Microbiology Drugs

Question 1

Penicillin G, V

Answer 1

Penicillin G, V

MECHANISM: Bind Penicillin Binding proteins (transpeptidases)
Block transpeptidase cross-linking of peptidoglycan in cell wall, weakening the cell wall.
Activate autolytic enzymes, which kill bacteria due to the previously damaged wall.

CLINICAL USE: Mostly gram+ organisms (S. pneumoniae, S. pyogenes, Actinomyces). Also used for gram- cocci (N. Meningitidis) and spirochetes (t. pallidum)
Bactericidal for g+ cocci, gram+rods, gram- cocci, and spirochetes. Penicillinase sensitive.

TOXICITY: Hypersensitivity reactions, hemolytic anemia, thrombocytopenia

RESISTANCE: Penicillinase in bacteria (a type of B-lactamase) cleaves B-lactam ring

Question 2

Penicillinase-sensitive penicillins

Amoxicillin, Ampicillin

Answer 2

Penicillinase-sensitive penicillins: Amoxicillin, Ampicillin

Mechanism: binds PBP. Wider spectrum than Penicillin. Penicillinase sensitive.
Combine with clavulinic acid to protect against destruction with B-lactamase

Clinical Use: Extended-spectrum Penicillin.
HHELPSS
H. influenzae, H. pylori, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci

Toxicity: Hypersensitivity reactions; rash; pseudomembranous colitis. Rash seen when aminoipenicillins are given to a patient w/mononucleosis (full body rash)

Mechanism of Resistance: Penicillinase in bacteria (a type of beta-lactamase) in periplasm, coded on a plasmid, cleaves B-lactam ring.

Question 3

Penicillinase-resistant penicillins

Dicloxacillin, nafcillin, oxacillin

Answer 3

Penicillinase-resistant Penicillins - Dicloxacillin, nafcillin, oxacillin

MECHANISM - Same as penicillin. Narrow spectrum; penicillinase resistant because bulky R group blocks access of B-lactamase to B-lactam ring

CLINICAL USE: S. Aureus (except MRSA; resistant because of altered penicillin-binding protein target site)

TOXICITY: Hypersensitivity reactions, interstitial nephritis

Question 4

Piperacillin, ticarcillin, carbenicillin

Answer 4

Piperacillin, ticarcillin, carbenicillin

MECHANISM: Same as penicillin. Extended spectrum.
CLINICAL USE: Pseudomonas and gram- rods; susceptible to penicillinase; use with B-lactamase inhibitors.
TOXICITY: Hypersensitivity reactions

Question 5

Beta-lactamase inhibitors

Answer 5

Clavulanic Acid, Sulbactam, Tazobactam.

Often added to penicillin abx to protect the antibiotic from destruction by B-lactamase (penicillinase)

ie. Amoxicillin + clavulanic acid for Resistant otitis media

Ampicillin + sulbactam (IV) for surgical infections

Question 6

Cephalosporin Generation 1

Answer 6

Cephalosporin Generation 1 - Cefazolin, cephalexin

MECHANISM: B-lactam drugs that inhibit cell wall synthesis, less susceptible to penicillinases.
Bactericidal.

CLINICAL USE: PEcK
Proteus, E. coli, Klebsiella

TOXICITY: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vit K deficiency .

Exhibit cross-reactivity with penicillins. Add nephrotoxicity of aminoglycosides.

MECHANISM OF RESISTENCE: Structural change in Penicillin-binding proteins.

Question 7

Cephalosporin Generation 2

Answer 7

Cephalosporin Generation 2 - Cefoxitin, cefaclor, cefuroxime

MECHANISM: B-lactam drugs that inhibit cell wall synthesis, less susceptible to penicillinases.
Bactericidal.

CLINICAL USE: HENS PEcK
Haemophilus, Enterobacter, Neisseria, Serattia, Proteus, E. coli, Klebsiella

TOXICITY: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vit K deficiency .

Exhibit cross-reactivity with penicillins. Add nephrotoxicity of aminoglycosides.

MECHANISM OF RESISTENCE: Structural change in Penicillin-binding proteins.

