• - Group A beta-hemolytic strep (strep pyogenes) – most common!  Group A strep is more common in children!!
• - Group C and G strep 4th most common 
•  Viruses (rhinovirus) are 3rd most common and produce most of acute cases - Other viruses include herpes, influenza virus, coronavirus and adenovirus 
• Others organisms - Arcanobacterium hemolyticus, corynebacterium dipthariae, neisseria gonorrhea, mycoplasma species, chlamydia species. 
•  “unknown” organisms account for 30% of infections

viruses

-          Viruses (rhinovirus) are 3^rd most common and produce most of acute cases

-          Other viruses include herpes, influenza virus, coronavirus and adenovirus

What is the difference between acute and chronic pharyngitis?

Acute pharyngitis is caused by viral infection, while chronic cases are caused by bacterial infection.

Streptococcus pyogenes: releases toxins à best to use a protein synthesis inhibitor to inhibit toxin production.

Rhinoviruse infection: no cytopathic effect, but inflammatory mediators are activated ex. Bradykinin, which causes pain.

How is pharyngitis diagnosed: 2 methods.

·         Which is the gold standard?

·         Which is commonly used?

-          Throat culture – gold standard for diagnosis of pharyngitis

-          Rapid strep test - commonly used

The 2 most common site of infection of sinusitis are?

-Bacteria sinusitis are more common in children ex. - Strep pneumoniae

- Staph aureus

- Strep pyogenes

- G negatives

- H. influenza

- superimposed H. influenza and strep pneumo infection

- moraxella catarrhalis

- anaerobes (peptostreptococcus, fusobacterium)

-          Viruses are most common in adults ex. Rhinovirus, influenza virus, parainfluenza virus, adenovirus

-          staph aureus, strep epidermidis, and gram (-) anaerobes.

Requirements for diagnosis of acute otitis media.

1.      Rapid onset

2.      Middle ear effusion

3.      Inflammation of middle ear

Differentiate between recurrent acute otitis media, persistent otitis media and chronic suppurative otitis media.

1.      Acute otitis media is recurrent if 3 episodes in 18 months

2.      AOM is persistent if it never completely resolves

3.      Chronic suppurative OM is persisten OM with discharge of pus through a perforated tympanic membrane.

Give 2 reasons why more children suffer from otitis media than adults.

1.  Slope of Eustachian tube: in kids is at a flatter angle than in adults (which is steeper),which makes it easier for organisms to cross from nose to ear.

2. Length of Eustachian tube: in kids are shorter than in adults

What are 3 functions of Eustachian tube?

1.      Protection: Protection from contamination from middle ear from nasal and oral organism, due to slope and length of the tube.

2.      Drainage: Drains middle ear secretions into nasopharynx.

3.      Ventilation: allows middle ear to equilibrate with atmospheric pressure of external ear canal.

4 common pathogens in otitis media. which is the most common cause in children younger than 3 yrs?

-          Streptococcus pneumonia

-          H. influenza

-          Morexella catarrhalis

-          Group A strep (S. pyogenes)

-          Viruses – common if younger than 3 yrs old

4 Difference between normal and abnormal tympanic membrane, as seen in AOM?

Abnormal tympanic membrane:

-          Erythematous

-          More opaque with pus/exudate

-          Landmarks structures are obscured

-          Tympanic membrane bulges outward

-          Low light reflection

Decreased mobility of tympanic membrane

5 Differences between middle ear effusions and otitis media.

-          MEE has fluid bubbles

-          No erythema is seen in MEE

-          TM is not opaque in MEE, but has a pink, yellow or gray color

-          Some landmarks are visible in MEE

-          Only similarity with AOM: decrease TM mobility and reduced hearing

___ is common organism if recurrent otitis media.

___ are common organism if chronic otitis media.

3 main pathogenesis of otitis media

1. -          Abnormal anatomy: eustachian tube dysfunction
2. -          Host defenses: weel IgG, IgA, abnormal ciliary function, HIV+
3. environmental factors: day care, URTI, bacterial colonization, bottle feeding

Complications of untreated or inadequately treated Acute otitis media.

1.      Hearing loss or speech problems

2.      Development delays

3.      Mastoiditis

4.      Chronic suppurative otitis media

5.      Cholesteatoma – cyst-like mass, lined with stratified epithelia cells, debris, and cholesterol

Difference between chronic and acute bronchitis.

·         Which is only seen in adults?

·         Which is self-limiting?

  Acute – occurs in all ages (self-limiting but can lead to asthma or COPD)

- Viruses are most common

-  Some due to bacteria ex. Mycoplasma, chlamydia, strep pneumo, H. influenza

Chronic – adults only

-          Nonspecific disease
-          Not specific group of pathogens causes bronchitis, both respiratory bugs are primary culprits

4 differences between acute and chronic bronchitis.

1.      In acute lasts no more than 5 days, while in chronic cough can be mild or severe and incessant

2.      Sore throat is seen in acute, while expectoration of purulent sputum and halitosis is seen in chronic.

3.      Fever is seen in acute but not in chronic

4.      Acute has rhonchi or coarse, moist bilateral rales, while chronic has inspiratory and expiratory rales, rhonchi and mild wheezing.

5.      Purulent sputum also seen in acute

6.      Cyanosis and digital clubbing can be seen in chronic but not acute

7.      Chest x-ray is often normal in acute, but abnormal in chronic

Pen V is 1^st line, macrolides (Azithromycin) or Cephalosporins

What is difference between chronic and acute osteomyelitis?

-          Acute: days to 1 week onset, but symptoms under 4 weeks

-          Chronic: symptoms last more than 1 month without treat or relapse of initial infection

•   Contiguous (most common – 47%): infection spreads from adjacent soft tissue infection or surgical/traumatic introduction of bacteria to bone.

