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Beta-Lactam Antibiotics Flashcards

1
Q

Beta-lactam MOA

A

Disrupt the synthesis of bacterial cell wall by interfering with the transpeptidase which catalyzes the cross linking process
Bind to PBPs to inhibit transpeptidation = cell wall destroyed and bacterial cell dies
Time-dependent killer: Time the AUC is above the MIC
Bactericidal to growing bacteria

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2
Q

Beta-lactam Resistance

A

Mutation of genes which control production of PBPs - alter the active site and binding affinity for beta-lactam
Synthesize b-lactamase (pencillinase) which breakdowns b-lactam ring inactivating the Abx

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3
Q

b-Lactam compounds

A 
penicillins
cephalosporins
carbapenems
monobactams
b-lactamase inhibitors - combined with PCNs
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4
Q

Natural PCNs

A

Penicillin G - IM

Penicillin VK - PO

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5
Q

Penicillinase-Resistant PCN

A 
Anti-staphylococcal PCNs
Nafcillin
Dicloxacillin
Oxacillin
Cloxacillin
Methicillin
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6
Q

Antipseudomonal PCNS

A

Extended/Broad Spectrum
Piperacillin
Carbenicillin
Ticarcillin

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7
Q

Aminopenicillins

A

Ampicillin

Amoxicillin

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8
Q

Pen G

A

Gm - cocci: strep, staph
Gm + rods: listeria, actinomyces
Gm - cocci: neisseria
Most anerobes: clostridium

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9
Q

Pen G Dosage

A

IM or IV
Pen G cannot be given oral b/c of the acidic conditions
Pen VK is oral - QID

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10
Q

PCN G benzathine and procaine

A

IM: lasts 10-12 days
used for strep or syphilis
IV: for meningitis and endocarditis

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11
Q

PCN Special Populations

A

Pregnancy Cat B
Lactation Safe
Renal dosing: adjust CrCl < 50
Hepatic Dosing: no adjustment required

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12
Q

PCN Adverse Reactions and CI

A

Local: injection site rxn
Significant: CV, CNS, derm, endocrine, metabolic, GI, Hemat, Onco, hypersensitivity, Immuno, renal
CI: hypersensitivity rxns

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13
Q

PCN warnings/precautions

A

Superinfection: super C.Diff
Seizure disorders: high levels with renal impairment = risk of seizure
Pediatrics: neonate decreased clearance of PCN = require frequent dose adjustments

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14
Q

Pen G/Pen VK DI

A

BCG - diminished BCG effect = X
Mtx - increased mtx conc = C
Probenecid - increase PCN conc = C
Na Picosulfate - lower therapeutic effect of Na Pico - D
Tetracycline derivs. - diminish PCN effect - D
Vitamin K antagonists - enhance anticoag effect - monitor INR
OCPs: PCN will decreased OCP efficacy

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15
Q

Pen VK

A

250-500 TID/QID - DOC for strep pharyngitis
>10% have GI issue
< 1% have acute interstitial nephritis, convulsions, hemolytic anemia, + Coomb’s test

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16
Q

Penicillinase-resistant PCNs - antistaphylococcal

A

semisynthetic - used for b-lactamase producing STAPH and PCN susceptible strains of Strep and Pneumococci
Inactive against enterococci and methicillin resist. strains

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17
Q

Penicillinase-resistant PCNs - antistaphylococcal

A

Dicloxacillin, Oxacillin, Methicillin, Nafcillin, Cloxacillin
Not affected by beta-lactamase enzyme

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18
Q

Penicillinase-resistant PCNs Special Populations

A

Preg. Cat B
Lactation - safety unknown
Renal/Hepatic Dosing: no adjustment required - use discretion

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19
Q

Penicillinase-resistant PCNs - Adverse Effects

A

1-10% GI w/ dicloxacillin

<1% = similar to extreme AE of PCN - look at notes

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20
Q

Penicillinase-resistant PCNs - DI

A

Ariprazole - decreased conc of arip - D
Ca Channel Blockers - naf increases CCB metabolism
Estrogens - naf increases metab of estrogen - D
BCG - Abx diminish bcg effect - X
MTX - increased conc of Mtx - C
Probenecid - increase PCN conc - C
Saxagliptin - 3A4 inducers decrease serum conc of sax - C
Vitamin K antag. - dicloxacillin will diminish anticoag effect - C

