ID BOARD REVIEW 2009

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ID BOARD REVIEW 2009

• Amanda Peppercorn, M.D.
• Assistant Professor of Medicine
• University of North Carolina at Chapel Hill

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Toxic Shock Syndrome

• Group A Strep
• Any invasive GAS infection (bacteremia, nec fasc,
  gangrenous myositis flesh eating) complicated
  by case definition of TSS
• Exotoxin superantigens (complicated about 1/3 of
  invasive GAS infections)
• Associated bacteremia common
• Staph aureus toxins
• Food poisoning?staph enterotoxin
• Staph Scalded Skin?exfoliative toxin
• CA-MRSA?Panton-valentine leukocidin toxin
• TSS?TSST-1 superantigen (interact directly with
  invariant region of MHC II molecule with
  activation of up to 20 of all T cells with
  massive cytokine storm)
• Previous association with tampons
• Usually MSSA but MRSA has been reported

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Desquamation
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TSS Case Definition

• Fever Tgt38.9C (102.0F)
• Hypotension
• SBPlt90 or lt5 percentile by age for childrenlt16
  years of age
• orthostatic drop in DPBgt15mmHg
• orthostatic syncope/dizziness
• Rash diffuse macular erthyroderma
• Desquamation 1-2 weeks after onset of illness,
  usually palms and soles
• Multisystem involvement (3 or more)
• GI (vomiting, diarrhea at onset of illness)
• Muscular (severe myalgias, elevated CPK)
• Mucous Membranes (vaginal, oropharyngeal or
  conjunctival hyperemia)
• Renal (creatininegt2 times ULN or pyuriagt5 WBC)
• Hepatic (elevated bilirubin or transaminasesgt2
  times ULN
• Hematologic (plateletslt100K)

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Treatment

• Supportive, often hemodialysis, pressors, ICU
  care (intractable hypotension/capillary leak)
• Strep
• Emergent surgical debridement if soft tissue
  primary source (pain out of proportion to exam)
• Empiric Clinda (900 iv q8) imi/dori/meropenem
  or pip/tazo? Taylored PCN G Clinda
• IVIG
• ?immunomodulators ex TNFa inhibitors?
• MSSA clinda oxacillin/naf/cefazolin, IVIG
• MRSA clinda vancomycin, IVIG

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NECROTIZING INFECTIONS

• Necrotizing fasciitis, type 1
• Mixed infection anaerobes plus strep or GNR
• Incubation 48-96 h progression hrs days
• Marked pain, tenderness, swelling, crepitus,
  foul-smelling
• Necrotizing fasciitis, type 2
• Grp A strep (flesh-eating bacteria)
• Incubation 6-48 h progression a few days
• Often with toxic shock, bullae, no crepitus
• Pain out of proportion to exam

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Acute Sinusitis

• Acute Fever, facial pain, edema, erythema,
  maxillary toothache
• Subacute Presumed viral sinusitis with no
  improvement in 7d
• S. pneumoniae H. influenzae M. catarralis
• Also MRSA, aspergillus, anaerobes from mouth
  flora (rare)
• Amoxicillin/Clavulanate 875 mg PO Q12h x 10 d
• Levofloxacin 750 mg PO Q24h x 10 d
• Reserve antibiotics for patients failing
  decongestant therapy and facial pain, purulent
  discharge and/or severe illness
• Treatment for full duration of therapy is
  essential to prevent relapses
• Supportive therapy decongestants and
  antihistamines
• Complications extension through bone to
  brain?brain abscess
• Diabetics, immunocompromised think rhinocerebral
  Mucor

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Actinomycosis

• Branching filamentous anaerobic gram positive
  rod, higher order bacteria appearance like a
  fungus
• Characteristic sulfur granules (balls of
  organisms) in tissue/pathology samples
• Normal part of oral flora
• Cause oropharyngeal disease (dental abscess, jaw
  osteo, etc)
• Also cause of uterine infection (IUDs), abdominal
  abscesses
• Differentiate from nocardia by anaerobic
  principally and modified AFB stain (nocardia,
  actino negative)
• Treatment PCN, cephalosprins (keflex), clinda

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Physiology and Resistance Mechanisms of S aureus

