Antimicrobials Flashcards
Trimethoprim
Bind AS of dihydrofolate reductase PO or IV Plasmid with alternative enzyme (dhfr gene) Teratogen (not used in first trimester) Rarely used alone
Sulfonamide
Comp inhibitor of dihydropteroate synthetase
PO or IV
Chrom mut inc PABA/alter bidning or plasmid with alternative enz
Kernicterus in newborn, drug toxicities with warfarin and phenytoin
Rarely used alone
Trimethoprim-Sulfamethoxazole
PO or IV
Very broad: GP, GN, protoza, fungi (pneumocystis jirovecci)
Lower potential for resistance
N/V, headache, rash; hyperfalemia, hep, pancreatitis; S-J, toxic epidermal necrolysis, aplastic/hemolytic anemia, thrombocytopenia
Penetrate tissues well (inc prostate CSF) and excellent bioavailability
UTI, RI, bacterial diarrhea (limited due to E coli res), skin/soft tissue infection (S aureus), MRSA
Quinolones (ciproflixacin, levo, moxi)
Stabilize topo II or IV complex with DNA via ds breaks, interfere with txn/rep, cell dies
PO or IV
All GN, atypicals, mycobacteria; levo/moxi GP, moxi anaerobes
muts (1 or 2) in target enzymes and efflux pumps
N/V, headache, nervous/anx; seizures, C diff, prolong QT, tendon rupture, arthropathies
Excellent bioavailability and tissue penetration; absorption poor with divalent cations; long half life; all but moxi excreted in urine
GI infections; UTIs (cipro; not moxi bc don’t penetrate UT); pneumonia (levo/moxi); mycobacterial infection; polymicrobial infection from anaerobic activity (moxi)
Nitrofurantoin
Damage DNA and bind RNA (no tln)
PO
GP, GN uropathogens
Resistance develops with repeated use
Nausea; pulmonary fibrosis, acute pulmonary reactions
Doesn’t reach adequate serum levels but concentrated in urine
Only used for UTIs
Rifamycin (rifampin, rifaximin)
Inhibit RNA pol (-static)
Rifampin (PO/IV) and Rifaximin (PO)
GP, GN, anaerobic, mycobacteria
Rapid/preexisiting resistance due to muts in target enzyme
Rifampin turn sec orange; N/V/D; thrombocytopenia, leukopenia, anemia; hepatitis
Rifaximin not abs; others good bioavailability and tissue penetration; metabolized by cp450 (rifampin inducer of p450)
Prophylaxis (N meningitides, S aurea); TB (with others); rifaximin only for GI infection
Fidaxomicin
Inhibit RNA pol opening of DNA PO Only GP Non-absorbable C diff treatment (less recurrence than in vanc)
Penicillin overview
Beta-lactam: 4 member ring resemble terminal D-ala-D-ala of peptidoglycan so irreversibly bind/inhibit transpeptidase Intrinsic resistance to Mycoplsama (no cell wall; beta lactamases; modified PBP (PBP2A from mecA in MRSA); efflux pumps; dec porins/permeability Hypersensitivity rxns (rash, serum sicknes, cytopenias, acute interstitial nephritis, hives, anaphylaxis); seizures at high conc Bactericidal, high TI, good penetration (CSF), excreted thru kidneys, short half life
Penicillin G
IV or IM
GP cocci (strep, enterococci), GN cocci, GP anaerobes, spirochetes
Penicillinase
Short half life
Strep infections (A: strep throat and skin/soft tissue; B: pneumonia); syphilis; anaerobic infections (dental abscess, human bite)
Semi-synthetic penicillins: nafcillin, dicloxacillin
Naf: IV; dicloxa: PO
Only GP of PenG
Resistant to beta-lactamases (s aureus)
MSSA infections
Aminopenicillins: ampicillin, amoxicillin
Amp: IV, amoxi: PO PenG with improved GN (H flu, E coli) Beta-lactamases GI distress; amoxi: maculopapular rash in patients with mononucleosis CA-HEENT/RI and CA-UTIs
Anti-pseudomonal: piperacillin, ticarcillin
IV
PenG with even better GN (pseudomonas)
Beta-lactamase limits use
Beta-lactamase inhibitors: amp-sulbactam, amoxi-clavulanic acid, pipercillin-taxobactam
Bind and hydrolyze beta-lactamase (suicide inhibitor)
Extend spectrum to include MSSA, and GN anaerobes (Pseudomonas)
Polymicrobial infections from anaerobes (skin/soft tissue in diabetics, intra-abdominal infections, odontogenic); empiric if causative agent unknown
Cephalosporin overview
Beta-lactam
GN spectrum inc with gen (except 5th)
