Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno Miroslav Votava AN OVERVIEW OF ANTIMICROBIAL AGENTS – II The 15th (the last) lecture for the 2nd-year students May 25th, 2015 ANTIMICROBIAL AGENTS – revision •= drugs used to treat infectious diseases •antibiotics – naturally occuring microbial products •chemotherapeutics – synthetic compounds • •Different types of antimicrobial agents: • ANTIBACTERIAL • ANTIFUNGAL • ANTIVIRAL • ANTIPARASITIC ANTIBACTERIAL AGENTS – revision • •1) Inhibitors of cell wall synthesis •2) Inhibitors of protein synthesis •3) Inhibitors of nucleic acid synthesis •4) Miscelanous agents 1. Inhibitors of bacterial cell wall synthesis – revision •β-lactam agents • penicillins • cephalosporins • monobactams • carbapenems •Glycopeptides • vancomycin • teicoplanin •Other inhibitors of bacterial cell wall • e.g. bacitracin • cycloserin • isoniazid • Penicillins – revision •Acidolabile: • benzylpenicillin (penicillin G) • procaine penicillin •Acidostable: • phenoxymethylpenicillin (penicillin V) •Resistant to penicillinase: • methicillin, oxacillin, flucloxacillin •Aminopenicillins: • ampicillin, amoxicillin, co-amp., co-amox. •Ureidopenicillins & carboxypenicillins: • co-piperacillin, co-ticarcillin Acidolabile penicillins – revision •Classical benzylpenicillin (penicillin G): • crystallic penicillin G – i.v. • procaine penicillin G – i.m. • benzathin penicillin G – i.m. •Spectrum: G+ cocci & rods, G- cocci, • G- spirals • •Acidostable penicillins – revision • •phenoxymethylpenicillin (penicillin V): • - peroral; the same spectrum • • •Used against infections caused by S. aureus • •Originally methicillin • staphylococci resistant to penicillinase = MRSA, methicillin-resistant S. aureus •Now in use oxacillin (but MRSA are also resistant to it) •Combination with ampicillin: cloxacillin • • Penicillins resistant to staphylococcal penicillinase – revision •Have a broader spectrum: • most strains of Enterococcus faecalis • Listeria monocytogenes is more sensit. •Above all many Gram-negative rods: • E. coli, Proteus mirabilis, bordetellae, • salmonellae, shigellae, hemophilli & oth. •Amoxicillin (p. os) •Co-amoxicillin (+ clavulanic acid) •Ampicillin (inj. prep. only) •Co-ampicillin (+ sulbactam) • • Aminopenicillins – revision •Broad spectrum: • effective also against Ps. aeruginosa •Co-piperacillin (+ tazobactam) • •Carboxypenicillins – revision • •Spectrum similar to ureidopenicillins • effective against resistant hospital strains incl. Pseud. aeruginosa •Co-ticarcillin Ureidopenicillins – revision Cephalosporins – revision •1st generation (spectrum like ampicillin) • cefazolin • cefadroxil (p.o.) •2nd generation (more resist. to β-lactamases) • cefuroxime • cefuroxime axetil (p.o.) •3rd generation (very effective against G-) • cefotaxime, ceftriaxone • ceftazidime, cefoperazone (P. aerug.) •4th generation (also against G+) • e.g. cefepime • Monobactams – revision •Aztreonam (against G- only) • •Carbapenems – revision •Imipenem (+ cilastatin = Thienam) • for multiresistant strains incl. G+ cocci and Kl. pneumoniae producing ESBL, extended spectrum beta-lactamases) •Meropenem (dtto; diffuses through inflammed meninges) •Ertapenem (against ESBL-producing strains) • 2. Inhibitors of bacterial protein synthesis – revision •Tetracyclines: doxycycline (very broad spectrum) •Chloramphenicol (very toxic) •Aminoglycosides: • streptomycin (now for tbc only) • gentamicin, amikacin (G- rods & staphs) • neomycin (toxic, for topical use only) •Macrolides, azalides, ketolides: •Lincosamides: •Newer antïbiotics: e.g. oxazolidinons, • streptogramins, glycylglycines etc. • • • Macrolides, azalides, ketolides – revision •Macrolides: • Erythromycin (like PNC, + some G- rods) • Roxithromycin (for atypical pneumoniae) • Spiramycin (little toxic, toxoplasmosis) •Azalides: • Azithromycin (better for G- rods) • Clarithromycin (better for G+) •Ketolides: • Telithromycin (even better for G+) Lincosamides – revision •Lincomycin •Clindamycin •Both for G+ (except enterococci), anaerobes, some protozoa • •Streptogramins – revision •quinupristin + dalfopristin (Synercid) (for G+) • • Oxazolidinons – revision •Linezolid (G+ incl. MRSA & anaerobes) • •Lipopeptides – revision •Daptomycin (kills MRSA) • •Glycylcyclins – revision •Tigecyclin (broad spectrum, ESBL producents) 3. Inhibitors of nucleic acid synthesis – revision •Sulphonamides: sulfamethoxazol (only in