An azole antifungal that decreases the synthesis of ergesterol by inhibiting fungal P450 enzymes

It is selective for fungal P450 

Has highest bioavailability and therapeutic index of all azoles

Oral or IV admin

Good CSF penetration

Water soluble

Renal excretion

Uses: cryptococcal meningitis (drug of choice), candidemia, mucocutaneous candidiasis, prophylaxis in high risk neutropenic patients and HIV/AIDS with recurrent oral or esophageal candidiasis

Adverse Effects: Stephens-Johnson syndrome

Drug Interactions: CYP2C9 inhibitor, increases serum concentrations of phenytoin, warfarin

An azole antifungal that decreases the synthesis of ergesterol by inhibiting fungal P450 enzymes

It is selective for fungal P450 

First azole 

Not used IV due to high level of P450 inhibition

Must monitor liver enzymes

Uses: topical for chronic mucocutaneous candidiasis, oral for dermatophytes

Adverse Effects: nausea, pruritis, risk of hepatitis, avoid in pts with previous hepatitis

A beta(1-3)glucan synthesis inhibitor

Inhibits gluca for cell wall maintenance

Water soluble

Well tolerated

IV admin

Uses: invasive aspergillosis in those not responsive to amphotericin B or voriconazole, candidemia

Monitor for liver toxicity

Do not co-admin with cyclosporine

Embrotoxic

A polygene anti-fungal that binds to ergosterol (non-selectively) to situates itself in the fungal membrane, creating pores

Ampipathic

Poorly absorbed, poor BBB penetration

Uses: systemic mycosis (IV) - has a very broad spectrum of action

Adverse Effects: slow excretion can lead to toxicity

Deoxycholate form: chills, fever, spasm, HA, vomiting, hypotension (toxicity limits use)

Lipid forms: can limit renal toxicity, but liver toxicity risk is worse

Long term toxicity: renal damage

Adverse effects are due to unwanted binding to cholesterol in host cells

A polygene anti-fungal that binds to ergosterol (non-selectively) to situates itself in the fungal membrane, creating pores

A Lanosterol Inhibitor that blocks the conversion of squalene to lanosterol in the ergosterol synthesis pathway. Squalene accumulates in fungi to toxic levels.

Keratophilic with fungal properties

Prevents fungi from attacking new nail AND attacks currently infected nail

Uses: dermatophytoses, esp onchymycosis (oral)

Adverse Effects: GI upset, HA

Generally well tolerated

Microtubule Inhibitor - inhibits microtubule assembly

Insoluble, oral administration

Microcrystalline deposited in newly growing keratin

Uses: dermatophytoses (onchyomycoses) - prevents infection in new nail growth

Takes 6-9 months for new nail growth

Adverse Effects: allergic syndrome, similar to serum sickness

Hepatitis, GI disturbances

Drug Interactions: warfarin, phenobarbital

Alternatives with less toxicity: Itraconazole, Terbinafine

DNA/RNA synthesis inhibitor

Antifungal that is taken up by cytosine permease and converted to 5-fluorouracil and anti-metabolites that block DNA, RNA synthesis

Oral, selective for fungi

Narrow spectrum, only used in combinations where syngery is seen

Uses: cryptococcus neoformans w/ amphotericin 

Chromoblastomycosis w/ itraconazole

Adverse Effects: serious toxicity - anemia, leukopenia, thrombocytopenia, esp in renal damage and AIDS patients

A beta-lactam that inhibits peptidoglycan transpeptidase by introducing an analog of

D-ala D-ala at the cross-linking step of cell wall synthesis

Activates endogenous autolytic enzyme murein hydrolase

Effects: inhibits cell wall synthesis, leads to bacterial cell lysis (due to unrestricted activity of murein hydrolase)

Uses: Gram + and anaerobes (narrow spectrum)

Adverse Effects: diarrhea, GI, thrombophlebitis, CNS tremors, convulsions, superinfection due to GI bacterial overgrowth (pseudomembranous colitis)