-          Most common in adults : ptns > 50 yrs old

-          Often due to multiple organisms (other types are usually caused by one organism)

   Vascular insufficiency (2^nd most common):

-          Extremely hard to manage

-          Ptns usually have an underlying disease (diabete mellitus, atheresclerosis) or older age > 50

-          Diabetic foot ulcers often becomes osteomyelitis.

•  Hematogenous (most common in children):  infection spreads via blood stream.

-          Common in kids < 16 yrs old and some adults > 50yrs old

-          Starts in the metaphysis and maybe preceded by minor injury

-          Neonates = joint osteomyelitis

-          Children = thin cortex and loose periosteum à “involucrum" development

-          Adults = thick cortex, tight periosteum à may spread to adjacent structures 

Which route of osteomyelitis infection is common in children? Which is common in adults?

Hematogenous = common in children

Contigous = common in adults >50 yrs

Vascular insufficiency = harder to manage & underlying disease usually present ex. diabetic foot ulcer

What are the site of hematogenous osteomyelitis involvement commonly seen in:

neonates, Adults, children, IV drug users, sickle cell patients?

-          Neonates: long bones and joints (multiple bones)

-          Children: long bones only (femur, tibia, humerus)

-          Adults > 50 yrs: vertebrae

-          Risk factors: DM, blunt trauma to spine, UTI

-          IV drug users: vertebral, sternum and pelvis

-          Sickle cell: long or tubular bones

   S. aureus (90%), Group B streptococci, GNB  

 Nafcillin + Cefotaxime

S . aureus (60-90%), Streptococci, (+/- H. influenza < 5 yrs)

Nafcillin + Cefotaxime OR Ceftriaxone for unvaccinated children (age < 5 yrs )

 S. aureus (major), Streptococci, (GNB, Mycobacterium)

Nafcillin

MRSA, Pseudomonas, other GNB, S. epidermidis  

Vancomycin + Antipseudomonal agent

Salmonella, S. aureus

Nafcillin + Cefotaxime / Ceftriaxone

Polymicrobial: S. aureus, S.epidermidis, Pseudomonas, other GNB, Streptococci, anaerobes

  Piperacillin/tazobactam  (or Imipenem, Cefepime plus metronidazole) + Vancomycin (for MRSA)

MRSA: vancomycin (target trough: 15-20 mcg/mL), daptomycin (6 mg/kg/day), linezolid, TMP/SMX (4 mg/kg/dose as TMP) BID + rifampin (600 mg QD), clindamycin (600 mg IV q8h)

When treating bone and joint infection, always cover ____.

Consider ___ for treating streptococci and gram (-) caused osteomyelitis in children.

What is the duration of treatment for osteomyelitis?

-          Treat for up to 4-6 weeks (IV then oral)

-          MRSA treak for minimum of 8 weeks

-          Do not stop treatment until clinical resolution of symptoms

What are the criteria for oral use for osteomyelitis?

-          Osteomyelitis is confirmed

-          Clinical improvement seen with IV treatment

-          Organism cultured is susceptible to oral therapy

-          Oral agent is bioavailable at site of infx

-          Surgical removal of necrotic tissue if needed

-          Patient is compliant with oral formulation

-          Monitor ptn closely

Who are candidates for oral therapy for osteomyelitis?

-          Children with good clinical response to IV therapy (dicloxacillin, cephalexin, or  amoxicillin, based on culture & sensitivity)

-          Adults without diabetes or peripheral vascular disease, with an organism that is susceptible to a fluoroquinolone

What are 2 non-drug therapy for osteomyelitis?

• Surgical debridement:

-          If chronic

-          always in chronic disease

-           if pus or dead bone is found

-           if patient fails to  respond to antibiotic therapy

•      Hyperbaric oxygen therapy

What are the 2 types of infectious arthritis?

Which is monoarticular?

Which is the most common in children?

Which is more common in males?

Which is more common in females?

Non-gonococcocal & Gonococcal

Monoarticular = non-gonococcal

Children & Males = non-gonococcal

Females = gonococcal

What are the 3 sources of infection in the pathophys of infectious arthritis?

Which is most common?

Which is commonly from osteomyelitis that drains into joints?

Hematogenous

Direct inoculation

Contiguous 

Most common = hematogenous

from osteomyelitis that drains into joints = contiguous

What is the treatment for infants with infectious arthritis ?

•      Infants < 1 month: S.aureus, Group B Strep, GNB

• 

Nafcillin + Cefotaxime or Aminoglycoside

What is the treatment for children with infectious arthritis without vaccination?

•      Children (immunized for H. influenza type B): S. aureus,  Streptococci, (age< 5 yrs: H. influenzae)

•    

Nafcillin + Cefotaxime or Ceftriaxone for unvaccinated children (age < 5 yrs)

What is the treatment for people with STD and infectious arthritis?

 Ceftriaxone or  Cefotaxime

What is the treatment for people with prothetic joints or post-surgery infectious arthritis?

•      Prosthetic joint or post-procedure/surgery: S. epidermidis, MRSA, Streptococci, GNB, pseudomonas

•  

 Vancomycin + Zosyn

What is the treatment for Adults unlikely to have STD but have infectious arthritis?

•      Nafcillin + Cefotaxime (or Gentamicin or Fluoroquinolone)

What is the treatment for IV drug user with infectious arthritis?

