Table of antimicrobial drugs RH

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Table of antimicrobial drugs RH Powered By Docstoc

Class                    Name                Mechanism/Pharmacodynamics                        Pharmacokinetics           Spectrum                                 Side effects/toxicities                                      Resistance and Combos vs. Resistance

                                                                                                                                                                   rare, most not dose-dep, idiosyncratic (hypersensitivity):
                                             (R-SO2-NH2): mimic p-aminobenzoic
                                                                                                                                                                   fever, skin rashes, synalgias, lymphadenopathy; Mech:
                                             acid (PAB), comp inhibit dihyropteroate           good po F(most SAs),
                                                                                                                          Strep (but not pharyngitis), some        slow acetylation allows for N-hydroxylation, toxic
                                             synthetase, hence block folate (FH4)              metabol=acetylation;                                                                                                             Reduced perm to SAs (most common), inc [PAB],
                         sulfonamides                                                                                     MS Staph, some GNR                       metabolite -> antigenic (*high in AIDS); kernicterus in
Anti-Metabolites                             synthesis; bacteriostatic; Selective              renal excretion (early                                                                                                           inc [dihyropteroate synthetase], mutations in
                         (SAs)                                                                                            (enterobacteriaceae, E.coli,             neonates: displace bilirubin on albumin, bilirubin -> brain;
                                             Toxicity: prokaryotes synth folate,               SAs caused                                                                                                                       dihyropteroate synthetase
                                                                                                                          enterobacter)                            more rare effects: blood dyscrasias (anemias,
                                             eukaryotes do not; eukaryotes transport           crystalluria)
                                                                                                                                                                   agranulocytosis), toxic hepatitis, CNS neurotox,
                                             folate, prokaryotes do not
                                                                                                                                                                   nephritis, cardiotox
                                             folate antagonists; inhib dihydrofolate
                                                                                                                          same as above; combo Tx, chronic
                                             reductase, blocks thymine synth and                                                                                   well tolerated, rash, nausea, vomiting, may cause folate     Combo: Resistance to TMP most critical, synergy
                                                                                               t1/2 = ~10 hrs for Co-     UTI (E. coli), acute ped otitis media,
                                             causes accumultn of FH2, thus inhibiting                                                                              def in nutritional-dep individuals resulting in              beneficial w/ TMP res; Mech: inc [DHFR] (most
                         trimethoprim                                                          Trimoxazole (combo         acute pneumo (Strep pn, H. influ),
                                             puring and pyrimidine biosynth -> arrest                                                                              megaloblastic anemia, thrombocytopenia, neutropenia;         imprtnt), develop thymine dependence (TS
                         (antifolates)                                                         Rx); tissue distribtn =    Shigellosis, pneumocystis carinii,
                                             DNA synth; bacteriostatic; Selective                                                                                  mostly due to SA; excreted in breast milk -> may be          defect), reduce DHFR suscept to TMP, cellular
                                                                                               20SMX:1TMP                 salmonella typhi (chloramphenical,
                                             Toxicity: mammalian DHFR exhibits                                                                                     teratogenic                                                  imperm to Rxs
                                                                                                                          ampicillin res)
                                             different folate binding

                                             Mimic D-Ala-D-Ala, bind transpeptidase
                                                                                               low po F, acid                                                      hypersensitivity (type 1 anaphylactic, type II cytolytic
                                             and other Pencillin Binding Proteins,
                                                                                               unstable, erratic; low                                              [hemolytic anemia], type III arthus [Ag-Ab complex
                                             inhibit transpeptidation of NAM/NAG
                                                                                               CNS penetration (inc                                                deposition, serum sickness], type IV delayed type            Altered PBP site, reduced permeability, β-
                                             backbones of peptidoglycan, causing                                          Strep, Neisseria meningitidis,
                                                                                               w/ inflamm); 10%                                                    [contact dermatitis]), GI (po), Na-overload (Ticarcillin),   lactamase (plasmids) * β-lactamase inhibitors
                                             inappropriate degradation of cell wall                                       syphilis, oral anaerobes (not B.
β-lactams                Penicillin G                                                          hepatic metabol, 90%                                                more rare: myelosuppression, hepatitis, platelet             developed, given in combo w/ PCN (inc potency),
                                             during turnover; Selective Toxicity:                                         fragilis), Clostridia, Actinomyces,
                                                                                               renal clearance                                                     aggregation (PCN, ticarcillin), seizures                     ex: augmentin (clavulanate -amoxicillin),
                                             humans don't have cell walls, D-Ala,                                         Listeria, P. multocida, B. anthracis
                                                                                               (filtered and secreted);                                            * Skin test important for determining allergy, future rxns   clavulanate = comp-inhib of β-lactamase
                                             transpeptidase; bactericidal, time-dep
                                                                                               t1/2 = 45 min (0.5-1.5                                              (anaphylaxis/accel uticaria vs cutaneous only in pts w/
                                             killing, post antibotic effect (bacteriostatic)
                                                                                               hrs for β-lactams)                                                  Hx of PCN allergy)
                                             for GPCs