Question 8

Cephalosporin Generation 3

Answer 8

Cephalosporin Generation 3 - Ceftriaxone, cefotaxime, ceftazidime

MECHANISM: B-lactam drugs that inhibit cell wall synthesis, less susceptible to penicillinases.
Bactericidal.

CLINICAL USE: serious gram- infections resistant to other B-lactams.
Ceftriaxone - meningitis, gonorrhea, disseminated Lyme disease
Ceftazidime for pseudomonas

TOXICITY: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vit K deficiency .

Exhibit cross-reactivity with penicillins. Add nephrotoxicity of aminoglycosides.

MECHANISM OF RESISTENCE: Structural change in Penicillin-binding proteins.

Question 9

Cephalosporin 4th Generation

Answer 9

4th Generation - Cefepime

MECHANISM: B-lactam drugs that inhibit cell wall synthesis, less susceptible to penicillinases.
Bactericidal.

CLINICAL USE: gram -, with increased activity against pseudomonas and gram+ organisms

TOXICITY: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vit K deficiency .

Exhibit cross-reactivity with penicillins. Add nephrotoxicity of aminoglycosides.

MECHANISM OF RESISTENCE: Structural change in Penicillin-binding proteins.

Question 10

Cephalosporin Generation 5

Answer 10

Generation 5 - Ceftaroline

MECHANISM: B-lactam drugs that inhibit cell wall synthesis, less susceptible to penicillinases.
Bactericidal.

CLINICAL USE: broad gram+ and gram- organism coverage, including MRSA. Does NOT COVER pseudomonas

TOXICITY: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vit K deficiency .

Exhibit cross-reactivity with penicillins. Add nephrotoxicity of aminoglycosides.

MECHANISM OF RESISTENCE: Structural change in Penicillin-binding proteins.

Question 11

Carbapenems

Answer 11

Carbapenem - Imipenem, meropenem, ertapenem, doripenem

MECHANISM: Imipenem is broad-spectrum, B-lactamase-resistant carbapenem. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to dec inactivation of drug in renal tubules.

CLINICAL USE: Gram + cocci, gram - rods, and anaerobes. Wide spectrum, but SE’s limit use to life-threatening infections or after other drugs have failed.
Meropenem has dec risk of seizures and is stable to dehydropeptidase I. (Does not cover MRSA)

TOXICITY: GI distress, skin rash, and CNS toxicity (seizures at high plasma level)

Question 12

Monobactams

Answer 12

Monobactams - Aztreonam “the Aminoglycoside pretender”

MECHANISM: Less susceptible to B-lactamases. Prevents peptidoglycan x-linking by binding to penicillin-binding protein 3. Synergistic with aminoglycosides. No cross-allergenicity with penicillins.

CLINICAL USE: Gram - rods only, no activity against g+ or anaerobes. Good for penicillin allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides.

TOXICITY: Usually nontoxic.

Question 13

Vancomycin

Answer 13

Vancomycin

MECHANISM: Inhibits cell wall peptidoglycan formation by D-ala-D-ala portion of cell wall precursors. Bactericidal. Not susceptible to B-lactamases.

CLINICAL USE: Gram + bugs only - serious multidrug-resistant organisms, including MRSA, S epidermidis, sensitive Enterococcus species, and C. difficile (oral dose for pseudomembranous colitis)

TOXICITY: Well tolerated in general. NOT

Nephrotoxicity, Ototoxicity, Thrombophlebitis

RESISTANCE: Occurs in bacteria via amino acid modification of Dala Dala to Dala- Dala-D-lac.

Question 14

Aminoglycosides

Answer 14

Aminoglycosides - Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin

MECHANISM: Bactericidal; irreversible inhibition of initiation complex through binding of the 30S subunit. Can cause misreading of mRNA. Also blocks translocation. Require O2 uptake, therefore ineffective against anaerobes.

CLINICAL USE: Severe gram- rod infections. Synergistic with B-lactam antibiotics.
Neomycin for bowel surgery.

TOXICITY: Nephrotoxicity, Neuromuscular blockade, Ototoxicity, especially when used iwth loop diuretics. Teratogen.