•      IV drug abusers: Pseudomonas, Enterobacteriaceae, S. epidermidis, MRSA

 Vancomycin + Zosyn

Nongonococcal: 2-3 weeks of antibiotics 

Gonococcal: 7-10 days of antibiotics 

Q1. AB, 10 years old girl c/o R leg pain (began 4 days ago) and fever (101.5⁰F)

PMH: acute otitis media x2 (at 2 years old)

PE: tenderness over right distal femur

Lab: WBC 9.5 x 10 ³ cells/mm³ (normal, 5-10), ESR 55 mm/hr (normal, 0-5)

Plain Radiograph: normal

Blood cultures: pending

→Sent home with pain medication

2 days later: hospitalized b/c severe pain and tenderness in her R leg and high fever

Blood cultures: S. aureus

Lab: CRP 10 mg/dL (normal, <2)

Plain Radiograph: normal

Bone scan: inflammation in the R distal femur

1. What findings are consistent with osteomyelitis? 

2.  What kind of osteomyelitis?

3. Give empiric treatment.

1. Bone inflammation, elevated ESR and CRP, fever, localized pain, inflammation of bone,  and positive blood culture.

2. Acute hematogenous (most common in neonates and children).

3. Empiric therapy: Nafcillin, Cefazolin or Oxacillin

Describe community-acquired pneumonia.

•      Community acquired pneumonia is  an acute infection of the alveoli,  distal airways and interstitial tissues of the lungs that occurs outside the hospital.

•       It is a lower respiratory infection

CD, 38 years old male, c/o R knee pain (x 5 days), swelling, unable to flex the joint

PE: fever (102⁰F), joint effusion→aspirated for cell count, Gram’s stain & culture

PMH: cellulitis (6 months ago)

Lab: WBC 12 x 10 ³ cells/mm³ (normal, 5-10), ESR 45 mm/hr (normal, 0-5)

Synovial fluid: WBC 80 x 10 ³ cells/mm³  with 90% neutrophils,

Gram-positive cocci (Gram’s stain)

Cultures: pending

1. What findings are consistent with septic/infectious arthritis?

 2.  What kind of septic/infectious arthritis?

 3. Empiric antibiotic therapy?

1. Elevated WBC & ESR, fever, acute monoarticular paint  and swelling.

2.  Non-gonococcal

3.  allergic history: PCN allergy

            most common pathogen: staph aureus

            Since PCN allergy, use: Clindamycin or Vancomycin

•      streptococcus pneumonia (75%) and H. influenza

•      atypicals - Legionella, chlamydia pneumonia, mycoplasma pneumonia

•      inhalation

•      aspiration

•      hematogenous spread

Altered sensorium and Neuromuscular disease

- resulting in decreased ability to clear organism from oropharynx

-          CBC with differentials : leukocytosis with high polymorphonuclear cells (PMNs)

-          Arterial blood gas or pulse oximetry : low O2 saturation

- Chest radiograph: Dense lobar or segmental infiltrate

a. previously healthy outpatient: macrolide  or doxycycline

b. hospitalized patient in general medical ward: respiratory flouroquinolone  or advanced macrolide + Beta lactam

c. hospitalized patient in ICU:

treat for MRSA with Vancomycin or Linezolid

for P. auriginosa with no BL allergy =  Zosyn (if no BL allergy) + azithromycin or respiratoryFQ or 750 mg Levofloxacin QD or aminoglycoside + azithromycin, or an antipseudomonal FQ with aminoglycoside .

If  allergic to Blactam=  aztreonam in place of the beta lactam.

If no pseudomonas and no allergies = beta lactam + azithromycin or respiratory FQ

but  if no pseudomonas and no allergy = beta lactama +azithromycin or respiratory flouroquinolones.

What is the treatment for a CAP out-patient that:

·         Has suspected aspiration with infection?

·         Was previously healthy?

·         Comorbid infection?

·         Recent use of antibiotics?

·         Influenza with bacterial superinfection?

-          Suspected aspiration with infection =      Augmentin or  Clindamycin

Previously healthy: Macrolide (Azithromycin, Clarithromycin or Erythro) or Doxycylcine

-          Comorbid conditions or recent antibiotic therapy (w/in 3 months):

-          respiratory floroquinolone (Levofloxacin, Moxifloxacin & Gemifloxacinà only Gemi is not IV) 

-          Advanced macrolide (or doxycycline) + High dose Amoxicillin  (1g Po TID)

-          Advanced macrolide (or doxycycline) + High Augmentin (2g PO BID)

-          Influenza with bacterial superinfection: Oral beta lactam (Aminopenicillins) or Respiratory FQ (Levo, Moxi & Gemi)

-          Confusion

-          Urea (>7mmol/L or BUN >20)

-          Respiratory rate (>30bpm)

-          Blood pressure (SBP <90 mmHg or DBP <60 mmHg)

-          65 – age greater than 65 yrs

what is the treatment for inpatient CA-pneumonia?

what if allergic to beta lactam?

-          Respiratory FQ – Levo, Gemi and Moxifloxacin

-          Or Advanced Macrolide (Azithromycin) + BL (Amoxicillin?)