                                                                                               very slow IM
penicillin depot forms   Procaine penicillin same mech; equimolar salt                                                    same as above                            same as above                                                same as above

                         Benzathine                                                            very, very slow IM
                                             same mech; another salt                                                      same as above                            same as above                                                same as above
                         penicillin                                                            absorption

acid stable pencillin    Penicillin V        same mech                                         good po F; acid stable same as above                                same as above                                                same as above

                                                                                                                          GPC, incl Strep pneumo and
                                                                                                                                                                                                                                organisms w/ β-lactamase:         combo +
aminopenicillins                                                                                                          others, enterococcus; GNR, incl H.
                         Ampicillin          same mech, improved spectrum vs GNR po F = 50%                                                                  diarrhea, rash (macular, evanescent), no allergy                   sulbactam iv (β-lactamase inhibitor) = Unaysn,
(extended spectrum)                                                                                                       influ, listeria, E. coli, proteus
                                                                                                                                                                                                                                extend spectrum to Staph a., H. influ., many GNRs
                                                                                                                          mirabilis (idole neg), salmonella

                                                                                                       GPC, incl Strep pneumo and
                                                                                                                                                                                                                                β-lactamase;                               combo
                                                                                                       others, enterococcus; GNR, incl H.
                                                                                                                                                                                                                                + clavulanate po (β-lactamase inhibitor) =
                         Amoxicillin         same mech, improved spectrum vs GNR po F = 100%; dose tid influ, listeria, E. coli, proteus
                                                                                                                                                                                                                                Augmentin, extend spectrum to Staph a., H. influ.,
                                                                                                       mirabilis (idole neg), salmonella;
                                                                                                                                                                                                                                many GNRs
                                                                                                       prophylaxis before oral surgery

                                                                                                                          same as amox/ampicillin, but incl.
Anti-Pseudomonal                             prototype, no longer used; little/no PAE
                         Carbenicillin                                                                                    Pseudomonas and other GNRs                                                                            β-lactamase;
Carboxypencillins                            vs. pseudomonas (GNRs)
                                                                                                                          (not Klebsiella)

                                                                                                                                                                                                                                β-lactamase;                              combo +
                                                                                                                          Pseudo. A., proteus, many other
                                             potency = 2 x carbenicillin; time-dep                                                                                                                                              clavulanate (β-lactamase inhibitor) extends
                         Ticarcillin (TCR)                                                                                GNR (not Klebsiella), Strep, some
                                             killing                                                                                                                                                                            spectrum to Staph a., H. influ., enteric GNRs
                                                                                                                    Rx Class: GNR incl Pseudo a.,
                        Pipercillin (PIP)                                                                           anaerobes incl Bacteroides,
                                                                                                                                                                                                                      β-lactamase;                         combo +
                        Azlocillin,                                                                                 enterococci, GPC (but not Staph);
Anti-pseudomonal                                                                                                                                                                                                      tazobactam (β-lactamase inhibitor) extends
                        Mezlocillin,                                                                                PIP-Specific: TCR's coverage +
Aminoacylpenicillins                                                                                                                                                                                                  spectrum to Staph w/ β-lactamase and many
                        Piperacillin/                                                                               Klebsiella, B. fragilis, some
                                                                                                                                                                                                                      GNRs (same as TCR vs. Pseudo a.)
                        tazobactam                                                                                  enterococci; Used in combos for
                                                                                                                    serious GNR infections