RESISTANCE: Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation or adenylation.

Question 15

30S inhibitors

Answer 15

“Buy AT 30, CCELL at 50.”

30 S inhibitors

Aminoglycosides (bacteriocidal

Tetracyclines (Bacteriostatic)

Question 16

50S inhibitors

Answer 16

“Buy AT 30, CCELL at 50.”

Chloramphicol, Clindamycin, Erythromycin, and Linezolid 50S inhibitors

Question 17

Tetracyclines

Answer 17

Tetracycline, doxycycline, minocycline, demeclocycline

MECHANISM: Bacteriostatic, bind 30S and prevent attachment of aminoacyl-tRNA; limited CNS penetration.
Doxycycline is fecally eliminated and can be used in patients with renal failure.

Do not take tetracyclines iwth milk (Ca) or antacids (Ca or Mg) or iron-containing preparations because divalent cations inhibit drugs absorption in the gut.

CLINICAL USE: “VACUUM THE BEDROOM”
Vibrio Cholera
Acne
Chlamydia
Ureaplasma Urealyticum
Mycoplasma Pneumoniae
Tularemia
Borrelia burgdoferi
Rickettsia

TOXICITY: GI, Discoloration of teeth and inhibition of bone growth in children, photosensitivity. Contraindicated in pregnancy

RESISTANCE: Dec uptake and inc efflux out of bacterial cells by plasmid-encoded transport pumps.

Question 18

Chloramphenicol

Answer 18

Chloramphenicol
MECHANISM: Blocks peptidyltransferase at 50S ribosomal subunit. Bacteriostatic.
CLINICAL USE: Meningitis, Haemophilus influenza, Neisseria meningitidis, Strep pneumo, Rickettsia Rickettsii.
Limited use owing to toxicities but still used in developing countries due to low costs.

TOXICITY: Anemia (dose dependent), Aplastic anemia (dose independent), gray baby syndrome
Gray baby syndrome: vomiting, ashen skin, dec muscle tone, cyanosis, CV collapse, treat with phenobarbital which induces UDP-glucuronyl transferase activity.

RESISTANCE: Plamid-encoded acetyltransferase inactivates the drug

Question 19

Clindamycin

Answer 19

Clindamycin

MECHANISM - Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic.

CLINICAL USE - Anaerobic infxns (Bacteroides, Perfingens), in aspiration pneumonia, lung abscesses, and oral infxns. Also effective against invasive group A strep infxn.

[Treats infxns above the diaphgragm vs. metronidazole (anaerobic infxns below the diaphragm)]
TOXICITY

Question 20

Oxazolidinones

Answer 20

Oxazolidinones (Linezolid)
MECHANISM: Inhibit protein synthesis by binding to 50S subunit and preventing formation of the initiation complex.

CLINICAL USE: G+ species including MRSA and VRE. Oral availability allows MRSA pts to be treated as outpatients.

TOXICITY: Bone marrow suppression (esp thrombocytopenia), peripheral neuropathy, serotonin syndrome

RESISTANCE: Point mutation of rRNA

Question 21

Macrolides

Answer 21

Macrolides - Azithromycin, clarithromycin, erythromycin

MECHANISM: Inhibit protein synthesis by blocking translocation (“macroslides”); bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic.

CLINICAL USE: “PUS”
P: Pneumonias (Atypical) - Mycoplasma, Chamydia, Legionella)
U: URI’s (Strep pneumo, strep pyogenes)
S: STI’s (Chlamydia, gonorrhea)

Also covers pertussis, safe in pregnancy.

TOXICITY: MACRO:

M - GI motility issues
A - Arrhythmia caused by prolonged QT interval
C - acute Cholestatic hepatitis
R - Rash
O - eOsinophilia

Increases serum concentration of theophyllines, oral anticoagulants.
Clarithromycin and erythromycin inhibit cytP450

MECHANISM OF RESISTANCE: Methylation of 23S rRNA-binding site prevents binding of the drug

Question 22

Trimethoprim

Answer 22

Trimethoprim

MECHANISM: Inhibits bacterial dihydrofolate reductase. Bacteriostatic.