• S aureus is a virulent human pathogen with the
  ability to elaborate a range of virulence factors
  and toxins gram positive cocci in clusters
• Resistance to methicillin first appeared in 1961,
  attributed to inheritance of a mecA gene found on
  the mobile staphylococcal cassette chromosome mec
  (SCCmec)
• Genetic analysis suggests that mecA has been
  transferred to S aureus over 20 times, resulting
  in 5 major lineages
• MecA gene cassette leads to genetic alteration of
  penicillin binding protein, conferring
  resistance to all penicillin and cephalosporin
  family of antibiotics

WTAwall teichoic acid PVLPanton-Valentine
leukocidin CHIPchemotaxis inhibitory protein.
Zetola N et al. Lancet Infect Dis.
20055275-286. Deresinski S. Clin Infect Dis.
200540562-573. Foster TJ. J Clin Invest.
20041141693-1696.
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COMPARISONCA-MRSA AND HA-MRSA
CA-MRSA HA-MRSA
Clinical spectrum Skin and soft tissue Respiratory tract, UTI, bloodstream infections
Epidemiology Clusters and outbreaks in closed populations Healthcare-associated outbreaks
Underlying condition Dermatological HAI risk factors
Age group Younger Older
Race/ethnicity
Resistance pattern Susceptible to multiple antibiotics Resistant to multiple antibiotics
Genotype sccMec IV sccMec I, II, or III
Virulence PVL present PVL absent
Diederen BMW, et al. JID 200652157-168
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Risk Factors for CA-MRSA

• Athletes (close phyical contact)
• Military personnel
• Children
• Native Americans
• HIV
• MSM
• Prisoners
• Young sexually active
• Family members (dont forget to ask!)
• Majority of patients have no identifiable risk
  factors

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Syphilis

• Early primary--painless chancre, secondary
  (weeks to couple months after primary)rash
  (infectious) rarely pustular, condyloma lata (MM,
  moist areas) and systemic sx (fever, HA, malaise,
  LAD), early latent (first year)
• Late late latent, tertiary (gummas,
  cardiovascular, neurosyphilisuveitis, ocular
  nerve damage, dementia, paresis, tabes dorsalis,
  meningitis, cranial neuropathies)
• HIV primary and secondary can overlap
• Syphilis a reportable disease
• Treatment earlyIM PCN, doxy as alternative,
  neurosyphilisIV PCN x 14 days
• Response to treatment 4 fold decrease in
  VDRL/RPR at 1 year

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Palmar involvementsecondary syphilis
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Labial Condyloma Lata, Secondary Syphilis
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CDC ISOLATION GUIDELINES

• Isolation Precautions
• Standard precautions
• Airborne precautions
• Special airborne precautions
• Droplet precautions
• Contact precautions
• Protective precautions

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STANDARD PRECAUTIONS

• Hand hygiene Before and after each patient
  contact after gloves removed
• The wearing of artificial fingernails or
  extenders is prohibited (based on CDC guidelines)
• Gloves When touching contaminated items (blood,
  body fluids, secretions, excretions)
• Mask, eye protection, face shield Whenever
  splashes or sprays of body fluids possible
• Gown Whenever splashes or sprays of body fluids
  possible

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AIRBORNE PRECAUTIONS

• Isolation
• Private negative pressure room
• Direct out exhausted air
• N95 respirator
• Representative pathogens
• M. tuberculosis
• Varicella, Zoster (immunocompromised)
• Measles

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SPECIAL AIRBORNE PRECAUTIONS

• Isolation
• Airborne eye shields
• Representative pathogens
• Avian influenza
• Monkeypox
• SARS Co-V
• Smallpox
• Viral hemorrhagic fever (e.g., Ebola, Lassa)

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DROPLET PRECAUTIONS

• Isolation
• Private room
• Mask
• Representative pathogens
• Invasive N. meningitidis
• RSV
• Bordetella pertussis
• Rubella, Mumps
• Group A streptococcal pharyngitis
• Invasive H. influenzae

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CONTACT PRECAUTIONS

• Isolation
• Gloves
• Gowns
• Representative pathogens
• Clostridium difficile
• HSV
• Varicella/zoster
• VRE, MRSA
• MDR pathogens (resistant to two or more classes
  of pathogens)

