3.1: Antibiotics

natural antibiotics

produced by living organisms, most toxic, least effective

synthetic antibiotics

created in a laboratory, most effective, least toxic

semi-synthetic antibiotics

natural antibiotics modified by biochemist

characteristics of an “ideal” chemotherapeutic agent

doesn’t induce drug allergy in host/patient, doesn’t induce drug resistance in target organism/pathogen, exhibits a high degree of selective toxicity (possesses a high therapeutic ratio

broad spectrum

less discrimination and targets a wide range of organisms

narrow spectrum

only targets a select group while leaving others unharmed

cell wall synthesis inhibitors

major means of bacterial control, highly favorable chemotherapeutic indices

B-lactam antibiotics

competitively bind to transpeptidase and prevents peptidoglycan crosslinking

Penicillin

beta lactam, G and V, targets primarily G+ organisms, susceptible to beta lactamase which is an enzyme that disrupts beta lactam

semi synthetic penicillin beta lactams

ends in “-cillin”

methicillin

primarily G+ organisms, increase resistance to beta lactamases

oxacillin

primarily G+ organisms, increase resistance to beta lactamases

cloxacillin

primarily G+ organisms, increase resistance to beta lactamases

dicloxacillin

primarily G+ organisms, increase resistance to beta lactamases

nafcillin

primarily G+ organisms, increase resistance to beta lactamases

amphicillin

broad (G-/G+), often combined with beta lactamase inhibitors

amoxicillin

broad (G-/G+), often combined with beta lactamase inhibitors

piperacillin

broad (G-/G+), often combined with beta lactamase inhibitors

augmentin/clavulin

combination of amoxicillin and calvulanate (beta lactamase inhibitor)

cephalosporin beta lactams

start with “cef-” or “ceph-”, generations 1-5, more resistant to beta lactamases, less likely to produce allergy than penicillin

monobactam beta lactam (aztreonma)

primarily aerobic G-, resistant to beta lactamase, can be nebulized to treat lung infections

carbapenem beta lactam

imipenem, meropenem

imipenem

broad (G-/G+), tend to be less susceptible to bacterial resistance mechanisms but can be toxic to host, typically reserved for drug-resistant pathogens

meropenem

broad (G-/G+), tend to be less susceptible to bacterial resistance mechanisms but can be toxic to host, typically reserved for drug-resistant pathogens

glycopeptides

vancomycin, dalbavancin, oritavancin

vancomycin

binds to the ala-ala of side chain, prevents formation of crosslinked interbridges and glycan backbone, G+ organisms, useful against MRSA, more toxic than other cell wall inhibitors

dalbavancin

binds to the ala-ala of side chain, prevents formation of crosslinked interbridges and glycan backbone, G+ organisms, useful against MRSA, more toxic than other cell wall inhibitors

oritavancin

binds to the ala-ala of side chain, prevents formation of crosslinked interbridges and glycan backbone, G+ organisms, useful against MRSA, more toxic than other cell wall inhibitors

bacitracin polypeptide

interferes with bactoprenol (prevents formation of cell wall), G+ organisms, common in topical antibiotic creams

isoniazid

acid fast organisms, interferes with synthesis of mycolic acid, cell wall synthesis inhibitor

ethambutol

acid fast organisms, interferes with synthesis of arabinogalactan, cell wall synthesis inhibitor

cycloserine

acid fast organisms, interferes with formation of peptidoglycan sidechain formation, cell wall synthesis inhibitor, can be useful against G+

Colistin

polymyxins, disrupts membrane and increases permeability to cause cell lysis, G- organisms, polymyxin E is considered “last resort” for multidrug resistant G- bacteria (has increased toxicity to host), polymyxin B is found in topical antibiotic creams

gramicidin

form pores in bacterial membrane, G+ organisms, often used in creams or eye drops

nisin

combines with Lipid II to form pores in membrane, broad spectrum, effective against endospores, often used as a food preservative

ionophores and bacteriocins

cell membrane inhibitors that form pores

pyrazinamide

diffuse into cells and converts to pyrazinoic acid to cause destructive physiological changes, acid fats organisms, cell membrane inhibitors

protein synthesis inhibitors

oxazolidinones, aminoglycosides, tetracyclines, macrolides, lincosamides, chloramphenicol, mupirocin, streptogramin

linezolid

protein synthesis inhibitor, synthetic peptide binds to 23S rRNA of 50S subunit and prevents initiation of ribosomal assembly, G+ organisms, substitute treatment for drug resistant S. aureus

