Antimicrobials Flashcards
Sub-classes of Beta-lactam antibiotics
Penicillins
Cephalosporins
Monobactams
Carbapenems
Beta-lactamase inhibitors
Clavulanic acid
Sulbactam
Tazobactam
NXL104
Penicillin mechanism of action
binds to penicillin binding proteins in bacterial cell wall - blacks transpeptidase crosslinking
Penicillin activity spectrum
Gram positives and syphillis
Penicillin toxicity
hypersensitivity rxns, hemolytic anemia
Penicillinase resistant penicillins
methicillin
nafcillin
dicloxacillin
Penicillinase resistant penicillin treats which orgs?
S. aureus
Penicillinase resistant penicillin toxicity
hypersensitivity,
methicillin: interstitial nephritis
Aminopenicillins
Ampicillin
Amoxacillin
Aminopenicillins mechanism of action
binds penicillin binding proteins (block transpeptidase activity), wider spectrum
Aminopenicillin use
select gram positive and negative bacteria, including: H. influenzae Listeria Proteus Salmonella Enterococci
Aminopenicillin toxicity
hypersensitivity
ampicillin rash
pseudomembranous colitis
Antipseudomonal drugs
Ticarcillin
Piperacillin
Cerbenicillin
Antipseudomonal mechanism of action
binds penicillin binding proteins (block transpeptidase activity), wider spectrum
Antipseudomonal use
Pseudomonas and gram neg rods
Antipseudomonal toxicitiy
hypersensitivity rxn
Bacteriostatic antibiotics
Erythromycin Clindamycin Sulfamethoxazole Trimethoprim Tetracycline Chloramphenicol
Bactericidal antibiotics
Vancomycin Fluoroquinolones Penicllin Amnioglycosides Cephalosporins Metronidazole
1st generation cephalosporins
narrow spectrum
Cefazolin
Cephalexin
Cefadroxil Cephaloridine Cephalothin Cephapirin Cephradine
1st generation cephalosporin coverage
Gram positive cocci
Proteus
E. coli
Klebsiella
Cephalosporin mechanism of action
beta lactams
inhibit cell wall synthesis
less susceptible to penicillinases
2nd generation cephalosporins
expanded spectrum
Cefoxitin
Cefaclor
Cefuroxime
Cefamandole Cefmetazole Cefonicid Cefotetan Cefprozil Loracarbef
2nd generation cephalosporin coverage
same as 1st gen. PLUS: H. influenzae Enterobacter Neisseria Serratia (inc. gram neg coverage)
3rd generation cephalosporins
borad spectrum
Ceftriaxone Ceftazidime Cefotaxime Cefdinir Cefditoren Cefpodoxime
Cefixime
Cefoperazone
Ceftibuten
Ceftizoxime
3rd generation cephalosporin coverage
serious gram neg. infections
Ceftriaxone: Neisseria
Ceftazidime: Pseudomonas
4th generation cephalosporins
Cefepime
Cefteroline
Cefpirome*
Ceftobiprole*
*not licensed for use in the US
cephalosporin toxicity
Hypersensitivity Vitamin K deficiency Cross-hypersensitivity w/ penicillins Nephrotoxicity of aminoglycosides rxn with alcohol
Monobactam
Aztreonam
Aztreonam mechanism
beta lactamase resistant monbactam
binds PBPs
Aztreonam use
Gram neg rods only
Aztreonam toxicity
occasional GI upset
Imipenem/Cilastatin mechanism
Beta lactamase resistant cerbapenem
Cilastatin is a renal dihydropeptidase 1 (to decrease renal inactivation)
Imipenem coverage
Broad spectrum
Gram positive cocci
Gram neg rods
Anerobes
Imipenem toxicity
GI distress
skin rash
CNS toxicity (seizures) at high levels
Vancomycin mechanism of action
Binds to terminal D-Ala D-Ala of peptide side chain of peptidoglycan to inhibit cell wall synthesis
Vancomycin coverage
Gram positives only reserved for resistant infections - S. aureus - Enterococci - C. diff
Vancomycin toxicity
(well tolerated in general)
Nephrotoxicity
Ototoxicity
Red man syndrome (hypersensitivity)
Mechanism of resistance to vancomycin
Bacteria changes terminal D-Ala D-Ala to D-Ala D-Lactate
30s ribosomal inhibitors
Tetracyclins
Aminoglycosides
50s ribosomal inhibitors
Clindamycin Chloramphenicol Erythromycin Linezolid Lincomycin
Aminoglycosides
Gentamicin Neomycin Amikacin Tobramycin Streptomycin
Mechanism of action of aminoglycosides
Bing to 30s ribosomal subunit to prevent protein synthesis
Requires O2 for uptakes
Aminoglycoside use
No anaerobe coverage
Severe gram neg. rod infections
Synergistic with Beta-lactams
Neomycin for bowel suregery