Hypersensitivity Rxns: immediate - anaphylactic, accelerated and delayed

Has a low direct toxicity due to specific bacterial target

Mechanism of Resistance:
Beta-lactamases, decreased permeability, alterations in transpeptidases

Resistance can be overcome by adding a Beta-lactamase inhibitor

Inactivated by gastric acid

Poor CNS penetration

Renal excretion (proximal tubule)

Liver metabolism

Half life: 30 min

Probenecid inhibits secretion and prolongs plasma levels

A beta-lactam that inhibits peptidoglycan transpeptidase by introducing an analog of

D-ala D-ala at the cross-linking step of cell wall synthesis

Activates endogenous autolytic enzyme murein hydrolase

Effects: inhibits cell wall synthesis, leads to bacterial cell lysis (due to unrestricted activity of murein hydrolase)

Uses: Gram + and anaerobes (narrow spectrum)

Same adverse effects as Penicillin G

Is not susceptible to Beta-lactamases 

Has variable GI absorption

Biliary excretion

An extended spectrum Beta-lactam (same mechanisms and effects of all Beta-lactams)

Uses: Gram + and Gram - 

Delayed hypersensitivity reaction is more common

Susceptible to same mechanisms of resistance as Penicillin G

Better absorbed with food

Biliary excretion

Amoxicillin + Clavulanic Acid 

(Augmentin)

Extended spectrum Beta-lactam antibiotic combined with a Beta-lactamase inhibitor to avoid resistance (this part of the drug has no intrinsic antibacterial resistance)

Biliary excretion

Penicillin with special anti-pseudomonal reactions

Uses: Pseudomonas

A first generation cephalosporin

Same mechanism and effects as penicillins

Has less susceptibility to Beta-lactamases

Uses: Gram +, esp for skin and soft tissue infections

Parenteral

Poor CNS penetration

Half life: 1/2 - 2 hours

Renal excretion

Probenecid delays tubular excretion

Preferred for surgery prophylaxis

Adverse Effects: thrombophlebitis, diarrhea, superinfection

Hypersensitivity: cross-reactions with other cephs and pens

Avoid use in patient with a history of anaphyllaxis

Mechanisms of Resistance: decreased uptake thru porins, super Beta-lactamases, and altered transpeptidases

Second generation cephalosporin that is particularly resistant to Beta-lactamases

Same mechanism and effects as penicillins

Uses: Gram + and some Gram - 

Good for PID or lung abscess (mixed aerobic and anaerobic)

Given IV 

Does not penetrate CNS well

Half life: 1/2 - 2 hours

Renal excretion

Probenecid delays tubular excretion

Adverse Effects: thrombophlebitis, diarrhea, superinfection

Hypersensitivity: cross-reactions with other cephs and pens

Avoid use in patient with a history of anaphyllaxis

Mechanisms of Resistance: decreased uptake thru porins, super Beta-lactamases, and altered transpeptidases

Third generation cephalosporin that is often used in combination with an aminoglycoside

Same mechanism and effects as penicillins

Uses: P. aeruginosa, gonorrhea, Lyme disease

Mechanism of Resistance: decreased uptake, super Beta-lactamases, and altered transpeptidases

Klebsiella and E. coli will elaborate super Beta-lactamases that hydrolyze the drug

Has better CNS penetration

Half life: 8 hour

Renal excretion

Probenecid delays tubular excretion

A carbapenem beta-lactam (drug combo) that is resistant to inactivation by Beta-lactamases

Same effects as beta-lactams

Not absorbed orally

Renal excretion

Uses: broadest activities of all antibiotics

Adverse Effects: cross allergy with other Beta-lactams, seizures in high doses or patients with CNS lesions or renal dysfunction, N/V

First drug is hydrolyzed by dehydropeptidase I 

Second inhibits dehyropeptidase I to prevent the breakdown of the first drug

A monobactam beta-lactam that is resistant to inactivation by Beta-lactamases

Same mechanisms and effects as pen and cephs

Uses: aerobic Gram - bacilli, enterobacteriacae, pseudomonas

Adverse Effects: hypersensitivity, thrombophlebitis

Little cross allergenicity with other pens and cephs

A glycopeptide that blocks peptidoglycan synthetase, an enzyme responsible for adding disaccharide units to the bacterial cell wall

Not a beta-lactam, but it still inhibits cell wall synthesis (at an earlier step)

Renal excretion

Given IV

Not removed by hemodialysis

Uses: Gram +, C. diff colitis (give orally!)