If patient is allergic to beta lactams? – if ptn cant remember PCN rxn, assume it’s anaphytic in nature

-          Ceftriaxone IV + clarithromycin PO

-          Unasyn

-          Doxycycline IV

-          Levofloxacin IV

Which of the followings is the most common pathogen to cause community-acquired pneumonia?

a.      Staphylococcus aureus

b.      Streptococcus pneumoniae

c.       H. influenzae

d.      Mycoplasma pneumoniae

AB, 40 years old female, came to the ER with chief complain of high fever, chills, and productive cough. After physical exam and lab tests (including chest x-ray), AB was diagnosed with community-acquired pneumonia. AB was previously very healthy and didn’t have any medical problem (no known drug allergy). Which antibiotic therapy will be the most appropriate for AB?

a.      Azithromycin

b.      Moxifloxacin

c.       Amoxicillin/clavulanate

d.      Ciprofloxacin

CD, 65 years old male, was just admitted to the medicine floor for CAP. CD was diagnosed as CHF 10 years ago and has been taking medications for CHF since then. CD reported he had allergy to penicillin, but didn’t remember what the reaction was. What antibiotic will be the most appropriate for the management of CD’s CAP?

a.      Ceftriaxone IV + clarithromycin  PO

b.      Ampicillin/sulbactam IV

c.       Doxycycline IV

d.      Levofloxacin IV

Answer = A

Medical ward/inpatient CAP = Respiratory FQ (Levo, Moxifloxacin & Gemifloxacin) or 

Advanced Macrolide (Azithro & Clarithromycin) + Beta Lactam

EF, 70 years old female, was admitted to ICU for CAP. What antibiotic will be the most appropriate for EF’s CAP? What are alternatives if patient has severe beta lactam allergy?

ICU therapy:

Pseudomonas + No allergy: BL + Respiratory FQ or Azithromycin

No pseudomonas + allergic: replace BL with Clindamycin

Pseudomonas + allergy: Antipseudomonal BL + Antipseudomonal FQ or Aminoglycoside + Azithro OR Aminoglycoside + Antipseudomonal FQ 

Pseudomonas + allergy: replace antipseudomonal BL with Aztreonam

Pseudomonas risk factors:

1. Severe structural lung disease (i.e. bronchiectasis, cystic fibrosis)
2. chronic steroid administration
3. alcoholism
4. frequent antibiotic therapy

5 days - must be afebrile 48-72 hrs and should have no more than 1 CAP-associated sign of clinical instability

1.       When patients are clinically stable for 24 hours

a.       Temperature ≤ 37.8^oC (100 ^oF) - no fever

b.      Respiratory rate ≤ 24 breaths/min - no tachyapnea

c.       Heart rate ≤ 100 beats/min - no tachycardia

2.       Be able to take oral medications

3.       Have adequate GI function to absorb the agent selected

Risk Factors for MDR Pathogens

• Antibiotics within 90 days
• Current hospitalization ≥ 5 days (Late-onset pneumonia)
• High frequency of antibiotic resistance in the community or in the specific hospital unit
• Immunosuppressive disease and/or therapy
• Risk factors for HCAP

6 Risk Factors for Health care acquired pneumonia

• Hospital stay ≥ 2 days within 90 days
• Nursing home or extended care facility resident
• Home infusion therapy
• Chronic dialysis within 30 days
• Home wound care
• Family with MDR pathogen

Which of the followings is NOT the risk factor for MDR pathogens?

a.      Patient lives in a nursing home

b.      Patient has been getting IV vancomycin therapy at home for osteomyelitis.

c.       Patient was treated for UTI with ciprofloxacin last week.

d.       Patient was admitted to the ICU for 5 days last year.

Early onset:

o   S. pneumoniae

o   H. influenzae

o   MSSA

o   E. coli

o   K. pneumoniae

o   Proteus

Late Onset - always a risk factor

o   ESBL producing K. pneumoniae

o   P. aeruginosa

o   Acinetobacter

o   MRSA

o   Legionella 

Agents for Patients with NO risk factors for multi-drug resistant pathogens or Early onset pneumonia

• Ampicillin/sulbactam  3 g q6h

• Ceftriaxone 1 g – 2 g q24h

• Ciprofloxacin (400 mg q12h), levofloxacin (750 mg q24h), or moxifloxacin (400 mg q24h)

• Ertapenem  1 g q24h

Anti-MRSA agent ( 600mg Linezolid Q12H or 15mg/kg Vancomycin Q12H) 

+

Anti-pseudomonal BL (Zosyn  or Ceftazidime or Cefepime or Imipenem/Cilastatin or Meropenem)

+

Antipseudomonal Aminoglycoside or Flouroquinolone

Which of the followings is NOT recommended for early onset pneumonia?

a.      Ampicillin/Sulbactam 3 g IV q6h

b.      Piperacillin/Tazobactam 4.5 g IV q6h

c.       Levofloxacin 750 mg IV q24h

d.      Ceftriaxone 1 g IV q8h

-          Water diarrhea is more common (90% of cases) than inflammatory

-          Inflammatory has blood in stool, while watery is just ….watery

-          Watery is less frequent (<10 per day) than inflammatory (>10)

-          There are few or no polymorphonuclear cells in watery but many in inflammatory

-          Toxins and reduced absorption are causes of watery, while mucosal invasion by microbes is cause of inflammatory

-          Organisms that cause watery include:

-          Vibrio cholera,

-          Enterotoxigenic E. coli (ETEC), Enteropathogenic E. coli (EPEC),

-          Rotaviruses,

-          Noroviruses

-          Organisms that cause inflammatory include:

-          Salmonella

-          Shigella

-          Campylobacter

-          Yersinia

-          Enetrohemorrhagic E. coli (EHEC),

-          Enteroinvasive E. coli (EIEC)

-          Enteroaggregative E. coli (EAEC)

-          Cytotoxigenic C. difficile

What are ways that GI infection is diagnosed?

•      Stool Culture -      very low yield      Routine culture: detect Campylobacter, Salmonella, Shigella

•      Toxin test - •      E coli O157:H7 and     C. difficile toxins A and B

•      Microscopic examination: fecal polymorphonuclear cells

•      Immunoassay: neutrophil marker lactoferrin

•      Can screen for Ova & Parasites

What is the most common cause of GI infections in the U.S? World?

US: bacteria

Worldwide = virus

What is the cause of antibiotics-associated non-infectious diarrhea?

