1.  Tx of untreatable infections

2.  Therapy of fever unknown origin

3.  Improper dosage

4.  Inappropriate use of chemotherapy alone

5.  Poor drug selection, due to lack of bacteriological information

Anti-infective agents:

1.  Primary use

2.  Potential bad thing?

1.  To kill or inhibit growth of organisms

2.  Too toxic to be used systemically

Antimicrobial agents

1.  Desired outcome of use

1.  Demonstrates selective toxicity

2.  No allergic reactions

3.  Is not destroyed, neutralized or excreted too rapidly by the host

4.  Therapeutic dose is established at site of infection

5.  Pathogens do not develop resistance to it

1.  Drugs MOA (most important)

2.  Microorganism's state of growth

3.  Concentration (MIC or minimum bacteriocidal concentration [MBC])

Narrow-Spectrum Antibiotics

1.  Define

2.  Benefit as far as antimicrobial stewardship

3.  Examples (7)

1.  Mainly go after Gm+ or Gm-; may even be specific against one type of organism

2.  Lower risk for development of bacterial superinfections

3.  Bacitracin; Clindamycin; Macrolides; Metronidazole; Penicillins (Except Extended-spectrum); Polymyxins; Vancomycin

Extended-Spectrum 

1.  Define

2.  Examples (6)

1.  Affects a variety of Gm+ and Gm-

2.  Aminoglycosides; Cephalosporins; Extended-spectrum penicillins; Fluoroquinolones; Carbapenems; Monobactams

Broad-Spectrum

1.  Define

2.  Examples (3)

1.  Affects both Gm+ and Gm- bacteria and other organisms (Rickettsia)

2.  Sulfonamides; Tetracyclines; Trimethoprim

1.  Host

2.  Drug

3.  Pathogen

1.  Drug blocks vital pathway unique to microorganism

2.  Drug blocks a reaction vital to microbe and host, but with greater blocking through microbe

3.  Drug blocks a pathway vital to both host and microbe, but only the microbe converts the drug to its active metabolite

1.  Cell wall synthesizing enzymes

2.  Bacterial ribosomes

3.  Enzymes required for DNA synthesis and replication

4.  Viral replication machinery

1.  Mutation of bacterial gene

2.  Transduction:  bacteriophage

3.  Transformation:  uptake of naked extrabacterial DNA

4.  Conjugation:  sex pilus (only Gm-)

1.  Only use antibiotics with well-established need

2.  Select based on bacteriologic tests

3.  Give at sufficient dose and for sufficient time to kill the bacteria

4.  Multiple drug therapy only when indicated (TB, HIV)

1.  Severe infection of unkonwn cause

2.  Polymicrobial infections (intestinal puncture or dog bite)

3.  Enhanced antibacterial activity specific infections

4.  Prevention of emergence of resistant microorganisms

1.  Antagonism:  one drug interferes with the other

2.  Addition:  net result is a summation of the drugs effects

3.  Synergism:  inhibition of growth by combinations at concentrations <25% MIC for each drug alone (sum greater than the parts)

1.  Each antibiotic affects different step in biochemical pathway

2.  One drug may enhance the uptake of a second

3.  One drug may prevent the degradation of the second

1.  Expensive

2.  One agent may enhance toxicity of other

3.  Allows for simultaneous selection of multiple drug resistant organisms

1.  Fosfomycin

2.  Cycloserine

3.  Bacitracin

4.  Vancomycin

5.  B-lactams

1.  Penicillins

2.  Cephalosporins

3.  Carbapenems

4.  Monobactams

Peptidoglycan

1.  2 units that repeat

2.  What mediates transpeptidation

1.  N-acetyl glucosamine (NAG) and N-acetyl muramic acid (NAM)

2.  Penicillin Binding Protein (PBP) which is a transpeptidase 

B-lactam MOA

1.  Structural analog of what?

2.  Competitive or Non-competitive inhibitor?

3.  Result of use (cidal or static)?

4.  What do you NOT combine them with and why?

1.  D-ala D-ala on peptidoglycan strand

2.  Competitive inhibitor by binding PBP

3.  Cidal b/c they prevent intact bacterial cell wall from forming

4.  Bacteriostatic drugs b/c you need the cell wall to be synthesized in order for them to work

P. aeruginosa and Enterobacter sp:

1.  Produce what kind of B-lactamase

2.  What drugs do the B-lactamases effect (2)?

1.  AmpC

2.  Penicillins and cephalosporins

1.  B-lactamases

2.  Alteration of PBPs

3.  Alteration of outer membrane (Gm-)

4.  Efflux pump (Gm-)

1.  Penicillin G (or benzylpenicillin)

2.  Penicillin V

1.  Methicillin (no longer on market)

2.  Nafcillin

3.  Oxacillin

4.  Dicloxacillin

1.  Aminopenicillins

2.  Carboxypenicillins

3.  Ureidopenicillins

1.  Ampicillin

2.  Amoxicillin

1.  Name the one carboxypenicillin

2.  Special feature

1.  Ticarcillin

2.  Anti-pesudomonal

1.  Name the 2 ureidopenicillins

2.  Special feature

1.  Peiperacillin and Azlocillin

2.  Anti-pseudomonal

Natrual Penicillins Spectrum of Activity (sensitive or not)

1.  Gm+ aerobes (1 sensitive, 1 not)

2.  Gm+ anaerobes 

3.  Gm-

4.  Spirochetes

1.  Streptococci:  sensitive

Staphylococci:  Resistant

2.  Some bacilli:  sensitive

3.  Mostly resistant

4.  T. Pallidum (drug of choice)

Natural Penicillins:  Pharmacokinetics

1.  Penicillin G (Procain and benzantine):  How is it administered?  

2.  Penicilin V:  How is it administered?

1.  Acid labile so parenterally

Also has a water insoluble depot for IM

2.  Acid stabile (oral)

Natural Penicillins Pharmacokinetics:

1.  How excreted

2.  What is given with them to alter excretion

1.  10% glomerular filtration; 90% tubular excretion

2.  Probenacid which impairs tubular secretion

Penicillin G

Drug of choice for:  (3)

1.  Sterptococci (pharyngitis)

2.  Meningococci (meningitis)

3.  T. Pallidum (syphilis)

1.  Poor oral bioavailability

2.  QID dosing

3.  Less active than Pen G

Antistaphylococcal (Penicillinase resistant) penicillins

Spectrum of activity against

1.  Staph aureus

2.  Compared to Pen G

3.  Gm -

1.  Effective against penicillinase producing Staphy aureus

2.  Much less active against some Gm+ than Pen G

3.  Inactive

*Used exclusively in the treatment of staphylococcal infections

MRSA and Methicillin-resistant Staph epidermidis (MRSE)

1.  Mechanism of resistance 

2.  You treat MRSA and MRSE with what?

1.  PBP alterations

2.  Vanc

Antistaphy Penicillins:  Pharmacokinetics

1.  Which are acid stable (2)

2.  Which is less acid stable and given IV (1)

3.  Which 2 are cleared renally?

4.  Which one is cleared primarily biliary?

1.  Dicloxacillin and oxacillin (also given IV for systemic Staph)

2.  Nafcillin

3.  Dicloxacillin and oxacillin

4.  Nafcillin (no need to adjust for renal failure)

Extended Spectrum Penicillins

1.  What do they hit that the other penicillins don't

2.  Why?

1.  Gm- bacteria

2.  Enhanced ability to penetrate the Gm- outer membrane

Extended Spectrum Penicillins Spectrum of Activity

1.  Many Gm+?

2.  Amoxicillin and ampicillin cover?

3.  Ticarcillin covers

4.  Piperacillin covers?

1.  Some Gm+ but not many

2.  Some Gm- (Haemophilus; Proteus; E.coli)

3.  Pseudomonas, Proteus, H. flu, E. coli

4.  Pseudomonas aeruginosa

Major therapeutic uses Amoxicillin and Ampicillin

1.  Drug of choice for ___ infections

2.  Tx of ___ infections caused by Gm+ and Gm- organisms

3.  Tx of penicillin-resistant ____

1.  Enterococci

2.  Mixed

3.  Pneumococci

*Infectinos due to susceptible Gm- microbes

Gm-:

Nosocomial infections

Sepsis

Pneumonias

Infected burns

P. aeruginosa with aminoglycoside

Extended Spectrum Penicillins Administration

1.  Aminopenicillins (which is given oral and/or IV)

2.  Carboxypenicillins given how

3.  Ureidopenicillins given how

1.  Amoxicillin and Ampicillin given orally (amoxicillin absorbed more completely)

Ampicillin also given IV

2.  IV (Ticarcillin)

3.  IV and IM (Piperacillin) 

Penicillin dosing adjustments

1.  Which do you not need to give 1-2 h before or after a meal?

2.  Which do you not need to dose for renal failure?

1.  Amoxicillin

2.  Nafcillin

Extended-Spectrum Penicillin / B-lactamase inhibitor combos

1.  What type of inhibitors are the B-lactamase?

2.  Examples of B-lactamase inhibitors (3)

3.  4 combinations currently on market

1.  Suicide

2.  Clavulanic acid

Sulbactam

Tazobactam

3.  Amoxicillin-Clavulanate; Ampicillin-Sulbactam; Piperacillin-Tazobactam; Ticarcillin-Clavulanate

ADEs Penicillins

1.  Major Type and frequency

2.  What metabolite causes this

3.  Cross-sesitivity with

1.  Hypersensitivity in 1-10% of individuals

2.  Penicilloic acid

3.  B-lactam antibiotics

3 Types of Allergic Reactions with Penicillins

1.  Acute:  occur within 30 mins of adminitration (life threatening anaphylaxis)

2.  Accelerated (30min to 48 hrs post-admin):  generally not lifethreatening

3.  Delayed (2+ days after admin):  generally mild, reversible rash (80-90% of all reactions due to penicillins)

*Can desnsitize by gradually increasing dose

1.  Hypersensitivity

2.  N/V/D:  more common with extended spectrum b/c of GI flora disruption

3.  Nephritis:  acute

4.  Platelet dysfunction:  ticarcillin

5.  Cation toxicity:  sodium and potassium salts

6.  Neurotoxicity:  seizures when blood levels are high or intrathecal injections

1.  Cefadroxil (PO)

2.  Cefazolin (IV)

3.  Cephalexin (PO)

Second Generation Cephalosporins and Administration Route (5)

*Which 2 are cephamycins

1.  Cefaclor (PO)

2.  Cefprozil (PO)

3.  Cefuroxime (IV, IM)

4.  Cefoxitin (IV)

5.  Cefotetan (IV, IM)

*  Cefoxitin and Cefotetan

1.  Cefixime (PO)

2.  Cefdinir (PO)

3.  Cefpodoxime (PO)

4.  Ceftibuten (PO)

5.  Cefotaxime (IV)

6.  Ceftazidime (IV/IM)

7.  Ceftizoxime (IV)

8.  Ceftriaxone (IV/IM)**Only one listed that isn't solely renal elimination

Genral Trends Cephalosporins as Generations Increase

1.  Gm+ vs Gm-

2.  Stability vs B-lactamases

3.  CNS penetration

1.  Gm- decreases while Gm+ increases

2.  Stability increases

3.  Penetration increses

First Gen Cephalosporins

1.  Spectrum of activity

2.  Pharamcokinetics

3.  Major therapeutic use

1.  Broad spectrum Gm+; Many Gm- including E.coli, Kelbsiella, Proteus

2.  Not well distributed to CNS

3.  Community acquired infections (RTI and uncomplicated UTI); Surgical prophylaxis (Cefazolin)

DO NOT use in serious infecitons

Second Generation Cephalosporins

1.  Spectrum of activity

2.  Major Therapeutic Use

1.  Less Gm + than first; Additionoal Gm- with B-lactamase producing H. flu and K. pneumonia

**Cephamycins = anaerobic activity

-No P. aeruginosa activity

2.  Oral members:  sinusitis and otitis

-Cefuroxime:  community acquired pneumonia

-Cephamycins:  Anaerobes, mixed aerobic/anaerobic infections of skin and soft tissue; intrabdominal and gyncecologic infections; surgical propylaxis