Adverse Effects: thrombophlebitis, chills, fever, ototoxicity in large doses

Flushing due to rapid infusion (histamine)

Mechanisms of Resistance: modification of peptide that is the main mechanism of action against the bacteria - affinity for vancomycin is vastly reduced

A macrolide lactone that binds to L-15 protein, promotes the dissociation of tRNA from ribosome and blocks translocation of tRNA from A to P site on the 50S subunit

Effects: inhibits translocation, premature release of peptides, slows growth of microorganisms (cytostatic - will not kill the bug, but will prevent growth)

Best absorbed when given as salt

Oral, parenteral, enteric coated

Biliary excretion

Half life: 1.5 hours

Will not reach CNS, but will reach fetus

Uses: Gram + cocci and bacilli

Adverse Effects: GI effects - N/V, diarrhea, anorexia, promotes peristalsis

Increased liver toxicity with estolate salt 

Acute cholestatic hepatitis (fever, jaundice)

Hypersensitivity: rash, fever, eosinophilia

Reversible hearing loss

Long QT and tachycardia

Drug Interactions: Inhibits P450 - warfarin, carbamazepine, cyclosporin, theophylline terfenadine, astemizole

Mechanisms of Resistance: enzyme methylation of 23S RNA disrupts drug binding (inducible and constitutive production),

Hydrolysis of the drug, and chromosomal mutation of 50S binding site

A macrolide lactone that binds to L-15 protein, promotes the dissociation of tRNA from ribosome and blocks translocation of tRNA from A to P site on the 50S subunit

Effects: inhibits translocation, premature release of peptides, slows growth of microorganisms (cytostatic - will not kill the bug, but will prevent growth)

Oral, more stable to acid

Liver metabolism

Active metabolite, renal excretion

Uses: alternative to penicillin for Gram + and Gram - 

More active against Myco avium

Adverse Effects: lower frequency of GI intolerance, reversible hearing loss, teratogenic

A macrolide lactone that binds to L-15 protein, promotes the dissociation of tRNA from ribosome and blocks translocation of tRNA from A to P site on the 50S subunit

Effects: inhibits translocation, premature release of peptides, slows growth of microorganisms (cytostatic - will not kill the bug, but will prevent growth)

Food decreases bioavailability

Antacids delay absorption

Does not inhibit P450

Penetrates tissues very well (not CNS)

Half life: 3 days

Shorter treatment duration

Resembles erithromycin in activity 

Binds to 50S subunit ribosome at the same site

Derived from lindomycin

Effects: inhibits protein synthesis by inhibiting translocation

Oral, parenteral 

No CNS penetration

Liver metabolism

Biliary and renal excretion

Half life: 2.5 hours

Uses: Gram + anaerobes, Gram - anaerobes

Adverse Effect: Pseudomembranous colitis (treat with oral vancomycin, oral metronidazole)

Diarrhea, N/V, skin rashes

Mechanism of Resistance: only constitutive methylase producing strains are resistant (will not induce methylase like erythromycin)

A macrolide that contains an NO2 group that is metabolized to radical reduction products that attack the bacterial DNA by forming covalent bonds

Kills bug under anaerobic conditions

Uses: anaerobes, C. diff colitis, yeast infections

Adverse Effects: Nausea, HA, dry mouth, metallic taste, dark red brown urine, CNS effects, vertigo, paresthesias, pancreatitis, ataxia, seizures, peripheral neuropathy

Drug Interactions: disulfiram like rxn with ethanol, P450 inhibition

Mechanisms of Resistance: bacteria reduces levels of nitroreductase (which activates the drug)

Well absorbed

CNS penetration

Liver metabolism, renal excretion

A cephalosporin that inhibits protein synthesis of the oxazolidine class

Binds to 23S RNA of 50S ribosome at a unique site

Effect: inhibits initiation steps of protein synthesis

Uses: vancomycin resistant infections (E. faecium, Staph, S. pneumo, skin infections due to MRSA)

