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1
Q

Top 5 drugs:

A
Amoxicillin
Azithromycin
Amoxicillin-clavulanic acid
Trimethoprim-sulfamethoxazole
Ciprofloxacin
2
Q

antibiotic Misuse may occur in a variety of ways:

A

Given when not needed
Continued when no longer necessary
Given at the wrong dose
Broad spectrum agents used for very susceptible bacteria
The wrong antibiotic given to treat infection

3
Q

inappropriate prescribing

A
Over 50% of antibiotic prescribing may be inappropriate
Most of this inappropriate use is for:
Acute respiratory infections
Pharyngitis
Sinusitis
Bronchitis

Antibiotics are a common cause of ADE-related ED visits, accounting for:
7 of top 15 drugs in pediatric patients ADE-ED visits
1 of 5 ADE-related visits to ED in adults

4
Q

A 37 y/o female with poorly controlled type 1 diabetes and end-stage renal disease, on hemodialysis, presents to the ED with 3-day history of dyspnea, cough with purulent sputum production, and intermittent fever.

She recently completed a course of meropenem for catheter-associated blood-stream infection 2 weeks ago.

Physical and laboratory findings are consistent with pneumonia. She is admitted to the hospital.

Questions to ask yourself about anti-microbial therapyp

A

Ask yourself whether an antimicrobial agent is warranted:

Is an antimicrobial indicated based on clinical findings? yes
Have appropriate cultures been obtained?
What is the most likely causative organism?-
What must be done to prevent secondary exposure?- not likely to have a 2ndary exposure in this case,

Is there clinical evidence or established guidelines that have determined antimicrobial therapy provides a clinical benefit?- yes, esp. for pneumonia

5
Q

A 37 y/o female with a history of end-stage renal disease, on dialysis, is admitted to the hospital with pneumonia. Antibiotics are initiated to cover the most likely pathogen(s).

Types & Goals of Therapy?

A

Empiric therapy; we suspect common organisms

6
Q

A 68 y/o male presents for a total hip replacement. Prior to surgery, he is given one dose of cefazolin to prevent development of a surgical wound infection.

Types & Goals of Therapy?

A

Prophylaxis

7
Q

A 37 y/o female with a history of end-stage renal disease, on dialysis, is admitted to the hospital with pneumonia. Cultures result with sensitive Pseudomonas, vancomycin (mostly for gram positive) discontinued.

Types & Goals of Therapy?

A

Definitive therapy

8
Q

An 8 y/o male presents to the ED with a perforated appendix. Antibiotics are initiated pre-operatively to reduce risk of intra-abdominal abscess & wound infection.

Types & Goals of Therapy?

A

pre-emptive; this patient already has appendicitis

to prevent abdominal abscess

9
Q

A 75 y/o male presents for follow-up of prosthetic hip joint infection. He receives continued, low dose antimicrobial therapy as hip prosthesis was unable to be removed.

Types & Goals of Therapy?

A

Suppressive

10
Q

Most valuable, time tested method for immediate ID of bacteria =

A

gram stain

11
Q

gram positive vs negative

A

neg- 2 cell membranes, LPS endotoxin

pos- thicker peptidoglycan layer, teichoic acid stabilizes peptidoglycan layer (rigid, provides structural shape)

12
Q

beta lactamase

A

an important resistance mechanism against beta lactam antibiotics

13
Q

Susceptibility Testing

A

Susceptible
- Likely to inhibit pathogenic microorganism

Intermediate
- May be effective at higher dosage, more frequent administration, or in specific body site

Resistant
- Not effective at inhibiting growth of microorganism

Types of Susceptibility Tests:
Dilution Tests
Disk Diffusion
Gradient Diffusion

14
Q

Minimum inhibitory concentration (MIC)

A

lowest concentration of drug required to inhibit growth

Breakpoints established by Clinical and Laboratory Standards Institute (CLSI)

15
Q

Antibacterial Spectrum

A

Narrow-spectrum
- Act on a single or a limited group of microorganisms

Extended-spectrum
- Active against gram-positive bacteria but also against significant number of gram-negative bacteria

Broad-spectrum
- Act on a wide variety of bacterial species, including both gram-positive and gram-negative