Most have some GP (not enterococci)
Most don’t have anaerobic activity)
More resistant to beta-lactamases than penicillin (ESBLs); intrinsic resistance to pseudomonas, enterococci; alter memb permebaility; alter PBP (MRSA)
Well tolerated (hypersenstivity and cross reactivity with penicillin allergy)
Eliminated in urine
1st gen: cefazolin, cephalexin
Cef: IV; ceph: PO (only PO cephalsporin)
GN; GP but limited by resistance
excellent tissue penetration
Cef for prophylaxis during clean surgery; no longer for strep/staph skin and soft tissue infection due to CA-MRSA
2nd gen: cefoxitin
IV
inc GN AND anaerobic
Prophylaxis for intr-abd surgery; intra-abd infection
3rd gen: ceftriaxone, ceftazidime
IV
inc GN; low GP activity; ceftazidime active against pseudomonas
Excellent tissue penetration (inc CNS)
CA-pneumonia, meningitis, serious infections (endocarditis, osteomyelitis); UTI in hospital
4th gen: cefepime
IV
broad: GN (inc pseudomonas) and GP
serious/resistant infections bc highly resistant to beta-lacatamases (even ESBL)
5th gen: ceftaroline
IV
similar to 3rd gen but include MRSA
Susceptible to ESBLs
used for MRSA
Carbapenems: imipenem, doripenem, ertapenem
IV
GN (pseudomonas), GP (E faecalis), anaerobes (erta = not for pseudomonas and acinetobacter)
Typically resistant to beta-lactamases (some carbapenemase)
Hypersenstivity and cross reactivity with penicillin allergy
Cidal, excreted through kidneys, imipenem not given with cilastatin
empiric treatment for serious/resistant infection
Monobactam: aztreonam
IV
GN only (anaerobe and aerobe)
Cidal, excreted by kidney
used if allergy to other beta-lactam (pen, cephalosporin)
Glycopeptide: vancomycin
bind terminal D-ala-D-ala of peptidoglycan and inhibit glycosyltransferase and transpeptidase
IV or PO
GP only (inc MRSA and anaerobies like C diff)
GN intrinsic resistance due to outer memb, vanA plasmid change d-ala to d-lac (VRE and VRSA), inc cell wall turnover (VISA)
red man syndrome from infusion, ototoxicity, nephrotoxicity
cidal, excreted by kidney, oral doesnt cross GI, fair tissue penetration (poor resp; into meninges when inflamed)
inferior to beta-lactams; GP bac infection resistant to beta-lactams (MRSA), allergies to pen/cephalosporins; empiric treatment of serious GP infection; C diff
Ccyclic lipopeptides
Lipophilic tail insert into membrane, membrane depol, cessation of vital cell processes, death (cidal but no lysis)
IV
GP (MRSA, VRE, anaerobes)
GN inherent resistance
GI, rash, headache; elevations of CPK and rhabdomyolysis; not given with statins
-cidal, conc-dep killing; doesnt cross BBB; excreted by kidneys
inhibited by pulmonary surfactant so not used for pneumonia
complicated skin/soft tissue infection, bacteremia, endocarditis
Polymyxin: polymyxin B, colistin (E)
amphipathic mols bind LPS and disrupt outer membrane
Mostly topical (also IV, aerolized)
GN bacilli only
IV use decline due to nephrotoxcitiy, neurotoxicity, poor efficacy/availability
ICU for resisant GN infections (acinetobacter and pseudomonas)
inhaled formulation for GN infection in lung (resistant GN pneumonia)
Bacitracin
inhibit synthesis of cell wall, LPS, capsule
topical (OTC ointment)
GP only (GAS- staph aureus, strep pyogenes)
superficial skin infection
Fosfomycin
No synthesis of acetyl muramic acid
oral (powder)
GP and GN
resistance devlops rapidly due to mut in transporter used to import drug
single dose therapy bc high/prolonged conc in UT
only for UTIs
Aminoglycosides: gentamicin, amikacin
bind 30S so misread/terminate DNA
IV
GN (pseudomonas), GP if used with beta lactams, mycobac, francisella tularensis, yersina pestis
Chrom (dec uptake of drug or enzyme that inactivate drug), lower rec affinity for drug (MTB)
ototoxicity (cochlear, vestibular damage), nephrotoxicity, neuromuscular block (not in MG patients)
high conc in renal cortex and inner ear, inactivated by acid (not for pneumonia), don’t penetrate liquid (not for abscess), cross placental barrier
