Open Wide: Big Bolus of ID 2014 Internal Medicine Board Review Friday, July 18 th Jason Parham, MD, MPH.

Open Wide: Big Bolus of ID

2014 Internal Medicine Board Review

Friday, July 18th

Jason Parham, MD, MPH

Board Question

Breakdown

• 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

Infectious Disease (9%) 19–21 Q

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 criteriaGAS & 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%)

• MinorFever, 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– 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

– 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

QuestionAn 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. Amoxicillinb. Bactrimc. Ceftriaxoned. Doxycyclinee. 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 GuidelinesOutpatient General Medical Ward ICU/Severe

If no significant risks for DRSP*:Macrolide or doxycyclineIf risks for DRSP*:Antipneumococcal fluoroquinoloneORHigh-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)ORAntipneumococcal fluoroquinolone alone

Beta-lactam (ceftriaxone, cefotaxime, ampicillin/sulbactam) plus IV azithromycin or IV fluoroquinoloneIf 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:

– 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, ampicillin-

sulbactam 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, piperacillin-tazobactam 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)

– 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• 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 MeningitisBacterial 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(less than 18 strongly predictive)

>45 (nl-50% of serum glu)

< 45 < 40

Protein 100-500 mg/dl (nl 20-401mg/1000 rbcs)

< 200 (slightly elevated)

50-300 >45

Gram stain (+60-90%)

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 TreatmentLocal Drainage Most Important for Skin/Soft Tissue Infections

Drug Issues

Doxycycline 15% resistance

Trimethoprim/sulfa Not good for group A strep

Fluoroquinolone Resistance frequent HA-MRSA

Clindamycin 15% resistance, inducible resistance, positive D test

Linezolid High cost, marrow suppression

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: life-

threatening 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 c-

section, 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 toxin-

producing 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

Osteomyelitis• Diagnostic tests

– 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 doseB) Benzathine penicillin G 2.4 million units IM in

three consecutive doses once a week for three weeksC) Aqueous crystalline penicillin G 4 million units IV q4hrs for 14 daysD) 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 slapArgyll 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-lecithin-cholesterol 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

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 ataxiaMRI shows cerebellar mass and brain biopsy shows septate hyphae with branching at acute anglesWhat is your diagnosis?A.) MucormycosisB.) CryptococcusC.) AspergillusD.) Blastomycosis

Fungal Question 1

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 lossExam: T 103, + cervical and axillary LAD, and splenomegalyWBC 2000, Hgb 8, Plts 75KHis peripheral smear is shown. What is your diagnosis?

A) BlastomycosisB) HistoplasmosisC) CoccidioidomycosisD) Disseminated tuberculosis

Fungal Question 2

39 year old woman from Chicago presents with 3 weeks of fever, dry cough, and pleurisyCXR shows LLL infiltrate, treated with azithromycin without reliefOver the next month, she develops raised, painless skin lesions on her face and cough persistsA skin biopsy is performedWhat is your diagnosis?A) Cryptococcal infectionB) HistoplasmosisC) BlastomycosisD) Coccidioidomycosis

Fungal Question 3

A 48 year old man with no PMHx presents with a non-pruritic rash on his neck and finger. He denies fevers or other symptomsCamped in AZ one month agoWBC 7000 with 12% eosinophils, CXR is clear. HIV Ab is negativeA skin biopsy is performedWhat is your diagnosis?A) HistoplasmosisB) CoccidioidomycosisC) BlastomycosisD) Paracoccidioidomycosis

Fungal Question 4

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

MMWR 2003

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=>hyperuricemiaEMB=>optic neuritis INH=>neurotoxicity

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• 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 + suladoxine-pyrimethamine

– 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: SmallpoxContact and Airborne Precautions NecessaryCDC 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, well-circumscribed; 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• 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 TreatmentS. Aureus, B. Cereus None

Non-typhoid Salmonella spp. (Treat if severe illness, elderly, bacteremic, prosthetics, valvular disease, atherosclerotic disease, IC, malignancy)

None

Shigella (Always treat, 3 days, or 7 days if IC)

Oral quinolone

Campylobacter (Treat only if severe illness, high fever, gross blood, elderly, pregnant or IC)

Azithromycin X 1-3 days

Yersinia(Treat only if IC, bacteremic or pseudoappendicitis syndrome)

Oral quinolone X 3 days

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 dThen 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– 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.