Third Generation Cephalosporins

1.  Spectrum of activity

2.  Major therapeutic use

1.  Expanded Gm-

-Susceptible to enterobacter B-lactamase (AmpC) but resistant to others

-Ceftriaxone and cefotaxime:  anti-pneumococcal

-Ceftazidime:  P. aeruginosa

2.  Ceftriaxone and Cefotaxime enter CNS so meningitis

-Ceftriaxone and Cefotaxime used empirically for seroius infectiont hat may be caused by PCN resistant pneumococci

Fourth Gen Cephalosporine

1.  Spectrum of activity

2.  Major therapeutic use

1.  Gm- with better Gm+ than 3rd

-Better resistance to Gm- B-lactamases (especially enterobacter and PCN resistant streptococci)

-Active against P.aeruginosa

2.  Simiarl to 3rd gen

-Enterobacter infections

-Severe infections (pneumonia, sepsis, meningitis)

Fifth Gen Cephalosporin

1.  Spectrum of activity

2.  Major therapeutic use

1.  Gm- similar to 4th gen

Gm+ against MRSA

2.  Community-acquired pneumonia

-Comnplicated skin and skin structure infection

ADEs Cephalosporins

1.  Major ADE

2.  Cephamycins (what are they and what do they do)

3.  Other ADEs

1.  Hypersensitivity:  1% cross reactivity with PCNs so do not give to pts with hx of PCN reaction

2.  Cefoxitin, Cefotetan:  contain MTT side chain with disulfiram reaction and hypoprothombinemia and bleeding b/c of anti-Vit K effects

3.  Pain after IM injection and thrombophlebitis IV

-Interstitial nephritis and tubular necrosis

1.  Imipenem

2.  Meropenem

3.  Ertapenem

4.  Poripenem

Carbapenem Spectrum of Activity

-Mmore efficient interactions with PBPs than PCNs and cephalosporins

-Great Gm- with broadest spectrum of activity of all B-lactams

-Resistant to most B-lactamases (susceptible to metallo-B-lactamase)

Carbapenems Pharmacokinetics

1.  How administered?

2.  How excreted

3.  What inactiavtes imipenem and what prevents this?

1.  IV and IM (ertapenem with 1% lidocaine)

2.  Renal

3.  Dehydropeptidases so give with equal amount cilastain which inhibits dehydropeptidases

Carbapenem Major Therapeutic Use

1.  Drug of choice for (2)?

2.  Plays role in ___ therapy

3.  Use w/ or w/o aminoglycoside for what type of infection

1.  ESBL infections; Enterobacter

2.  Empirical

3.  P. aeruginosa

Adverse Effects Carbapenems (4)

*most common with imipenem

1.  H/S

2.  NVD

3.  Local Reactions

4.  Seizures

Monobactams

1.  Drug (Route)

2.  Spectrum

1.  Aztreonam (IV)

2.  Resistant to B-lactamases

-**No cross reactivity with PCNs

-Narrow spectrum (Gm- including Pseudomonas)

*no activity against Gm+ or anaerobes

Fosfomycin

1.  Route

2.  MOA

3.  Spectrum

4.  Excretion

5.  Major therapeutic use

1.  PO

2.  Inhibits step 1 in cell wall synthesis

-Structural analog of PEP

Inhibits enol pyruvate transferase:  blocking addtion of PEP to UDP-N-acetyl-glucosamine 

-PEP provides linker for glycan and peptide

3.  Broad

4.  Renal

5.  Uncomplicated lower UTI

Bacitracin

1.  MOA

2.  Spectrum

3.  Major therapeutic use

1.  Inhibits step 3 in cell wall synthesis

-Blocks dephosphorylation of isoprentyl pyrophosphate, a lipid which arries the building blocks of peptidoglycan outside the plasma membrane

2.  Gram +:  Neisseria; T. pallidum

3.  Topical only

-Localized skin and eye infections

-Propylaxis for wounds

• Bind with high affinity to D-ala D-ala terminus of pentapeptide
• Block transglycosylase (elongation of peptidoglycan)
• Block transpeptidation (cross-linking)

Vancomycin Major Thearpeutic Use

1.  Cidal against?

2.  Static against when given alone?

3.  What combo kills #2?

4.  Active, but not first line for what infection?

1.  Streptococci and staphylococci including MRSA

2.  Enterococci

3.  Vanc + aminoglycoside (gent)

4.  C. diff

*Not active against VRSA or VRE

Vancomycin Pharmacokinetics

Two ways administered?

1.  IV (slow infusion)

2.  Orally for pseudomembranous colitis caused by C. diff; however, Flagyl is initial therapy

1.  Red Man Syndrome:  caused by vanc-induced histamine release due to rapid infusion

2.  Phlebitis at injection site

3.  Ototoxicity

4.  Nephrotoxicity

Bacterial resistance to vanc

1.  MOA in VRE

2.  MOA in VRSA

1.  Synthesize pentapeptide with D-ala-D-lactate or D-ala-D-serine to reduce affinity for drug

2.  Overexpress D-ala-D-ala which competes to bind up the drug

Short acting tetracycline (1)

1.  Drug

2.  Administration

3.  Elimination

1.  Tetracycline

2.  PO, IV, IM

3.  Renal

Intermediate Acting Tetracycline

1.  Drug (1)

2.  Admin

3.  Elimination

1.  Demeclocycline

2.  PO

3.  Renal

Long Acting Tetracyclines (3 drugs)

1.  Drug

2.  Admin

3.  Elimination

Doxycycline:  PO; Renal

Minocycline:  PO, IV; Hepatic

Tigecycline:  IV; Hepatic

Tetracyclines

1.  MOA

2.  Static or Cidal?

1.  Reversible binding of 30S subunit of bacterial ribosome blocking aminoacyl tRNA from entering A site of ribosome

2.  Static

Tetracyclines:  Spectrum of Activity

What is it active and not active against?

