-
Bactericidal
kills bacteria
-
Bacteriostatic
stops active growth of bacteria but they remain viable - host defenses important to eliminate pathogens
-
MBC
minimal bactericidal concentration, kills 99.9% bacteria
-
MIC
minimal inhibitory (static) concentration
-
Time-dependent killing
amount of time above MIC, best clinical effect whe 4-fold above MIC for >50% of total time
-
Concentration-dependent killing
maximize peak concentration, Cmax/MIC ratio greater than 8 is best
-
Killing dependent on concetration X time
area under the curve
AUC24/MIC greater than 125
-
Penicillin G & V
- Use: gram-pos.
- anaerobes
- non-beta lactamase producing
- strep throat
- limited gram-neg.
- syphilis
- Mechanism:
- inhibit transpeptidases (penicillin-binding proteins) which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxn
- anaphylaxis
- rash, fever
- diarrhea, enterocolitis
- increased liver enzymes
- hemolytic anemia
- seizures
-
Oxacillin
Use: beta-lactamase producing staph (MSSA)
- Mechanism: inhibit transpeptidases (penicillin-binding proteins) which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxn
- anaphylaxis
- rash, fever
- diarrhea, enterocolitis
- increased liver enzymes
- hemolytic anemia
- seizures
-
Ampicillin
- Use:
- gram +
- expanded gram -
- meningitis
- GI infections
- Mechanism:
- inhibit transpeptidases (penicillin-binding proteins) which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxn
- anaphylaxis
- rash, fever
- diarrhea, entercolitis
- increased liver enzymes
- hemolytic anemia
- seizures
-
Amoxicillin
- Use:
- gram +
- expanded gram -
- otitis media
- Mechanism:
- inhibit transpeptidases (penicillin-binding proteins) which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxn
- anaphylaxis
- rash, fever
- diarrhea, enterocolitis
- increased liver enzymes
- hemolytic anemia
- seizures
-
Ticarcillin
Use: extended gram(-) spectrum
- Mechanism:
- inhibit transpeptidases (PBPs) which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxn
- anaphylaxis
- rash, fever
- diarrhea, enterocolitis
- increased liver enzymes
- hemolytic anemia
- seizures
-
Piperacillin
Use: extended gram(-) spectrum
- Mechanism:
- inhibit transpeptidases (PBPs) which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxn
- anaphylaxis
- rash, fever
- diarrhea, enterocolitis
- increased liver enzymes
- hemolytic anemia
- seizures
-
Clavulanic Acid
beta-lactam analog, acts as suicide inhibitor (binds irreversibly to beta-lactamase)
-
Sulbactam
beta-lactam analog that acts as suicide inhibitor (binds irreversibly to beta-lactamase)
-
Cefazolin
- 1st generation cephalosporin
- best gram + activity of cephalosporins
- some use for some gram (-)
- IV/IM
- uncomplicated skin infections
- surgical prophylaxis (skin flora)
- not for meningitis
- Mechanism:
- inhibit transpeptidases (PBPs) which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxns
- nausea, vomiting, diarrhea, enterocolitis
- hepatocellular damage
-
Cephalexin
- 1st generation cephalosporin
- gram+
- some use for some gram(-)
- oral
- uncomlicated skin infections
- surgical prophylaxis (skin flora)
- not for meningitis
- Mechanism:
- inhibit transpeptidases (PBPs) which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxn
- nausea, vomiting, diarrhea, enterocolitis
- hepatocellular damage
-
Cefuroxime
- 2nd generation cephalosporin
- increased gram(-) activity
- less active against some gram-pos
only 2nd generation to penetrate CSF
- Mechanism:
- inhibit transpeptidases (PBPs) which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxn
- nausea, vomiting, diarrhea, enterocolitis
- hepatocellular damage
-
Cefotetan
- 2nd generation cephalosporin
- increased gram(-) activity
- less active against some gram+
- also good for anaerobes
- Mechanism:
- inhibit transpeptidases (PBPs) which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxn
- nausea, vomiting, diarrhea, eneterocolitis
- hepatocellular damage
-
Ceftriaxone
- 3rd generation cephalosporin
- more active against gram-
- used for Klebsiella, Enterobacter, Proteus
- use: gonorrhea, empiric therapy for meningitis
- long T1/2
- Mechanism:
- inhibit transpeptidases (PBPs) which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxn
- nausea, vomiting, diarrhea, enterocolitis
- hepatocellular damage
-
Ceftazidime
- 3rd generation cephalosporin
- more active against gram-
