Antibiotics

BACTERICIDAL Aminoglycosides Quinolones Cycloserine Vancomycin Carbapenems Penicillins Cephalosporins All ANTI TB meds except ETHAMBUTOL BACTERIOSTATIC Chloramphenicol Nitrofurantoin Clindamycin Tetracycline Erythromycin Trimethoprim Lincomycin Sulfonamide Ethambutol

Natural Penicillin
Pen G oral, IV, IM Pen V Oral Pen G Procaine IM Pen G Benzathine IM (Rheumatic Fever Prophylaxis)

True or False?
1. 2. 3. 4. Pen is for Gram (+) only Pen can Kill Pen is rarely used Nowadays Pen is best given with food
False False True False

Coverage of Penicillin
Streptococcus Meningococcemia Clostridium Listeria Enterococci Diphteria Anthrax Syphilis Actinomycosis Bacteroides (except fragilis) Anaerobics that do not produce B lactamase

Adverse Effects
Hypersensitivity (do skin testing. Ask for hx of allergy!) Seizures- in those with renal problems/newborns Diarrhea Hemolytic anemia Hypernatremia or hyperkalemia if in extremely high doses
Hypersensitivity to Pen Cross allergenicity Anaphylaxis

Antistaphylococcal Penicillin
Methicillin, Nafcicillin, Oxacillin, Dicloxacillin, Cloxacillin Narrow spectrum Beta lactamase resistant For staph that produces penicillinase ADR: granulocytopenia Methicillin can cause interstitial nephritis

Extended Spectrum Penicillin

-Amoxicillin, ampicillin -Spectrum of natural penicillin + HELPSS (H. influenza, E.coli, Listeria, Proteus, Salmonella, Shigella) -Beta Lactamase Susceptible -Clavulanic Acid and Sulbactam Sa Ampi at Amox, may katulong ka! (may HELPSS ka! Hehe)

ADR: Rash Pseudomembranous colitis Often given with Beta lactamase inhibitors Co-Amoxiclav (augmentin) Ampi-Sulbactam (Unasyn) Piper-Tazobactam (Zosyn)

CEPHALOSPORIN
Classified by generations 5-10% cross reactivity with penicillin Nephrotoxicity, disulfiram effects with EtOH 1st 3rd Decrease in g(+) coverage Increase in g (-) coverage Increase in CNS penetration Increase in B lactamase

st 1

generation

Cefadroxil, Cefazolin, Cephalexin, Cephalothin, Cephaprin, Cephadrin PeCK Proteus Mirabilis, E.coli, Klebsiella Surgical Prophylaxis

nd 2

Generation

Cefuroxime, Cefamandole, Cofonicid, Cefotetan, Cefoxitin, Ceforanide, Cefuroxime, Cefmetazole, Cefaclor A FAMily is gathered, some wearing FUR and your FOXy cousin is drinking TEA. HEN PeCKS (add H. influenza, Enterobacter aerogenes, Neisseria, Serratia marcescens)

rd 3

Generation

Cefotaxime, Ceftazidime, Ceftriaxone, Cefbuten, Cefoperazone, Cefixime For serious g(-) infectious enterobacter, neisseria (ceftriaxone), Haemophilus Antipseudomonas Ceftazidime, Cefoperazone Taz, Fop, Fep

th 4

Generation

Cefipime Increase activity against pseudomonas and g(+) organism

- CEPHALOSPORINS are LAME (no coverage on the following) - Listeria - Atypicals - MRSA - Enterococci

Other Cell Wall Synthesis Inhibitors

Monobactams (Substitute Antibiotics) Axtreonam For patients with penicillin allergy who cannot take AMG No cross allergenicity Beta Lactamase resistant G(-) rods (klebsiella, Pseudomonas, Serratia)

Carbapenems
Resistant to B lactamase Imipenem Usually Combined with Cilastatin WHY? SUPER DRUG (for g(+), g(-) and anaerobic organisms ADR: seizures, GI effects

VANCOMYCIN
Binds to D-ala-D-ala portion of Cell wall precursors inhibits peptidoglycan polymerization SUPER DRUG for all G(+) includes MRSA, C.difficile Renally excreted ADR: shock, redman s syndrome, ototoxicity, nephrotoxicity

BACITRACIN
Blocks transfer of peptidoglycan unit to growing cell wall For topical use only WHY???