tedizolid

protein synthesis inhibitor, synthetic peptide binds to 23S rRNA of 50S subunit and prevents initiation of ribosomal assembly, G+ organisms, substitute treatment for drug resistant S. aureus

oxazolidinones

linezolid, tedizolid

tetracyclines

“-cycline”, binds to 30S subunit and inhibits tRNA from entering A site, protein synthesis inhibitor, G-/G+/cell wall less, reduced usage due to wide spread resistance, used to treat sever acne, not recommended for pregnant/nursing individuals or children

macrolides

azithromycin, clarithromycin, erythromycin, natamycin, telithromycin, most prescribed class of antibiotics

azithromycin

binds reversible to 23S rRNA in P-site of 50S subunit and inhibits peptidyl transferase and translocation, protein synthesis inhibitor, G-/G+

clarithromycin

binds reversible to 23S rRNA in P-site of 50S subunit and inhibits peptidyl transferase and translocation, protein synthesis inhibitor, G-/G+

erythromycin

binds reversible to 23S rRNA in P-site of 50S subunit and inhibits peptidyl transferase and translocation, protein synthesis inhibitor, G-/G+

natamycin

binds reversible to 23S rRNA in P-site of 50S subunit and inhibits peptidyl transferase and translocation, protein synthesis inhibitor, G-/G+

telithromycin

binds reversible to 23S rRNA in P-site of 50S subunit and inhibits peptidyl transferase and translocation, protein synthesis inhibitor, G-/G+

lincosamides

clindamycin, bind to 23S of rRNA of 50S subunit and prevent translocation, protein synthesis inhibitor, G+ and anaerobic G-, increases risk of opportunistic Clostridioides difficile colitis

chloramphenicol

protein synthesis inhibitor, G-/G+, severe side effects, many drug interactions, rarely preferred IV/orally, used in eye drops

mupirocin

protein synthesis inhibitor, G+, topical antibiotic, used to treat MRSA

streptogramin

combination drug (dalfopristin, quinupristin), protein synthesis inhibitor, G-/G+, often effective at treating vancomycin resistant organisms, bactericidal when administered together

nucleic acid synthesis inhibitors

quinolones, nitroimidazoles, acid-fast drugs

quinolones

ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, nalidixic acid

ciprofloxacin

target DNA gyrase and topoisomerase IV, prevents DNA replication, nucleic acid inhibitor, G-/G+, many side effects, not given to pregnant/nursing/elderly/children

levofloxacin

target DNA gyrase and topoisomerase IV, prevents DNA replication, nucleic acid inhibitor, G-/G+, many side effects, not given to pregnant/nursing/elderly/children

moxifloxacin

target DNA gyrase and topoisomerase IV, prevents DNA replication, nucleic acid inhibitor, G-/G+, many side effects, not given to pregnant/nursing/elderly/children

ofloxacin

target DNA gyrase and topoisomerase IV, prevents DNA replication, nucleic acid inhibitor, G-/G+, many side effects, not given to pregnant/nursing/elderly/children

nalidixic acid

target DNA gyrase and topoisomerase IV, prevents DNA replication, nucleic acid inhibitor, G-/G+, many side effects, not given to pregnant/nursing/elderly/children

nitroimidazoles

“-nidazole”, produce ROS that damage DNA, nucleic acid inhibitor, anaerobic bacteria as well as some parasitic infections

acid fast nucleic acid synthesis inhibitors

clofazimine, rifamycin

clofazimine

bind to guanine to prevent replication and transcription, nucleic acid synthesis inhibitor, acid fast

rifamycin

bind to RNA polymerase to prevent transcription, nucleic acid synthesis inhibitor, acid fast but also some select G-/G+

metabolite inhibitors

antifolates (sulfonamides, trimethoprim), acid fast drugs

sulfonamides

“sulfa-”, competitively inhibit dihydropteroate synthetase, metabolite inhibitor, G-/G+, second generation enhance effectiveness of inhibition

trimethoprim

competitively inhibits dihydrofolate reductase, metabolite inhibitor, G-/G+, often given together with sulfonamides as co-trimoxazole to prevent mutation resistance

dapsone

competitively inhibits dihydropteroate synthetase, acid fast, metabolite inhibitor, anti-inflammatory properties

bedaquiline

blocks ATP synthase, metabolite inhibitor, acid fast, used to treat multi drug resistant tuberculosis (MDR TB)