16
Q

Bacteriostatic vs. Bactericidal

A

Bacteriostatic: arrests growth and replication of bacteria (limits spread of infection)

Bactericidal: kills bacterial

  • Concentration-dependent killing: rate and extent of killing increase with increasing drug concentrations
  • Time-dependent killing: activity continues as long as serum concentration above minimum bactericidal concentration

This concept is relative
Certain drugs are –cidal against specific bacteria while –static against others

Drug-drug enhancement or synergism
Gentamicin – ineffective against enterococci in the absence of a cell-wall inhibitor
Combining penicillin with gentamicin leads to bactericidal activity

17
Q

Antimicrobial Classification

A

Antimicrobials classified based on:
Class and spectrum of microorganisms it kills
Biochemical pathway it interferes with
Chemical structure

18
Q

Sites of Antibacterial Action

A
Cell wall synthesis
Cell membrane synthesis
Protein synthesis
Nucleic acid metabolism
Function of topoisomerases
Folate synthesis
19
Q

β-Lactams- MOA, list, resistance

A

cell wall inhibitors

Penicillins
Cephalosporins
Monobactam
Carbapenems

Time-dependent; structural analogs of D-Ala-D-Ala; covalently bind penicillin-binding proteins (PBPs), inhibit the last transpeptidation step in cell wall synthesis

Structural difference in PBPs
Decreased PBP affinity
Inability for drug to reach site of action (i.e. gram-negative organisms)
Active efflux pumps
Drug destruction/inactivation by B-lactamases

20
Q

β-Lactamase Inhibitors

A

Amoxicillin + clavulanic acid,
ticarcillin + clavulanic acid,
ampicillin + sulbactam,
piperacillin + tazobactam

MOA: prevent destruction of B-lactam antibiotics

21
Q

Fluoroquinolone Mechanism of Action

A

Concentration-dependent, targets bacterial DNA gyrase & topoisomerase IV. Prevents relaxation of positive supercoils

22
Q

Inhibitors of Protein Synthesis- areas of action

A

Formation of initiation complex
Amino-acid incorporation
Formation of peptide bond
Translocation

23
Q

Aminoglycosides MOA

A

blocks initiation of protein synthesis
blocks further translation and elicits premature termination
incorporation of incorrect amino acid

Bind 30S subunit

24
Q

Tetracyclines MOA

A

Bind 30S subunit

25
Q

Macrolides MOA

A

Bind 50S subunit

26
Q

Sulfonamides and Trimethoprim

A

Inhibit folic acid synthesis; block sequential steps in pathway.

27
Q

Natural Penicillins spectrum, use

A

Penicillin G (IV, IM), penicillin V (PO)

Spectrum: highly effective against gram-positive cocci (GPC) but easily hydrolyzed by penicillinase

Therapeutic Use: narrow-spectrum, Streptococcus pneumoniae pneumonia and meningitis. Penicillin V for Streptococcus pyogenes pharyngitis, toxic shock, viridians streptococci endocarditis if susceptible, syphilis

28
Q

Anti-Staphylococcal Penicillins spectrum, therapeutic use

A

Oxacillin (IV, IM), dicloxacillin (PO), nafcillin (IV, IM)

Spectrum: penicillinase resistant; agents of first choice for Staphylococcus aureus (MSSA) and Staphylococcus epidermidis (MSSE) that are not methicillin-resistant

Therapeutic Use: restricted to infections with known Staphylococcus sensitivity

29
Q

Aminopenicillins

A

extended spectrum

Ampicillin (PO, IV, IM), amoxicillin (PO)

Spectrum: extended-spectrum; extends beyond gram-positive to gram-negative (Haemophilus influenzae, Escherichia coli, Proteus mirabilis), Listeria monocytogenes, susceptible meningococci, enterococci

Therapeutic Use: upper respiratory tract infections (S. pyogenes, S. pneumoniae, H. influenzae), sinusitis, otitis media, enterococcal infections

30
Q

Antipseudomonal Penicillins

A

piperacillin (IV)- use with tazobactam

Spectrum: extends spectrum to Pseudomonas aeruginosa, Enterobacter, and Proteus spp.

