Vancomycin

Natural Product

Route:IV Administration (can be used orally for C. difficile)

Indication: Serious Gram + infections

Side Effects: infusion related anaphylaxis, rash, neprotoxicity, and ototoxicity.

MOA: Inhibits peptidoglycan synthesis (H Bonds to peptidoglycan pentapeptide)

Telavancin

Semisynthetic

Route: IV admin

Indication: treat skin and soft tissue infections, last resort treatment for nosocomial pneumonia caused by S. aureus.

Side Effects: None listed, same as Vancomycin?

MOA: Inhibits cell wall/cell membrane synthesis.

Bacitracin

Natural Product

Route: Frequently topical, oral (against drug resistant gram +), IM.

Side Effects: Nephrotoxicity

MOA: Binds to dolichol pyrophosphate (inhibits glycosyl transfer), inhibits peptidoglycan synthesis. 

*Selective because cell wall synthesis is extracellular*

Clindamycin  (Lincosamide)

Semisynthetic (modified lincomycin)

Route: IV or Oral

Indication: Serious Gram + Infection (strepto/pneumo/staphylococci)

MOA:Binds 50s Subunit-Inhibits bacterial protein synthesis

Side Effects: GI distress, Stevens-Johnson Syndrome, C. difficile associated diarrhea.

Linezolid (oxazolidinone)

Synthetic Product

Route:IV administration

Indication: MRSA, serious gram + infections.

MOA: Binds and prevents transpeptidation in protein synthesis.

Side Effects: Myelosuppression, optical neuropathy in long term (>28 day) use.

Tedizolid  Phosphate (oxazolidinone)

Synthetic Product

Route: IV

Indication: MRSA skin infections

MOA: Binds and blocks transpeptidation/protein synthesis

Side Effects: Optical Neuropathy

Quinupristin/Dalfopristin (streptogramins)

Natural Products

Route: IV - drugs are synergistic and used in combination (30:70 ratio)

Indication: Vancomycin resistant E. faecium, skin infections caused by methicillin suseptible S. aureus and S. pyogenes.

MOA: Quinupristin binds to "exit tunnel", Dalfopristin causes 180 degree flip of nucleotide, inhibit bacterial protein synthesis. Both components interact with each other and share contacts with a common nucleotide leading to synergism.

Side Effects: Adverse reactions at injection site (pain, swelling), C. diff diarrhea. Inhibits cytochrom P450 3A4 (possilbe drug interactions).

Retapamulin

Semisynthetic Product

Route: Topical

Indication: Impetigo caused by S. aureus & S. pyogenes

MOA: Bonds to 50s and blocks peptide bond formation.

Side Effects: Allergic reaction, irritation.

Mupirocin

Natural Product

Route: Topical (broad spectrum antibacterial agent)

Indication: skin infections caused by strepto/staphylococcus, and MRSA (in nasal cavity)

MOA: Inhibits bacterial aminoacyl tRNA synthetase 

Side Effects: None listed.

Fidaxomycin

Natural Product

Route: Oral (poorly absorbed >90% excreted in feces)

Indication: Selective bacteriocidal activity against C. diff

MOA: Inhibits C. diff RNA polymerase.

Side Effects: Minor, include GI effects.

Polymyxin B

Natural Product

Route: Parenteral (IV or IM) also topical in Neosporin.

Indication: Last resort antibiotic for multidrug-resistant Gram neg. bacterial infections. Urinary tract infections, meningitis, septicemia, pneumonia.

MOA: Binds to Lipid A component of LPS (lipopolysaccharide), disrupts outer and inner membrane layers.

Side Effects: Neurotoxicity, nephrotoxicity - caution coadministration with other nephrotoxic drugs.

Colistimethate Sodium (Colistin Prodrug)

Semisynthetic Product

Route: Parenteral (IV or IM)

Indication: Last resort for multidrug resistant gram neg. bacterial infections. Urinary tract infections, meningitis, septicemia, pneumonia.

MOA: Must be converted to Colistin (PME) for activity. Binds to Lipid A component of LPS in gram neg. bacteria, disruption of cell wall/membrane.

Side Effect: Neurotoxicity, nephrotoxicity - caution coadministration with other nephrotoxic drugs.

Nitrofurantoin

Synthetic Product

Route: Oral (q.i.d.)

Indication: Bacterial urinary tract infections. (gram neg.)

