Block 4

kills bacteria

stops active growth of bacteria but they remain viable - host defenses important to eliminate pathogens

minimal bactericidal concentration, kills 99.9% bacteria

minimal inhibitory (static) concentration

amount of time above MIC, best clinical effect whe 4-fold above MIC for >50% of total time

maximize peak concentration, C_max/MIC ratio greater than 8 is best

area under the curve

AUC₂₄/MIC greater than 125

• V: oral
• G: injection

• 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

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

• 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

• 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

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

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

beta-lactam analog, acts as suicide inhibitor (binds irreversibly to beta-lactamase)

beta-lactam analog that acts as suicide inhibitor (binds irreversibly to beta-lactamase)

• 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

• 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

• 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

• 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

• 3rd generation cephalosporin
• more active against gram-
• used for Klebsiella, Enterobacter, Proteus

• use: gonorrhea, empiric therapy for meningitis
• long T_1/2

• 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

• 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

• 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

• broad spectrum beta-lactam
• resistant to many beta-lactamases, including ESBLs (extended spectrum beta-lactamases)
• not effective against MRSA
• given with cilastatin (to extend T_1/2)

• 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

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

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

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

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

Mechanism: cationic detergents that disrupt the bacterial membranes

• Use: 
• topical for Pseudomonas and other gram(-) infections
• systemic use - causes potential serious nephrotoxicity & neurotoxicity

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

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

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 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

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

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

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

Mechanism: inhibitor of RNA polymerase, inhibits RNA synthesis, bactericidal

Use: C. difficile infection

Administration: oral, poorly absorbed

• SE:
• GI upset, GI bleeding

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

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

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

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

Tetracycline, bacteriostatic, least affinity for Ca²⁺

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

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

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

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

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

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

Mechanism: bind to 50S ribosomal subunit

Use: respiratory and genital infections

• SE: 
• fewer GI disturbances than erythromycin
• few drug interactions

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

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

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)

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)

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