- used for Klebsiella, Enterobacter, Proteus
use: effective against many strains of Ps. aeruginosa, short T1/2, poorest 3rd gen. for gram+
- Mechanism:
- inhibit transpeptidases (PBD)s which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxn
- nausea, vomiting, diarrhea, enterocolitis
- hepatocellular damage
-
Cefepime
- 4th generation cephalosporin
- similar to ceftazidime, except more resistant to type I beta-lactamases
use:broad gram(-), empircal tx of serious inpatient infections
- Mechanism:
- inhibit transpeptidases (PBPs) which catalyze cell wall crosslinks
- murein hydrolases
- analog of D-Ala-D-Ala linkage
- SE:
- allergic rxn
- nausea, vomiting, diarrhea, enterocolitis
- hepatocellular damage
-
Imipenem
- broad spectrum beta-lactam
- resistant to many beta-lactamases, including ESBLs (extended spectrum beta-lactamases)
- not effective against MRSA
- given with cilastatin (to extend T1/2)
- use:
- mixed or ill-defined infection, those not responsive to resistant to other drugs
- SE:
- hypersensitivity; some cross-allergies with penicillins/cephalosporins
- seizures, dizziness, confusion
- nausea, vomiting, diarrhea, pseudomembranous colitis; superinfection
-
Aztreonam
beta-lactam, used against gram-neg aerobic rods
not useful against gram+ & anaerobes, not indicated for meningitis
resistant to many beta-lactamases
can be used in those w/ known hypersensitivities to penicillins
- SE:
- seizures
- cramps, nausea, vomiting, enterocolitis
- anaphylaxis, transient EKG changes
-
Vancomycin
not beta-lactam
- mechanism:
- bactericidal
- inhibits cell wall synthesis: binds to free carboxyl end (D-Ala-D-Ala) of the pentapeptide; interferes with transpeptidation (crosslinking) and transglycosylation (elongation of the peptidoglycan chains)
- use:
- gram+ only
- MRSA
- C. difficile enterocolitis (2nd choice)
- administration:
- IV for systemic infections
- oral for C. difficile enterocolitis
- SE:
- red man/red neck syndrome
- nephrotoxicity
- phlebitis
- ototoxicity
-
Fosfomycin
Mechanism: inhibits peptidoglycan synthesis by inactivating enolpyruvyl transferase, an early-stage cell wall synthesis enzyme
Use: uncomplicated UTIs caused by E. Coli, Enterococcus
SE: headache, diarrhea, nausea, vaginitis
-
Bacitracin
not a beta-lactam
mechanism: interferes with cell wall synthesis by interfering with carrier that moves early wall components through the cell membrane
Use: topical only, gram+
SE: allergic dermatitis
-
Polymyxin B
Mechanism: cationic detergents that disrupt the bacterial membranes
- Use:
- topical for Pseudomonas and other gram(-) infections
- systemic use - causes potential serious nephrotoxicity & neurotoxicity
-
Daptomycin
Mechanism: binds bacterial membranes, causing rapid membrane depolarization
- Use:
- uncomplicated skin and skin structure infections
- MSSA, MRSA
- Streptococcus
- Enterococcus
- Bactermia
- Not pneumonia
- SE:
- nausea, diarrhea, GI flora alterations
- muscle pai and weakness
-
Norfloxacin
Fluorinated quinolone, well distributed, oral administration
Mechanism: inhibits DNA gyrase, interfering with control of bacterial DNA supercoiling; bactericidal; killing dependent on AUC 24hr/MIC (area under curve)
Resistance: altered DNA gyrase, decreased permeability
Use: urinary tract infection
- SE:
- nausea, vomiting, abdominal pain, enterocolitis
- dizziness, headache, restlessness, depression
- seizures
- peripheral neuropathy
- arthropathy, tendon rupture
- rashes
- EKG irregularities
CI: seizure disorder, pregnancy, children
-
Ciprofloxacin
Fluorinated quinolone, well distributed, oral administration
- mechanism: inhibits DNA gyrase, interfering with control of bacterial DNA supercoiling; bactericidal; killing dependent on AUC24hr/MIC (area under curve)
- Resistance: altered DNA gyrase, decreased permeability
- Use:
- urinary tract infections
- infectious diarrhea
- skin infections
- bone and joint infections
- anthrax
- SE:
- nausea, vomiting, abdominal pain, enterocolitis
- dizziness, headache, restlessness, depression
- seizures
- peripheral neuropathy
- arthropathy, tendon rupture
- rashes
- EKG irregularities
CI: seizure disorder, pregnancy, children
-
Moxifloxacin
Fluorinated quinolone, well distributed, oral administration
mechanism: inhibits DNA gyrase, interfering with control of bacterial DNA supercoiling; bactericidal; killing dependent on AUC 24hr/MIC (area under curve)