Aminoglycoside toxicity
Nephrotoxicity (esp. w/ cephalosporins)
Ototoxicity (esp. w/ loop diuretics (for hypertension))
Teratogen
Mechanisms of aminoglycoside resistnace
Inactivating enzymes - phosphorylation, adenylation, acetylation
Methylation of 16s ribosomal RNA - high resistance to all aminoglycs
Efflux pumps
Tetracyclin mechanism of action
Binds to 30s ribosomal RNA to block tRNA and inhibit protein synthesis
Tetracyclins (drugs)
Tetracyclin
Doxycyclin
Tigecyclin (similar struct)
Tetracyclin coverage
Most GPs and GNs, esp:
- Brucella
- B. bergdorferi
- Chlamydia (intracel. accumulation)
- H. pylori
- Rikettsia
Tetracyclin toxicicty
GI ditress
Teeth discoloration
Inhibited bone growth in children
Photosensitivity
Tetracyclin administration considerations
Absorption inhibited by milk/antacids/iron preps
Can be used in pts w/ kidney failure (b/c poor urine conc)
Mechanisms of resistance to tetracyclins
Ribosomal protection proteins
Efflux pumps
Reduced uptake
Macrolide drugs
Erythromycin
Azithromycin
Clarithromycin
Macrolide mechanism of action
Binds to 50s subunit of ribosome to inhibit translocation and protein synthesis
Macrolide uses
Atypical pneumonias from mycoplasma, chlamydia, legionella
URIs
STDs
Gram pos cocci (in pts allergice to penicillin)
Neisseria
Macrolide toxicity
(Generally very safe!) Prolonged QT GI discomfort Hypersensitivity Transient hearing loss Acute cholestatic hepatitis
Mechanism of resistance to macrolides
Methylation of the 50s ribosomal subunit (23s binding site) by the erm gene (for erythromycin)
Efflux pump encoded by the mef gene (low level resistance)
Chloramphenicol mechanism of action
Binds to 50s ribosomal subunit, blicks tRNA
Chloramphenicol use/coverage
Broad Crosses BBB well - Meningitis (esp low income countries): - H. flu - Neisseria - S. pneumo
Chloramphenicol toxocity
Dose-related bone marrow suppression (resolves)
Rare but irreversible aplastic anemia (why not available in US)
Clindamycin mechanism of action
Binds to 50s ribosomal subunit, inhibits RNA dependent protein synthesis (bacteriostatic)
Clindamycin coverage
Excellent for anerobes esp aspiration pneumonia and lung abcesses
Reduces toxin production (S. pyogenes and S. aureus)
Clindamycin toxicity
Pseudomembeanous colitis
Fever
Diarrhea
Sulfonamide mechanism of action
Competitively inhibits PABA incorporation into folic acid (used in purine synthesis)
Sulfonamide coverage
Broad spectrum Gram pos and Gram negs
Also opportunistic infection prophylaxis (in HIV pts)
Sulfonamide toxicity
Hypersensitivity, Serum sickness GI intolerance Hemolysis in pts w/ G6PD Nephrotoxicity Photosensitivity
Mechanism of resistance to sulfonamide
Decreased permeability
Decreased target enzyme affinity
Increased PBPA synthesis
Trimethoprim mechanism of action
Inhibits dihydrofolate reductase, potentiating sulfonamide activity
Trimethoprim coverage/use
used in combo with sulfamethoxazole for recurrent UTIs, Shigella, Salmonella, pneumocystis
Trimethoprim toxicity
Bone marrow suppression (leucopenia, agranulocytosis, thrombocytopenia)
Fluoroquinolone mechanism of action
Inhibits bacterial DNA gyrase (exhibits post-antibiotic effect, inc w/ longer exposure or higher dosage)
Sulfonamide drugs
Sulfamethoxazole
Sulfisoxazole
Sulfadiazine
1st generation fluoroquinolones
Naladixic acid
2nd generation fluoroquinolones
Norfloxacin
Ciprofloxacin
Ofloxacin
3rd generation fluoroquinolones
Levofloxacin
Moxifloxacin
4th generation fluoroquinolones
Trovafloxacin (withdrawn)
1st generation fluoroquinolone coverage
(Naladixic acid)
Good for gram negs. (not pseudomonas)
Indicated for uncomplicated UTIs
2nd generation fluoroquinolone coverage
Gram negs (inc Pseudomonas), some gram pos (not pneumo) Indicated for UTIS, STDs, skin/soft tissue infections
3rd generation fluoroquinolone coverage
Like 2nd generation, but expanded gram pos coverage (inc pneumo)
Indicated for COPD, comm. acq. pneumonia, sinusitis
(not for GC b/c of high resistance)
Fluoroquinolone toxicity
GI upset