Change intestinal mucosa (caused by Neomycin)

•      Stimulate motilin receptors (caused by Erythromycin à increased GI motility)

What is the difference between acute, persistent and chronic diarrhea?

-          Acute diarrhea: Duration of symptoms is less than 14 days

-          Persistent diarrhea: Duration of symptoms is greater than 14 days

-          Chronic diarrhea: Symptoms have been present for greater than 4 weeks

-          Fluid replacement (dehydration if >10 diarrhea per day) à replace water and electrolyte

-          Oral rehydration therapy (245 mmol/L) contains: Glucose, Na, K, Cl, and water (e.g.; Pedialyte)

-          IV hydration (if severe or hypovolemic shock) : LR or Normosaline

What type of anti-motility is recommended for GI infection? When is it contraindicated?

-Antimotility agents (diphenoxylate  and loperamide) 

-Symptom relief

-Contraindicated with presentation of high fever or bloody diarrhea --> prevents elimination of toxins

•Delays clearance of infectious microbes

•Increases toxin absorption

•Extended toxin-associated damage

What type of absorbent is recommended for GI infection?

-          Kaolin-pectin/aluminum hydroxide 

What type of anti-secretory agent is recommended for GI infection? What is the caveat?

-          Bismuth subsalicylate

•       not recommended for routine use due to the risk of bismuth subsalicylate overdose

When is antibiotics used for GI infections?

•      Antibiotics

•      Usually not indicated and empiric use may worsen condition

Only used antibiotics for some confirmed infections due to Shigella, Campylobacter and Yersini

What antibiotics increase risk of c. diff.

•      More frequent: Clindamycin, ampicillin, cephalosporins, fluoroquinolones

•      Less frequent: Aminoglycosides, erythromycin, TMP-SMX, vancomycin, metronidazole.

Differentiate between toxin A and B of C. diff. which one is an enterotoxin? Which one is most potent?

-          Toxin A (TcdA) – enterotoxin: fluid secretion and inflammation, also mucosal damage

-          Toxin B (TcdB) – nonenterotoxic cytotoxin: more potent colonic mucosa damage

-          Others – CDT: cytolethal distending toxin.

How many cultures is needed for C. diff diagnosis? List them. which one is the preferred method?

2 cultures:

ELISA for toxin A & B - preferred method but low sensitivity and specificity

&

Stool culture - sensitive but gives false positives

What is the treatment for C. diff infection:

·         Initial or Mild-to-moderate?

·         Initial but severe?

·         Initial, severe and complicated?

·         First relapse?

·         Second relapse?

-          Initial infection, mild or moderate:

-          Metronidazole 500 mg PO q 8 hours x 10-14 days

-          Initial infection, severe:

-          Vancomycin 125 mg PO q 6 hours x 10-14 days

-          Initial infection, severe & complicated:        Vancomycin 500 mg PO q 6 hours + Metronidazole 500 mg PO q 8 hours

-          May add PR vancomycin for complete ileus

-          First relapse (10-25%) -     Treat with same agent as before but according to severity

-          Second relapse

-          Vancomycin (with taper and/or pulse dose)

What is the duration of treatment for GI infections?

Which other type of C. diff treatment has only local GI effect?

Which other type of C. diff treatment is an alternative agent in recurrent C.diff infection following metronidazole therapy?

IV immunoglobin G (IVIG) - •      Multiple relapses due to impaired antigenic response to toxins

Which other type of C. diff treatment is as effective as PO vancomycin with lower recurrent rate?

Which other type of C. diff treatment is reserved for severe, refractory C.diff infection?

Tigecyclive - a Glycylcycline (IV form only)

•      inhibits protein synthesis in bacteria by binding to the 30S subunit

Majority of Traveler’s diarrhea is caused by ____

-          bacterial enteropathogens ex.

•      Enterotoxigenic Escherichia coli (ETEC),      Shigella, Campylobacter, and Salmonella

What agent is best for prevention of Traveler’s diarrhea?

•      Bismuth subsalicylate

Donot use if:

•      allergic to aspirin

•      during pregnancy (D)

•      Should not be used > 3 weeks

Which antibiotic is used for Traveler’s diarrhea?

·         Preferred ABX overall?

·         Preferred if in Asia?

·         Preferred if in Mexico or Jamaica?

·         Is NEVER recommended?

   Preferred ABX overall? Fluoroquinolones

·         Preferred if in Asia? Azithromycin

·         Preferred if in Mexico or Jamaica? Rifamixin

·         Is NEVER recommended? Bactrim and Dopxycycline

Q1. Which of the followings dose cause watery diarrhea?

a.       E. coli – enterotoxigenic and enteropathogenic species only

b.      C. difficile

c.       Campylobacter

d.      Salmonella

Q2. Which of the followings is not recommended for treatment of C. difficile?

a.       Metronidazole PO

b.      Metronidazole IV

c.       Vancomycin PO

d.      Vancomycin IV (never use IV vancomycin, metronidazole can be IV or oral)

Q3. Which of the following is the LEAST recommended for prevention of traveler’s diarrhea?

a.       Hand hygiene   

b.      Avoid raw food

c.       Antibiotics – due to high risk of resistance    

d.      Bismuth subsalicylate

Q1. A

Q2. D

Q3. C

What is intra-abdominal infection (IAI)?

2 common organisms found in stomach that cause IAI?

-          Stomach: streptococcus and lactobacillus

Differentiate between primary secondary, and tertiary peritonitis.

·         Which is most common?

·         Which is monomicrobial or polymicrobial?

