Week 4: antibiotics Anti-Bacterial Agents: Cell Wall Synthesis Inhibitors

Question 1

What are characteristics of Anaerobes?

Answer 1

Grow only in the absence of O2​
Found in oral and GI tract and vagina​
Most anaerobes are medically important to know​
Cause diseases when normal mucosal barriers do not function normally​
Can be classified as gram negative vs positive​

Question 2

What color are gram positive vs gram negative microbs and why?

Answer 2

Gram positive are purple

Gram negative are pink since when cleaned with ethanol it becomes clear

Question 3

Broad spectrum vs narrow spectrum bacteria

Answer 3

broad: effective against multiple organisms from more than a single class, more likely to disrupt normal flora, risk of superinfection by a second organism
narrow: effective against limited number of organism, unlikely to disrupt normal flora

Question 4

bacteriostatic vs bactericidal?

Answer 4

bacteriostatic: capbale of inhibiting growth or reproduction of bacteria, does not kill them.

bacterialcidal:
capable of actively killing bacteria, 99.9% killing within 18 to 24 hours in lab condition

Question 5

MIC (Minimum inhibitory concentration)

Answer 5

:the lowest concentration of antibiotics that inhibits bacterial growth

Question 6

MBC (Minimum bactericidal concentration):

Answer 6

Lowest concentration of antibiotics that kills 99.9 % of bacteria

Question 7

Cell Wall Synthesis Inhibitors

Answer 7

Beta Lactams
-Penicillin
-Cephalosporins
-Carbapenems
-Monobactams
Beta-Lactamase Inhibitors
Vancomycin
Others

Question 8

What is Atypical bacteria?

Answer 8

An inexact term applied to bacteria which are particularly “unusual” in structure, morphology, biochemistry, or life cycle.​

Question 9

Gram positive

Cocci

Answer 9

Staphylococcus aureus
Streptococcus
Enterococcus

Question 10

Gram positive

Rods

Answer 10

(Corney
Mike’s list of basic cars)

Corneybacterium
Mycobacteria 
Listeria 
Bacillus
Nocardia

Question 11

Gram positive

Anaerobes

Answer 11

(CLAP)

Clostridium
Lactobacillus
Actinomyces
Propionibacterium

Question 12

Gram negative

Answer 12

Aerobes:
Neisseria meningitidis (Meninogococcus)
Neisseria gonorrhoeae

Anaerobes: 
Haemophillus influenzae
Escherichia coli (E. coli)
Klebsiella pneumoniae
Proteus mirablilis 
Pseudomonas aeruginosa
Moraxella catarrhalis

Question 13

Atypicals

Answer 13

Mycoplasma pneumoniae : Walking pneumonia​

Chlamydia trachomatis & pneumoniae: PID, STD , pneumonia​

Rickettsia : Rocky mountain spotted fever, typhus fever​

Legionella :Legionnaires’ disease (severe pneumonia)​

Question 14

Enterococci

Answer 14

UTI, bacteremia, endocarditis, meningitis

Question 15

strep pnumoniae

Answer 15

sepsis, pneumonia, meningitis, middle ear infection in children, sinusitis

Question 16

Group B strep

Answer 16

sepsis, pna, meningitis in newborns, mostly not harmful, natrually comes and goes in our body,mild idsease UTI, vaginitis,

Question 17

group A strep (s.pyogenes)

Answer 17

strep throat, rheumatic fever, post-streptococcal glomerulonephritis, impetigo, sinusitis, cellulitis, necrotizing fasciitis

Question 18

Gram Positive: Clostridium Difficile risk factors

Answer 18

Diarrhea to life threatening inflammation of colon
older adults in hospital or nursing homes
after abx use

Question 19

Gram Positive: Clostridium Tetani risk factors

Answer 19

tetanus

Question 20

Gram Positive: Clostridium Perfringens risk factor

Answer 20

most common causes of food poisoning

Question 21

Gram negative: Pseudomonas

Answer 21

UTI, respiratory, soft tissue infection, GI infection, sepsis, usually form hospitalized patients

Question 22

Gram Negative: Hemophilus influenzas

Question 23

Gram negative: escherchia coli

Answer 23

most strain is not harmful, diarrhea, UTI

Question 24

Gram Negative: Kiebsiella Pneumoniae

Answer 24

mostly not harmful, lives in GI and feces normally, can cause pneumonia, UTI, cellulitis, etc