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21
Q

Aminopenicillins and uses

A

Ampicllin and Amoxicillin - same antimicrobial spectrum as PCN G
Also cover E. coli, Proteus mirabilis, Salmonella, Shigella, H. flu
For otitis, sinusitis, and lower RTI
Amox is better absorbed

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22
Q

Dose in Peds of Aminopenicillins

A

20-40 mg/kg/d divided q8h
Otitis = amox 90mg/kg/day in two doses
3 g/day cut-off in peds

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23
Q

Augmentin

A

amox with clavulanic acid (beta-lactamase inhibitor)

Expands coverage to gram +, gram -, and anerobic organisms

24
Q

Aug. Special Populations

A

Preg Cat B
Lactation = safe
Renal = adust if CrCl < 30
Hepatic = no adjustment nedded

25
Augmentin/Amoxicillin/Ampicillin AE
CNS, Derm (SJS), GI (black tongue), Hemat, Hepatic, Renal, anaphylaxis, serum-sickness Rash in patients with mono
26
Aminopenicillin DI
allopurinol = increased allergic or hypersensitivity rxn to amox - C BCG = dimished BCG effect - X MTX = increased mtx conc - C Probenecid = increased conc of PCNs Na Picosulfate = diminished effect of Na P. - D Tetracyclines - diminished PCN effect - C Vitamin K antagonists - enhanced anticoag effect OCPs - PCN may decrease OCP efficacy
27
Antipseudomonal PCNs Drugs
Extended/broad spectrum Carbenicillin, Piperacillin, Ticarcillin IV only - standard anti-pseudomonas in hospitals
28
Antipseudomonal PCNs Activity
Strep Enteric Gm - bacilli (E. coli, Klebsiella pneumo, Enterobacter cloacea & aerogenes, Proteus miriabilils) Pseudomonas Anaerobes
29
Antipseudomonal PCNs Dosage
Ticarcillin IV 3g q4-6h Peds 150-200 mg/kg/d in 2-3 doses Adjust for renal disease
30
Timectin
Ticarcillin with Clavulunate - broadens spectrum to gram neg aerobes Actinobacter, Pasteurella, Proteus
31
Piperacillin | Zosyn
Pip: more active against Klebsiella, enterococci, and bacteroides = 3-4 g q4-6h - adjust for renal failure Zosyn = pip with tazobactam = broad spectrum for cellulitis, postpartum endometritis, peritonitis, CA Pneumo, HA pneumo Dose = 4.5 g q6h - adjust for renal failure
32
Antipseudomonal PCNs SE, AE
AE: same as PCNs Jarisch-Herxheimer Rxn - common in 2nd syphilis SE: bleeding problems, rash, GI Sx
33
Jarisch-Herxheimer Rxn
Common in 2ndary Syphilis Release of spirochetal lytic products - heat stable proteins and endotoxins Fever, myalgia, exacerbation of lesions Occurs w/in 2 hrs of 1st dose Tx with NSAIDs and corticosteroids Also in borreliosis, leptospirosis, and brucellosis
34
Beta-Lactamase Inhibitor
Clavulanic acid, Sulbactam, Tazobactam | Inhibits bacterial b-lactamases and inhibits aminoglycosides
35
Beta-Lactamase Inhibitor Use
in combo with PCN to broaden spectrum of activity Intra-abdominal/gyn infx Skin and soft tissue infx RTI, sinusitis, and lung abscesses
36
Beta-Lactamase Inhibitor Combo's
Augmentin - amox-clavulanic acid Zosyn - piperacillin-tazobactam Unasyn - ampicillin-sulbactam Timectin - ticarcillin-clavulanate Antipseudomonals - Zosyn and Timectin Aminoampicillins - Augmentin and Unasyn
37
Interstitial Nephritis
AI rxn to PCN-protein complex
38
Cephalosporins
6 member ring instead of 5 member ring 2 modifiable side chains = b-lactamase cannot hydrolyze as well Progression from 1st-3rd gen = increase in gm- coverage and loss in gram + coverage Well absorbed in GI tract 3-10% cross reactivity with PCNs
