Antibacterials Flashcards
Lactulose
MOA: degraded by intestinal flora to lactic acid and other acids
Effect: acids trap the ammonia in the GIT so it cannot enter circulation and exacerbate the encephalopathy
Uses: hepatic encephalopathy, use as osmotic laxative, prebiotic
SE: osmotic diarrhea, flatulence, abd pn
Quinolones Drug Interactions
Theophylline, NSAIDS, corticosteroids = enhanced toxicity of quinolones
3rd and 4th gen = raide serum levels of Warfarin, Caffeine and Cyclosporine
Clindamycin PK and SE
PK: PO or IV, good penetration (gets to abscesses/bones)
SE: C. difficile, GI sx’s, skin rash, neutropenia and impaired liver fxn
2nd Gen Quinolones
Ciprofloxacin
Spectrum: extended G-ve activity, some G+ve, and some atypicals
DOC: anthrax
Use: ETEC, Pseudomonas (CF pt’s), meningitis prophylaxis (alt to Ceftriaxone and Rifampin)
Cefaclor / Cefoxitin / Cefotetan / Cefamandole
2nd generation Cephalosporins
Active against: H.influenzae, Enterobacter, some Neisseria
Use: sinusitis, otitis infections and LTIs
Cefotetan/Cefoxitin use: prophylaxis and therapy of abd/pelvic cavity infections
Sulfonamides PK, SE, CI
PK: PO or topical, acetylated in liver, eliminated via urine
SE: photosensitivity, crystalluria, HS rxn, hematopoietic disturgances (G6PD), kernicterus
CI: newborns/infants < 2 yo
Drug interaction: displace Warfarin, Phenytoin and Methotrexate from albumin
Tetracyclines (names)
Doxycycline / Minocycline / Tetracycline
Concentration-dependent Killing
Bigger the dose the better effect (covalent bonding so it doesnt matter if you keep giving it, the blockade is already in place)
*e.g. - aminoglycosides
Oxacillin
Excretion: renal and biliary
SE: hepatitis
Use: meningitis s/p trauma or surgery (S. aureus)
Aminoglycosides PK and SEs
PK: once daily admin, IV only, well distributed, high levels in renal cortex and inner ear
Excretion: kidney
SE: ototoxicity, nephrotoxicity, NM blockade
CI: MG (bc of NM blockade), pregnancy (unless benefits outweigh risks)
Tetracyclines DOC
Chlamydia, M. pneumoniae, Lyme dz, cholera, anthrax prophylaxis, RMSF, Typhus
Combo therapy for: H. pylori eradication, Malaria prophylaxis/tx, tx plague, Tularemia, Brucellosis
Polymyxin B
Spectrum: G-ve (bactericidal) MOA: acts as detergent, attach to and distrupt the cell membrane, binds and inactivates endotoxin Effect: cell lysis Use: topically for skin infections SE: nephrotoxic if given systemically
Ampicillin / Amoxicillin
‘Extended spectrum penicillins’
MOA: sensitive to β-lactamases, so activity is enhanced w/ β-lactamase inhibitor
PK: Amoxicillin has higher oral bioavailability than other penicillins
Use: children and pregnancy for acute otitis media, GAS pharyngitis, pneumonia, skin infection, UTIs, URIs (H. flu and S. pneumo)
SE: maculopapular rash, C. difficile
Neomycin
Use: bowel surgery, adjunct in hepatic encephalopathy, topical infections
SE: dermatitis
Cephalosporins SE
Pain @ infections ite, thrombophlebitis, superinfections (C. difficile), kernicterus (pregnancy)
Tetracyclines PK and SE
PK: variable PO absorption (decreased by divalent and trivalent cations)
Excretion: kidney
SE: teratogenic (category D), N/V/D, discoloration and hypoplasia of teeth, stunting growth, fetal hepatotoxicity, photosensitization, dizziness
