Antibiotics Flashcards
Penicillin G (IV); penicillin V (PO)
Penicillins
MOA: Form a complex with a PBP, prevent extracellular transpeptidase activity
Streptococcal species, resistance in some species (S. pneumoniae, S. anginosus group, viridians group); mouth anaerobes; syphilis; poor Staph
Hypersensitivity reactions Seizures at high doses in patients w/ renal dysfunction.
Not effective against β-lactamase-producing bacteria.
Oxacillin (IV); Nafcillin (IV); Dicloxacillin (PO)
Penicillinase-resistant penicillin
Penicillin with bulky side group to stop penicillinases
Methicillin-sensitive S. aureus (MSSA)
Hypersensitivity reactions, Hepatotoxicity & neutropenia w/ oxacillin; neutropenia & thrombophlebitis w/ nafcillin
Bulky side chain shields β-lactam ring from penicillinase
Ampicillin (IV, PO); Amoxicillin (PO)
Aminopenicillin
Semi-synthetic penicillins with special side group allows improved penetration into Gram (-) membrane
Streptococcus (DoC for Enterococcus); mouth anaerobes; E. coli, Proteus mirabilis, Listeria
Amox: OTITIS MEDIA, URTI/LRTI IN CHILDREN
Ampicillin: LISTERIA MENINGITIS
HHELPSS kill enterococci
H. influenzae, H. pylori, E. coli, Listeria, Proteus, Salmonella, Shigella
Hypersensitivity reactions
Amoxicillin better absorbed than ampicillin PO. Gram-negative activity improved compared to PCN.
Piperacillin (IV); Ticarcillin
Extended spectrum penicillin
More manipulations to extend aminopenicillin spectrum
Activity of aminopenicillins plus Proteus; Klebsiella, Serratia, Enterobacter, PSEUDOMONAS
Hypersensitivity reactions
Rarely used without tazobactam
Zosyn IV (piperacillin + tazobactam) Augmentin PO (amoxicillin + clavulanate)
Combination therapy penicillins
Suicide inhibitors that allow penicillins to do their job
Retention of spectrum of parent drug with increased activity against β-lactamase producing organisms
(S. aureus, gut anaerobes, all Haemophilus, E. coli)
Hypersensitivity reactions; Augmentin: diarrhea
Immune-mediated thrombocytopenia
Cefazolin (IV); cephalexin (oral)
1st generation cephalosporin (Cell wall synthesis inhibitor)
Form a complex with a PBP, prevent extracellular transpeptidase activity
Broader spectrum than penicillins: MSSA; streptococci (NO Enterococcus); mouth anaerobes
PEcK: Proteus, E. coli, Klebsiella
Hypersensitivity reactions
Cefazolin-DOC for surgical prophylaxis
Cefuroxime
2nd generation cephalosporin
1st generation plus Haemophilus (including penicillinase strains); above and below diaphragm anaerobes
HENS PEcK: H. influenzae, Enterobacter, Neisseria, Serratia, Proteus, E. coli, Klebsiella
Hypersensitivity reactions
Cefoxitin; cefotetan
2nd generation cephalosporin
HENS PEcK
More active against E. coli & Klebsiella than 1st generation; B. fragilis
Hypersensitivity reactions
Ceftazadime (IV); cefpodoxime (PO); ceftriaxone (IV)
3rd generation cephalosporin
Ceftazidime: poor gram-positive activity, PSEUDOMONAS
Ceftriaxone: CAP, meningitis, complicated UTI, gonorrhea, CSF Lyme disease
Higher association with C. difficile diarrhea than other classes
Ceftriaxone-biliary sludging, precipitation with calcium containing solutions in neonates
Cefepime (IV)
4th generation cephalosporin
3rd generation, plus Staphylococcus coverage, PSEUDOMONAS
Ceftaroline (IV)
5th generation cephalosporin
Possesses a side chain that acts as a “Trojan horse” allowing access to PBP2a
Gram positive-MRSA, MSSA, Streptococci, E. faecalis not faecium Gram negative activity similar to ceftriaxone -
Only cephalosporin with activity against MRSA!
Ceftazidime/Avibactam (IV)
Extended-spectrum cephalosporin/b-lactamase inhibitor combination
B-lactamase inhibitor increases gram(-) spectrum.
Increased Psuedomonas, CRE, ESBL activity
Higher association with C. difficile diarrhea than other classes
Ceftolozane/Tazobactam (IV)
Increased activity against Pseudomonas, ESBLs. Not active against CREs.