-          Primary peritonitis (one organism): GI integrity is not compromised. --> is monomicrobial & most common (Chronic Ambulatory Peritoneal Dialysis)

-          Secondary peritonitis (polymicrobial organisms): infection from microscopic or macroscopic perforation of a hollow viscus

-          Tertiary peritonitis: secondary infection that fails to respond to therapy.

1. Individuals with Chronic Ambulatory Peritoneal Dialysis (CAPD)

-          Most common complication

-          Can lead to hospitalization or technique failure.

2.   Spontaneous Bacterial Peritonitis:  Individuals with ascites secondary to liver disease; often called

(SBP)

-          Less common

-          Seen in 10-30% of patients with cirrhosis of the liver

Causative organisms in CAPD and SBP?

1.      Primary peritonitis (often monomicrobial)

•      CAPD – coag negative Staph, S. aureus, Streptococci, Enterococcus, Pseudomonas

•      SBP – E. coli most common, Klebsiella, S. pneumoniae.

2.      Secondary peritonitis (often polymicrobial)

•      Community infections: Enteric Gram negatives (e.g. E. coli), Streptococcus sp., Bacteroides

•      Nosocomial and severe infections: consider Candida sp., Enterococci, MRSA, other MDR organisms

•      Consider likely pathogens based on site of infection origin

Which of the followings is the LEAST recommended to the patients with health care-associated Intra-abdominal infection?

a.      piperacillin-tazobactam

b.      doripenem

c.       ciprofloxacin + metronidazole

d.      tigecycline 

Altered mental status is seen in what type of peritonitis, while cloudy effluent is observed in what type?

Altered mental status - Spontaneous Bacterial Peritonitis (SBP)

loudy effluent - chronic ambulatory peritoneal dialysis

Which type of peritonitis has more polymorphonuclear cells upon diagnosis

•      CAPD: >50% PMNs/mm³ is diagnostic
 

•      SBP: ≥250 PMNs/mm³ is diagnostic

What is the treatment for peritonitis?

CAPD:     Gram positive coverage (Cefazolin or Vancomycin) + Gram negative coverage (aminoglycoside, ceftazidime, cefepime, carbapenem, ciprofloxacin, levofloxacin)

SBP: a.      Cefotaxime, ceftriaxone, fluoroquinolones

2° SBP prophylaxis (fluoroquinolone or Bactrim)

Secondary peritonitis: Antipseudomonal beta lactam or Moxifloxacin + Levofloxacin/Ciprofloxacin 

     ______and ____are not recommended because of resistance among B fragilis.

What are 6 causes of systemic fungal infection?

-Common in immune-compromised patients

-Patients exposed to broad spectrum antibiotics

-          Normal microorganisms are suppressed with fungal overgrowth

-Widespread use of indwelling medical devices

-           Intravenous catheters, joint replacements

-Long-term maintenance of burn, trauma and diabetic patients

Describes the 3 types of fungus.

Yeast
-          Invasive and causes most infections
-          Unicellular and oval or spherical shape

Molds

-          Free-living
-          Multicellular
-          Have filament

Dimorphic forms – exists as yeast or mold depending on conditions

-          The yeast form infects humans
-          Free-living form exists as mold

This fungi is typically not susceptible to most anti-fungals.

Describe lipid amphotericin B.

-          Polyene structure - Large, open  lactone ring with amphipathic property

Given IV and excreted via urine

Safe in pregnancy

•      Traditional Amphotericin = Amphotericin B deoxycholate complex (AmB) - Fungizone

Lipid formulations:

• Amphotericin B colloidal dispersion (ABCD) - Amphotec- “discs” of lipids
• 
  
• •      Liposomal Amphotericin B formulation (L-AmB) - Ambisome- 
•  With artificial lipid vesicles
• 
  
• •      Amphotericin B lipid complex (ABLC) - Albecet
• •      Has a phosphatidyl choline and phosphatidic acid in ribbon-like sheets

____is also a polyene antibiotic like amphotericin B but is too toxic systemically; used topically and orally (not absorbed from gut). No parenteral form of Nystatin.

What is the MOA of amphotericin B?

-          Binds to ergosterol in fungal cell membranes, forms pores in cell membrane which causing ions to leak and causing cell death (fungicidal)

-          Broad spectrum

How is AmB absorbed.

  - Does AmB have CNS/CSF penetration?

     - Can it be used in pregnancy?

No CNS penetration, only with inflammation

Safe in pregnancy

What is the half-life of AmB?

What are main ADR of AmB? Does it require hepatic or renal adjustment.

Renally excreted, so Nephrotoxicy is major issue:

Also

1. Hypokalemia
2. Hypomagnesemia
3. Hypotension and Stridor
4. Anemia
5. Thrombophlebitis

What is the MOA of flucytocine?

Converted to 5-fluorouracil (5-FU) and to 5-fluorodeoxyuridylic monophosphate (5-FdUMP) .

-          5-FdUMP inhibits the enzyme thymidylate synthase, which means no thymidiylic acid for DNA synthesis.

-          Flucytosine is also metabolized to 5-FUTP which disrupts RNA and protein synthesis when incorporated into fungal RNA.

What is the spectrum of activity of flucytosine?

-          Small spectrum: Cryptococcus and Candida

-          Not good for coccido meningitis

-          Resistance is common if used alone, so use in combination

-          Synergistic effect when used with Amphotericin B

What other antifungal is synergic of flucytosine?

What is the route of admin for flucytocine?

What is the half-life of flucytocine?

Does flucytosine penetrate CNS?

Oral absorption

half-life = 3-6 hrs

Penetrates into CNS

Compare flucytocine and AmB.

What are the ADR of flucytocine.

Give the imidazoles.

Give the 4 members of triazoles.

Which are 2^nd gen of triazoles.