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BOARD REVIEW QUESTIONSINFECTION CONTROL

• 42 TB airborne, removal isolation
• 61 Varicella airborne contact
• 88 Tularemia no person-to-person
• 113 C. difficile contact enhanced
  environmental cleaning (spores)

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POST-EXPOSURE PROPHYLAXIS

• Animal bite wound
• Anthrax
• Avian influenza
• Diphtheria
• Hepatitis A
• Hepatitis B
• HIV
• Human bite wound
• Influenza A
• Influenza B
• Measles

• Meningococcal infection
• Monkey bite (B virus)
• Monkeypox
• Pertussis (whooping cough)
• Rabies
• Smallpox
• Syphilis
• Tuberculosis (TB)
• Varicella (chickenpox)
• Zoster (shingles)

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POST-EXPOSURE PROPHYLAXISUSING VACCINES

• Hepatitis B lt7 days (alternative HBIG)
• Measles lt3 days (alternative Ig)
• Rabies ASAP (plus RIG) prior to symptoms
• Tetanus Post-wound (no time limit)
• Small Pox lt4 days
• Varicella lt4 days (alternative VZIG or
  acyclovir)
• Outbreak control Hepatitis A, pertussis,
  meningococcal
• May need to be provided with an immunoglobulin
  preparation

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POST-EXPOSURE PROPHYLAXIS USING ANTI-INFECTIVES

• Animal bite Amoxacillin-sulbactam x 5 days
• Influenza Oseltamivir or zanimivir
• Lyme disease can offer Doxy 200 mg x 1 (with
  many caveatsdefinite Ixodes, long
  attachment36hrs, high endemic region20 ticks
  with disease, present within 72hrs, adults and
  childrengt8, non-pregnant)
• Meningococcus Ciprofloxaxin 400 mg (alternative
  ceftriaxone IM)
• Pertussis Azithromycin x 5 days (alternative
  TMP-SMX for 7-14 days)
• HIV combination antiretrovirals, data supports
  starting ASAP, no benefit after 72 hours (CDC 36
  hours)

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NO POST-EXPOSURE PROPHYLAXIS

• Adenovirus conjunctivitis
• Hepatitis C
• Mumps
• Parvovirus B19
• Rubella
• Severe acute respiratory distress syndrome (SARS)

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PATHOGENS ASSOCIATED WITH SKIN AND SOFT TISSUE
INFECTIONS
Cat bite Pasteurella sp (P. multocida), Franciscella tularensis
Dog bite P. multocida, Capnocytophaga canimorsus, CDC group EF-4
Human bite Eikenella corrodens, Fusobacterium, streptococci, Preotella, etc.
Rat bite Spirillum minor (systemic Streptobacillus moniliformis)
Snake bite Aeromonas hydrophila
Shark bite Vibrio carchariae
Pig bite Erysipilothrix rhusiopathiae
Animal hides Bacillus anthracis, Franciscella tularensis
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PATHOGENS ASSOCIATED WITH SKIN AND SOFT TISSUE
INFECTIONS
Injection drug use S. aureus, Clostridium sp., E. corrodens, Grp A strep
Salt water injury Vibrio Vulnificus
Fresh water injury Aeromonas hydrophila
Fish tank exposure Mycobacterium marinum
Fishmonger Erysipilothrix rhusiopathiae, Streptococcus iniae
Medicinal leeches A. hydrophila, Aeromonas sobria, Vibrio fluvialis
Hot tubs Pseudomonas aeruginosa
Plant/soil exposure Sporotrichosis
Soil contamination Nocardia, Clostridium sp., Serratia
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TREATMENT OF MRSA ORAL THERAPY

• Oral regimens (use only after susceptibility
  testing)
• Linezolid (expensive)
• Clindamycin (use only if erythromycin susceptible
  or D test performed to confirm susceptibility)
• Trimethoprim-sulfamethoxazole
• Minocycline
• Monitoring
• Daptomycin CPK each week stop if CPK gt5x ULN
  (symptomatic) or gt10x ULN (asymptomatic) or gt1000
  U/L
• Linezolid CBC with platelets each week do not
  treat gt28 days