comb.) •Pyrimidines: trimethoprim (bacteriostatic), plus • sulphamethoxazol = bactericidic co-trimoxazole • (most G+ cocci & G- rods, nocardiae, Toxopl. gondii, Pneumocystis jirovecii) •Quinolones: • nalidixic acid & norfloxacin (urine tract inf.) • ciprofloxacin, ofloxacin (multiresistant G- rods) •Nitroimidazoles: metronidazol, ornidazol (anaerobes & some parasites) •Nitrofurans: nitrofurantoin, nifuratel (urine tract inf.) •Ansamycins: rifampicin, rifabutin (mainly tbc) • rifamixin (travellers diarrhoea) 4. Miscelanous antibacterial agents – revision •Polypeptids: colistin (some G- rods incl. P. aerugin.) • polymyxin B (for local use only) •Antimycobacterial agents (in combinations only!) • streptomycin • rifampicin • isoniazid • ethambutol • pyrazinamide • cycloserine • paraaminosalicylic acid (PAS) • dapsone (for lepra) • • ANTIFUNGAL AGENTS (ANTIMYCOTICS) •Specific antimycotics •Imidazoles •Triazoles •Polyenic antimycotics •Other systemic antimycotics •Local antimycotics •Nonspecific antimycotics (rather antiseptics then chemotherapeutics) Imidazoles •ketokonazole •other imidazoles – for local use only • e.g. clotrimazole, oxiconazole • •Triazoles •flukonazole •posaconazole •vorikonazole Polyenes •amphothericine B • •Other systemic antimycotics • •flucytosin •terbinaphine • Newer antimycotics •Ecchinocandines: e.g. anidulafungin •Pneumocandines: e.g. caspofungin • •Antipneumocystic agents • •co-trimoxazole •pentamidine • Local antimycotics •Imidazoles: e.g. clotrimazole, oxiconazole •Polyenes: e.g. natamycin •Broad-spectrum: amorolfine • ciclopirox olamine •Nystatin •Antimycotic antiseptics: undecylenic acid • chlornitrophenol • ANTIVIRAL AGENTS •Systemicaly used antivirotics •Antiherpetics •Anticytomegalovirotics •Antinfluenza agents •Antiretrovirotics •Interferons •Others systemic antivirotics •Local antivirotics Antiherpetics •Systemic antiherpetics •aciclovir •valaciclovir •famciclovir •brivudin • Anticytomegalovirotics •ganciclovir •cidophovir •foscarnet • •Antiinfluenza agents •amantadin •oseltamivir •zanamivir • Antiretrovirotics – I •Nucleoside inhibitors of reverse transcriptase •zidovudine •lamivudin •abacavir •adefovir dipivoxil •tenofovir •Non-nucleoside inhibit. of reverse transcript. •nevirapin •efavirenz Antiretrovirotics – II •Inhibitors of viral protease •ritonavir •lopinavir •Inhibitors of virion fusis with cell surface •enfuvirtid •Inhibitors of viral entry into the cell •maraviroc • Interferons • •natural interferon α •recombinant interferon α-2a •recombinant interferon α-2b •interferons β •interferon γ •pegylated interferons Other systemic antivirotics •ribavirin • •Local antivirotics •idoxuridin •trifluridin •topically given aciclovir •fluorouracil •podophylotoxin ANTIPARASITIC AGENTS • •Antiprotozoics • •Anthelminthics • •Antiectoparasitics Antiprotozoics – I •Vaginal trichomonosis: • metronidazol • ornidazol • clotrimazol •Giardiosis & amoebic dysentery: • metronidazol • ornidazol •Naeglerial meningoencephalitis: • amphothericin B •Acantamoebic conjunctivitis: • propamidin isethionate • • • Antiprotozoics – II •Toxoplasmosis: • pyrimethamine & sulphadiazine • spiramycin •Malaria: • chloroquine, event. & proguanil • mefloquine • quinine • primaquin • derivatives of artemisin • atovaquone • • Antiprotozoics – III •Leishmanioses: • pentavalent antimony compounds • new forms of amphotericin B •Cryptosporidiosis: • azithromycin •Trypanosomiases: • at first pentamidine • later 3-valent arsenicals, e.g. tryparsamide • • Anthelminthics •Intestinal nematode infections: • albendazole • mebendazole •Tissue nematodes: • ivermectin • albendazole •Flukes: • praziquantel •Tapeworms: • praziquantel Antiectoparasitics •Insecticids • • permethrin • malathion • carbaryl •Repellents • • benzoic acid derivatives • •… Recommended reading material •Paul de Kruif: Microbe Hunters •Paul de Kruif: Men against Death •Axel Munthe: The Story of San Michele •Sinclair Lewis: Arrowsmith •André Maurois: La vie de Sir Alexander Fleming •Hans Zinsser: Rats, Lice, and History •Michael Crichton: Andromeda Strain •Albert Camus: Peste •Victor Heisser: An American Doctor Odyssey •Richard Preston: The Hot Zone •Mika Waltari: The Egyptian •Richard Gordon: Doctor in the House •Richard Gordon: Doctor at Large •Richard Gordon: Doctor at Sea •Richard Gordon: Doctor in Love • •Please mail me other suggestions at: •mvotava@med.muni.cz •Thank you for your attention •