MOA: Bioreductive activation-creation of radical species superoxide and nitric oxide. 

Side Effects: Common-nausea, vomiting. Rare-pulmonary reactions, liver toxicity, possibly mutagenic/carcinogenic.

Metronidazole

Synthetic Product

Route: Oral

Indication: Trichonomiasis, giardiasis, amebiasis, anaerobic bacteria, C. diff colitis, and Helicobactor pylori.

MOA: Bioreductive activation, creation of radical reactive species nitric oxide and superoxide.

Side Effects: nausea, allergic rashes, CNS disturbances, discoloration of body fluids. Carcinogenic in rats.

Tinidazole

Synthetic Product

Route: Oral

Indication: trichonomiasis, giardiasis, amebiasis.MOA: MOA: Bioreductive activation, creation of radical reactive species nitric oxide and superoxide.

Side Effects: nausea, allergic rashes, CNS disturbances, discoloration of body fluids. Carcinogenic in rats.

Isoniazid

Synthetic Product

Route:Oral

Indication: Primary drug treatment for Tuberculosis

MOA: Prodrug, activated by catalase-peroxidase katG. Once activated, acylates NADH cofactor of protein InhA.

Side Effect: INH-Mediated hepatotoxicity, peripheral neuropathy due to Vitamin B6 deficiency. (Vit B6 structure similar to cofactor bound by INH) 

Pyrazinamide

Synthetic Product

Route: Oral (prodrug-converted to pyrazinoic acid)

Indication: First-line tuberculosis drug (more active against latent bacilli).

MOA: Poorly understood-may disrupt membrane potential and/or inhibition of translation rescue mechanism.

Side Effect: Hepatotoxicity 

Ethambutol

Semisynthetic Product

Route: Oral

Indication: Front-line Tuberculosis drug

MOA: Inhibits arabinose polymerization

Side Effect: Visual disturbances (track closely in children), hepatotoxicity, teratogenic at high doses in mice (don't use with pregnant women).

Rifampin

Semisynthetic Product

Route: Oral

Indication: First-line Tuberculosis drug (reserved for TB combination chemotherapy due to rapid development of resistance.)

MOA: Inhibits prokaryotic RNA polymerase.

Side Effect: Cytochrom P450 inducer-possible drug interaction (lower serum levels of P450 substrates).

GI difficulties, elevation of liver enzymes, reversible thrombocytopenia.

Rifapentine

Semisynthetic Product

Route: Oral

Indication: First-line tuberculosis drug (reserved for combination chemotherapy due to rapid resistance development)

MOA: Inhibits prokaryotic RNA polymerase.

Side Effect: Cytochrom P450 inducer-possible drug interaction (lower serum levels of P450 substrates).

GI difficulties, elevation of liver enzymes, reversible thrombocytopenia.

Bedaquiline

Second Line Tuberculosis Drug

Capreomycin

Second Line Tuberculosis Drug

Cycloserine

Second Line Tuberculosis Drug

Ethionamide

Second Line Tuberculosis Drug

Levofloxacin

Second Line Tuberculosis Drug

Moxifloxacin

Second Line Tuberculosis Drug

Para-aminosalicylic Acid (PAS)

Second Line Tuberculosis Drug

Streptomycin

Second Line Tuberculosis Drug

Amphotericin B

Natural Product

Route: IV

Indication: Fungizone(AmB+Deoxycholate): Life-Threatening fungal infections.  AmBisome: visceral leishmaniasis. 

MOA: Binds ergosterol, forms pore in membrane.

Side Effect: Severe Nephrotoxicity, fever, low BP, chills, shaking.

Nystatin

Natural Product

Route: Topical

Indication: fungal infections of skin, mouth, GI tract.

MOA: Not mentioned

Side Effect: Not Mentioned

Miconazole

Synthetic Product 

Route: Topical

Indication: Ringworm, athlete's foot, oral/vaginal thrush.

MOA: Fungal 14-alpha demethylase (CYP51) inhibitor.

Side Effect: Inhibition of CYP450 (drug interaction), Hepatotoxicity. P-Glycoprotein inhibitor. 

Fluconazole

Synthetic Product

Route: Oral, IV

Indication: Cadidiasis, cryptococcal meningitis.

MOA: Fungal 14-alpha demethylase (CYP51) inhibitor.

Side Effect: Hepatotoxicity, weak CYP4503A4 inhibitor, strong CYP2C9 inhibitor (drug interaction), weak p-glycoprotein inhibitor.