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BOARD REVIEW QUESTIONSSKIN

• 68 Osteo in drug user
• 71 Human bite
• 83 Cat bite
• 85 IDU joint infection
• 94 SA infection
• 107 - NTM

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CAP PATHOGENS
Outpatient Inpatient (non-ICU) Inpatient ICU
S. pneumoniae M. pneumoniae H. influenzae C. pneumoniae Respiratory viruses S. pneumoniae M. pneumoniae C. pneumoniae H. Influenzae Legionella spp. Aspiration Respiratory viruses S. pneumoniae S. aureus Legionella spp. Gram-negative bacilli H. influenzae
Influenza A and B, adenovirus, RSV,
parainfluenza
Mandell LA, et al. Clin Infect Dis 200744(suppl
2)27-72
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CAP THERAPY OUTPATIENTS

• Previously healthy and no risk factor for DR-SPn
• No recent antibiotics Macrolide (I),
  doxycycline (III)
• Recent antibiotics FQ, advanced macrolide
  high-dose amoxicillin, advanced macrolide
  high-dose amoxicillin/clav
• Comorbidities Chronic heart, lung, liver, or
  renal disease
• No recent antibiotics Advanced macrolide, FQ
• Recent antibiotics FQ (I), ?-lactam macrolide
  (I), ?-lactam doxycycline (II) ?-lactam high
  dose amoxicillin or amox-clav
• Regions with gt25 high level macrolide resistant
  SPn use alternative agent

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CAP THERAPY INPATIENTS, NON-ICU

• Non-ICU
• FQ (I)
• ?-lactam macrolide (I)
• ?-lactam cefotaxime, ceftriaxone, ampicillin
• ICU
• ?-lactam FQ (I)
• ?-lactam cefotaxime, ceftriaxone,
  ampicillin-sulbactam
• ?-lactam advanced macrolide (II)
• ?-lactam cefotaxime, ceftriaxone,
  ampicillin-sulbactam
• Advanced macrolide azithromycin or
  clarithromycin

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Pneumococcus

• 50 resistance at UNC to all macrolides
  (mechanism alteration of ribosome binding site)
• Vanc susceptible--universal
• Resistance an issue for
• Beta-lactams (penicillins, cephalosporins, and
  carbapenems) 20 PCN R, 5 Cephalosporin R
• Macrolides (erythromycin, azithromycin,
  clarithromycin and lincosamines (clindamycin)
• Tetracyclines and folate inhibitors
  (trimethoprim-sulfamethoxazole TMP-SMX)
• Fluoroquinolones (ciprofloxacin, levofloxacin,
  gemifloxacin, moxifloxacin)
• Meningitis vanc (to cover R pneumococcus), ctx
  (better CNS penetration, good for meningococcus
  and pneumoncoccus), steroids (particularly for
  pneumococcus, to prevent hearing loss and other
  long term complications) although steroids may
  decrease CNS penetration of vancomycin
  ampicillin for young and old and
  immunocompromised (to cover listeria)
• No steroids in places with HIV prevalence and
  presumed meningitis

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BROAD SPECTRUM ANTIBIOTICS

• Carbapenems Imipenem, meropenem (not ertapenem)
• Coverage GPC, GNRs, P. aeruginosa, anaerobes
• Holes MRSA, Listeria, Legionella
• Piperacillin-tazobactamn (not ticar/clav or
  amp/sulbactam)
• Coverage GPC, GNRs, P. aeruginosa, anaerobes,
  enterococci
• Holes MRSA, Listeria, Legionella
• Tigecycline
• Coverage GPC (including MRSA, VRE), GNRs
  (including ESBL producers and Acinetobacter),
  anaerobes
• Holes Pseudomonas aeruginosa, Proteus spp.