Calvulanic acid / Sulbactam / Tazobactam
MOA: β-lactamas inhibitors
Effect: bind to and inactivate β-lactamases
Use: used in fixed combinations w/ specific penicillins but never used as abx themselves
Quinolones PK, SE, CI
PK: good oral bioavailability, high Vd, divalent cations interfere w/ absorption, adjust dose w/ renal dysfunction pt
SE: connective tissue damage (tendon rupture), peripheral neuropathy, QT prolongation, superinfections
CI: pregnancy/nursing mother, children < 18
Fosfomycin
MOA: inhibition of enolpyruvate transferase
Effect: inhibits CW synthesis
Admin: PO
Use: uncomplicated lower UTI
Aminoglycosides MOA
Amikacin / Gentamicin / Tobramycin / Streptomycin / Neomycin
Bactericidal, assoc. w/ serious toxicities so used mostly in combo w/ other Rx
MOA: passively diffuse across membrane of G-ve, then actively transported (O2 dependent) across cytoplasmic membrane then bind irreversibly (covalently) to 30S subunit of ribosome
Effect: prevent complex formation = prevent transcription = death of organism
Penicillin V
Administration: PO
Use: URIs, skin infections d/t strep
DOC: GAS pharyngitis
SE: +ve Coomb’s Test
β-lactamase inhibitors
Protect penicillins (β-lactams) from inactivation
Vancomycin
MOA: binds D-Ala-D-Ala pentapeptide terminus of PG, inhibits transglycosylation
Effect: inhibits CW synthesis and prevents elongation/polymerization of PG
Spectrum: G+ve only (MRSA, enterococci, PRSP)
Resistance G-ve (intrinsic), plasmid-mediated changes in drug permeability, modification of attachment site (adding D-lactate to terminus)
Minimal Bactericidal Concentration (MBC)
Lowest concentration of abx that results in a 99.9% decline in colony count after overnight incubation
*MBC of truly bactericidal agent is = to or slightly above the MIC
Respiratory Quinolones
Levofloxacin / Moxifloxacin / Gemifloxcin (3rd and 4th gen)
Target: S. pneumoniae, H. influenzae, M. catarrhalis
Use: when 1st line agents have failed, in presence of comorbidities, inpt management
Tetracyclines
MOA: entry via passive diffusion and energy-dependent transport, then bind the 30S subunit of ribosome to prevent attachment of animoacyl tRNA
Effect: protein synthesis halted = bacteriostatic
Spectrum: aerobic and anaerobic G+ve and G-ve
Resistance: impaired influx or increased efflux (plasmid-encoded), enzymatic inactivation, proteins that interfere w/ binding
Use: severe acne, rosacea, syphilis (pt’s w/ penicillin allergy)
Nafcillin
Excretion: primarily in bile
PK: not good for PO administration
Penicillins SEs
HS rxn, diarrhea, interstitial nephritis, hepatitis
Linezolid PK and SE
PK: PO, weak inhibitor of MAO, high Vd
SE: BM suppression, neuropathy, lactic acidosis
CI: caution when coadministration of drugs to increase adrenergic and serotonergic neurotransmitter levels
Penicillins resistance
Inactivation by β-lactamase, modification of target PBP, impaired penetration, increased efflux by pumps
*MRSA: altered target PBPs (low affinity for β-lactam abs)
Bacitracin
MOA: interferes w/ CW synthesis Active against: G+ve organisms Admin: topical use mainly Use: skin infections etc SE: nephrotoxic
Macrolides