Resistance: altered DNA gyrase, decreased permeability
- Use:
- better gram+ activity than many quinolones
- respiratory infections, NOT strep throat
- community acquired pneumonia, bacterial bronchitis
- SE:
- nausea, vomiting, abdominal pain, enterocolitis
- dizziness, headache, restlessness, depression
- seizures
- peripheral neuropathy
- arthropathy, tendon rupture
- rashes
- EKG irregularities
CI: seizure disorder, pregnancy, children
-
Nitrofurantoin
Mechanism: nitroreductase enzyme converts drug to reactive compound (incl. free radicals) which can damage DNA
Use: urinary tract infections
- SE:
- nausea, vomiting, diarrhea
- peripheral neuropathy
- pulmonary rxns (fibrosis)
- liver damage
- granulocytopenia, leukopenia, megaloblastic anemia
- acute hemolytic anemia
-
Rifampin
Mechanism: inhibits bacterial RNA synthesis by binding RNA polymerase B
Use: pulmonary tuberculosis, prophylaxis meningococcal meningitis, prophylaxis of Haemophilus influenza type b meningitis
- SE:
- serious hepatoxicity
- CYP inducer (inactivates other drugs)
- Orange color to urine, saliva, sweat, tears
-
Fidaxomicin
Mechanism: inhibitor of RNA polymerase, inhibits RNA synthesis, bactericidal
Use: C. difficile infection
Administration: oral, poorly absorbed
-
Metronidazole
Mechanism: anaerobes reduce nitro group, resulting product disrupts DNA
USE: anaerobes, C. difficile enterocolitis, combination therapy for H. pylori, Gardnerella vaginalis
- SE:
- nausea, vomiting, anorexia, diarrhea
- transiet leukopenia, neutropenia
- thrombophlebitis after IV infusion
- bacterial and fungal superinfections
-
Gentamicin
aminoglycoside, bactericidal, glomerular filtration, IV/IM
- Mechanism:
- transported into cell by an energy-requiring aerobic process, binds to several ribosomal sites, stops initiaion, causes mRNA misreading
- post-antibiotic effect
- concentration-dependent killing
Resistance: enzymatic modification of the aminoglycosides
- Use:
- most effective against gram(-) (gram- aerobic bacilli)
- ineffective against anaerobes
- use restricted to serious infections
- streptomycin
- SE:
- nephrotoxicity
- ototoxicity
- neuromuscular blockade
-
Tobramycin
aminoglycoside, bactericidal, glomerular filtration, IV/IM
- Mechanism:
- transported into cell by an energy-requiring aerobic process, binds to several ribosomal sites, stops initiation, causes mRNA misreading
- post-antibiotic effect
- concentration-dependent killing
Resistance: enzymatic modification of the aminoglycosides
- Use:
- most effective against gram (-) (gram- aerobic bacilli)
- ineffective against anaerobes
- use restricted to serious infections
- streptomycin
- covers those resistant to gentamicin
- SE:
- nephrotoxicity
- ototoxicity
- neuromuscular blockade
-
Amikacin
aminoglycoside, bactericidal, glomerular filtration, IV/IM
- Mechanism:
- transported into cell by an energy-requiring aerobic process, binds to several ribosomal sites, stops initiation, causes mRNA misreading
- post-antibiotic effect
- concentration-dependent killing
Resistance: enzymatic modification of the aminoglycosides
- Use:
- most effective against gram (-) (gram- aerobic bacilli)
- ineffective against anaerobes
- use restricted to serious infections
- streptomycin
- covers those resistant to gentamicin & tobramycin
- SE:
- nephrotoxicity
- ototoxicity
- neuromuscular blockade
-
Doxycycline
Tetracycline, bacteriostatic, least affinity for Ca 2+
Mechanism: transported into cells, binds to 30S ribosomal subunits; prevent attachment of aminoacyl-tRNA to the acceptor site
Resistance: increased transport of the drugs out of the bacterial cells, resistance to one tetracycline often implies resistance to them all
- Use: were once broad spectrum
- preferred agents for unusual organisms: rickettsia, chlamydia, etc.
- SE:
- GI disturbances
- Candida superinfection in colon
- photosensitization with rash
- teeth discolorization
- Administration:
- oral
- food and milk decrease absorption
-
Minocycline
Tetracycline, bacteriostatic
Mechanism: transported into cells, binds to 30S ribosomal subunits; prevent attachment of aminoacyl-tRNA to the acceptor site
Resistance: increased transport of the drugs out of the bacterial cells, resistance to one tetracycline often implies resistance to them all
- Use: were once broad spectrum
- preferred agents for unusual organisms: rickettsia, chlamydia, etc.