1.  Broad spectrum, but more Gm+ than Gm-

2.  MRSA

3.  Atypical bacterial:  rickettsia, chlamydia, mycoplasma pneumoniae, yersinia pestis, vibrio cholera, borrelia

4.  Inactive against:  Proteus and pseudomonas (efflux pumps)

1.  Atypical pneumonia (mycoplasma or chlamydia)

2.  Genital infection (chlamydia)

3.  Tick-borne disease (borrelia, reckettsia

4.  Acne (propionibacterium acnes)

5.  Peptic ulcer (H. pylori) in combo

6. Severe infections (MDR infections with GM-...tigecycline)

Tetracycline Pharmacokinetics

1.  Absorption oral

2.  What alters oral absorption

3.  Distribution

1.  30-100% so highly variable

2.  Divalent and trivalent cations decrease; decreased with elevated gastric pH (PPIs etc)

3.  Wide:  accumulating in liver, spleen, bone marrow, and in newly formed bone, dentine, and enamel of unerupted teeth

-Good CNS penetration

-Crosses placenta

1.  Tetracyclines Mechanism of Bacterial Resistance (3)

2.  What 3 tetracyclines do resistance not typically develop to?

1.  Increased efflux or decreased influx; Ribosomal protection; Enzymatic inactivation

2.  Doxycycline, minocycline, tigecycline (Long acting)

1.  GI (NVD) and superinfections

-To avoid:  food, carboxymethylcellulose, dec dose, D/C

2.  Photosensitivity

3.  Hepatotoxicity

4.  Renal toxicity

5.  Permanent discoloration of teeth so avoid in pregnant women and kids under 8

Aminoglycosides 

1.  MOA

2.  Cidal or static?

3.  ____ dependeint killing

4.  Significant ____

1.  Irreversible 30S binding 

-Interferese with initiation complex, produces mRNA misreading, blocks translocation of ribosomes

2.  Cidal

3.  Concentration

4.  PAE

 Aminoglycoside

1.  Spectrum

2.  Which one hits P. aeruginosa?

3.  No activity against?

1.  Aerobic Gm-

2.  Tobramycin

3.  Anaerobes

Major Therapeutic Use Aminoglycosides

1.  Combo with what to treat what

2.  Gentamycin

3.  Tobramycin

4.  Amikacin

5.  Neomycin

1.  PCN or vanc to act synergistically on Staph and S. epidermidis

2.  IV:  Severe Gm- infections; topical:  infected burns

3.  Inhalation:  P. aeruginosa cystic fibrosis

4.  TB

5.  Preoperative bowel prepartion (PO) and skin infections (topical)

Aminoglycoside Pharmacokinetics

1.  Absorption

2.  Distribution

3.  Excretion

1.  Highly polar so poor GI; IV/IM administration

2.  Not well to most cells, eye, or CNS

High concentration only in inner ear and renal cortex (toxicity here)

3.  Renal 

1.  Ototoxicity (irreversible):  avoid in pregnancy

2.  Renal toxicity (reversible):  Gentamycin, tobramycin

3.  Neuromuscular blockate (reversible) when used in very high doses...curare like effect

1.  Enzymatic inactivation of the drug 

2.  Mutation of bacterial ribosome

3.  Impaired entry of drug into cell (decreased influx)

Spectinomycin (Aminocyclitol not aminoglycoside)

1.  Route of admin

2.  MOA

3.  Spectrum

4.  Therapeutic use

5.  ADEs

6.  Static or cidal?

1.  IM

2.  Reverible binding to 30S

3.  Gm-

4.  Antibiotic resistant gonorrhea, or gonorrhea in PCN-alergic pts

5.  Nephrotoxicity, anemia (rare)

6.  Static

1.  Erythromycin:  PO/IV (lactobionate); Hepatic

2.  Clarithromycin:  PO; Renal

3.  Azithromycin:  PO/IV; Hepatic

Macrolide Antibiotics MOA

1.  MOA

2.  Static or Cidal?

3.  Site of action very close to what 2 other drugs?

1.  Binds reversibly to 50S blocking aminoacyl translocaiton

2.  Static

3.  Clindamycin; streptogramin type B

Macrolide Spectrum of Activity

1. General

2.  Clarithromycin and azithromycin more effective than ___ against ___

3.  Azithromycin highly active against what bacteria

1.  Gm+ including PCN-resistant streptococci

2.  Erythromycin against anaerobes

3.  Chlamydia

Macrolide Antibiotics 

1.  Distribution

2.  Major therapeutic use (general and then azithromycin)

1.  Poor CNS penetration

2.  Alternative to PCNs in case of allergy

-Azithromycin:  community acquired pneumonia, atypical infection; mycobacterium avium complex infection (MAC)

1.  GI disturbance b/c of GI motility stimulation

2.  H/S

3.  Telithromycin:  hepatotox (BBW) and worsening myasthenia gravis (BBW)

4.  Local reaction at injection site (erythromycin lactobionate)

5.  QT prolongation

6.  Ototoxicity

Macrolide Drug interactions and why

*Which one doesn't

1.  Inhibit CYP3A4:  Theophylline, Warfarin, Cyclosporine, Methylprednisolone

*Azithromycin

1.  Efflux

2.  Modificaiton of bacteiral ribosome, rendering it unable to bind the antibiotic (MLSb resistance)

3.  Enzymatic inactivation of drug

*most resistant strains susceptible to telithromycin:  less efflux and higher ribosomal affinity