Erythromycin / Clarithromycin / Azithromycin / Telithromycin
Bacteriostatic (bactericidal @ high concentration)
MOA: reversibly bind 23S rRNA of 50S subunit (same binding site as Clindamycin and Chloramphenicol)
Effect: blocks translocation halting transcription
Amoxicillin DOC
For endocarditis prophylaxis during dental or respiratory tract procedures (S. viridans)
*Amoxicillin + clavulanic acid is prophylactic for bites
Aminoglycosides DOC
Used in combo - septicemia, nosocomial RTIs, complicated UTIs, endocarditis
*once organism is identified these abx are usually d/c’d
Ampicillin Use/SE
Used in combo w/ Aminoglycosides to tx Enterococcus and Listeria (meningitis)
SE: pseudomembranous colitis
Chloramphenicol Uses
Serious infections resistant to less toxic drugs, or if it can reach the site of infection better it can be used, infections w/ VRE, topical tx of eye infections
Penicillins G Procaine
Developed to prolong duration of Penicilling G
Administration: given IM, seldom used (increases resistance)
PK: t1/2 = 12-24h
Co-trimoxazole (TMP-SMX)
Trimethoprim + Sulfamethoxazole = bactericidal
MOA: synergistic inhibition of sequential steps in folic acid synthesis
PK: PO, high Vd
DOC: uncomplicated UTIs, PCP, Nocardiosis
Use: toxoplasmosis (alt drug), URI d/t H. inflluenzae, M. catarrhalis
SE: dermatologic, GI, hematolytic anemia, high incidence of SE in AIDS pt
CI: pregnancy
Penicillin G Benzathine
Prolongs duration of Penicillin G
Administration: IM
PK: t1/2 = 3-4 wks
DOC: Syphilis, and RF prophylaxis
1st Gen Quinolones
Nalidixic acid
Spectrum: moderate G-ve activity
Use: uncomplicated UTIs
CW Synthesis Inhibitors
Require actively proliferating bacteria
3rd Gen Quinolones
Levofloxacin
Spectrum: G-ve, G+ve, atypicals but especially S. pneumoniae
Use: DOC for prostatitis (E. coli), non-syphilis STDs, CAP, TB, sinusitis, bronchitis
Minimal Inhibitory Concentration (MIC)
lowest concentration of abx that prevents visible growth of a bacteria (so you have to target above the MIC)
Quinolones MOA and Resistance
MOA: enter via porins, inhibit topoisomerase II aka DNA gyrase (G-ve) and IV (G+ve)
Effect: inhibit DNA replication
Resistance: efflux pumps, diff subunits of the enzyme target, cross-resistance
Sulfonamides
MOA: structural PABA analogues so they competitively inhibit dihydropteroate synthase
Effect: inhibition of folic acid synthesis
Resistance: altered enzyme, decreased permeability
Use: topical for infections, PO for simple UTIs
4th Gen Quinolones
Gemifloxacin / Moxifloxacin
Spectrum: G+ve and anaerobes
Use: CAP
Trimethoprim
MOA: similar structure to folic acid, inhibits bacterial dihydrofolate reductase
Effect: inhibits purine, pyrimidine and AA synthesis
Spectrum: G+ve and G-ve (bacteriostatic)
Use: UTIs, bacterial prostatitis and vaginitis
PK: excreted via kidney, reaches high concentrations in sex fluids
CI: pregnancy (bc anti-folate effects)
Tx of Hepatic Encephalopathy
PO Neomycin, Lactulose, PO Vancomycin, PO Metronidazole, Rifaximin (the abx are aiming to reduce the # of intestinal bacteria that are responsible for responsible for the production of ammonia)
Ceftriaxone / Cefoperazone / Cefotaxime / Cefatazimide / Cefixime