CYCLOSERINE
Analog of D-alanine 2nd line drug for TB

Protein Synthesis Inhibitors

Formation of initiation complex
Aminoglycoside

Amino Acid Incorporation

Tetracyclines

Formation of Peptide Bond

Chloramphenicol

Translocation
Macrolides and Clindamycin

Buy at 30, CELL at 50

Agents that binds to 30s ribosomal unit Aminoglycoside (Bactericidal) Tetracyclines (bacteriostatic) Agents that binds to 50s ribosomal subunit (bacteriostatic) Macrolides Chloramphenicol Lincosamide

AMINOGLYCOSIDES
>Amikacin, netilmicin, neomycin, tobramycin, gentamicin, streptomycin >Accumulate in the renal cortex and endolymph of the inner ear significance? >Excreted unchanged by the kidneys >ALL are given IV except NEOMYCIN (topical) >For anaerobic g(-) enteric bacteria such as E.coli, Enterobacter, Klebsiella, Pseudomonas >ADR: triple PUNCH:
Ototoxicy Nephrotoxicity Acute Tubular Nephrosis NMJ blockade

MOA of AMG
Bind to outer bacterial membrane thereby disrupting membrane integrity Bind to 30s ribosomal subunit Interfere with formation of the initiation complex Induce misreading of the mRNA template Cause polysomes to break up into monosomes Concentration-dependent killing

Postantibiotic Effect Concentration dependent Explains why AMG can be given in single daily doses despite the short half life

Mechanism of Resistance
>Production of inactivating enzymes, called group transferases . These enzymes can inactivate AMG >Reduced active transport of AMG >Modification of the ribosomal binding site

Ototoxicity Cochlea normally lined with hair cells are destroyed by high concentrations of AMG Increased with diuretics (FUROSEMIDE)

TETRACYCLINES
>Tetracyclines, doxycycline, demeclocycline, minocycline, oxytetracycline (terramyccin) >VACUUM your Bedroom Tonight
Vibrio cholera Acne Chlamydia Ureaplasma urealyticum Mycoplasma pneumonia Borrelia burgdorferi Rickettsia Tularemia

>Therapeutic uses >Chlamydia: Psittacosis, inclusion conjuctivitis, trachoma, non specific urethritis >STD
Syphilis in penicillin allergic patients Endocervical or rectal infection caused by Chlamydia

>Bacillary Infections: Brucellosis, Cholera >Acne

>MOA of Tetracyclines
Inhibit protein synthesis

>Excreted in the urine except for doxycycline which is excreted via GI Tract >ADR
NV-most common Bone and teeth destruction Liver Toxicity Photosensitivity Vestibular Reactions

>Examples Tetracyclines Doxycyclines Minocyclines Demeclocyclines >Contraindications: Should not be used in pregnant women and children under 8 yo. >TETracycline is a TERatogen that causes staining of teeth in the newborn

Chloramphenicol (chloromycetin)

Chloramphenicol (chloromycetin)
Because of potential toxicity, should be employed only in well defined and indicated conditions >MOA of Chloramphenicol? >Broad spectrum: >Gram-negative bacteria: H. influenza, N. meningitidis, N. gonorrhoea, Salmonella typhi, Brucella & Bordetella pertussis >Anaerobic bacteria: gram-positive cocci; clostridium & gram-negative rods >Otherspecies: E. coli, V. cholerae, Shigella, Chlamydia & Mycoplasma >Not effective against Pseudomonas, histolytica, Entamoeba

Chloramphenicol (chloromycetin)
>Resistance >Acetylation of chloramphenicol by acetyltranferase enzyme acetylated form cannot bind ribosome >Decreased cellular permeability >Mutation leading to ribosomal insensitivity

Chloramphenicol (chloromycetin)
Therapeutic uses
Typhoid fever Bacterial Meningitis Certain anaerobic infections Rickettsial diseases Epidemic, murine, scrub and recrudescent typhus Rocky Mountain spotted fever Q fever Brucellosis (tetracycline-sensitive patients)

Chloramphenicol (chloromycetin)
>Adverse Effects >Neonatal toxicity:gray baby syndrome >Hematological toxicity >Most important side effect is on bone marrow >Idiosyncratic reactions: aplastic anemia >Dose-related reactions: erythroid suppression of bone marrow

