Antibiotics 2 and 3 Flashcards
Lipoglycopeptides (analogues of vancomycin): dalbavancin, telavancin, oritavancin
Spectrum: gram positives INCLUDING MRSA, coag-neg staph, strep, enterococcus; oritavancin, telavancin active against VRE;
Place in therapy: skin and soft tissue infection;
Dosing: telavancin: daily; dalbavancin 2 doses a week apart (has longest half-life); oritavancin: 1 time dose (long half-life);
SE’s: nephrotoxicity, metallic taste, nausea in telavancin;
Pearels: more rapidly bactericidal than vanco; resistance a concern with dalbavancin and oritavancin due to LONG HALF LIFE;
Mech of dalaba is same as vanco; oritavancin also has interaction and disruption of cell membrane, and binds to pentaglycl bridging segment in peptidoglycan and inhibits transpeptidation; telavancin: can also interact and disrupt cell membrane
Daptomycin (cyclic lipopeptide):
Spectrum: gram positives INCLUDING MRSA, caog-negative staph, strep, enterococcus including VRE;
Place in therapy: alternative to vancomycin (NOT EFFECTIVE FOR PNEUMONIA b/c of surfactant inactivation);
SE’s: myalgia that can result in rhabdo; rare: eosinophilic pneumonia;
mech: inserts into gram-pos cell membrane and causes depol and cell death
Aminoglycosides: gentamicin, tobramycin, amikacin, streptomycin:
Mech: binds 30S subunit of bacterial ribosomes (interferes with initiation complex b/w mRNA and the 30S subunit; O2 dependent transport across bacterial cell membrane);
Spec: gram negs including PSEUDOMONAS; NO ANAEROBES, gram positives ONLY if used with cell-wall active agent for synergy;
Place in therapy: no better agent empirically when gram-neg sepsis suspected especially if URINARY SOURCE; MDR infections especially with Pseudomonas could still have susceptibility to aminoglycosides;
SE’s: renal dysfunction (reduce with extended-interval dosing); ototoxicity: incidence likely underreported; NEUROMUSC BLOCKADE;
Pearls: rapidly bactericidal with post anti-biotic effect; Cmax:MIC ratio 8-10 x MIC associated with IMPROVED OUTCOMES; think about extended-interval dosing (once-daily dosing)!!!
Tetracyclines: doxy, minocycline, tetracycline
MOA: bind to 30S ribosomal subunit of bacterial ribosomes and use passive diffusion through porins;
Spectrum: ATYPICALS, some gram pos like CA-MRSA, limited gram negs; Borrelia;
Place in therapy: tick-borne illnesses, uncomplicated URTI’s (bronchitis, sinusitis, CAP), option for CA-MRSA uncomplicated infections;
SE’s: GI (N/V, diarrhea), phototoxicity, discoloration of teeth;
Drug interactions: chelates and gets divalent cations (Ca, Mg, Fe)
Glycylcyclines: tigecycline
MOA: binds to 30S subunit of bacterial ribosome; glycyl side chain prevents efflux that causes resistance with other tetracyclines;
Spectrum: ATYPICALS; broad spectrum; some gram-neg “holes” including Pseudomonas;
Place in therapy: “back-pocket” drug for MDR infections or polymicrobial infections where a single agent is desired; intra-abdo infections;
SE’s: GI, N/V, diarrhea, increased LFT’s, increased all-cause mortality;
Pearls: not for BACTEREMIA due to large Vd
Macrolides: azithromycin, clarithromycin, erythromycin:
Mech: reversible binding to 50S subunit of ribosome;
Spectrum: atypicals, strep (30% of S pneumoniae is resistant to azithromycin), some gram-negs (respiratory pathogens like H influenzae);
Place in therapy: uncomplicated respiratory tract infections (use now limited by resistance);
SE’s: GI (more so erythromycin); QT prolongation if IV erythromycin
Pearls: Clarithromycin and erythromycin are strong inhibitors of CYP 3A, so you have increased concentrations of 3A substrates like statins
Clindamycin (lincosamide class):
MOA: bind to 50S ribosomal subunit
Spectrum: gram pos including MRSA, however resistance increasing; mouth anaerobes;
Place in therapy: comm-acquired skin and soft tissue infection if uncertain about pathogen (S aureus vs strep); adjunct for severe group A strep (GAS) infections; alternative surgical prophylaxis in PCN-allergic patients;
SE’s: higher incidence of C difficile infection than other antibiotics, diarrhea
Oxazolidinones: Linezolid, tedizolid
MOA: binds 23S ribosomal RNA of 50S subunit
Spec: gram-pos including MRSA, VRE, coag-neg staph, strep (resistance rare);
Place in therapy: VRE infections, alternative to vnaco, avoid for MRSA bacteremia/endocarditis;
SE’s: bone marrow suppression (thrombocytopenia), usually after 2 wks of use); peripheral neuropathy with long-term use;
drug interactions: weakly inhibits MAOI, so risk of serotonin syndrome with serotonergic agents (monitor for signs of serotonin syndrome; jury still out on tedizolid)
Quinolones: Ciprofloxacin, levofloxacin, moxifloxacin
MOA: inhibits DNA gyrase, topo IV
Spec: moxi and levo termed “respiratory quinolones” and target S pneumoniae; ATYPICALS; gram negs like Pseudomonas (minus moxifloxacin); moxifloxacin only one with anaerobic activity;
Place in therapy: upper and lower RTI’s, intra-abdo and GI infections, UTI, bone and joint (osteomyelitis), maybe cutaneous anthrax;
SE’s: GI, CNS (confusion, dizziness, headache), QT prolongation, tendon rupture/tendinitis
Drug interactions: oral can chelate with Fe, Al, Mg, Ca; Cipro can inhibit CYP 1A2 and decrease theophylline clearance
Pearls: resistance problematic, could exacerbate myasthenia gravis
Metronidazole:
MOA: interact with DNA to cause loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis;
Spec: anaerobes (B fragilis, Clostridium), trichomonas;
Clinical uses: C diff diarrhea, intra-abdo infections, surgical prophylaxis in colon surgery, trichomoniasis;
SE’s: metallic taste, minor GI disturbances, peripheral neuropathy, DISULFIRAM RXN with alcohol
Trimeth-Sulfa (Bactrim):
MOA: interference with folic acid synthesis (sulfa prevents dihydrofolic acid formation from PABA, while trimeth prevents tetrahydrofolate production from dihydrofolic acid)
Spec: some gram-pos activity (CA-MRSA/MSSA), beta-hemolytic strep activity is poor, some gram negs (resistance problems), stentrophomonas (nosocomial pathogen and DOC), listeria, nocardia, toxoplasmosis, pneumocystis jiroveci;
Place in therapy: uncomplicated cystitis, path-specific therapy against organisms listed above; PCP prophylaxis;
SE’s: Derm (SJS and TEN possible), renal (TMP can inhibit creat secretion and sulfa leads to AIN), hematologic (bone marrow suppression);
Drug interactions: warfarin: increases INR if CYP 2C9 inhibited by TMP/SMX