3rd generation cephalosporins
Active against: G-ve cocci, Enterobacteriacae, Neisseria, H. influenzae, Pseudomonas
Cefotaxime/Ceftriaxone: active against pneumococci
Use: prophylaxis fo meningitis, tx Lyme dz
DOC: gonorrhea, meningitis d/t ampicillin-resistant H. influenzae
PK: only generations that reaches adequate levels in CSF
Daptomycin
MOA: binds to cell membrane via Ca2+ dependent insertion of lipid tail
Effect: depolarization of cell membrane w/ K+ efflux = cell death
Spectrum: resistant G+ve (MRSA, enterococci, VRE, VRSA)
Inactive against: G-ve (ineffective in tx of pneumonia too)
Cefepime
4th generation Cephalosporins
Admin: IV only
Active against: wide spectrum (H. influenza, Neisseria, E. coli, S.pneumo, Proteus, Pseudomonas)
Use: mixed infections w/ susceptible organisms
Abx Combinations (antagonistic or nah)
NOT to give: tetracyclines (static) + β-lactam (cidal) = nothing happens if you’re targeting one bacteria
DO give: macrolide (static) + β-lactam (cidal) = good bc macrolide is for atypicals and β-lactam is targeting S. pneumoniae (diff bacteria are targets)
Ceftaroline
5th generation Cephalosporin
Admin: IV only
Active against: MRSA, similar spectrum to 3rd generations
Use: skin and soft tissue infections d/t MRSA, particularly w/ G-ve confection, CAP (when first-line agents are unsuccessful)
Time-dependent Killing
Exposure to the drug for longer will cause more of an effect (four small doses better than one big dose)
*e.g. - penicillins, cephalosporins
Clindamycin Uses
Anaerobic infections, skin and soft tissue infections (Strep, Staph, and some MRSA), combo w/ Primaquine as alt in PCP, combo w/ Pyrimethamine as alt tx for brain Toxoplasmosis, prophylaxis of IE in valvular pt’s w/ penicillin allergy
Macrolides Resistance
Decreased influx or increased efflux, production of esterase that hydrolyzes the drug, modification of binding site (plasmid encoded)
*complete cross resistance of all macrolides except Telithromycin), partial cross-resistance w/ clindamycin and streptogramins
Telithromycin
Resistance: no cross-resistance like other macrolides
SE: fatal hepatotoxicity, exacerbations of MG, visual disturbances *(so dont use this abx for minor illnesses)
Carbapenems
Resistant: β-lactamases
PK: admin IV only,
Active against: penicillinase-producing G+ve, aerobes and anaerobes, Pseudomonas
Inactive against: carbapenemase producers, MRSA
DOC: Enterobacter infections, extended spectrum β-lactamase producing G-ve organisms
SE: N/V/D, sz, allergic rxns
CW Synthesis Inhibitors (names)
β-lactam abx (penicillins, cephalosporins, carbapenems, monobactams), Vancomycin, Daptomycin, Bacitracin, Fosfomycin
Mupirocin
Spectrum: G+ve cocci including MRSA and streptococci (but not enterococci)
PK: topical/intranasal
MOA: binds isoleucyl transfer-RNA syhtnetase
Effect: inhibit protein synthesis
Use: intranasal to eradicate nasal colonization w /MRSA, topically to t impetigo or skin infections
Vancomycin PK and SE
PK: poor oral absorption, given via slow IV infusion, penetrates CSF, Excretion: kidneys
SE: “Red man” syndrome (mediated by histamine release if infused too quickly), ototoxicity, nephrotoxicity
Ertapenem
Not active against Pseudomonas
Metranidazole