Lincosamides-Clindamycin

1.  MOA

2.  Spectrum

1.  Reversible binding 50S

-Bacteriostatic blocking of aminoacyl translocation

2.  Most Gm+ and anaerobes (esp B. fragilis)

*NO activity against Gm-

Clindamycin

1.  Administration

2.  Distribution

3.  Excretion

1.  PO/IV

2.  Widely distributed; low concentrations CNS; Penetrate well into abcess

3.  Hepatic

1.  Skin and soft tissue infection

2.  Anaerobic infections

3.  Prophylaxis of endocarditis in patients with valvular heart disease undergoing dental surgery

1.  NVD, abdominal pain, psudomembranous colitis

2.  Local reactions at injection site

3.  Impaired hepatic function

4.  Neutropenia

Clindamycin Mechanism of Bacterial Resistance (2)

1.  Modifications of bacterial ribosome rendering it unable to bind antibiotics (MLSb resistance)

2.  Enzymatic inactivation of drug

Streptogramins

1.  Drug

2.  MoA

1.  Quinupristin/dalfopristin (30:70)

2.  Quinupristin binds 50S at same site as macrolites and dalfopristin binds nearby acting synergistially with quinupristin

Quinupristin/dalfopristin

1.  Spectrum of activity

2.  Cidal or static?

3.  Administration

4.  Elimination

1.  Gm+ including VRSA and VRE

2.  Individually:  static; Combined:  cidal

3.  IV

4.  Hepatic

Quinupristin/dalfopristin

1.  ADE

2.  Drug interactions

1.  Pain and phlebitis at injection site

2.  Inhibits 3A4 (warfarin and cyclosporine)

1.  Efflux

2.  Modification of bactierial ribosome (MLSb)

3.  Enzymatic inactivation of drug

 Chloramphenicol:

1. MOA

2.  Static or cidal?

3.  Spectrum?

1.  Binds reversibly to 50S blocking transpeptidation

2.  Static

3.  Broad spectrum (Gm+ and Gm-; anaerobes; rickettsiae)

1.  Serious infections for which other drugs are ineffective or contraindicated:

Severe rickettsial infection

B-lactam H/S with meningitis

1.  GI (NVD)

2.  BBW:  Bone marros suppression/aplastic anemia

3.  Grey baby syndrome:  inadequate glucuronidation leading to sock and death of 40% of patients in 2 days

*Do not use in infants

Oxazolidinones-Linezolid

1.  MOA

2.  Spectrum

3.  Major therapeutic use

4.  Static or cidal?

1.  Binds 50S of bacterial ribosomes preventing formation of initation complex

2.  Mostly Gm+ including VRSA and VRE

3.  Antibiotic resistant Gm+ VRSA and VRE

4.  Static

Linezolid

1.  Admin

2.  Elimination

3.  ADEs (2)

4.  Reason for bacterial resistance

1.  PO/IV

2.  Hepatic

3.  Hematologic disturbances (thrombocytopenia, anemia, neutropenia)

--Serotonin syndrome when combined with serotonergic drugs

4.  Mutation of binding site

1.  Macrolides

2.  Clindamycin

3.  Streptogramin type B (quinuprist)

*Mustation of 50S gives resistance to all these agents

Concentration Dependent activity with Significant PAE

1.  Drugs (4)

2.  Goal of therapy

1.  Aminoglycosides; Daptomycin; Fluoroquinolones; Ketolides

2.  Maximize concentrations

Time-dependent activity and minamal PAE

1.  Drugs (5)

2.  Goal of therapy

1.  Carbapenems; Cephalosporins; Erythromycin; Linezolid; Penicillins

2.  Maximize duration of exposure

Time-dependent actvity and moderate to prolonged PAE

1.  Drugs (5)

2.  Goal of therapy

1.  Azithromycin; Clindamycin; Oxazolidinones (Linezolid); Tetracyclines; Vancomycin

2.  Maximize amount of drug

Gram Staining

1.  Gm+ are what color?

2.  Gm- are what color?

1.  Blue/Vilet

2.  Pink/Red

Gram Negative Bacteria

1.  No ___ acid

2.  Outer membrane anchored to cell wall by what?

3.  What component of LPS is toxic to humans and what does it cause?

4.  What does outer LPS-containing layer block?

1.  Teichoic acid

2.  Murein lipoprotein

3.  Lipid A (endotoxin) which is released upon lysis causing fever, diarrhea, septic shock (endotoxic)

4.  Blocks out antibiotics and lysozyme

Gram Positive Bacteria

1.  Contains ___ acid not found in Gm-

2.  What does the inner surface of the cell wall touch?

3.  Reason they end up stained purple?

1.  Teichoic acid

2.  Outer surface of cytoplasmic membrane

3.  Meshed enough to allow crystal violet in, but traps it so it cannot be washed away by alcohol

1.  Cocci

2.  Bacilli

3.  Spiral forms

4.  Pleomorphic-lacking a specific shape

1.  Streptococcus sp:  chains of cocci

2.  Staphylococcus sp:  clumps of cocci

3.  Bacillus sp:  rods that form spores

4.  Clostridium sp:  rods (no spores)

5.  Corneybacterium sp:  rods (no spores)

6.  Listeria sp:  rods (no spores) only Gm+ organism that has endotoxin

1.  Neisseria sp:  diplococci

2.  Spirochetes:  treponema pallidum-->too small to be seen with light microscopy

3.  The rest are rods

Cell structure Bacteria

1.  Define nucleoid 

2.  Transcription and translation are ____ 

3.  Function of plasmids

4.  Function fo plasma membrane

5.  Gm+ or Gm- contains teichoic acid?

1.  Contains circular DNA (one chromosome) and no nuclear membrane 

2.  coupled:  can be done at same time unlike eukaryotic cells 

3.  Extra DNA usually with resistance genes

4.  Energy production, metabolite transport, synthesis of cell wall and capsule, support

5.  Gram +

Mycobacterium Cell Wall

1.  What surrounds peptidoglycan-like layer and acts as a drug target?

2.  #1 also responsible for what?