Question 25

Gram negative: moraxella catarrhalis

Answer 25

normally present in oropharynx, skin and genital area, could cause conjunctivitis, upper and lower respiratory infection in kids and adults

Question 26

Gram negative: shigella and salmonella

Answer 26

shigellosis-diarrhea, fever, stomach cramp, salmonellosis

Question 27

inhibitors of metabolisms

Answer 27

sulfonamides, trimethoprim

Question 28

inhibitors of cell wall synthessis

Answer 28

Beta-lactams, daptomycin, fosfomycin, lipoglycopeptide, vancomycin

Question 29

inhibitors of protein synthesis

Answer 29

ahminoglycosides, chloramphenicol, clindamycin, macrolides, oxazolidinone, tetracyclines

Question 30

inhibitors of cell membrane function

Answer 30

amphotericin B, isonizaid, polymyxins

Question 31

inhibitors of nucleic acid function or synthesis

Answer 31

fluoroquinolones, rifampin

Question 32

Penicillin

Answer 32

PCNs: 1st Antibiotic: 1928​ For Streptococcal and staphylococcal infections​ Synthetic PCNs: Developed to overcome resistance issues​ Classified based on the spectrum of activity​ Have both narrow and broad spectrum

Question 33

What is the penicillin class/clinical indication?

Answer 33

Narrow and Broad spectrum Time-dependent bactericidal Effective for Gram-positive organisms : Upper /Lower respiratory . UTI, STIs, Endocarditis Extended spectrum PCNs: Pseudomonas​ (G -)

Question 34

Penicillin pharmacokinetics

Answer 34

Oral formulations are acid-stable​ PO absorption is inhibited by co-ingestion of food​ Widely distributed​ Penetrate CSF in presence of inflammation​ ( penicillin can cross BBB well without inflammation) Excreted by kidneys​ Dosage adjustment with impairment​ Prolonged effects by administration with Probenecid by inhibiting tubular secretion Half-life is typically 30 – 90 minutes​

Question 35

What are drawbacks of penicillin?

Answer 35

Seizure activity: high-dose with renal impairment Rare: leukopenia, thrombocytopenia and hemolytic anemia Allergic reactions:​ Urticaria to hemolytic anemia and anaphylaxis,​ Assume cross-reactivity throughout class,: 10% of persons who are allergic to PCN are also allergic to Cephalosporins​ GI Disturbances:​ N/D caused by oral medications via direct irritation or over growth of G+ organisms or yeast;​ Ampicillin implicated in pseudomembranous colitis​ Drug Interaction Rare

Question 36

What are action of resistance in penicillin?

Answer 36

β-lactamase produced by bacteria cause enzymatic hydrolysis of the B-lactam ring, resulting in loss of antibacterial activity​ ​

Question 37

Cephalosporins

Answer 37

Structurally similar to PCNs​ “Generations”​ Based on spectrum of activity 1st → 5th : increase in gram (-) coverage and loss of gram (+) activity ​

Question 38

What class are Cephalosporins?

Answer 38

- Time-dependent bactericidal effect - Gram positive to Gram negative - newer generation covers more gram negative

Question 39

Cephalosporins pharmacokinetics?

Answer 39

A: IV and PO, Well-absorbed from GI tract Food may enhance absorption D: Most 1st & 2nd –generation do not cross BBB, even with inflamed meninges M: Cephalosporins with side chains may undergo hepatic metabolism E: Majority excreted unchanged in urine via active tubular secretion; EXCEPT cefoperazone and ceftriaxone, which are mainly excreted in bile