Posaconazole

Synthetic Product

Route:Oral, IV

Indication: prophylaxis of Candida and Aspergillus.

MOA: Fungal 14-alpha demethylase (CYP51) inhibitor.

Side Effect: Hepatotoxicity, fewer P4503A4 interactions, p-glycoprotein inhibitor

Echinocandins (Caspofungin, Anidulafungin, Micafungin)

Natural/Semisynthetic Products

Route: IV

Indication: Candida and Aspergillus infections.

MOA: Beta(1,3)-glucan synthase inhibitor (cell wall synthesis inhibition).

Side Effect: Poor sustrates for CYP450, and p-glycoprotein (improvement over azole, AmB), infusion related swelling and rash, caution use during pregnancy.

Flucytosine

Synthetic Product

Route:Oral

Indication: systemic fungal infections of Candida and Cryptococcus (meningitis).

MOA: Inhibition of DNA and protein synthesis. (coverted to 5-FU within fungal cells)

Side Effect: Drug accumulation in patients with impaired renal function, bone marrow depression, hepatotoxicity, cardiotoxicity, teratogenic in rats.

Tavaborole

Synthetic Product

Route: Topical

Indication: toenail fungus caused by Trichophyton rubrum, and Trichophyton mentagrophytes.

MOA: Inhibits fungal leucyl-tRNA synthetase

Side Effect: Inflammation of the skin, redness, and ingrown toenail.

Terbinafine

Route: Oral, Topical

Indication: Fungal infections of the skin and nails.

MOA: Inhibitor of squalene epoxidase (inhibition of ergosterol creation).

Side Effect: Hepatotoxicity and hematologic effects.

Chloroquine

Semisynthetic

Route: Oral

Indication: Active against erythrocyte stage malaria

MOA: Inhibits hemozoin production

Side Effect: Retinopathy in long term use, caution because drug concentrates in liver.

Quinine

Natural Product

Route: Oral, Parenteral

Indication:Malaria

MOA: Inhibition of Hemozoin creation.

Side Effect:Heomlysis, kidney damage, tinnitus, cardiotoxicity, vision problems (cinchonism) CYP450 3A4 substrate (possible drug interaction)

Mefloquine

Semisynthetic

Route: Oral 

Indication: Malaria, taken for prophylaxis once a week

MOA: Inhibition of Hemozoin production

Side Effect: Neurological (vivid dreams), psychiatric reactions (suicidal ideation), GI disturbance, cardiotoxicity.

Lumefantrine

Semisynthetic

Route: Oral (used in combination with artemether, called Coartem)

Indication: Acute malaria

MOA: Inhibits creation of Hemozoin

Side Effect: Cardiotoxicity

Primaquine

Semisynthetic

Route: Oral

Indication: Malaria (active against liver stage, including latent hepatic form)

MOA: Creation of reactive oxygen species

Side Effect: Hemolytic Anemia(Glucose-6-Phosphate Dehydrogenase deficiency), Reactive oxygen species 

Pyrimethamine/Sulfadoxine (Fansidar)

Semisynthetic Product

Route: Oral

Indication: Active against erythrocyte stage malaria

MOA: Dehydrofolate Reductase Inhibitor

Side Effect: Severe allergic reactions, hematologic disturbances, teratogenicity. 

Atovaquone/Proguianil 

Semisynthetic

Route: Oral

Indication: malaria prophylaxis

MOA:Inhibits electron transport, inhibits dihydrofolate reductase.

Side Effect:abdominal pain, vomiting, and headache.

Doxycycline

Semisynthetic

Route:Oral

Indication: short term prophylaxis of malaria, adjunct in malaria treatment.

MOA: not elucidated, may inhibit protein synthesis

Side Effect: GI disturbances, effects on bone & tooth development, and photosensitivity

Artemether

Semisynthetic

Route: Oral (used with Lumefantrine as Coartem)

Indication: Malaria treatment, erythrocyte stage

MOA: Iron in heme activates peroxide, adds to porphorin ring.

Side Effect:Drug Interaction (CYP4503A4 substrate), headache, GI distress.

Artemisinin

Natural Product

Route: Oral

Indication: Erythrocyte Stage malaria

MOA: Iron in heme activates peroxide, adds to porphorin ring.

Side Effect:None listed, likely same as artemether.