Imidazole (2 nitrogens in 5-mem ring): -ketoconazole, miconazole

Triazoles: -fluconazole, itraconazole, voriconazole, posaconazole

What is the spectrum of activity of azoles?

What is a problem seen with azoles? Which azoles are the exception?

What is the MOA of azoles?

MOA- azoles Inhibits synthesis of Ergosterol by stopping the conversion of lanosterol to ergosterol =  components of fungal cell membrane are inhibited. 

Which azole shows up on CT scan?

Which azole is only oral?

Voriconazole - shows on CT scan

Posaconazole - oral only

Which azole is 1^st line for Cryptococcus and Coccidio infection?

Which azole is used against zygomycetes?

Which azole is used against Aspergillus? 

1st line for Crytococcus and Coccidio meningitis = Fluconazole

Zygomycetes = Posaconazole

Voriconazole = Aspergillus

Stomach acids have the least effect on this azole.

Which azole have the least CYP interaction

Posaconazole

Posaconazole

Which azoles are eliminated via hepatic metabolism? Which are renal?

Hepatic metabolism: Ketoconazole, Itraconazole, Voriconazole, Posaconazole

Renal: Fluconazole, Itraconazole, Voriconazole (excreted if with cyclodextrin, but not if CrCl is <50ml/min), 

Parenteral formulations of ____have cyclodextrin, which is renally eliminated, so contraindicated if CrCl <50 ml/min.

What is the CYP inhibited by:

·         Itraconazole

·         Fluconazole

·         Voriconazole

·         Posaconazole

·         Itraconazole - CYP 3A4 

·         Fluconazole - 3A4 and 2C9

·         Voriconazole - 3A4, 2C9 and 2C19

·         Posaconazole - no cyp inhibited

What are some ADR seen with azoles?

What is the difference between rifamycins and azoles in terms of CYP.

Rifamycins (except Rifabutin) = CYP induction

Azoles (except Posaconazole) = CYP inhibition

What is the MOA of echinocandins?

What is the spectrum of activity of echinocandins.

Candida, Invasive and refractory aspergillus

Never use echinocandin for cryptococcus

Why are echinocandins not used for Cryptococcus Neoformans

which echinocandins are used for invasive aspergillus?

Which is preferred in refractory aspergillus or if ptn is intolerant of other therapies?

Which is used for systemic candida?

Which echinocandin has CYP interaction?

What are major ADR of echinocandins.

What is the MOA of griseofulvin?

What is the MOA of Terbinafine?

Invasive aspergillus - Caspofungin and Micafungin

Refractory (failed due to previous azole use) - Caspofungin

Systemic candida - Caspofungin and Anidulafungin

What is the route of admin for echinocandins?

Describe PK of echinocandins.

Which echinocandin has CYP interaction?

Admin = IV only

Caspofungin & Micafungin = liver metabolism

Anidulafungin = spontaneous breakdown with no liver or renal help

CYP interaction = Micafungin

What are major ADR of echinocandins.

Generally safe

Hypokalemia - esp. Anidulafungin

Hypersensitivity - esp. Micafungin

rash and facial swelling due to rapid infusion

Altered renal and liver function trst

phlebitis, fever, N/V

What is the MOA of griseofulvin?

What is the MOA of Terbinafine?

Griseofulvin - Acts on microtubule system to disrupt mitosis in certain fungal cells

Terbinafine - Reduces synthesis of ergosterol by inhibiting conversion of squalene to lanosterol by squaleneepoxidase

What is a capsid?

What is a nucleocapsid?

What is a capsomere?

•      Viruses are obligate intracellular parasites

•      Introduce nucleic acid into the host cell – can be single or double stranded DNA or RNA in a protein covering called capsid

•      the capsid + nucleic acid = nucleocapsid

•      Capsomere:  repeating protein unit found on surfaces of viruses – extend into glycoprotein that determined host range.

•      An outer phospholipid envelope is common, with glycoproteins extending from surface (e.g. influenza “A” virus has hemagglutinin and neuraminidase; “H” and “N”)

What determine virus host range?

___ promotes attachment and entry of virus?

Why is the development of new antiviral agents limited?

•      Antiviral drug agents inhibit specific viral events, so targets are limited; this hampers new drug development 

What are the 3 types of viruses. Give examples of each.

DNA viruses: small pox, varicella (chicken pox), hepatitis B, Cytomegalovirus, human papilloma virus, herpes

RNA non-retrovirus: Hepatitis A & C, influenza, rabies, measles, mumps, polio

RNA retroviruses: HIV, Human T-cell Leukemia (HTLV)

Explain the 6 steps of replication of a virus.

•      Adsorption/Attachment of virus to host cell

•      Entry (or Fusion) 

•      Uncoating and the release of the viral nucleic acid

•       Replication of viral genome & protein synthesis

•      Assembly

What is the MOA of acyclic guanosine analogs?

What is the spectrum of activity of acyclic guanosine analogs?

Which acyclic guanosine analogs are prodrugs? What are their active forms?

Which acyclic guanosine analogs has the best oral absorption?

Which acyclic guanosine analogs has best activity against cytomegalovirus?

2 guanine analogs that have the worse myelosuppression are

Give the 4 main ADR of guanosine analogs.

Myelosuppression/Bone marrow suppression

Nephrotoxicity

Neurotoxicity

What is the preferred route of elimination for guanosine analogs?

What is the MOA of Cidofovir?

Compare and contrast Cidofovir MOA vs. Acyclovir

What is the spectrum of activity of Cidofovir?

Cidofovir is especially useful when virus enzyme ____   is inactive/deficient

What is the preferred route of admin for Cidofovir compared to guanosine analogs?