Imipenem - cilastatin; Meropenem; Ertapenem; Doripenem (all IV)
Carbapenam (Cell wall synthesis inhibitor)
Similar to pencillins
Broad spectrum (excludes MRSA) Ertapenem: not effective against Pseudomonas, Acinetobacter Used for highly-resistant organisms
Imipenem: higher risk of seizures than other β-lactams (cumulative dose-dependent) if dose not adjusted for renal failure
Significant interaction with valproic-acid (VPA) (reported predominantly with meropenem)-significant reduction in VPA concentration leading to seizures
Low cross-reactivity with PCN (~1%)
Aztreonam (IV)
Monobactam (Cell wall synthesis inhibitor)
Similar to pencillins
Gram- aerobic bacilli including PSEUDOMONAS, NO G+, NO ANAEROBES
Not usually used as monotherapy
Vancomycin (IV, PO)
Cell wall synthesis inhibitor (Glycopeptide)
Binds rapidly and irreversibly to the D-alanyl-D-alanine group on the peptide side-chain of the membrane-bound precursor; glycan chain extension, transpeptidation inhibited
G+s only (MRSA, Enterococcus, coagulase-negative Staph, Strep)
PO: C. difficile
Red Man syndrome (IgE hypersensitivity reactions (histamine mediated)); dose-dependent nephrotoxicity; immune-mediated thrombocytopenia Dose-dependent ototoxicity and nephrotoxicity; immune-mediated thrombocytopenia
Inferior to β-lactams for MSSA infection
Dalbavancin; Telavancin; Oritavancin
Lipoglycopeptides (anaolgs of vancomycin)
Binds to same target as vancomycin and inhibits transglycosylation
Similar to vancomycin but active against VRE & more anaerobe coverage
Metallic taste, nausea, HA, nephrotoxicity, teratogenic Pregnancy test needed for women of childbearing potential.
Daptomycin (IV)
Cell wall toxin (cyclic lipopeptide)
Penetrates bacterial cell wall, forming a channel for subsequent leakage of intracellular ions
G+ cocci only; use for VRE, VRSA
NOT USED FOR PNEUMONIA: surfactant inactivates
Myalgia and rarely rhabdomyolysis
Colistin (IV, INH)
Cell wall toxin (polymixin)
Penetrates bacterial cell wall, forming a channel for subsequent leakage of intracellular ions
G- only; usually reserved for Pseudomonas species resistant to all other antibacterials
Nephrotoxicity, neurotoxicity
Ciprofloxacin (IV, PO)
1st generation fluoroquinolone / Nucleic acid synthesis inhibitor
Inhibits DNA gyrase at low concentrations
Enterobactericeae, including Pseudomonas;
Atypicals
Gram (-) rods of UTI and GI tracts
GI, AMS QT prolongation, tendon rupture
Divalent cations chelate ORAL quinolones decreasing bioavailability
Levofloxacin (IV, PO); Moxifloxacin (IV, PO)
2nd generation fluoroquinolone / Nucleic acid synthesis inhibitor
Inhibits DNA gyrase at low concentrations; inhibits topoisomerase IV at high concentrations
Adds pneumococcus (Strep pneumoniae) to spectrum of 1st generation fluoroquinolones. Levofloxacin: Pseudomonas Moxifloxacin: No Pseudomonas, but has anaerobic activity
As with cipro; QT prolongation: moxi>levo>cipro
Moxifloxacin urine concentrations low-not ideal for UTI
Levofloxacin and ciprofloxacin are the only PO agents effective against Pseudomonas
Metronidazole (IV, PO)
Nucleic acid synthesis inhibitors (Nitroimidazole)
Reduced (only under anaerobic conditions, which generate lots of acid) to an active free radical, which damages bacterial and certain protozoal DNA
Anaerobes excluding Actinomycetes and Peptostreptococcus (DoC for C. difficile); some protozoa; H. pylori
Metallic taste,disulfiram-like reaction (because it blocks aldehyde dehydrogenase)
CNS toxicity-seizure, neuropathy with long-term/high dose therapy
Rifampin (IV, PO)
Nucleic acid synthesis inhibitor
Inhibits DNA-dependent RNA polymerase to halt RNA transcription)
Mycobacterium tuberculosis; Staph aureus
RNA polymerase inhibitor
Ramps up CYP 450
Red/orange body fluids
Rapid resistance if used alone
Centrilobular hepatitis; serious flu-like hyper-sensitivity syndrome characterized by fever, myalgias, interstitial nephritis, thrombocytopenia, hemolytic anemia (occurs if drug given in intermittent dosing regimens)
Isoniazid (INH)
Antitubercular (M tuberculae)
Inhibition of mycolic acid synthesis
INH injures Neurons and Hepatocytes
Hepatitis; neurotoxicity, memory loss, psychosis (pyridoxine can alleviate); hypersensitivity reactions
SE: Phenytoin toxicity potentiated by INH.