                        Cloxacillin,                                                                                                                                                                                  "Methicillin resistant" Staph a. (MRSA) or
PCNase (β-lactamase)-                                                                                               Staph w/ β-lactamase (ie Staph a.),
                        Dicloxacillin,                                                                                                                  methicillin nephritis (interstitial nephritis)                epidermidis; mech: altered PBPs; also resistant to
Resistant Penicillins                                                                                               Pneumococci, Grp A Strep
                        Nafcillin                                                                                                                                                                                     cephalsporins and imipenem

                        t1/2 generally 0.5-   Exceptions: meningitis - q2h,
Dosing info for         1.5 hrs, but can      amoxicillin - tid, benzathine and
penicillins             dose q4h b/c of       procaine penicillins - less frequent
                        PAE.                  (long t1/2s)

                        2nd gen
                                                                                                                    GPC and GNR, incl Staph (not
                                                                                        most dosed q8h;             MRSA) and others w/ β-lactamase;
                        (Rocepherin),                                                                                                                   as safe or safer than PCNs; hypersensitivity, X-
                                              same mech as PCNs, time-dep killing,      ceftriaxone - qd;           varies by generation: anti-anaerobe                                                               MRSA/methicillin resistant Staph; mech: altered
Cephalosporins          Cefotetan,                                                                                                                      allergenicity w/ PCNs (don't give to PCN-allergic), rare
                                              bacteriocidal, PAE (bacteriostatic) vs G+ iv, cont infusion more      = 2nd gen (ceftriaxone, cefotetan);                                                               PBPs
                        3rd gen                                                                                                                         nephrotox, GI tox (there Rx no longer used)
                                                                                        efficient                   anti-pseudom = 3rd gen
                                                                                                                    (ceftazidime, cefepime)

                                                                                          t1/2 = 1 hr; renal
                                                                                          clearance (filtered and
                                              same mech as PCNS, time-dep killing,        secreted); Cilastatin     very broad; GPC incl enterococci
                        Imipenem (given                                                   inhibits renal prox
                                              bacteriocidal, PAE (bacteriostatic) vs                                (not as good as vancomycin), GNR                                                                  rare; MRSA/methicillin resistant Staph; mech:
Carbanepems             w/ Cilastatin =                                                   tubule                                                     seizures, nausea, vomiting, and diarrhea
                                              GPC and GNR; pore in GNR cell wall                                    incl pseudom a., anaerobes incl                                                                   altered PBPs; emerging resistance w/ Pseudom.
                        Primaxin)                                                         dehydropetidase I
                                              important                                                             bacteroides
                                                                                          from metabolizing
                                                                                          imipenem into renal
                                                                                          tubular toxin

                                                                                                                    narrow; β-lactamase-resistant;
                                              same mech as PCNs, non-                     dose im or vi, renal
Monobactams             Aztreonam                                                                                   GNR coverage (esp                      NO X-allergenicity w/ PCNs, rel non-toxic
                                              aminoglycoside "aminoglycoside"             clearance

                                                                                          NO po F (use to treat
                                                                                          C. difficile
                                              Prevents access of transpeptidase to D-     pseudomemb colitis!),                                            allergenicity (skin rash, eosinophilia, Rx fever), phlebitis,
Non β-lactam Cell Wall                                                                                             all GPCs except enterococcus
                       Vancomycin             Ala-D-Ala by H-bonding, thus inhibiting     poor CSF penetration,                                            "red man" (flushing w/ rapid iv dosing--alleviate by          D-Ala-D-Ala to D-Ala-D-Lactate
Agent                                                                                                              fcm., niche = Staph a.!
                                              peptidoglycan X-linking; time-dep killing   little/no metabol, renal                                         reducing infusion rate), doubtful oto/nephrotox
                                                                                          clearance (filtered,
                                                                                          GFR), t1/2 = 6 hr

