) • Day 2 – Rapid strep test – Evaluated in office—exudative pharyngitis with • ACP (American College of Physicians) and the AAFP tender anterior cervical adenopathy, h/o fever and (American Academy of Family Practice) no (4/4 of Centor Criteria) – Modified Centor Criteria – Azithromycin started (within 24 hours of onset of symptoms)

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Modified Centor Criteria Case Presentation

• 20 year old previously healthy male

• Day 1 – Onset of sore throat with fever • Day 2 – Evaluated in office—exudative pharyngitis with tender anterior cervical adenopathy, h/o fever and no cough (4/4 of Centor Criteria) – Azithromycin started (within 24 hours of onset of symptoms) Score 3 or 4 —> Rx empirically

Case Presentation Case Presentation

• Day 3 – PC—not better—still with sore throat and fever – Plan—continue azithromycin • Day 5 • Day 6 – Phone Call—not better – PC‐‐SOB and pleuritic chest pain • Diffuse , difficulty swallowing, pain on – Instructed to go to ED for evaluation (R) side of neck – Plan‐‐to finish Azithromycin; encourage fluids; ibuprofen for symptom relief; call if not better

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Case Presentation Case Presentation‐‐CXR

• ED evaluation – WBC—21,400 with 51% PMNs and 42% bands – Plts—16,000 – BUN 80, Cr 4.2 – PTT 50; FDP elevated – pH 7.29 with elevated lactic acid – CXR, chest CT and BCs obtained

Case Presentation—Chest CT Case Presentation—

Fusobacterium necrophorum

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Lemierre’s Syndrome What Went Wrong?

• Natural History of GpA Streptococcal Pharyngitis • Infection with Fusobacterium necrophorum – w/o therapy, symptoms better in 3‐4 days resulting in septic thrombophlebitis of the internal jugular vein often associated with – With early therapy (24 hours) symptoms bacteremia and septic pulmonary emboli. resolve 24‐48 hours sooner

Fusobacterium necrophorum Fusobacterium necrophorum

• Anaerobic gram‐negative rod • Student Health Service in the US • Common upper respiratory organism in • Students age 15‐30 presenting with a sore ADOLESCENTS AND YOUNG ADULTS (age 15‐30) • Can isolate F. necrophorum from 10% with sore throat throat (equal in frequency to gp A streptococcus) – F. necrophorum detected (by PCR) in 20.5% • Peritonsillar abscesses—F. necrophorum isolated in 23% (most in pure culture) c/w gp A – Gp A strep detected in 10.3% streptococcus—17%

Ann Int Med 2009; 151:812‐ Ann Int Med 2009; 151:812‐815 815 Ann Int Med 2015;162:241‐247 Ann Int Med 2015;162:241‐247

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Pharyngitis in Adolescents Take Home Points

• Pharyngitis in the adolescent and young adults • Fusobacterium necrophorum (ages 15‐30) can be more complicated than – Resistant to azalides and macrolides previously thought (azithromycin/clarithromycin) • ALTHOUGH CONTROVERSIAL, SOME HAVE – Sensitive to penicillins, cephalosporins and RECOMMENDED clindamycin – In patients 15‐30 years of age, with a Centor score of >3 and negative diagnostic tests for gp A strep to treat with penicillin, amoxicillin or a cephalosporin

Trivia Question # 1‐‐Which President Take Home Points Died of ?

100% 1. John Quincy • WHAT IS NOT CONTROVERSIAL (Quinsy ?) Adams? – Remember the natural history of pharyngitis 2. Thomas Jefferson – If patients do not improve as expected think about complications 3. George • Peritonsillar abscess Washington • Retropharyngeal abscess 4. Andrew Jackson • Lemierre’s syndrome

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