This is an agent of last resort

Adverse Effects: N/V, diarrhea, HA, rash, reversible thrombocytopenia, leukopenia

Oral formulation contains phenylalanine (not appropriate for PKU)

Drug Interactions: MAO inhibitor - HTN in tyramine foods, pseudoephedrine, SSRIs

Mechanisms of Resistance: mutation of ribosomal binding site of 23S RNA (enterococci)

Rarely cross resistant with other protein synthesis inhibitor

Oral, parenteral

Liver metabolism

Renal excretion - do not need to adjust doses for renal dysfunction

A macrolide that is a cyclic lipopeptide membrane depolarizer

The bacteria will lose ions and cell death ensues

Cell death more rapid than with Vancomycin, Linezolid, and Streptogram (within hours)

Uses: vancomycin resistant MRSA, S. aureus, and Gram +, Skin infections

Adverse Effects: fever, HA, insomnia, injection site reactions 

High doses can cause CrP increase

Reversible muscle weakness, discomfort

Stop statins

In vitro resistance is rare

Must be given IV

Renal excretion unchanged

Half life: 9 hours

Anti-protozoal agent - a weak basic compound that selectively accumulates in acidic food vacuoles of intra-RBC form of the parasite

Effects: inhibits heme polymerase, disrupting heme conversion to hemozoin (only effective against erythrocytic forms)

Allows accumulation of heme moiety to inhibit the parasite proteases

Blocks parasite replication

Clinical cure - kills merozoites and some gameocytes

Uses: uncomplicated malaria - falciparum, vivax, and oval (with Primiquine)

Adverse Effects: pruritis, vomiting, HA, confusion, depigmentation of hair, dermatoses, myalgias

Mechanism of Resistance: impaired drug concentrating mechanism, decreased drug efflux

Oral or IM

Accumulation in spleen, liver, kidneys, lungs, and leukocytes

Anti-protozoal agent - a weak basic compound that selectively accumulates in acidic food vacuoles of intra-RBC form of the parasite

Effects: inhibits heme polymerase, disrupting heme conversion to hemozoin (only effective against erythrocytic forms)

Allows accumulation of heme moiety to inhibit the parasite proteases

Blocks parasite replication

Clinical cure - kills merozoites and some gameocytes

Uses: Chloroquine resistant uncomplicated vivax, falciparum (with Primiquine), and severe malaria

Adverse Effects: Cinchonism: tinnitus, HA, nausea, ab pain

Visual disturbances, hemolytic anemia, blood dyscrasias, photosensitivity, long QT syndrome

Oral or IV

Half life: 12 hours

Anti-protozoal agent - a weak basic compound that selectively accumulates in acidic food vacuoles of intra-RBC form of the parasite

Effects: inhibits heme polymerase, disrupting heme conversion to hemozoin (only effective against erythrocytic forms)

Allows accumulation of heme moiety to inhibit the parasite proteases

Blocks parasite replication

Clinical cure - kills merozoites and some gameocytes

Uses: chloroquine resistant uncomplicated vivax, falciparum (with Primiquine), severe malaria

Also useful for prophylaxis of Chloroquine resistant falciparum, vivax

Resistance is rapid (same resistance as Chloroquine)

Half life: 2-4 weeks

Adverse Effects: CNS effects, vertigo, lightheadedness, nightmares, GI disturbances, Confusion, Teratogenic

Contraindications: depression, anxiety, psychosis, schizophrenia, Beta blockers, Ca channel blockers

Anti-protozoal drug that acts on persisting exo-erythrocytic forms of malaria in the liver of unknown mechanism

Effects: kills hypnozoites in liver, kills falciparum gameocytes, and prevents relapse of malaria

Uses: malaria with chloroquine for radical cure of vivax, ovale 

Adverse Effects: hemolytic anemia and methemoglobinemia (in G6PD), neutropenia, GI disturbances