Question 40

What are drawback of Cephalosporins

Answer 40

``` Safe with favorable toxicity profile Allergic Reactions: 5-15% of persons allergic to PCN are also allergic to cephalosporins Anaphylaxis Fever Skin rash Nephritis Granulocytopenia Hemolytic anemia Other reactions: MT sidechain causes hypoprothrombinemia and inhibits aldehyde dehydrogenase (can cause disulfiram-like reaction with ETOH ingestion) Local irritation at injection site Drug Interaction Rare May ↑ aminoglycoside toxicity Probenecid & loop diuretics Increases half-life of some cephalosporins, inhibiting tubular secretion ```

Question 41

What are action of resistance for Cephalosporins?

Answer 41

Less than seen with PCNs due to more stable β-lactam ring Via production of β-lactamase Via decreased membrane permeability to cephalosporins Via mutation in the binding site on cell membrane

Question 42

What are the First generation of Cephalosporins and spectrum of activity

Answer 42

-cefazolin, cefadroxil, cephalexin -Best for G + cocci​ G – (P. mirabilis, E coli, K. pneumoniae) Susceptible to B-lactamase​ Does not cross BBB -

Question 43

First generation of Cephalosporins clinical use and indication

Answer 43

Skin Infections​ Pneumococcal respiratory infections​ UTI​ Surgical Prophylaxis​

Question 44

What are the second generation of Cephalosporins and spectrum of activity

Answer 44

``` Cefaclor Cefprozil Cefuroxime sodium Cefuroxime axetil Cefotetan/Cefoxitin ----- Extended G – coverage​ (H. flu) Less activity against G+ organisms than 1st Generation​ Does not cross BBB ```

Question 45

Second generation of Cephalosporins clinical use and indication

Answer 45

CAP​ Respiratory infections​ Skin infections​

Question 46

What are the third generation of Cephalosporins and spectrum of activity

Answer 46

Cefdinir Cefixime Cefotaxime Ceftazidime/Ceftriaxone ----- Active against G- bacilli​ (H. flu, Meningococcus) May be useful for G + infections​ (Pneumococcus)

Question 47

Third generation of Cephalosporins clinical use and indiciations

Answer 47

Generally reserved for serious infections (i.e. Bacterial meningitis)​ PCN-resistant Neisseria gonorrhoeae infection Pseudomonas Lyme disease

Question 48

What are the fourth generation of Cephalosporins and spectrum of activity

Answer 48

Cefepime G+ activity of 1stGeneration​ Active for G- organisms​ as 3rd generation More resistant to β-lactamases produced by G- organisms​ Does cross BBB

Question 49

Fourth generation of Cephalosporins clinical use and indiciation?

Answer 49

Better or infections caused by Beta-lactamase-producing G- organisms: Enterobacter, Haemophilus, Neisseria​, Pseudomonas, nosocomial bacterial infection In general, administer with other agents(aminoglycosides) to prevent resistance​ As the generation increases, so does the potency and spectrum, esp. against G- species​

Question 50

What are the fifth generation of Cephalosporins and spectrum of activity

Answer 50

Ceftaroline Broad spectrum Does not cross BBB

Question 51

Fifth generation of Cephalosporins clinical use and indications

Answer 51

MRSA

Question 52

Beta-Lactamase Inhibitors

Answer 52

Clavulanic acid , sulbactam, tazobactam ---- Prevents the breakdown of the beta-lactam ring by beta lactamase producing the bacteria But NO significant antibacterial activities or cause side effects Usually used as combination drugs Bacteria can produce penicillinases or beta-lacatmases​ 🡪 Inactivate PCN and cephalosporines​

Question 53

Beta-Lactamase Inhibitors class/clinical indications

Answer 53

Broad spectrum Intraabdomen and GYN infections Skin & Soft tissue infection: human and animal bites Diabetic foot infections Respiratory track aspiration: pneumonia sinusitis abscess

Question 54

Beta-Lactamase Inhibitors pharmacokinetics

Answer 54

Penetrates most body tissues Exception: CNS/Brain Elimination: glomerular filtration: renal dysfunction & dialysis necessitate dosage change

Question 55

Beta-Lactamase Inhibitors action of resistance

Answer 55

- Bacteria produce β-lactamase → breaks down β-lactam → penicillin inactive - Diminishes cell wall permeability to drug - Via mutation in the binding site on cell membrane

Question 56

Vancomycin

Answer 56

cell wall synthesis inhibitor, bactericidal, mostly gram positive (including MRSA) but covers gram negative for c.diff serum concentration needed for IV

Question 57

Which generation achieves therapeutic level at CSF for cephalosporin?

Answer 57

3rd generation

Question 58

which generation of cephalosporin treats MRSA?

Answer 58

5th generation

Question 59

Which PCN have pseudomonas coverage?

Answer 59

ampicillin, amoxicillin