Antibacterials Flashcards
Penicillin mechanism
G - IV, V - oral
- bind penicillin-binding proteins (transpeptidases)
- block transpeptidase cross-linking of peptidoglycan
- activate autolytic enzymes
penicillin clinical use
- usually used for gram +ves, bactericidal for gram positive cocci and rods, gram negative coci, and spirochetes
- S. pneumo, S. pyogenes, Actinomyces, N. meningitidis, T. pallidum
- “STAN’S” favorite drug is penicillin
penicillin toxicity and resistance
- tox: hypersensitivity reactions, hemolytic anemia
- resistance: penicillinase in bacteria cleaves B lactam ring
ampicillin, amoxicillin mechanism
- same as penicillin, wider spectrum, also combined with clav to protect against b-lactamase
amp/amox clinical use
- extended spectrum penicillin - H flu, E coli, listeria, proteus, salmonella, shigella, enterococci
- HELPSS kill enterococci
amp/amox tox and resistance
- tox: hypersensitivity reactions, rash, pseudomembranous colitis
- resistance: penicillinase in bacteria cleaves B lactam ring
oxacillin, nafcillin, dicloxacillin mechanism
- same as penicillin, narrow spectrum because of bulky R group blocking access to B lactam ring
oxacillin, nafcillin, dicloxacillin clinical use and tox
- s. aureus (not MRSA), skin/soft tissue infections
- tox: hypersensitivity reactions, interstitial nephritis
ticarcillin, piperacillin mechanism, clinical use and tox
- same mechanism as penicillin, extended spectrum
- used against psuedomonas and GNR, use with B lactamase inhibitors, susceptible to penicillinase
- tox: HS reactions
B lactamase inhibitors
- CAST: clavulanic acid, sublactam, tazobactam
- added to penicillins to protect from destruction by B lactamase (penicillinase)
cephalosporin mechanism of action
- B lactams that inhibit cell wall synthesis, but are less susceptible to penicillinases
- bind to PBPs irreversibly, bactericidal
1st gen cephalosporins clinical use
- cephalexin, cefazolin
- PEcK - proteus, E coli, Klebsiella
2nd gen cephalosporin clinical use
- cefoxitin, cefaclor, cefuroxime
- HEN PEcKs - H flu, Enterobacter, Neisseria, proteus, E coli, Klebs, Serratia
3rd gen cephalosporin clinical use
- ceftriaxone, cefotaxime, ceftazidime
- serious gram negative infections
- ceftriaxone –> meningitis and gonorrhea
- ceftazidime –> pseudomonas
4th gen cephalosporin clinical use
- cefepime
- increased activity against pseudomonas and gram positives
5th gen cephalosporin clinical use
-ceftaroline - broad GN and GP coverage, including MRSA but not psuedo
cephalosporin tox
- HS reactions, Vit K deficiency, low cross-reactivity with penicillins, increased nephrotoxicity of aminoglycosides
aztreonam mechanism and tox
- a monobactam, resistant to B lactamases
- prevents peptidoglycan cross-linking by binding to PBP3
- synergistic with aminoglycosides
- no cross-allergenicity with penicillins
- usually non-tox, some GI upset
aztreonam clinical use
GNR only, no activity against gram + or anaerobes
- for pen allergic patients with renal insufficiency who cannot tolerate aminoglycosides
carbapenems mechanism
- broad spectrum beta lactamase resistant
- imipenem always given with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of the drug in the renal tubules
carbapenems clinical use and tox
- gram + cocci, GNRs, and anaerobes
- life-threatening infections
- tox: GI distress, skin rash, seizures (dec risk with meropenem)
Vancomycin mechanism
- inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors
- bactericidal
vanc tox and mech of resistance
- NOT trouble free
- nephrotoxic, ototoxic, thrombophlebitis
- red man syndrome
- bacteria change D-ala D-ala to D-ala D-lac to become resistant
vanc clinical use
- gram positive only
- MRSA, enterococci and C. diff
protein synthesis inhibitors
buy AT 30, CCEL at 50
- 30s inhibitors: aminoglycosides (cidal), tetracyclines (static)
- 50s inhibitors: chloramphenicol, clinda, erythromycin, linezolid (all static, linezolid is variable)
aminoglycosides (names)
gentamycin, neomycin, amikacin, tobramycin, streptomycin
- “Mean” (amino…) GNATS caNNOT kill anaerobes
aminoglycosides mechanism
bactericidal
- inhibit formation of initiation complex and cause misreading of mRNA
- also block translocation
- require O2 for uptake, therefore ineffective against anaerobes
aminoglycosides clinical use
severe GNR infections
- synergistic with beta lactams
- neomycin for bowel surgery
aminoglycosides toxicity
caNNOT kill anaerobes
- nephrotoxic, neuromuscular blockade, ototoxic, teratogen
aminoglycosides mechanism of resistance
- bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation
tetracyclines names and mechanism
- tetracycline, doxycycline, minocycline