Bactericidal
Spectrum: anaerobes (bacteriodes and Clostridium)
MOA: requires anaerobic conditions to work, undergoes reduction by ferredoxin
Effect: forms cytotoxic products that interfere w/ nucleic acid synthesis
DOC: C. difficile infections, Bacteriodes, Giardia, Trichomonas
Use: anaerobic/mixed abd infections, vaginitis, brain abscesses, H. pylori eradication (below diaphragm anaerobe infections)
Cefamandole / Cefoperazone / Cefotetan SEs
Contain methyl-thiotetrazole group and thus can cause hypoprothrombinemia (vitamin K can prevent this), and Disulfiram-like reactions (pt should avoid EtOH)
Tigecycline
MOA: similar to tetracyclines
Spectrum: work against MDR G+ve, some G-ve and anaerobic organisms
Resistance: Proteus and Pseudomonas (efflux pumps)
Use: complicated skin and intra-abd infections
PK: IV only
Elimination: bile
SE: N/V/D, discoloration of teeth, dizziness, photosensitivity (all same as tetracyclines)
CI: pregnancy and children < 8yo
Streptogramins
Quinupristin / Dalfopristin (alone they’re bacteriostatic)
*given together as combo so they are bactericidal
MOA: they bind to separate sites on 50S ribosome
Spectrum: G+ve cocci, MDR bacteria (Streptococci, PRSP, MRSA, E. faecium)
PK: IV only, penetrates Mϕ and PMNs, inhibit CYP-3A4
Use: restricted to tx of infections d/t drug resistant Staph or VRE
SE: GI sx’s, HA, infusion related sx’s
Penicillin + Aminoglycoside
MOA: synergistic bc penicillins facilitate movement of aminoglycosides through the CW
Administration: placed in different infusion fluid (diff IVs etc)
Use: empiric tx for infective endocarditis
Methicillin / Nafcillin / Oxacillin / Dicloxacillin
Resistance: β-lactamase resistant
Use: β-lactamase producing staphylococci, first line for staph endocarditis
Excretion: via bile bc they’re lipid soluble
Penicillins
Structure: β-lactam ring
MOA: bactericidal; inhibit last step in PG synth through binding PBPs in cytoplasmic membrane and autolysin production
Effect: CW synthesis disrupted, bacterial lysis induced
Spectrum: ability to reach target PBPs based on size/charge/hydrophobicity, Gram staining (+ve is more sensitive in penicillins)
Metranidazole PK and SE
PK: PO, IV, rectal or topical; high Vd
Elimination: hepatic
SE: GI sx’s, neuropathy, dark urine, metallic taste, Disulfiram-like effect (avoid EtOH)
CI: 1st trimester
Imipenem PK and SE
PK: nephrotoxic bc of its metabolism by dehydropeptidase I so must be given w/ enzyme inhibitor (Cilastatin) to prevent the metabolism and nephrotoxicity
SE: seizures at high levels
Doxycycline
Lipid soluble so preferred for parenteral administration and good choice for STDs and prostatitis
Excretion: bile
SE: dizziness
Ceftriaxone and Cefoperazone Elimination
Excreted by bile not kidneys
Macrolides DOC
M. pneumonie
Linezolid
*Bacteriostatic for most organisms, -cidal for Strep and C. perfringens
Spectrum: G+ve including MRSA and VRE, some activity against M. tuberculosis
MOA: binds unique site on 23S ribosomal RNA of 50S subunit (no cross-resistance)
Effect: inhibits formation of 70S initiation complex = halting transcription
Resistance: decreased binding, point mutation of RNA
Use: tx MRD infections
Best drugs for targeting anaerobes?