Therapeutic Use: serious gram-negative infections, hospital acquired pneumonia (HAP), immunocompromised patients, bacteremia, burn infections, UTI

31
Q

Penicillins ADRs

A

Allergic reactions
Anaphylaxis
Nausea, vomiting, mild to severe diarrhea
Pseudomembranous colitis

32
Q

1st-Generation Cephalosporins spectrum and therapeutic uses

A

Cefazolin (IV, IM), cephalexin (PO)

Spectrum: good gram-positive coverage, modest gram-negative (covers Moraxella, E. coli, Klebsiella pneumoniae, P. mirabilis), orally active anaerobes

Therapeutic Use: skin and soft tissue infections (SSTIs), surgical prophylaxis

33
Q

2nd-Generation Cephalosporins spectrum and use

A

Cefoxitin (IV), cefuroxime (PO, IV, IM)

Spectrum: somewhat increased activity against gram-negative, but less active than 3rd-generation. Subset active against Bacteroides fragilis

Therapeutic Use: used in gram-negative mixed anaerobic (intra-abdominal infections, pelvic inflammatory disease, diabetic foot infections)

34
Q

3rd-Generation Cephalosporins MOA and uses

A

Ceftriaxone (IV, IM), ceftazidime (IV, IM)

Spectrum: less active against gram-positive, more active against Enterobacteriaceae (although resistance increasing due to B-lactamase producing strains)

Therapeutic Use: serious gram-negative infections (Klebsiella, Proteus, Providencia, Serratia, Haemophilus), ceftriaxone DOC for all forms of gonorrhea & severe Lyme’s disease; meningitis. Ceftazidime covers Pseudomonas

35
Q

4th-Generation Cephalosporin

A

Cefepime (IV, IM)

Spectrum: extends beyond 3rd-generation, useful in serious infections in hospitalized patients. Effective against Pseudomonas

Therapeutic Use: empirical treatment of nosocomial infections

36
Q

Cephalosporins ADRs

A

1% risk of cross-reactivity to penicillins

Diarrhea

37
Q

Carbapenems spectrum, use, ADRs

A

), meropenem (IV), ertapenem (IV, IM)

Spectrum: aerobes & anaerobes; gram-positive, Enterobacteriaceae, Pseudomonas, Acinetobacter. Stenotrophomonas maltophilia is resistant.

Therapeutic Use: UTI, lower respiratory tract infection (LRTI), intra-abdominal, gynecological, SSTI, bone and joint infections

ADRs:
Nausea/vomiting (1-20%), seizures (1.5%), hypersensitivity

38
Q

Monobactam spectrum, therapeutic use

A

Aztreonam (IV, IM, INH)

Spectrum: activity against gram-negative (Enterobacteriaceae, Pseudomonas, H. influenzae, gonococci), no activity against GPC or anaerobes

Therapeutic Use: patients who are allergic to B-lactams appear not to react to aztreonam  effective for gram-negative infections which would usually be treated with B-lactam

39
Q

Glycopeptides MOA, resistance, spectrum, ADRs

A

Vancomycin (PO, IV)

MOA: inhibits cell wall synthesis binding with high affinity to D-Ala-D-Ala terminal of cell wall precursor units.

Resistance: alteration of D-Ala-D-Ala target to D-alanyl-D-lactate or D-alanyl-D-serine which binds glycopeptides poorly. Intermediate resistance may also occur

Spectrum: broad gram-positive coverage – S. aureus (including MRSA), S. epidermidis (including MRSE), Streptococci, Bacillus, Corynebacterium spp., Actinomyces, Clostridium

Therapeutic Use: osteomyelitis, endocarditis, MRSA, Streptococcus, enterococci, CNS infections, bacteremia, orally for C. difficile

ADRs:
Macular skin rash, chills, fever, rash
Red-man syndrome (histamine release): extreme flushing, tachycardia, hypotension
Ototoxicity, nephrotoxicity - watch out with renal patients!

40
Q

Fluoroquinolones MOA, spectrum, therapeutic use, ADRs

A

MOA: concentration-dependent; targets bacterial DNA gyrase & topoisomerase IV.

Spectrum: E. coli, Salmonella, Shigella, Enterobacter, Campylobacter, Neisseria, Pseudomonas aeruginosa, S. aureus (not MRSA), limited coverage of Streptococcus spp.
Levofloxacin, moxifloxacin, “respiratory fluoroquinolones” cover Streptococcus spp.