Ribosome Inhibitors
                                          bacteriocidal, concentration-dep killing,       poor po F, dosed iv
                  gentamicin              30S rRNA A site: blocks initiation,             (loading dose not GFR-
                                                                                                                                                           nephrotox (reversible, more common), ototox (50%
                  tobramycin              terminates, misreads; actively                  dep, maint dose is), no
                                                                                                                  GNRs, not all Pseudom.; GPCs             irreversible, less common), neuromuscular paralysis
                  amikacin                transported w/ accumulation and                 metabol, poor CSF                                                                                                            enzymatic modification of Rx; choose AG Rx
aminoglycosides                                                                                                   only in synergy w/ β-lactams; TB         (very rare); Tx monitoring: daily serum creatinine; qd
                  neomycin                retention, PAE vs GN organisms;                 penetration, renal                                                                                                           based on local resistance
                                                                                                                  (streptomycin)                           dosing - lower nephrotox vs q8h; steptomycin: ototox
                  (neosporin - topical)   selective tox: poor 80S ribosomes               clearance (GFR),
                  streptomycin            binding, no transport (except renal PCT,        reabsorbed in renal
                                          inner ear, pigmented retinal epithelia)         PCT

                                          bacteriostatic, concentration-dep killing,
                                                                                                                    chlamydial infections, borrelia
                                          binds 30S rRNA A site via polar areas of        doxycycline - po/iv,
                  Tetracycline                                                                                      burgdorferi, H. pylori (in comb w/     chelates calcium, deposited in teeth/bones (aesthetic,
                                          Rx molecule: allow tRNA binding but not         qd/bid; minocycline -
tetracyclines     Doxcycline                                                                                        other Abx, bismuth subsalicylate),     imprtnt late prenatal to age 6), some GI (doxycycline       genetically altered active transport system
                                          alignment (no A/T to A/A); actively             iv, qd/bid; tetracyline -
                  Minocycline                                                                                       other atypicals; MS Staph, some        least)
                                          transported and accumulated; selective          q6-8h
                                          tox: only passive transport in eukaryotes

                                          bacteriostatic ('cidal in Strep pneumo w/       good po F, t1/2 = 5
                                          autolysins), time-dep killing, binds 50S        hrs, better Vd than
                                                                                                                    "worst of the worst" resistant
                                          rRNA P site: blocks fMet tRNA binding,          beta lactams, less
                                                                                                                    GPCs: vanc-resist enterococcus
Oxazolidinones    Linezolid               formation of 70S initation complex              than quinolones;                                                 headache, nausea, diarrhea, hypotension (rare)
                                                                                                                    (VRE) fcm, MRSA, PCN-resist
                                          (peptidyl transferase cavity); PAE vs           clearance = 65%
                                                                                                                    Strep pneumo
                                          GPs; selective tox: does not bind to 80S        metabol, 35%
                                          ribosome                                        excretion unchanged

                                                                                          palmitate -po,
                                          bacteriostatic ('cidal for meningitis), binds   succinate - iv;
                                          50S rRNA A site: inhib peptidyl                 Vd: 100% BW,                                                     myelosuppression (reversible, transient, dose-dep),
                                          transferase (peptidyl transferase cavity);      intracell, good CSF    *CNS infections!* Strep pn, N.            aplastic anemia (rare, irreversible, often fatal), gray baby
Chloramphenicol   Chloramphenicol         selective tox: no binding to 80S ribosome,      penetration; metabol: meningitidis ('cidal), H influ ('cidal),   syndrome (ineff glucuronidation; gray color, cyanosis,       acetylation
                                          no inhib of eukary cytosolic peptidyl           glucurodination, renal many GNR and anaerobes                    tachypnea, vomiting, diarrhea, abd distentn,
                                          transferase (PT), but inhibs mitochondrial      elim glucuronide>free                                            hypothermia, flaccidity, death)
                                          PT                                              Rx; t1/2 = 6 hr, 3-4x
                                                                                          inc neonates, premie

                                          bacteriostatic, binds 50S rRNA A and P
                                                                                          po F, dose q6-8h; Vd:
                                          sites: inhib peptidyl transferase (peptidyl                             GPC (Strep pn, Grp A Strep, MS           colitis (C.difficile pseudomembranous colitis w/ diarrhea,
                                                                                          good except CSF;
Clindamycin       Clindamycin             transferase cavity); selective tox: no                                  Staph, not entercocci), most             esp in institutional settings, Tx = metronidazole, po      seldom; but C. difficile always resistant
                                                                                          phase I metabol,
                                          binding to 80S ribosome, no inhib of                                    anaerobes incl B. fragilis               vancomycin)
                                                                                          renal/hepatic excretion
                                          eukary peptidyl transferases