3.  What other 2 species also produce #1

1.  Mycolic acid in lipid coat

2.  Virulence and antiphagocytic activity of mycobacteria

3.  Corneybacterium and nocardia spp.

Bacterial component definitions

1.  Capsule and which 4 bacteria found in

2.  Pili (fimbrae)

3.  Flagella

1.  Polysaccharide capsule surrounding some bacteria which is poorly antigenic and also makes phagocytosis more difficult

-S. pneumoniae, Klebsiella pneumoniae, Neisseria meningitidis, and H. flu b

2.  Short appendages that promote adherence to host cells (sex pili)

3.  Long appendages for motility

Bacterial Oxygen Requirements

1.  Obligate aerobes

2.  Anaerobes

3.  Aerotolerant anaerobes

4.  Facultative anaerobes

1.  Require O2

2.  Do not require O2

3.  Can survive with low O2, but thrive without it

4.  Can grow under both anaerobic and aerobic conditions

1.  Enzyme-mediated tissue damage

2.  Adherence:  pili

3.  Toxin-induced localized and systemic effects:  LPS

4.  Resistance to antibiotics

5. Invasion and growth in normally sterile sites (blood, lung, CNS)

6.  Circulation via the blood or other means spreading from primary infection site:  tissue damage

7.  Evasion of host immune response by capsule, catalase, intracellular growth, or other mechanims

Staphylococcus aureus

1.  Most __ of staphylococcus spp

2.  2 toxin-mediated diseases

3.  Inflammatory diseases 

1.  Virulent

2.  food poisoning, toxic shock syndrome

3.  With pyrogenic and necrotic functions-range from mild skin lesions to life-threatening systemic disease and bacteremia 

Staphyloccus epidermidis

-Most common site of infection

Staphyloccus saprophyticus

-Common type of disease caused

1.  Serious neonatal disease

2.  Endocarditis

3.  Dental caries

Streptococcus pyogenes

1.  Group __ Strep

2.  Types of infections caused (5)

1.  A

2.  Strep throat

Skin infections

Postsurgical cellulitis

TSS, scarlet fever

Nonsuppurative autoimmune sequelae (glomerulonephritis and rheumatic fever)

Enterococcus spp.

1.  Normal flora where?

2.  What is common in this species

3.  3 common diseases

1.  Large intestine and feces

2.  Antibiotic resitance is common

3.   UTIs (hospital pts); Endocarditis; Wound infections

Bacillus spp.

1.  Cause what?

2.  Produce what that is highly toxic, causing localized edema and cell death

3.  What are the 2 forms

4.  Were to do spores live?

1.  Anthrax

2.  Exotoxin

3.  Cutaneous and pulmonary

4.  Spores can survive in soil, wool, hair, and animal hides for years

Clostridium spp

1.  4 major types

2.  Gm+/-?

3.  Aerobic or anaerobic

4.  Form ___ and produce potent ___

1.  C. botulinum, difficile, perfringens, tetani

2.  Gm+

3.  Anaerobic

4.  spores and produce potent exotoxins

*gas gangrene, tetanus, botulism, necrotizing enterocolitis

Corynebacterium diphtheriae

1.  Causes of what?

Enterobacteriaceae

1.  Includes what (6)

1.  E. coli

2.  Klebsiella spp

3.  Salmonella spp

4.  Shigella spp

5.  Yersinia spp

6.  Proteus spp

1.  Gastroenteritis

2.  UTI

3.  Neonatal meningitis

4.  Septicemia

1.  Enteritis

2.  Typhoid fever

1.  Meningitis

2.  Epiglottis

3.  Arthritis

4.  Otitis

Opportunistic:

UTI, burn/wound infections, ear infections, skin infections, pulomary infections (CF pts)

Fungi

1.  Membranes contain what instead of cholesterol

1.  Molds (filamentous fungi):  granching tubular filaments (hyphae) that elongate at the tipes; may be segmented or longa nd multinucleated

2.  Yeasts:  unicellular, round or slightly oblong; may develop pseudohyphae

3.  Dimorphic fungi:  exist as molds or yeasts depending on environment

Fungi reproduction

1.  Molds

2.  Yeasts

1.  spores

2.  budding

Define the following categories of fungal infections

1.  Superficial mycoses

2.  Cutaneous mycoses

3.  Subcutaneous mycoses

4.  Systemic mycoses

5.  Cadidiasis

1.  Surface of hair, nails, skin

2.  Epidermis and deeper layers of skin, hair, and nails

3.  Dermis and subcutaneous tissues and muscles-cause chronic nodules or ulcers in SC tissue

4.  Inhaled from the environment and produce lung infections that spread in immunocompromised host

5.  Cause by candida albicans-opportunistic pathogen

Superficial mycoses

1.  Immune response?

2.  __ problem

3.  What do they alter in the body

4.  Use ___ tx

1.  No

2.  Cosmetic

3.  Change color of skin or infect hair

4.  Topical

Cutaneous mycoses

1.  Caused by 30 different fungi called ___

2.  Includes what diseases

3.  Type of tx

1.  Dermatophytes

2.  Ringworm, jock itch, athlete's foot, scalp infection, nail infection, cutaneous candidiasis (oral thrush), vulvovaginitis

3.  Topical

Subcutaneous mycoses

1.  Often caused by what that may contain melanin

2.  How do they enter the person?

3.  What one is associated with thorn pricks in gardeners

1.  Organisms in the soil

2.  Breaks in skin

3.  Sporothrix schenckii

Systemic Mycoses:  Basics about the following

1.  Aspergillus spp

2.  Pneumocystic jiroveci

3.  Coccidiodes immitis

1.  Induces allergic rxns and becomes systemic in immunocompromised patients

2.  May be classified as protozoan; interstitial pneumonia in AIDS patients

3.  Endemic in desert areas of southwestern US; San Joaquin Valley fever which is an acute, self-limiting flu-like illness