UTIs in hospital, tularemia and plague, TB, GN infection (bacteremia, sepsis), GP infection (staph auerues or enterococcal endocarditis)
Tetracycline: doxycycline, tetracycline, minocycline
reversibly bind 30S and block access to tRNA
IV or PO
GN (no pseudomonas), GP (CA-MRSA), atypicals (chlamydia, mycoplasma), spirochetes (borelia, leptospira)
resistance is widespread so limit use (plasmids encode prots for efflux and RPPs)
discoloration and hypoplasia of teeth, stunted growth, photosensitivity, hypersensitivity, lupu-like rxn, rarely hepatoxic/vestibular effects
static, incomplete abs with oral, dec abs with dairy/calcium carbonate, bind tissues undergoing calcifcation (bone, teeth), cross placenta (not given in kids/pregnant owmen)
Bronchitis (CA-pne), chlamydia, lyme disease, leptospirosis, ricketsial infection, erhlichiosis, doxy for malaria prophylaxis and mino for acne
Glycyclines: tigecycline
semi-synthetic derivative of tetracycline
IV
GN (not pseudomona, proteus, morganella, providencia), GP (inc MRSA, VRE), most anaerobes
enhanced protection against resistant compared to tetracycline
complicated skin/soft tissue infection
complicated intra-abdominal infection
CA-pneumonia (inc mortality risk)
macrolides: azithromycin, erythromycin, clarithromycin
bind 50s and block txn
IV (clari is PO)
GN (no pseudo), GP, some GN anaerobes (prevotella, prophyromonas), atypicals
efflux pumps, target site alterations (erm), dec cell wall permeability (intrinsic resistant of enterobacteriaceae, pseudmonas, acinetobacter), enzymatic drug interaction
epigastric distress, prolong QT, hypkalemia, hypomagnesemia, bradycardia/arrhythmia
widely distirbuted in tissue except CSF, metabolzied by cyp450
azi: CA-pneumonia/bronchitis, atypical pneumonia, chlamydia, travelers diarrhea, prophylaxic myocbac avium in HIV patient
ery: drug motility
clari: H pylori and mycobacterium avium
Lincosamides: clindamycin
bind 50S and block txn
IV or PO
GP (inc MRA), oral anaerobes (above dia; like bacteriodes fragilis), parasites (malaria, toxoplasmosis, babesia
inducible clindamycin resistance by erm gene
c diff, hepatotoxicity, agranulocytosis
good penetration of most tissues except CNS
CA aspiration pneumonia due to oral anaerobes, oral/ENT infection, human bite wounds, skin/soft tissue infection from CA-MRSA, TSS from GAS (im combo)
oxazolidinones: linezolid, tedizolid
bind 50s and prevent formation of 70s initiation complex/inhibit translocation
tedizolid also target site interaction with peptidyl trnasferase
IV or PO
GP (inc MRSA and VRE); mycobacteria
resistance is uncommon (spont mut at drug target site, plasmid cfr)
bone marrow suppression (thrombocytopenia) with prolonged use, inhibit monoamine oxidase when givven with SSRIs (serotonin syndrome); lactic acidosis
100% bioavailability
VRE infections (not VRE endocarditis), nosocomial pneumonia due ot MRS, ocmplicated skin/soft tissue infection from GP (tedizolids only use)
Mupirocin
Bind reversibly to isoleucyl tRNA synthetase so arrest prot and RNA synth (also prevent DNA synth and inhibit cell wall prod)
topical (poyethylene glycol water miscible ointment)
GP only (not enterococci)
MRSA may display low/high levels of resistance (mut in gene, plasmid resp)
propylene glycol base may irrate mucous memb/broken skin
uncomplicated skin and soft tissue infections by GP (impetigo, folliculitis), MRSA declonization of anterior nares, prophylaxis for cather-related infection
DNA synthesis inhibitor: imidazole (metrionidazole, tinidazole)
enter by diffusion and produce free radicals
IV or PO
GN anaerobes (bacteroides fragilis, c diff (below dia)), protozoa (trichomonas, amoeba, giardia)
metallic taste and huge pulls; HA, vertigo, confusion, psychosis; vomiting and flushing when taken with alcohol
anaerobic infections below dia like intra-abdominal infections/abscess and C diff
trichomonas, bac vaginosis
aemeobiasis, giardiasis
bac overgrowth syndromes
crohns fistulae