- SE:
- GI disturbances
- Candida superinfection in colon
- photosensitization with rash
- teeth discolorization
- Administration:
- oral
- food & milk decrease absorption
-
Tigecycline
Mechanism: binds 30S ribosomal subunit and blocks aminoacyl-tRNA entry, also binds additional unique sites in the ribosomes
- Use:
- skin/skin structure infections
- complicated intraabdominal infections
- community acquired pneumonia
- E, Coli, Citrobacter, Klebsiella, Enterobacter, NOT Pseudomonas
- Enterococcus faecalis
- MSSA, MRSA
- Bacteroides
- Clostridium perfringens
- S. pneumoniae, Haemophilus
- SE:
- nausea, vomiting
- caclium binding
- increased risk of death
-
Chloramphenicol
Mechanism: binds 50S ribosomal subunit, interferes with binding of aminoacyl-tRNA, inhibits peptide bond formation
Resistance: acetylated by chloramphenicol acetyltransferase
- Use:
- broad spectrum of activity (but SE limit)
- alternate agent for meningitis
- brain abscesses
- severe Salmonella
- secondary agents for ricketssial diseases, brucellosis
- SE:
- bone marrow depression, can progress to fatal aplastic anemia
- Grey baby syndrome
- optic neuritis and blindness
-
Erythromycin
Mechanism: binds 50S ribosomal subunit, blocks translocation step
Resistance: plasmid-mediated methylation of 23S rRNA of 50S subunit
Use: primarily against gram+, also effective against typical bugs
- SE:
- nausea/vomiting
- inhibits CYP3A4
- increases risk of arrhythmias and cardiac arrest
-
Clarithromycin
Mechanism: Bind to 50S ribosomal subunit
- Use:
- alternatives to erythromycin
- pharyngitis, respiratory infections, soft tissue infections, sinusitis
- H. pylori
- atypical myobacterial infections in AIDS patients
-
Azithromycin
Mechanism: bind to 50S ribosomal subunit
Use: respiratory and genital infections
- SE:
- fewer GI disturbances than erythromycin
- few drug interactions
-
Clindamycin
Mechanism: binds to 50S ribosomal subunit, blocks translocation step
Resistance: plasmid-mediated methylation of 23S rRNA of 50S subunit
Use: most gram+ cocci and many anaerobes incl. Bacteroides fragilis; not for MRSA
- SE:
- serious antibiotic associated enterocolitis
- GI irritation diarrhea
- hepatotoxicity
-
Linezolid
Mechanism: interferes with translation: binds 50S ribosomal subunit, interfering with formation of 70S initiation complex; bacteriostatic
- Use:
- VRE: vancomycin-resistant Enterococcus faecium
- MRSA and MSSA
- Streptococcus
- Streptococcus pneumoniae
- SE:
- non-selective MAOI (avoid tyramine)
- diarrhea, headache, nausea/vomit, superinfection, enterocolitis
- bone marrow supression
-
Sulfamethoxazole
Mechanism: inhibit folate synthesis by inhibiting dihydropteroate synthase
Resistance: reduced uptake of drug, mutation in dihydropteroate synthase
- Use:
- given with trimethoprim
- urinary tract infections
- bacillary dysentery
- typhoid fever
- SE:
- hypersensitivity
- rashes, serum sickness
- GI disturbances
- renal damage from crystalluria
- potentiate action of other drugs (CYP2C( inhibitor)
-
Silver Sulfadiazine
Mechanism: inhibit folate synthesis by inhibiting dihydropteroate synthase
Resistance: reduced uptake of drug, mutation in dihydropteroate synthase
- Use:
- urinary tract infections
- bacillary dysentery
- typhoid fever
- topically in burns
- SE: hypersensitivity
- rashes, serum sickness
- GI disturbances
- renal damage from crystalluria
- potentiate action of other drugs (inhibit CYP2C9)
-
Trimethoprim
Mechanism: inhibit folate synthesis by competitively inhibiting dihydrofolate reductase
Resistance: mutated dihydrofolate reductase, decreased permeability
- Use: most often in conjunction with sulfamethoxazole (TMP/SMX)
- urinary infections
- upper respiratory tract and ear infections
- Pneumocystis jiroveci, Salmonella, Shigella
- SE:
- nausea, vomiting, diarrhea, rashes
- eosinophilia, neutropenia, bone marrow supression
|
|