Cidofovir is IV

Guanosine analog is oral

what is the preferred route of excretion for cidofovir compared to acyclovir?

why does cidofovir have a long half-life (up to 87 hours)?

Cidofovir = renal excretion

Acyclovir = renal excretion

Give the 2 main ADR of cidofovir.

What is the MOA of Foscarnet?

What is the spectrum of activity of Foscarnet?

What makes Foscarnet special compared to cidofovir and acyclovir?

ADR: all 3 cause nephrotoxicity, but Foscarnet's nephrotoxicity can be prevented with prior saline hydration, and cidofovir with probenecid to prevent reservoir.

Admin: bith foscarnet and cidofovir are IV, while acyclovir is oral.

Note: Foscarnet causes hypocalcemia but not myelosuppression, while both acyclovir and cidofovir causes bone marrow suppression

Both Foscarnet and acyclovir causes neurotoxicity but not cidofovir

What is the preferred route of admin for Foscarnet?

What is the preferred route of elimination for Foscarnet?

Give the 3 main ADR of Foscarnet.

Foscarnet is IV

Renal excretion for Foscarnet

ADR:

• Hypocalcemia
• Nephrotoxicity (prevent with saline hydration prior)
• Neurotoxicity 

How can you prevent nephrotoxicity with foscarnet use?

What is the MOA of Fomivirsen?

What is the spectrum of activity of Fomivirsen?

What makes Fomivirsen special compared to Foscarnet?

What is the MOA of Amantadine & Rimantadine?

What is the spectrum of activity of Amantadine & Rimantadine?

How is influenza A classified?

What is the MOA of Oseltamivir and Zanamivir?

Give their brand names and spectrum of activity.

Compare and contrast the MOA of Amantadine & Rimantadine vs. Oseltamivir and Zanamivir.

Compare their spectrum of activity and route of admininistration and excretion.

Amantadine/Rimantadine MOA = prevents viral uncoating & assembly

Oseltamivir/Zanamivir =inhibits sialic acid = prevents viral progeny spread

Spectrum of activity:

Amantadine/Rimantadine = Influenza A only

Oseltamivir/Zanamivir  = Influenza A and B

Route of admin:

Amantadine/Rimantadine = both are oral

Oseltamivir = oral

Zanamivir = intranasal (do not use if bronchospasm)

Excretion:

Amantadine (no longer in use) = renal excretion

Rimantadine (still used) = 75% liver and 25% renal

Oseltamivir/Zanamivir = both renal

Adefovir

Ribavirin

Lamivudine and Telbivudine

Recombinant and Natural Interferons

What is the MOA of adefovir?

Give its spectrum of activity.

what is the preferred route of admin and elimination?

Give one major ADR.

Give its spectrum of activity.

what is the preferred route of admin and elimination?

Give major ADRs.

Give its spectrum of activity.

what is the preferred route of admin and elimination?

Give major ADRs.

Give its spectrum of activity.

what is the preferred route of admin and elimination?

Give major ADRs.

Describe the 3 major genes of HIV virus.

•      Gag – encodes proteins to cause release of the major structural proteins

•      Pol – encodes RNA-dependent DNA polymerase (reverse transcriptase), protease and viral integrase

•      Env – encodes transmembrane envelope protein responsible for cell binding and entry (gp120 & gp41).

Describe the enzyme reverse transcriptase.

•      RNA dependent DNA polymerase viral enzyme that synthesizes duplex strands of DNA from a single strand of viral RNA (the reverse of transcription) in three steps.

•      Has no proofreading function, so mutations are common at rate of about 3 errors/cycle (humans have a 3’ to 5’ exonuclease that excises errors, so they can be corrected).

Describe the 3 steps of retrovirus replication.

Describe the 6 major phases of HIV life cycle.

What are the functions of glycoproteins of HIV?

What is tropism?

gp120 selectivity for either CXCR4 or CCR5 co-receptors on immune cells.

Can be dual tropism.

Describe the course of HIV infection starting from the initial infection to the critical threshold and setpoint.

Describe the 4 lab tests for HIV detection.

which is for screening and which is for confirmation?

ELISA = sensitive = for screening

Western blot = specific = for confirmation

Viral isolation and culture 

PCR

HIV vaccine development have been limited by what is called _____.

1. Suppress viral load to <50 RNA copies/mL
2. Preserve immune function

WHat is Immune Resconstitution Syndrome?

Name the 6 classes of anti-HIV drugs.

What is the MOA of NRTI?

competitive inhibition viral reverse transcriptase.

NRTI --> phosphorylated in cells into triphosphates which compete with native molecules for incorporation into viral DNA via viral reverse transcriptase. Incorporated analogs block DNA chain elongation due to absence of 3-hydroxyl group on the ribose-like moiety; thus viral DNA synthesis from the RNA template is inhibited. The absence of a 3-OH group prevents continuation of the 5’ to 3’ to 5’ to 3’ etc link through viral DNA.

Antimetabolites - Nucleosides and Nucleotides 

Cytidine Nucleoside analogs = Zalcitabine, Emtricitabine, Lamivudine

Thymidine Nucleoside  analogs = Zidovudine & Stavudine

Adenosine nucleoside analog = Abacavir

Adenosine nucleotide analog = Tenofovir disproxil

Didanosine = I 

What is the preferred route of admin for NRTI?

which NRTI has the lowest overall bioavailability?

which has the longest half-life?

What is the preferred route of excretion?

Oral, except Didanosine

Tenoforvir = lowest overall bioavailability

longest t.5 = Tenofovir

Route of excretion =  renally except for Zidovudine, Didanosine and Abacavir

This NRTI is the only member affect by acid and needs to be taken with antacid to improve overall bioavailability.