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BROAD SPECTRUM ANTIBIOTICS USES

• Sepsis of unknown etiology (GPC, GNR)
• Neutropenic fever (GNR, PA, SA)
• Severe intra-abdominal infections (GNR,
  Enterococcus, anaerobes)
• Gangrenous soft tissue infections (diabetic)
  (GNR, PA, SA)
• Known resistant pathogens (ESBL, Acinetobacter,
  Burkholderia, Pseudomonas)

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Endocarditis

• Updated Duke Criteria 2-1/3-5 (major/minor
  criteria)
• Major sustained bacteremia by organism known to
  cause endocarditis (SA, S viridans, enterococcus,
  HACEK, CNS with pv), endocardial involvement seen
  by echocardiogram (vegetation, abscess OR new
  valvular regurgitation)
• Minor predisposing condition (PPM/vascath, HD,
  IVDA), fever, vascular signs (septic emboli,
  janeway lesions, mycotic aneurysms), immune
  complex phenomena (osler nodes, roth spots,
  glomerulonephritis) blood culture not meeting
  standard criteria
• Categories native valve (bicuspid,
  calcification, prior endocarditis, any valvular
  disease), prosthetic valve (high mortality, need
  rifampin/gent, often requires surgery), IDU (can
  use shorter course of treatment with right sided)
• Culture negative q fever, brucella, bartonella,
  legionella, chlamydia, HACEK, nutritionally
  deficient strep
• Indications for valve surgery persistent
  bacteremia, refractory CHF, myocardial
  abscess/purulent pericarditis, difficult
  organisms (PsA, yeast, MRSA), recurrent septic
  embolic complications, large vegetation

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Tuberculosis

• PPD treatment
• gt5mm HIV, immunosuppressed (TNF inhibitor,
  prednisone 15 mg/d x 1 month), known close
  contact
• gt10mm all other high risk populations
  (prisoners, healthcare worker, RF, homeless,
  immigrants, DM, malignancy, hx gastrectomy,
  malnutrition, etoh, long-term care)
• gt15mm everyone else
• Treatment rule out active disease by CXR and
  symptom screening
• TB considerations BCG (no change in
  interpretation, esp if gt5 years ago), prophylaxis
  and treatment in setting of MDR
• Primary disease?dissemination?control or active
  disease (lungs, LNs, pleurisy, CNStuberculomas,
  basilar meningitis, GI, GUuterine, kidneys,
  bonePotts disease, neck LNScrofula), HIV,
  miliary

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AHA Guidelines for Endocarditis Prophylaxis 2007
Update

• IE is much more likely to result from frequent
  exposure to random bacteremias associated with
  daily activities (eg, tooth brushing) than from
  bacteremia caused by a dental, gastrointestinal,
  or genitourinary procedure.
• Prophylaxis may prevent an exceedingly small
  number of cases of IE, if any, in individuals who
  undergo these procedures.
• The risk of antibiotic-associated adverse events
  exceeds the benefit, if any, from prophylactic
  antibiotic therapy.
• Maintenance of optimal oral health and hygiene
  may reduce the incidence of bacteremia from daily
  activities and is therefore more important than
  prophylactic antibiotics for a dental procedure
  to reduce the risk of IE.

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Updates

• Patients with the following cardiac conditions
  were considered to meet this criterion
• Prosthetic heart valves, including bioprosthetic
  and homograft valves
• Prosthetic material used for cardiac valve repair
  
• A prior history of IE
• Unrepaired cyanotic congenital heart disease,
  including palliative shunts and conduits.
• Completely repaired congenital heart defects with
  prosthetic material or device, whether placed by
  surgery or by catheter intervention, during the
  first six months after the procedure.
• Repaired congenital heart disease with residual
  defects at the site or adjacent to the site of
  the prosthetic device.
• Cardiac "valvulopathy" in a transplanted heart.
  Valvulopathy is defined as documentation of
  substantial leaflet pathology and regurgitation

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• No longer indicated  Common valvular lesions for
  which antimicrobial prophylaxis is no longer
  recommended include bicuspid aortic valve,
  acquired aortic or mitral valve disease
  (including mitral valve prolapse with
  regurgitation and those who have undergone prior
  valve repair), and hypertrophic cardiomyopathy
  with latent or resting obstruction
• Procedures that may result in transient
  bacteremia and are recommended for prophylaxis  
• All dental procedures that involve manipulation
  of either gingival tissue or the periapical
  region of teeth or perforation of the oral
  mucosa.
• Procedures of the respiratory tract that involve
  incision or biopsy of the respiratory mucosa
• Procedures in patients with ongoing GI or GU
  tract infection
• Procedures on infected skin, skin structure, or
  musculoskeletal tissue
• Surgery to place prosthetic heart valves or
  prosthetic intravascular or intracardiac
  materials.