- bacteriostatic, bind to 30s and prevent attachment of aminoacyl-tRNA
- limited CNS penetration
- doxy is fecally eliminated and can be used in patients with renal failure
- dont take with milk or antacids or iron because divalent cations prevent absorption
tetracyclines clinical use
- borrelia burgdorferi, M. pneumoniae
- ability to accumulate intracellularly makes it good against rickettsia and chlamydia
- also used to treat acne
tetracyclines tox and resistance
- tox: GI distress, discoloration of teeth and inhibition of bone growth in kids, photosensitivity
- contraindicated in preggos
- resistance: decreased uptake or increased efflux though plasmid-encoded transport pumps
macrolides mechanism and clinical use
- azithro, clarithro and erythromycin
- inhibit protein synthesis by blocking translocation: bind to the 23S rRNA of the 50S
- used in atypical pneumonia, STDs and g+ cocci
macrolides toxicity and resistance
- tox: MACRO – GI Motility issues, Arrhythmia (prolonged QT), acute Cholestatic hepatitis, Rash, eOsinophilia
- increases serum concentration of theophyllines, oral anticoagulants
- resistance: methylation of 23S rRNA-binding site preventing binding of the drug
chloramphenicol mechanism and clinical use
- blocks peptidyltransferase at 50S ribosomal subunit, bacteriostatic
- used in meningitis and RMSF
chloramphenicol tox and resistance
- tox: anemia, aplastic anemia, gray baby syndrome,
- resist: plasmid-encoded acetyltransferase inactivates the drug
clindamycin mechanism, clinical use and tox
blocks peptide transfer (translocation) at 50S
- anaerobic infection in asp pneumo, lung anscesses and oral infections
- also good for GAS
- treats anaerobes above the diaphragm, metronidazole treats below the diaphragm
- C diff, fever, diarrhea
sulfonamides mechanism and clinical use
- SMX, sulfisoxazole, sulfadiazine
- inhibits folate synthesis, PABA antimetabolites inhibit dihydropteroate synthase, bacteriostatic
- used for gram +, gram -ve, nocardia, chlamydia, UTI
sulfonamides tox and resistance
- HS reactions, hemolysis in G6PD, nephrotoxic, photosensitivity, kernicterus in infants, displace other drugs from albumin
- resist: altered enzyme, decreased uptake or increased PABA synthesis
trimethoprim mechanism and tox
- inhibits bacterial dihydrofolate reductase
- tox: megaloblastic anemia, leukopenia, granulocytopenia (may alleviate with supplemental folic acid)
trimethoprim clinical use
- used in combo with SMX, causing sequential block of folate synthesis
- UTI, shigella, salmonella, PCP and toxo prophylaxis
fluoroquinolones (-oxacins) mechanism and use
- inhibit DNA gyrase (topoisomerase II) and topo IV, bactericidal, must not be taken with antacids
- used in GNR infections of GI and urinary tracts, neisseria, some g+
fluoroquinolone tox and resist
- tox: GI upset, superinfections, skin rashes, headache, dizziness
- less commonly tendonitis, tendon rupture, leg cramps and myalgias
- no preggos, nursing mothers and kids < 18 due to cartilage damage
- may prolong QT
- resist: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps
metronidazole mechanism and tox
- forms free radical toxic metabolites in the bacterial cell that damage DNA
- bactericidal, antiprotozoal
- tox: disulfram-like reaction (flushing, tachy, hypotension) with alcohol, headache, metalic taste
metronidazole clinical use
GET GAP on the metro
- giardia, entamoeba, trichomonas, gardnerella vaginalis, anaerobes, h Pylori
MAC treatment
- azithro or clarithro + ethambutol, can add rifabutin or cipro
leprae treatment
long term treatment with dapsone and rifampin for TB form
add clofazimine for lepromatous form
HIV prophylaxis
< 200 - TMP/SMX for PCP
< 100 - TMP/SMX for PCP and toxo
< 50 - azithro for MAC
MRSA treatment
vanco, dapto, linezolid, tigecycline, ceftaroline
VRE treatment
linezolid and streptogramins
INH mechanism, use and tox
- decreased sythesis of mycolic acids, catalase needed to convert INH to active metabolite
- only solo prophylaxis for TB
- tox: INH Injures Neurons and Hepatocytes
- B6 can prevent neurotox
Rifamycins mech, use, tox
- inhibit DNA-dep RNA polymerase
- used for TB, delays resistance to dapsone for leprosy
- only indication for monotherapy is meningococcal prophylaxis
- can also be used for HiB prophylaxis in contacts
- tox: minor hepatotox and inc 450, orange body fluids (rifabutin> rifampin in HIV b/c less p450 stim)
pyrazinamide mech, use, tox
- uncertain mechanism, effective at acidic pH
- used for TB
- tox: hyperyuricemia, hepatotox
ethambutol mech, use, tox
- mech: decreased polymerization of mycobacterium cell wall by blocking arabinosyltransferase
- used in TB
- tox: optic neuropathy (R/G color blindness)