Oral admin

Renal excretion

Half life: 3-6 hours

Pyrimethamine-Sulfadoxine

(Fansidar)

Anti-protozoal drug that is a long acting sulfonamide that causes clinical cure of malaria by selectively inhibiting Plasmodium dihydrofolate reductase

Effects: inhibition of thymidilate, purines, and amino acids - parasite cannot replicate

Uses: falciparum (therapeutic and prophylactic)

Adverse Effects: blood dyscrasias, folic acid deficiency

Artemether-Lumefantrine

(Coartem)

Anti-protozoal drug that is an active metabolite that produces reactive oxygen species with iron

Effects: unsure, but inhibits formation of B-hematoin

Uses: chloroquine resistant falciparum

Adverse Effects: joint stiffness, insomnia (generally well tolerated)

Systemic ambecidial that binds to macromolecules

Causes cell death - acts on active trophozoites

Uses: active infections of amebiasis, esp if liver abscesses

Adverse Effects: GI upset, metallic taste, yeast infections in mouth, dark reddish brown urine, and disulfiram like reaction with EtOH

Metabolized by P450

Accumulates in patients with hepatic disease

A luminal ambecidial that is activated in intestinal mucosa - mechanism unknown

Will not have systemic effects on trophozoites

Uses: asymptomatic infections

Adverse Effects: flatulence, itchiness, dry mouth

90% of drug absorbed

10% that is not absorbed is the active form

Anti-protozoal that probably interferes with DNA and RNA synthesis - unknown mechanism

Uses: PCP (second line therapy)

Adverse Effects: renal dysfunction, toxic to pancreatic beta cells

Given aerosol or IM

Poor CNS penetration

Atovaquone

An anti-protozoal that inferferes with mitochondrial electron transfer in PC

Uses: PCP - second line therapy

Adverse Effects: rash

Take with food to increase absorption

Not metabolized

A bacteriocidal drug that inhibits cell wall mycolic acid synthesis via binding to InhA

Effects: penetrates macrophages, effective against intra and extracellular organisms

Uses: Tuberculosis

Adverse Effects: peripheral neuropathy, liver damage, glossitis, GI disturbances, allergic reactions, CNS effects

Mechanism of Resistance: InhA mutation, loss of catalase-peroxidase activity

Oral admin

Rapid/slow acetylators determines half life

Renal excretion

9 mo INH + Rif

If Rif resistant: 18-24 mo INH + Eth

If INH resistant: 12 mo Rif + Eth OR

12 mo Rif + Eth + PZA

Anything resistant to these treatments need to be treated for 24 months

Bactericidal drug that interacts with Beta-subunit of bacterial DNA and RNA polymerase

Effects: inhibits initiation of transcription

Uses: tuberculosis

Adverse Effects: hepatotoxicity, flu-like syndrome, orange-red feces, urine, saliva, and sweat

Mechanisms of Resistance: RNA polymerase mutation (decreased drug affinity), decreased cell permeability

Oral admin, biliary excretion

Enterohepatic cycling

Half life: 2-5 hours

Bactericidal drug with an unknown mechanism

Must be hydrolyzed to pyrazinoic acid by pyrazinamidase

Uses: Tuberculosis

Adverse Effects: liver damage, GI disturbances, exacerbates gout

Mechanisms of Resistance: loss of pyrazinamidase function

Bacteriostatic drug that inhibits cell wall synthesis

Enhances the actions of other lipophilic drugs like Rifampin

Uses: tuberculosis

Adverse Effects: optic neuritis, loss of green-red vision, allergic rxn

Mechanism of resistance is unknown, but it occurs frequently and rapidly is used alone

Anti-protozal that inhibits bacterial protein synthesis

Uses: TB

Adverse Effects: impaired vestibular function, impaired hearing, allergic rxn

Mechanism of Resistance: point mutation of ribosomal binding site

Give parenteral (IM) 
Half life: 3 hours

Renal excretion

Bactericidal drug that is similar to Rifampin

Inhibits initiation of transcription

Uses: prevention of disseminated MAC in HIV pts alone or in combination

Adverse Effects: GI effects, rash, discoloration or body fluids and skin

Oral admin

Half life: 4.5 hours

P450

PABA antagonist that inhibits folate biosynthesis (similar to sulfonamides)