MACROLIDES
Examples: Erythromycin (prototype) Clarithromycin Azithromycin

Erythromycin
>Narrow spectrum antibiotic used as a substitute for penicillin G >Antimicrobial activity:
Very effective against gram-positive bacteria Bacteriostatic at low concentrations Bacteriocidal at high concentrations

Erythromycin
>Antimicrobial spectrum >Gram-positive: pneumococci, streptococci, staphylococci, corynebacteria >Atypicals: mycoplasma, legionella, chlamydiae, listeria, helicobacter, mycobacteria >Gram-negatives: Neisseria, Bordetella, some rickettsia, campylobacter, H. influenzae )less susceptible > Legionnaires Camp on My Border

Clinical Use
Corynebacteria infections Chlamydial infections Community-acquired pneumonia As penicillin substitute in allergic patients

Azithromycin
High active vs. chlamydia Half life 3 days Does not inactivate cyto chrome P450

Clindamycin
>Mechanism of Action >Inhibits protein synthesis by binding to 50s subunit of bacterial ribosome >Exhibits cross-resistance with macrolides

Clindamycin
>Antimicrobial spectrum >Gram-positives: streptococci, staphylococci, pneumococci >No activity vs. enterococci & gram-negative aerobic bacteria >Anaerobes: both gram(+) & gram (-) Clostridium difficile is resistant

Clindamycin
>Clinical Use >Treatment of severe anaerobic infections >Treat penetrating wounds of abdomen & gut >Female genital tract infections >Aspiration pneumonia

Clindamycin
Adverse Effects: Diarrhea Nausea Skin rash Antibiotic-associated colitis

Spectinomycin
>Not an aminoglycoside >Spectinomycin is very specific for neisseria only

Fluoroquinolones
>MOA: DNA gyrase inhibitor >Not absorbed in the CNS >Broad spectrum but not against anaerobes >For UTI, skin,bone,soft tissue,resptract infections,prostatitis,stda, diarrhea due to campylobacer, salmonella,shigella e. coli

Fluoroquinolones
Adverse effects: Headache Diarrhea Photosensitivity Fluoroquinobones Cartilage erosion in children Tendonitis and tendon rupture in adults

Sulfomides
>Modern sulfa drugs >Paba analog-competitive inhibitor of dihydropteroatesynthetase which is responsible for combining paba and pteride >Sulfamethoxazole, sulfasalazine,silver sulfadizine >Well absorbed orally,displaces substances bound to albumin >For g(+) and g (-) including nocardia, chlamdia, e. coli >Klebsiella, enterobacter

Indications
UTI sulfamethoxazole UC sulfasalazine Burn infection silver sulfadiazine Ocular infection sulfacetamide Nocardiosis sulfisoxazole Toxoplasmosis sulfadiazine with pyrimethamine

Adverse effects:crank
>Crystalluria >Rashe-sjs >Anemia >N&V >Kernicterus >Crosses placenta and breast milkcontraindicated

Trimethoprim
>Dihydrofolate reductase inhibitor >Given with sulfamethaxazole >Doc for pcp-must know >For complicated uti, bacteriaprostatis, gonorrhea,sinusitis,aom,pnuemonia >For chancroid, shigellosis, typhoid fever, nocardiosis

Trimethoprim
Adverse effects: Megaloblatic anemia Leukopenia Granulocytopenia

Anti-TB drugs
Anti tb meds Isoniazid Rifampicin Pyrazinamide Ethambutol streptomycin

Isoniazid
>Inhibits mycolic acid >Antacids-impair absorption >Inhibits P450 system-increases >phenytolin,BZD, warfarin >Adverse effects:
Neurotxic-peripheral neuritis-B6 Rashes SLE like syndrome Crosses the placenta causing peripheral neuritis

Rifampicin
>Inhibits B-subunit of DNA dep RNA polymerase >Induces P450 system >Also used in meningococci, leprosy, Legionnaires disease >Adverse effects:
Red-orange urine,tears Rash,fever,flulike sx

Pyrazinamide
Unknown MOA ADR: Gout inhibits uric acid secretion Arthralgia Myalgia

Ethambutol
>MOA: unknown >Bacteriostatic >ADR: Optic Neuritis/ red green >blindness EYEthambutol >Gout