Clindamycin (infections above diaphragm) and Metranidazole (infections below diaphragm)
Macrolides Spectrum
G+ve (some activity against G-ve), similar to penicillins (Erythromycin has smaller spectrum than the other 3)
Streptomycin DOC
Plague (Y. pestis)
Macrolides PK and SE
PK: CYP inhibition (EXCEPT for Azithromycin)
SE: GI irritation, hepatic probs (erythromycin and azithromycin, QT prolongation, anyphylaxis is rare
Sulfasalazine Use
PO for UC, enteritis, IBD
Macrolides Uses
Tx of CAP, tx of URT or soft tissue infections (Staph, H. influenzae, S. pneumoniae, enterococci), used in pt w/ penicillin allergy
Cefazolin / Cephalexin
1st generation Cephalosporins
Active against: G+ve cocci, Proteus, E. coli, Klebsiella
Resistant: staph penicillinase
Use: penicillin G substitutes
DOC (Cefazolin): parenterally for surgical prophylaxis
Daptomycin Uses, PK, SE
Use: severe infections d/t MRSA or VRE, tx of complicated skin infections d/t S. aureus
PK: IV only, eliminated by kidneys
SE: constipation, nausea, HA, insomnia, rhabdomyolysis (so monitor CK and d/c coadministratoin of statins)
Vancomycin Uses
Tx infections d/t β-lactam resistant G+ve (or pt’s allergic to β-lactams), used in combo w/ aminoglycoside for empirical tx of IE ❤️, enterococcal endocarditis or PRSP, given PO for tx of Staph enterocolitis or abx-assoc C. difficile
Fidaxomicin
Spectrum: C. difficile
MOA: binds and inhibits RNA polymerase
Effect: inhibits protein synthesis
Use: tx recurrent C. difficile in adults
Carbenicillin / Ticarcillin / Piperacillin
‘Antipseudomonal’
Spectrum: broad but especially Pseudomonas
MOA: often combined w/ β-lactamase inhibitor
Use: injectible tx for G-ve, tx of moderate-severe infections of susceptible organisms
Erythromycin
PK: less PO absorption, shorter t1/2, less bioavailability than other macrolides, CYP inhibitor
DOC: Whooping cough (Bordatella pertussis)
SE: hepatic probs
Chloramphenicol
MOA: enters via active transport and reversibly binds 50S subunit (site adjacent to site of macrolides and clindamycin)
Effect: inhibits peptidyltransferase = stops protein synthesis (bacteriostatic)
Spectrum: broad (G+ve and G-ve, aerobes and anaerobes), esp N. meningitidis, H. influenzae, Salmonella and baceriodes
Resistance: acetyltransferases inactivate drug, changes in membrane permeability
Aminoglycosides Resistance
Inactivate drug by acetylation, phosphorylation and adenylation (plasmid-encoded), altered receptor protein on 30S subunit
Aztreonam SEs
Skin rashes or elevation of serum aminotransferases and GI upset,
Chloramphenicol PK and SE
PK: PO, IV and topical, high Vd (enters CSF), inhibits CYP-3A4 and CYP-2C9
SE: GI sx’s, BM suppression (dose-related), Gray baby syndrome d/t drug accumulation in newborns
Penicillins G
aka Benzylpenicillin
Administration: IV only
Active against: G+ve cocci (not staph), Listeria, C. perfringens, Neisseria sp, anaerobes
DOC: syphilis, strep (esp RF), pneumococci
SE: +ve Coombs’ Test
Cephalosporins
β-lactam
MOA: same as penicillin (bactericidal)
Inactive against: LAME (Legionella/Listeria, actinobacter, Mycoplasma, Enterococcus)
PK: mainly admin IV, elimination mainly by kidneys
Nitrofurantoin
Bacteriostatic/bactericidal
Spectrum: G+ve and G-ve (specifically E. coli)
MOA: reduced then the drug intermediate causes DNA damage
Effect: cell lysis
Use: prophylaxis and tx of lower UTI
PK: rapid elimination
SE: anorexia, N/V, neuropathies, hemolytic anemia (G6PD), colors urine brown
CI: renal insufficiency, pregnancy after 38 wks gestation, infants < 1 mo
Clindamycin
MOA: binds 50S subunit (same as macrolides)
Effect: inhibits translocation (bacteriostatic)
Spectrum: good for G+ve anaerobes, bacteriodes and G+ve aerobes
Resistance: modified receptor site, enzymatic inactivation, G-ve aerobes and enterococci intrinsically resistant
*cross-resistant w/ macrolides
Aztreonam
Monobactam
MOA: same as all
PK: IV or IM, via inhalation in CF pt’s, penetrates CSF
Elimination: urine
Spectrum: aerobic G-ve rods only (Pseudomonas esp)
Inactive against: G+ve and anaerobes
Resistance: β-lactamases
Use: UTI, LTI, septicemia, skin/suture infections, intraabd infections, gym infections d/t susceptible G-ve’s