39
Cephalosporin Generation Trends
1st: Gram + = cephalexin and cefazolin 2nd: decreasing Gram + and increasing gram - = ceftin for otitis, sinusitis, and RTI 3rd: gram - with some Gm + 4th: Gram + and Gm -
40
3rd and 4th generation cephalosporins
DOC for Gm - meningitis Good alternative to aminoglycosides Watch for resistance - combo therapy best w/ pseudomonas Ceftriaxone DOC for gonorrhea Ceftazidime effective in pseudomonas meningitis
41
1st Gen. Cephalosporins
cephalexin (Keflex), cefazolin (Ancef), cefadroxil Good Gm + coverage - strep and staph Some Gm - Good for anaerobic cocci - peptococcus, peptostreptococcus
42
1st Gen Cephs Dosage, Use, SE
Cephalexin: 250-500 mg QID - uncomp. cellulitis Cefazolin: 1-2 gm IV - complicated cellulitits or surgical prophylaxis SE: GI, allergy, C. diff
43
2nd Gen Cephalosporins
cefaclor (Ceclor) PO 250-500 mg 2-4/day cefuroxime (Ceftin) PO 250-500 mg bid; IV 1-1.5 g q8h cefoxitin (Mefoxin) IV 1-2 g q6-8h cefotetan (Cefotan) IV 1-2 g q12h
44
2nd Gen Ceph Activity
Gm + cocci Gm - for Klebsiella, H. influenzae No pseudomonas coverage Cefaclor susceptible to b-lactamase hydrolysis
45
2nd Gen Ceph uses
Cefuroxime - sinusitis, otitis, RTI, CA pneumo because H. flu, Klebsiella, and penicillin-resistant pneumo coverage Cefoxitin - anaerobic activity, GI surgery prophylaxis, peritonitis and diverticulitis b/c Gm - rods and bacteroides coverage
46
3rd Gen Cephalosporins
Cefotaxime: IV 1-2g q6-12h Ceftaidime: IV 1-2g q8-12h Ceftriaxone: 1-2g q 24h - IV or IM
47
3rd Gen Cephalosporins Activity
Gm - against meningococcus, citrobacter, b-lactamase resistant H. flu and Neisseria Ceftazidime good for pseudomonas aeruginosa Cefotaxime and ceftriaxone cross BBB
48
3rd Gen Cephalosporins Use and SE
ceftriaxone and cefotaxime treat meningitis Empirical therapy b/c cover PCN-resistant pneumococci Ceftriaxone: treats gonorrhea and Lyme SE: rash, NV, elevated LFTs, eosinophilia, HA
49
4th Gen Cephalosporins and Activity
Cefepime (Maxipime) - IV 0.5-2g q12h Peds: 75-120mg/kg/d divided in 2-3 days Gm + and Gm - Pseudomans, Staph aureus, Strep pneumo, H. flu, Neisseria
50
4th Gen Cephalosporins Use and SE
Crosses BBB - can treat meningitis, sepsis etc. Combo with aminoglycoside when treating pseudomonas SE: NVD, HA, rash
51
Carbapenems - General
Treat MDR bacteria Hospitalized patients More resistant to resistance than other b-lactams Some klebsiella and enterobacteria resistance
52
Carbapenems Drugs
Imipenem/cilastatin - IV 250-500 mg q6-8h, better coverage than meropenem Meropenem - IV 1-2 q8h
53
Carbapenems Activity
Very resistant to b-lactamase cleavage Gm+ coverage - enterococcus faecalis & listeria G - coverage - H. flu, N. gonorrhea, enterobacter, pseudomonas Anaerobes (bacteroides)
54
Carbapenems Uses and SE
meningitis, intra-abdominal infx, resistant UTIs Pseudomonas w/ or w/o aminoglycoside for neutropenic patient SE: NVD, rash, infusion site rxn Imipenem: renal failure + seizures
55
Monobactams
``` b-lactam ring is alone, not fused Gm - only (Neisseria, Pseudomonas) aztreonam (Azactam) AE: rash, abnormal LFTs No cross reactivity Can trigger seizures at high doses ```

ID Pharm (6 decks)

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