Systemic Mycoses:  Basics about the following

1.  Cryptococcus neoformans

2.  Histoplasma capsulatum

1.  Found in pigeon droppings; Can appear as a tumor on scans; Can spread to CSF in AIDS patients

2.  Endemic in Ohio and Mississippi river valley; Found in bird and bat droppings; pulmonary granulomas visible on X-ray

Introduction to parasites

1.  2 Groups causing human dissease

2.  Pro or Eukaryotes?

3.  Replicaiton occurs in?

4.  How are human tissues damage?

1.  Protozoa and helminths

2.  Eukaryotes

3.  Specific cell types or organs; may be species specific

4.  Toxic substances produced by parasite; Mechanical damage from size or movement of parasite; Immune response

Describe the following intestinal and urogenital protozoa

1.  Cryptosporidium spp

2.  Entamoeba histolytica

3.  Giardia lamblia

4.  Trichomonas vaginalis

1.  Self-limited watery diarrhea and flu-like sx (severe and prolonged diarrhea in AIDS pts)

2.  Watery diarrhea with blood and mucus in stools (amebic dysentary); liver abcesses

3.  Watery, foul-smelling diarrhea with malabsorption, flatulence, and cramps; often acquired from drinking contaminated creek water (hikers, campers)

4.  Vaginitis with frothy discharge (due to flagella motion); STD

Describe the following blood and tissue protozoa

1.  Leishmania spp

2.  Plasmodium spp

1.  Endemic in tropical and subtropical regions

-Sandfly transmision

-Infects macrophages:  cutaneous, mucocutaneous, and visceral disease

2.  Endemic to tropical regions

-Transmitted by female Anopheles mosquito

-Causes malaria

-Life cycle takes place in mosquito, human liver, and human RBCs

Describe these blood and tissue protozoa

1.  Toxoplasma gondii

2.  Trypanosoma cruzi

1.  Cat litter, ingestion of undercooked meat, in utero

-Mononucleosis-like syndrome in healthy people

-Potentially fatal encephalitis in immunocompromised pts

2.  Endemic to South America

-Transmitted by reduviid bug

-Causes Chagas' disease:  cardiomyopathy, megacolon, megaesophagus

Describe the following blood and tissue parasite

1.  Trypanosoma brucei

1.  Endemic to West Africa

2.  Transmitted by tsetse fly

3.  Causes sleeping sickness (early enlargement of posterior cervical lymph nodes-later CNS involvement)

Describe the following helminths:  

1.  Ascaris lumbricoides (roundworms)

2.  Enterobius vermicularis (pinworms)

1.  Ingestion of food or soil containing larvae

-May cause intestinal obstruction with growth

-Pneumonitis with eosinophila with larval migration

2.  Perianal pruritis and itching

-Fecal-oral transmission and self-reinfection from touching anus and then mouth

-Scotch tape test

Describe the following helminths:

1.  Necator and Ancylostoma spp.:  hookworms

2.  Strongyloides stercoralis:  threadworm

1.  Located in soil, enter humans between toes

-Diarrhea, abdominal pain, weight loss

-Worm sucks blood from intestine:  anemia

-Larvae travel to lung:  pneumonitis

2.  Soil

-Dermatitis

-Larval migration causes pneumonitis

-Immunicompromised pts:  disseminated infection

Describe the following helminth

1.  Trichinella spiralis

1.  Transmitted by undercooked meet...pork

-Encysted larvae in muscle:  extreme muscle pain

-Fever, diarrhea, eye edema, hemorrhages under nails

Describe the following helminths:  flukes and flatworms

1.  Schistosoma spp:  blood an bladder flukes

2.  Taenia spp:  beef and pork tapeworms (up to 10m)

1.  Transmission:  skin penetration by motile larvae-snails are intermediate hosts

-Fibrosis of live rand ascites

-Bladder granulomas and hematuria

-Eggs are covered with spines-stool or urine

2.  Suckers and hooks on larvae

-Abdominal pain, diarrhea, weight loss

-Brain, eye, and muscle involvement (cysts and inflammation) due to ingestion of eggs rather than larvae...rare in US

Describe the following helminths:  flukes and flatworms

1.  Diphyllobothrium latum:  fish tapeworm (45 m long)

2.  Echinococcus granulosus:  dog tapeworm

1.  Raw or undercooked freshwater fish

-Human, crustacean, fish involved in lifecycle

-Can absorb B12:  anemia

2.  Dogs and sheep invovled in lifecycle

-Humans ingest eggs, which hatch in intestine, bore through intestinal wall, and disseminate