                                                                                          po F, dosing:
                                          bacteriostatic, binds 50S rRNA exit tunnel
                                                                                          erythromycin - q6h,
                  Erythromycin            via H-bonding, blocks polypeptide                                         atypicals (mycoplasma pn,
                                                                                          azithromycin -qd                                                                                                             becoming problematic (dec Rx uptake, methylation
                  Azithromycin            elongation and thus translation (peptidyl                                 chlamydia pn, legionella               SAFEST OF ALL ANTIBIOTICS; nausea, vomiting
Macrolides                                                                                clarithromycin -qd; Vd;                                                                                                      dec 23S rRNA affinity for Rx, plasmid-assoc ERY
                  (Zithromax)             transferase cavity); selective tox: no                                    pneumophila), PCN-allergy: Strep       (ERY>AZI)
                                                                                          good except CSF,                                                                                                             esterase)
                  Clarithormycin          binding to 80S ribosome, no inhib of                                      pn, Grp A Strep, MS Staph
                                          eukary translation
                                                                                          penetration : AZI>ERY

DNA Inhibiton

                                          bacteriocidal, bind DNA-topoisomerase           po F, rapid 100%
                                          intermed ("cleavable complex"), uncomp          absrptn; iv req H2O- varies by generation; 2nd gen: all                                                                      increasing w/ widespread use:
                  2nd gen                 inhibition, causes replication fork             sol. proRx; Vd: wide, GNR (except some Pseudom), all             generally safe and well tolerated; GI (nausea, vomiting,
                                                                                                                                                                                                                       For GPs: Gyrase DNA-binding subunit, then
                  Ciprofloxacin           collision, dsDNA breaks, cell death (due        fairly good access to atypicals; 4th gen: all GPC (except        diarrhea), CNS (headache, dizziness, fatigue, sleep
                                                                                                                                                                                                                       ATPase subunit, then topo IV.
Quinolones        (Cipro)                 to persistent cleavable complexes on            CSF, intracell;                                                  disords, neuropsych more rare), skin (phototox,
                                                                                                                  enterococcus fcm, MRSA), all GNR                                                                     For GNs: Topo IV DNA-binding subunit, then
                  4rd gen                 DNA); target varies: DNA gyrase for             metabol/ elim: 2nd gen- (except some Pseudom), all               hypersensitivity [rash, pruritis]), arthopathy (not FDA-
                                                                                                                                                                                                                       ATPase subunit, then gyrase.
                  Trovafloxacin           GNs, Topo IV for GPs; selective tox:            phase I/renal/6h, 4th anaerobes and atypicals                    approved in peds), tendon rupture (achilles, rare)
                                                                                                                                                                                                                       altered efflux less common
                                          binds selectively to prokary gyrase/topo        gen-phase
                                          IV complexes; non-homologous regions            II/hepatic,GI/10h
                                       General Principles: long-term Tx (6-12
                                       months or more), imprtnt for toxicities;
                                       standard Tx protocol for suspected TB: 4
Anti-Mycobacterial                     months w/ 4 Rxs (INH, rifampin, PZA, and                                                                                                                                       primary (genetic diversity), 2ndary (non-
agents                                 streptomycin or ethambutol), then 2                                                                                                                                            compliance); mech = chromo mutation
                                       months w/ Rxs to which isolate is
                                       sensitive. Combo Tx to prevent

                                                                                      t1/2 = 1-6 hr (varies w/
                                       bacteriocidal, isopropyl metabolite more                                                                        hepatitis (reversible, inc w/ age, slow acetylators, Tx
                                                                                      acetylator status);
                                       potent, inhibs mycolic acid synth, at high [                                                                    monitoring w/ ALT/ASTs), neurotox (periph neurpath,            katG gene (catalase-peroxidase, "activiates" INH),
                                                                                      metabol by N-acetyl
anti-tuberculosis    Isoniazid (INH)   ]s, inhibs energy-req pathways (eg                                      M. tuberculosis                         prevented by co-admin of pyroxidine/vitamin B6),               inhA gene (enzyme for mycolic acid synth, X-
                                                                                      transferase and
                                       glycolysis), intracell accumulatn, forms                                                                        hypersensitivity, Rx-induce lupus (also seen w/ para-          resistance to INH analog ethionamide)
                                                                                      hepatic mixed funxn
                                       oxygen free radicals                                                                                            aminosalcyclic acid)