Pyrazinamide
Antitubercular (M tuberculae)
Unknown MOA
SE: N&V; hepatotoxicity; hypersensitivity reactions
Ethambutol
Antitubercular
Inhibits arabinosyl transferase enzymes involved in cell wall synthesis
SE: Neuropathy; optic neuritis
Gentamicin; tobramycin
Aminoglycoside / Protein synthesis inhibitor
Inhibits 30S ribosome: forms a tight complex with ribosomal protein, causing codon-anticodon misreading and production of inactive proteins (bactericidal); also, inhibits initiation
Extremely effective against G- rods; ineffective against anaerobes due to an oxygen-dependent uptake mechanism
SE: Dose-dependent oto/nephrotoxicity (not observed if used less than 48 hours)
Doxycycline; Minocycline (both IV, PO)
Tetracycline / Protein synthesis inhibitor
Inhibits 30S ribosome: blocks access of tRNA anticodon to its codon
Utility for Gram+ (S. pneumoniae, MRSA); very effective against intracellular pathogens (mycoplasma, chlamydia, legionella, rickettsia)
SE: GI; skin photosensitivity, pill esophagitis if not taken with water
ORAL forms are chelated with divalent cations (Calcium, Mg, iron, etc.)
Discolors teeth of younger children-avoid use in pregnancy as well
Tigecycline (IV)
Glycylcyline
Inhibits 30S ribosome: glycyl group prevents efflux out of cell
Broad spectrum including MRSA, VRE, Enterobacteriaceae, and anaerobes.
DOES NOT have activity against Pseudomonas. Often one of few drugs effective against carbapenem-resistant Enterobacteriaceae
Much higher tissue concentrations than serum. Not effective in bacteremia
Higher all-cause mortality than other drugs
Clindamycin (IV, PO)
Protein synthesis inhibitors
Binds to 50S subunit at “A site,” blocking peptide bond formation
CA-MRSA/MSSA, Strep (resistance in Group B strep and S. aureus increasing , Mouth anaerobes
NO gram negative
Antibiotic-associated diarrhea; C. difficile colitis
Azithromycin (Z-Pak PO, IV)
Macrolide /Protein synthesis inhibitors
Binds to 50S subunit & blocks translocation by interference with tRNA release following peptide bond formation (inhibiting the peptide exit tunnel)
Effective for intracellular pathogens (mycoplasma, chlamydia, legionella). H. influenzae; ; S. pneumoniae (high level of resistance)
GI distress with oral administration, less so than with erythromycin Potential for polymorphic ventricular tachycardia (TdP)
Very long half life (68 hours), very high tissue distribution
Linezolid & Tedizolid (both IV, PO)
Protein synthesis inhibitor
Binds to 50S ribosome and inhibits peptidyl transferase
Gram+ organisms; MRSA, MSSA, Enterococcus including VRE
Bone marrow suppression; most often thrombocytopenia after 2 weeks
Lactic acidosis, optic neuritis, peripheral neuropathy (with long-term use)
Irreversibly inhibits MAO which poses a risk for serotonin syndrome with serotonergic drugs
Trimethoprim
Antimetabolite (DHFR Inhibitor)
Prevent folic acid from being reduced (active); DHF –> THF
Uncomplicated UTIs; Pneumocystis pneumonia & Toxoplasmosis infections in immunocompromised patients
Hyperkalemia in patients with severe renal insufficiency
At very high concentrations will inhibit mammalian DHFR; usually given as combo with sulfamethoxazole (Bactrim)
Sulfamethoxazole
Antimetabolite (Dihydropterate synthase inhibitor)
Prevent pteridine + PABA –> dihydropteric acid
Uncomplicated UTIs; Pneumocystis pneumonia & Toxoplasmosis infections in immunocompromised patients
Usually given as combo with trimethoprim (Bactrim)
