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Flashcards in Antibiotics_WalworthPilch Deck (70)
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1

MBC (minimal bacteriacidal concentration) - YES within therapeutic range of drug

Bacteriacidal (cell-wall active agent) - Rifampin, quinolones

2

Toxic Dose/Effective Dose

Therapeutic Index

3

Therapeutic Index >1 __
Therapeutic Index

Susceptibility
Resistance

4

Timeline of Antibiotic Drug Therapy

1. Prophylactic (no infection) -> Pre-emptive
2. Empiric (after infection, cultures of blood/infection site + lab techniques [gram stain/strep test]) - single, broad spectrum agent [causative microorganism NOT yet defined]
3. Definitive - Specific and narrow-spectrum agent
[causative microorganism YES defined]

5

Type of empiric therapy used to:
INCREASE antimicrobial activity for specific infection
DECREASE resistance + host toxicity

Combination Therapy

6

Combination Therapy Criteria

Usually use two agents that differ in mechanism (SIGNIFICANTLY lowered frequency of resistance)

7

What disease do you especially use combination therapy?

Tuberculosis

8

COMBINATION THERAPY: Relationship between bacteriostatic and bacteriacidal drugs

Bacteriostatic (Tetracyclins) ANTAGONIZE bacteriocidal (beta-lactams, rifampin, quinolones, aminoglycoside)

9

COMBINATION THERAPY: Relationship between combined usage of bacteriacidal drugs

Synergistic (one drug potentiates the inhibitory effect of the other)
Additive (one drug independent of action of other drug)

10

MIC (minimal inhibitory concentration) - YES, within therapeutic range of drug
MBC (minimal bacteriacidal concentration) - NO within therapeutic range of drug

Bacteriostatic agent (protein synthesis inhibitors)

11

MDR

Multi-drug resistant bacteria

12

4 Genetic Mechanisms of Developing Antibiotic Resistance

1. Transformation - uptake of DNA from environment
2. Transduction - uptake of DNA from bacteriophage (viral vector)
3. Conjugation - transfer of plasmid from one bacterial cell to another by direct contact and pilus formation
4. Transposition - for the antibiotic resistance gene to be phenotypically expressed by the bacteria, the gene has to be transferred from the plasmid to the bacterial chromosome (via insertion sequences)

13

beta-lactam antibiotics

penicillin (subclass: amoxicillin), methicillin, oxacillin, nafcillin, ampicillin + cephalosporins

14

AMINOGLYCOSIDE Antibiotics

Gentamicin
Neomycin
Amikacin
Tobramycin
Streptomycin
Kanamycin

15

beta-lactamase inhibitor

* beta-lactamase: bacteria evolved and acquired mutation in beta-lactamase that cleaves/renders inactive beta-lactams (penicillin/cephalosporin)
* CLAVULANIC ACID

16

Combination Therapy: Amoxicillin (beta-lactam) + Clavulanic acid (beta-lactamase inhibitor)

Augmentin

17

Most common anti-fungal agent and its action

5-flucytosine
Action: Inhibits formation of dTMP -> Decreases fungal DNA synthesis
Caveat: Requires 3 metabolic enzymes to work - cytosine deaminase, UMP pyrophosphorylase, ribonucleotide reductase

18

Resistance to 5-flucytosine (anti-fungal agent) is most likely due to __

Downregulation of UMP PYROPHOSPHORYLASE - Enz required for the conversion of 5-flucytosine to a more active compound and its effect of decreasing fungal dTMP (DNA) synthesis

19

Combination Therapy: Sulfonamide + Trimethoprim (Synergistic Relationship)
Block 2 steps within the same pathway

Bactrim

20

Only time that bactrim will not work:
Mechanism of bacteria developing bactrim resistance

Overproduction of p-aminobenzoic acid (PABA): Increased flux of reacting metabolite to overcome competitive, antagonistic drug sulfonamide (part of bactrim)

21

LARGEST GROUP of ANTIBIOTICS = cell wall inhibitors
[ALL BACTERIACIDAL by weakening cell wall -> bacteria rupture by osmotic lysis]

beta-lactams (penicillin/amoxicillin + cephalosporins)
NOT beta-lactams (vancomycin)
carbapenems
monobactams

22

Mechanism in which bacteria acquired VRE (mostly enterocci and moderately in staphylococci)

Bacteria acquired DNA to produce a mutational proteoglycan matrix of the cell wall:
3 genes (VanHAX operon) that encoded for D-Ala-D-lactate (instead of D-Ala-D-Ala, target of vancomycin) -> Vancomycin can NO LONGER BIND

23

Resistances of S. aureus

1) PENICILLINASE - Resistant to penicillin
MRSA - methicillin resistant S. aureus (methicillin = "penicillinase-resistant" anti-staphylococcal beta-lacftams
2) VISA / VRSA - vancomycin intermediate/resistant S. aureus

24

beta-lactamase resistant penicillins (beta-lactam)

Nafcillin

25

Macrolide used to treat Chlamydia AND also gonorrhea or neonatal conjunctivitis (N. gonorrheae infections)
**We have to assume Chlamydia co-infection whenever patient has gonorrhea**

Azithromycin
Erythromycin
Clarithromycin
Telithromycin

26

N. gonorrheae is resistant to which antibiotics

Penicillin
Tetracycline
Quinolones
**Reason: 20-30% of new gonorrhea cases are PPNG (penillinase-producing)/ TRNG (tetracycline resistant)/ QRNG (quinolone resistant)**

27

2 IV aminoglycoside antibiotics used to treat SERIOUS infections

Gentamicin
Tobramycin

28

2nd line agent used to treat tuberculosis = __
What drug is this antibiotic combined with __

Streptomycin
Combined with INH or Rifampin - To prevent emergence of drug resistance

29

Aminoglycoside drug used when bacteria develops inactivating enzymes against tobramycin and gentamycin

Amikacin

30

Topical aminoglycoside antibiotics used to treat skin/eye

Neomycin
Kanamycin