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Botulism gram positive anaerobic rod, toxin
releasing, spore producing, with bioterrorism
potential

• The modern syndrome of botulism occurs in five
  forms, differentiated by the mode of acquisition
  2
• Food-borne botulism ingestion of food
  contaminated by preformed botulinum toxin
• Infant botulism the ingestion of clostridial
  spores that then colonize the host's
  gastrointestinal (GI) tract and release toxin
  produced in vivo
• Wound botulism infection of a wound by
  Clostridium botulinum with subsequent in vivo
  production of neurotoxin
• Adult enteric infectious botulism or adult
  infectious botulism of unknown source similar
  to infant botulism in that toxin is produced in
  vivo in the GI tract of an infected adult host.
• Inhalational botulism the form that would occur
  if aerosolized toxin was released in an act of
  bioterrorism.
• Cranial neuropathies, symmetric descending
  paralysis, no fever, no sensory loss
• The differential diagnosis for food-borne, wound,
  and adult enteric botulism includes myasthenia
  gravis, Lambert-Eaton myasthenic syndrome (LEMS),
  tick paralysis, Guillain-Barré syndrome,
  poliomyelitis, stroke, and heavy metal
  intoxication. Less likely diagnoses include
  tetrodotoxin and shellfish poisoning and
  antimicrobial-associated paralysis
• Dx clinical syndrome, EMG studies, reportable
  disease, stool studies, serum toxin assays
• Treatment supportive (most need intubation),
  antitoxin (equine trivalent anti-toxin for gt1
  year of age, botulism immunoglobulin for
  infants), PCN G for wound botulism

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Giardia

• Flagellated protozoan parasite
• Cysts (live in environment), trophozoites
  (reproductive form)--pear-shaped, binucleate,
  multi flagellated organisms,measures 9-15 µm
  long, 5-15 µm wide, and 2-4 µm thick
• Worldwide, food-borne, water-borne,
  person-person, especially children in developing
  countries
• Other common GI parasite is Cryptosporidium
  parvumGiardia and Crypto problem in normal hosts
  and important in HIV and immunocompromised (less
  common protozoan is E. histolytica)
• Dx stool O and P (cyst and troph), stool
  antigenic testing (ELISA)

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Giardia trophozoite
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Giardiasis

• 60 asymptomatic
• Diarrhea that is sudden in onset and may be
  initially watery 90 percent
• Malaise 85 percent
• Foul-smelling and fatty stools (steatorrhea) 70
  percent
• Abdominal cramps and bloating 70 percent
• Flatulence 75 percent
• Nausea 70 percent
• Weight loss 65 percent
• Vomiting 30 percent
• Fever 10 percent
• Manifestations often wax and wane over many
  months
• Malabsorptionlactase (causes lactose
  intolerance), vitamin A, B12, folate, etc

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Miscellaneous

• Remember syphilis!!
• African tick feverR. africae (look for eschars,
  early fever/myalgias)Amblyoma tick, doxycycline
• Other tick borne diseasesR. rickettsia (dog
  tick, RMSF), Erlichia (deertickIxodes or lone
  star tick), Borrelia (Lyme, Ixodes), Babesia
  (protozoa looks like malaria, only in NE, fatal
  in asplenic pts, Ixodes)
• Anthraxcutaneous (Edema toxin), eschar also
  inhalational (hemorrhagic, widened mediastinum)
  and GI (ingestion of infected animal)
• Candidemia
• Smallpox versus Chickenpoxdegree of fever and
  early timing of systemic symptoms, stage of
  lesions
• Drugs
• daptomycin contraindicated for MRSA pneumonia,
  follow CPK
• Linezolidthrombocytopenia, bone marrow
  suppression, serotonin syndrome
• HIV medsabacavir (fatal hypersensitivity
  syndrome, HLA B5701), protease inhibitorselevated
  lipids, DM, nucleoside RTIsmitochondrial
  toxicity (lipodystrophy, visceral adiposity,
  myalgias, neuropathy), nevirapine (fatal liver
  disease esp in women with high CD4)

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Thank You