                                                                                  variable t1/2; non-
                                                                                  linear PK, Rx can             M. tuberculosis; highly bacteriocidal
                                                                                                                                                      orange discoloration (urine, sweat, tears, soft contact
                                       bacteriocidal, broad spectrum inhibitor of accumulate; metabol           vs. most GPs and some GNs
                     Rifampin                                                                                                                         lenses), hepatitis, hypersensistivity (flu-like), ligh chain    RNA Pol genes
                                       bacterial DNA-dep RNA Pols                 by deacetylation,             (Neisseria, H influ) (used as single
                                                                                  biliary excretion w/          agent vs non-mycobacteria)
                                                                                  enterhepatic recircultn

                                       highly bacteriocidal, nicotinamide analog,
                                                                                     long t1/2 = 12-24 hrs,                                            hepatotox (hi doses, now rare), hyperuricemia
                     Pyrazinamide      active at low pH, effective intracell but not
                                                                                     metabol by CYP 450s M. tuberculosis                               (common), photosensitive dermatitis (rare, give at
                     (PZA)             vs dormant organisms (not good for long
                                                                                     then renal elim                                                   bedtime)
                                       term Tx)

                                       bacteriostatic, mech unknown, inhib RNA ophthal monitoring for                                                  Periph neuropath, esp retrobulbar optic neuritis (color
                     Ethambutol                                                                       M. tuberculosis
                                       synth and mycolic acid metabol          tox                                                                     blindness, eventual loss of periph vision - Tx monitoring)

                                                                                                                                                       severe hemolytic anemia in pts w/ G6PD def,
                                                                                      t1/2 = 10-50 hrs;                                                methemoglobinemia and subclinical hemolysis,
                                                                                      variation in acetylator                                          hypersensitivity (rash, fever), rare: agranulocytosis, fatal
anti-leprosy         Dapsone           inhib folate synth like SAs                                              broad like that of SAs; M. leprae
                                                                                      status, variation in                                             mononucleosis-like syndrome. Reversal reactions
                                                                                      clearance                                                        (fever, arthralgias) and erythema nodosum leprosum at
                                                                                                                                                       initation of Tx

                                                                                      t1/2 = 70 days; mech
                                                                                      clearance unknown,
                                       phenzine dye, mech unknown, may inhib                                                                           reddish-blue skin pigmentation, small bowel thickening
                     Clofazimine                                                      maybe via RES,            M. leprae
                                       DNA synth; highly lipophilic                                                                                    (Rx accumultn), abdom pain
                                                                                      uptake by

                                                                                                                                                       orange-brown discoloration (urine, sweat, tears, soft
                                       aka ansamycin, "me too" analog of              t1/2 = 16hrs; hepatic     M. avium intercellulare (FDA-          contact lenses), uveitis (dose-dep, rare w/out hi doses
anti-MOTT            Rifambutin
                                       rifampin, but more potent, longer-lasting      clearance?                approved prophylaxis in AIDS pts)      except when co-admin w/ Rxs that slow hepatic
Rx Interactions

Displaces tolbutamide (oral hypoglycemic Rx) on
albumin -> hypoglycemia

Rx Combo: Co-Trimoxazole (fixed ratio
Trimethoprim + sulfonamide (sulfamethoxazole);
Bactrim, Septra) Synergy: inc MIC of each Rx,
bacteriostatic to 'cidial, dec resistance; mech:
SMX blocks FH2 synth, TMP works upstream.
Also, anti-malarial pyrimethamine (Daraprim) +
sulfadoxine (sulfamethoxine)

none indicated; problems w/ PCN G: short t1/2,
unstable to gastric acidity, inactivation by β-
lactamase, poor G- spectrum, allergenicity

same as above

same as above

same as above
synergy w/ β-lactams; anatogonism w/

anatogonism w/ aminoglycosides; inhib some
hepatic mixed function oxidases, dec metabol of
warfarin, phenytoin, tolbutamide, chlorpropamide

fluroquinolone po absorption dec by co-admin w/
Mg, Al-containing antacids or w/ Fe
inhib monoamine oxidase (MAO)

P 450 inducer (dec efficacy of po contraceptives,
cyclosporine, theophylline, coumarins, other Rxs)