CLINICAL USE: Used in combo with sulfonamides. (TMP/SMX) causing sequential block of folate synthesis. COmbination used for UTI, skin infxn, Shigella, Salmonella, Pneumocystis jirovecci (PCP pneumonia), pneumonia treatment and prophylaxis.

TOXICITY: Megaloblastic anemia (folic acid deficiency) - may alleviate with supplemental folinic acid)

“TMP Treats Marrow Poorly”

Question 23

Sulfonamide

Answer 23

Sulfamethaxole (SMX) Sulfisoxazole, sulfadiazine

MECHANISM: Bacteria cannot absorb folic acid, they must synthesize it. SMX inhibits folate synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase. Bacteriostatic.
*Bacteriocidal when combined with trimethoprim (TMP)
*Dapsone, used to treat lepromatous leprosy, is a closely related drug that also inhibits folate synthesis

CLINICAL USE: Gram+, Gram-, Nocardia, Chalmydia. Triple sulfas or SMX for simple UTI, skin ifxn.

TOXICITY: Hypersensitivity rxn, hemolysis of G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin, Steven Johnson Syndrome.

Sulfa allergies: “Sulfa Pills Frequenlty Cause Terrible Acute Symptoms”
Sulfasalazine
Probenacid
Furosemide
Celecoxib
Thiaxides/TMP-SMX
Acetazolamide
Sulfonylureas

MECHANISM OF RESISTANCE: Altered enzyme (bacterial dihydropteroate synthase), decreased uptake or increased PABA synthesis

Question 24

Fluoroquinolones

Answer 24

Fluoroquinolones - Ciprofloxacin (early generation), norfoxacin, levofloxacin (IV Generation), ofloxacin, moxifloxacin (IV Generation), gemifloxacin, enoxacin

MECH: Inhibit prokaryotic enzyme topoisomerase II (DNA gyrase) and topoisomerase IV.
Bactericidal. Must not be taken with antacids (that includ Ca, Mg, inhibit absorption)

CLNICAL USE: Gram- rods of urinary and GI tracts (including Pseudomonas), Neisseria, some gram+ organism.

TOX: GI upset, superinfections, skin rashes, HA, dizziness. Less commonly, can cause leg cramps and myalgias.
Contraindicated in pregnant women, nursing moethers, and children<18 due to dmg to cartilage. [Ciprofloxacin for CF children, but joints/tendons must be monitored]

Some may prolong AT interval. May cause tendonitis or tendon rupture in ppl >60 years old and in pts taking prednisone.

“Fluoroquinolones hurt attachments to your bones”

RESISTANCE: Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps

Question 25

Daptomycin

Answer 25

Daptomycin

MECH: lipopeptide that disprupts cell membrane of G+ cocci

CLINICAL USE: S. aureus skin infxns (especially MRSA), bactermia, endocarditis, VRE. NOT used for pneumonia (avidly binds to and is inactivated by surfactant)

TOX: Myopathy [elevated CPK, esp in pts taking statins also], rhabdomyolysis

Question 26

Metronidazole

Answer 26

Metronidazole

MECH: Forms toxic free radical metabolites in the bacterial cell that damage DNA. Bactericidal, antiprotozoal.

CLINICAL USE: “GET GAP on the Metro”

Giardia
Entamoeba
Trichomonas
Gardnerella vaginalis
Anaerobes (Bacteroides, C. diff, C. perfinigens)
P H. pylori

TOX: Disulfiram-like reaction. (inhibits aldehyde dehydrogenase –> accumulation of aldehyde)

Treats anaerobic infxn below the diaphragm vs. clindamycin (anearobic infxns above the diaphragm)

Question 27

Nitrofurantoin

Answer 27

Nitrofurantoin

MECH: Bacteriocidal, reduced by bacterial proteins as reactive intermediate that inactivates bacterial ribosomes.

CLINICAL USE: UTI cystitis, not pyelonephritis) by E. coli or Staph saprophyticus. (Not proteus)

TOX: Rarely nausea, HA, diarrhea.

Safe in pregnancy.