Therapeutic Use: UTI, prostatitis, STI (chlamydia, Neisseria gonorrhoeae), traveler’s diarrhea, shigellosis, bone, joint, SSTI infections, diabetic foot infections

ADRs:
GI 3-17% (mild nausea, vomiting, abdominal discomfort)
CNS 0.9-11% (mild headache, dizziness, delirium, rare hallucinations)
Rash, photosensitivity, Achilles tendon rupture (CI in children)

41
Q

Aminoglycosides MOA, spectrum, therapeutic uses, ADRs

A

gentamicin (IV, IM, topical)

MOA: concentration-dependent (one high dose can do the trick); binds 30S ribosomal subunit, disrupts normal cycle of ribosomal function

Spectrum: aerobic gram-negative bacteria, limited action against gram-positive, synergistic bactericidal effects in gram-positive with cell wall active agent

Therapeutic Use: UTI (not uncomplicated), used if resistance to other agents, seriously ill patients, pneumonia (infective against S. pneumoniae and anaerobes), HAP, peritonitis, synergy in bacterial endocarditis, tobramycin inhalation in CF

ADRs:
Ototoxicity (may be as high as 25%)
Nephrotoxicity (8-26%)
Neuromuscular block and apnea

42
Q

Tetracyclines/Glycylcyclines MOA, spectrum,

A

doxycycline

MOA: bacteriostatic; binds 30S bacterial ribosome. Prevents access of aminoacyl tRNA to acceptor (A) site on mRNA ribosome complex

Spectrum: wide range of aerobic/anaerobic gram-positive and -negative activity; useful for atypical presentations and/or in outpatient setting

Therapeutic Use: CAP, atypical CAP coverage, community acquired SSTIs, community acquired MRSA, acne, Rickettsial infections (Rocky Mountain Spotted Fever), Q fever, anthrax

ADRs:
GI (epigastric burning, nausea, vomiting, diarrhea)
Superinfections of C. difficile
Photosensitivity
Teeth discoloration (it chelates calcium)
Thrombophlebitis

43
Q

Macrolides/Ketolides MOA, uses, etc.

A

Clarithromycin (PO), azithromycin (PO, IV, topical)

MOA: bacteriostatic; binds reversibly to 50S ribosomal subunit, inhibits translocation

Therapeutic Use: respiratory tract infections (spectrum S. pneumoniae, H. influenzae, and atypicals: Mycoplasma, Chalmydophilia, Legionella), alternative for otitis media, sinusitis, bronchitis, and SSTIs. Pertussis, gastroenteritis, H. pylori, Mycobacterial infections

ADRs:
GI (epigastric distress)
Hepatotoxicity
Arrhythmia
* QT prolongation

DDIs: CYP3A4 inhibition – prolongs effects of digoxin, warfarin….

44
Q

Lincosamides MOA, spectrum, uses

A

Clindamycin (PO, IV, IM, topical)

MOA: binds 50S subunit of bacterial ribosome, suppresses protein synthesis

Spectrum: pneumococci, S. pyogenes, viridans Streptococci, MSSA, *** anaerobes (B. fragilis)

Therapeutic Use: SSTIs, necrotizing SSTIs, lung abscesses, anaerobic lung and pleural space infections, topically for acne vulgaris

ADRs:
GI diarrhea
*** Pseudomembranous colitis Due to C. difficile
Skin rashes
Reversible increase in aminotransferase activity
May potentiate neuromuscular blockade

45
Q

Oxazolidinones

A

Linezolid (PO, IV)

MOA: inhibits protein synthesis binding P site of 50S ribosomal subunit, prevents formation of initiation complexes

Spectrum: gram-positive Staphylococcus (MSSA, MRSA, VRSA), Streptococcus (penicillin resistant S. pneumoniae), enterococci (VRE), gram-positive anaerobic cocci, gram-positive rods (Corynebacterium, L. monocytogenes)

Therapeutic Use: VRE faecium (SSTI, UTI, bacteremia), nosocomial pneumonia caused by MSSA and MRSA, CAP, complicated/uncomplicated SSTI infections

ADRs:
Myelosuppression [thrombocytopenia (2.4%),anemia, leukopenia]
Headache
Rash

DDIs: weak, nonspecific inhibitor of monoamine oxidase