Prevents growth of bacteria

Uses: leprosy - with other drugs, for 2 years

Adverse Effects: rash, hemolytic anemia (esp in G6PD), GI effects, liver damage, peripheral neuropathy

Oral admin

Renal excretion

Anti-mycobacterial drug that binds to DNA to inhibit DNA template function and production of cytotoxic oxygen radicals

Destruction of bacteria

Uses: leprosy

Adverse Effects: red discoloration of skin, urine, sputum, sweat, GI effects

Oral admin

Very lipid soluble

A broad spectrum bacteriostatic antibiotic that inhibits protein synthesis 

Enters cell via passive diffusion and active transport into bacteria

Bacteria accumulates the drug and it binds reversibly to 30S subunit of prokaryotic ribosome

Prevents addition of amino acids

Seldom a first line drug due to cross resistance
Taken orally, cannot be taken with food

Uses: Gram +, Gram - 
NOT on pseudomonas, proteus, staph, or candida

Adverse Effects: N/V, GI effets, Fanconi syndrome, superinfection due to proteus, pseudomonas, and staph growth

Photosensitivity, tooth discoloration, impair bone growth in developing fetus

Not recommended in kids < 8 or during pregnancy, breast feeding

Mechanism of Resistance: decreased influx and increased efflux, ribosome protection, enzymatic inactivation by the organism 

A broad spectrum tetracycline

Same mechanism, effects, uses, and adverse effects as tetracycline

Differences: oral admin and can be taken with food, increased lipid solublity, low renal clearance, longer half life, wider activity, liver metabolism

An aminoglycoside that is isolated from actinomycetes as natural products or semi-synthetic derivatives

Irreversible inhibition of protein synthesis

Enter cells via passive diffusion (porins) in an O2 dependent fashion

Increased uptake facilitated by cell wall inhibitors

Does not enter CNS or eyes

Once daily dosing

Binds to 30S subunit to disrupt initiation, misread mRNA, incorporation of incorrect amino acids

Exhibits concentration dependent killing

Uses: aerobic Gram - enteric bacteria 

Synergystic with Beta lactams, vancomycin for endocarditis by enterococci, streptococci, staphylococci, tuberculosis

Adverse effects: ototoxicity, nephrotoxicity, neuromuscular toxicity

Mechanism of Resistance: enzymatic inactivation, impaired uptake - porin gene mutation, mutation of ribosomal protein

Enterococci are resistant to aminoglycosides, pens and vancomycin

An aminoglycoside that is isolated from actinomycetes as natural products or semi-synthetic derivatives

Irreversible inhibition of protein synthesis

Enter cells via passive diffusion (porins) in an O2 dependent fashion

Binds to 30S subunit to disrupt initiation, misread mRNA, incorporation of incorrect amino acids

Exhibits concentration dependent killing

Uses: aerobic Gram - enteric bacteria 

Synergystic with Beta lactams, vancomycin for endocarditis by enterococci, streptococci, staphylococci, tuberculosis

Preoperative oral bowel sterilant

Adverse effects: ototoxicity, nephrotoxicity, neuromuscular toxicity

Binds to 50S subunit of ribosome to inhibit peptidyltransferase activity

Does not appreciably interact with eukaryotic 80S ribosomes

Uses: aerobic and anaerobic Gram + and Gram - 

Used as alternative to Beta-lactam abx for meningiococcal meningitis, bacterial conjunctivitis

Adverse Effects: bone marrow suppression, aplastic anemia, Gray Baby Syndrome

Drug Interactions: increased half life of Warfarin, Phenytoin, protease inhibitors

Can interfere with eukaryotic, mitochondrial ribosomes - can cause cell death

Rarely used in the US

Oral admin

Rapid penetration of CSF and CNS

Crosses placenta and breast milk

A sulfonamide drug that is structurally similar to PABA to inhibit dihydropteroate synthase to prevent folic acid utilization for bacterial nucleic acid synthesis