-Larva forms a cyst which can grow 5-10 cm in liver, lung, or brain

-Humans allergic to cystic fluid:  cyst rupture can be fatal

-May be misdiagnosed as tumors

1.  Define viral Virion

2.  Enveloped?

1.  Genome (DNA or RNA) packaged in a protein coat (capsid)

2.  May or may not be enveloped

1.  ssDNA

2.  dsDNA

3.  +RNA=mRNA

4.  -RNA

5.  dsRNA

6.  Segmented genome in several small pieces 

Viral Replication Basics

1.  DNA viruses

2.  RNA viruses

3.  Retroviruses

1.  DNA enters nucleus of host and is translated into mRNA/protein

2.  Already mRNA or converted to mRNA (-RNA virus) to make viral proteins

3.  Reverse transcriptase makes DNA from RNA and DNA inserts into host genome

1.  Viral attachment

2.  Entry into host cell

3.  Uncoating of viral nucleic acid

4.  Synthesis of early regulatory proteins

5.  Synthesis of RNA or DNA

6.  Syntehsis of late structural proteins

7.  Assembly of viral particles

8.  Release from host cell

Types of Viral Infections:  Define

1.  Cytolytic

2.  Chronic

3.  Latent

4.  Immortalizing 

1.  Viral replicaiton kills host cell

2.  Continual production of virions without host lysis or immune resolution

3.  Dormant virus until stress or immunosuppression activates it to cytolytic or chronic infection

4.  Persistant infection leads to cancer:  inhibits activation, acts as mitogen, inhibits tumor suppressor proteins

1.  Inhibit cellular protein synthesis

2.  Inhibit cellular DNA synthesis or degrade DNA

3.  Alteration of cell membranes (glycoprotein insertion, syncytia formation, permeability changes)

4.  Disruption of cytoskeleton

5.  Formation of inclusion bodies

6.  Toxicity of virion components

7.  Immunosuppression

Incubation period

1.  What determines?

Usual length of time

2.  Disease manifesting at site of entry

3.  Disease manifesting in tissues distant from site of entry

4.  Diseases resulting from immune system damage

1.  Site of disease and time needed for damage to occur 

2.  <1 week (exception is papillomavirus:  7-21 wks)

3.  1 wk to several months

4.  Several weeks to years

Clinical course of viral disease:  Explain

1.  Acute infections

2.  Persistent infections

3.  Conventional slow infections

1.  Immune system can eliminate virus and infection resolves

2.  Immune system only partially eliminates virus

3.  All involve neuronal tissue and have a very slow increase in viral load

Nonenveloped DNA virus

1.  Example given

2.  Mechanism of infection

3.  Production of proteins that do what?

4.  How transmitted

1.  Human papillomavirus

2.  Infects and replicates in cutaneous and mucosal epithelial tissue

3.  Inactive tumor suppressor proteins Rb and p53 leading to host cell hyperplasia

4.  Direct contact:  sex or child birth

Herpesviridae

1.  Type of virus

2.  What distinuishes different families

3.  2 types of infections caused

4.  Unique feature of the example virus given

1.  Enveloped DNA

2.  Glycoprotein spikes on envelope

3.  Cytolytic or persistent infection

4.  Latent infection for life of host

Herpesviridae

1.  Where does envelopment of virus occur

2.  What are the primary sites of HSV-1 and HSV-2, even though they can infect either

3.  Why doesn't immune system clear it?

1.  Nuclear membrane after capsid formed

2.  HSV-1:  oral

HSV-2:  genital

3.  No viral antigens expressed on nerves where it lies dormant

Varicella zoster virus

1.  Type of virus in what family

2.  2 diseases caused

1.  Enveloped dsDNA virus in herpesviridae family

2.  Chickenpox:  bad in immunocompromised ppl

Shingles:  VZV reactivation

1.  Infection at respiratory tract, migration to lymphoid tissue

2.  After 14 days, goes out to skin and cause the formation of swollen, multiucleated cells creating lesions 

Shingles

1.  What % of individuals get it with prior exposure to VZV

2.  What happens when it occurs

1.  20%

2.  Virus reactivates in ganglion and travels to sensory nerves in skin

-Restricted to area of skin innervated by infected nerve

-Associated with intense destructive inflammatory changes in ganglion

-Most reactivation occurs spontaneously, but stress and trauma can also cause

Epstein-Barr Virus (EBV)

1.  Type of virus and family

2.  What type of cell is infected

3.  How transmitted

4.  Diseases associated with EBV

1.  Enveloped dsDNA virus of herpes family

2.  B-lymphocytes:  can be latent until activation with lytic infection

3.  Oral secretion

4.  Infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, other lymphoid and epithelial tumors

Pox viruses

1.  Type of virus

2.  What specific virus is usually asymptomatic in children and adults?

1.  Enveloped DNA viruses

2.  Cytomegalovirus

Hepadnaviridae

1.  Type of virus

2.  Only human pathogen is?

1.  Enveloped DNA

2.  Hepatitis B

1.  Poliovirus

2.  Coxsackieviruses

3.  Hep A

4.  Rhinoviruses (common cold)

5.  Rotoviruses

6.  Norwalk virus

Poliovirus

1.  Type of virus

2.  3 outcomes

3.  Infected cells

1.  Nonenveloped RNA

2.  Paralytic, nonparalytic, minor illness

3.  Receptors on muscle and nerve cells

Coxsackievirus A

1.  AKA

2.  Type of virus

1.  Hand-foot-and-mouth

2.  Nonenveloped RNA

Rotovirus

1.  Type of virus

2.  How transmitted

3.  Results of infection

4.  Can be deadly in what pt population

1.  Nonenveloped RNA

2.  Fecal-oral

3.  Diarrhea and vomiting

4.  Infants (dehydration)

1.  Measles

2.  Mumps

3.  Influenza

4.  RSV

5.  SARS

1.  Rabies

2.  Ebola

3.  Marburg

4.  Hantavirus

5.  Rubella

6.  Hep C

1. HIV

2.  Human T-cell lymphotropic virus 1 (HTLV-1)

Influenza

1.  Type of virus and family

2.  2 key glycoproteins

3.  How often dose large antigenic shift occur?

4.  Major site of infectivity (specific cells)

1.  ssRNA virus from Orthomyxoviridae family

2.  Hemagglutinin:  attachment

-Neuraminidase:  aid in release of virions from host

3.  10-40 years

4.  Ciliated columnar epithelial cells

*no explanation for many of symptoms:  myalgia

RSV

1.  Type of virus

2.  Difference in infections betwen infants and older children/adults

3.  What age group gets the lower respiratory tract version of the infection

1.  Enveloped ss - RNA virus

2.  Infants:  pneumonia and brhonchiolitis

Children/Adults:  trachobronchitis and upper RTIs

3.  <3 yrs old

RSV

1.  Transmission

2.  Best way to limit transmission

3.  What happens as disease progresses

1.  Contact with large particles of respiratory secrestion through eyes and nose

2.  Handwashing b/c it can live for awhile on hands

3.  Necrosis and sloughing of bronchiolar epithelia causing dead cells to plug up airways blocking airflow