Microbiology Unit 2D

Antimicrobial chemotherapy

Administration of a drug to an infected person that destroys the infective agent without harming the host's cells

Selectively toxic

Kills or inhibits microbes without simultaneously damaging host tissues

Antibiotics

Substances produced by the natural metabolic processes of some microorganisms that can inhibit or destroy other microorganisms

Bacteriostatic

Inhibits bacterial growth but does not necessarily kill the organisms

Bactericidal

Kills the organisms

Mechanisms of drug action

Inhibition of cell wall synthesis, disruption of cell membranes, interference with DNA/RNA, inhibition of protein synthesis, and blockage of metabolic pathways

Narrow-spectrum drug

Effective against a small range of microorganisms

Medium-spectrum drug

Effective against some gram-positive and some gram-negative bacteria

Broad-spectrum drug

Effective against gram-positive, gram-negative, rickettsias, mycoplasmas, and spirochetes

Cell wall inhibitors

Antimicrobials that attack peptidoglycan or interfere with enzymes that cross-link glycans

Cell membrane disruptors

Antimicrobials that damage membranes causing lysis and cell death

Drugs affecting nucleic acid synthesis

Drugs that block nucleotide synthesis, replication, transcription, or act as base analogs

Drugs blocking protein synthesis

Drugs that target bacterial ribosomes to stop protein production

Metabolic pathway inhibitors

Drugs that interfere with essential metabolic reactions such as folic acid synthesis

Beta-lactam drugs

Antibiotics containing a beta-lactam ring that interfere with bacterial cell wall synthesis

Beta-lactam drugs include

Penicillins, cephalosporins, carbapenems, and monobactams

Beta-lactamase

Bacterial enzyme that cleaves the beta-lactam ring and causes resistance

Penicillinase

Enzyme that hydrolyzes penicillin and provides resistance

Penicillin G

First antibiotic derived from mold, acid labile, given IM, penicillinase sensitive, narrow spectrum

Penicillin G targets

Streptococcus, meningococci, and Treponema pallidum

Penicillin V

Oral, acid stable, penicillinase sensitive, narrow spectrum penicillin

Amoxicillin

Aminopenicillin with broad-spectrum activity including H. influenzae, P. mirabilis, and E. coli

Ampicillin

Broad-spectrum aminopenicillin effective against many gram-negative pathogens

Carbenicillin

Carboxypenicillin effective against Pseudomonas species

Ticarcillin

Carboxypenicillin with broad to very broad spectrum including Pseudomonas

Oxacillin

Methicillin-type penicillin resistant to penicillinase

Dicloxacillin

Methicillin-type penicillin resistant to penicillinase

Methicillin-type penicillins

Used for penicillinase-producing Staphylococcus infections

Nafcillin

Penicillinase-resistant penicillin given IM or IV

MRSA

Methicillin-resistant Staphylococcus aureus

Clavulanic acid

Beta-lactamase inhibitor that protects beta-lactam antibiotics

Augmentin

Amoxicillin plus clavulanic acid

Timentin

Ticarcillin plus clavulanic acid

Cephalosporins

Beta-lactam antibiotics generally resistant to many penicillinases

First-generation cephalosporins

Cephalothin and cefazolin

Second-generation cephalosporins

Cefaclor and cefonicid

Third-generation cephalosporins

Cephalexin and ceftriaxone

Fourth-generation cephalosporins

Cefepime with widest range of activity

Carbapenems

Broad-spectrum beta-lactams with increased resistance to beta-lactamases

Imipenem

Carbapenem with broad-spectrum activity

Ertapenem

Carbapenem with broad-spectrum activity

Monobactams

Beta-lactams with narrow-spectrum activity

Aztreonam

Monobactam useful for pneumonia, septicemia, UTIs, and penicillin-allergic patients

Vancomycin

Narrow-spectrum cell wall inhibitor used for MRSA, C. difficile, and Enterococcus endocarditis

Bacitracin

Cell wall inhibitor found in Neosporin used for superficial skin infections

Isoniazid (INH)

Drug used to treat tuberculosis, effective only against growing cells

Rifater

Combination of INH, rifampin, and pyrazinamide used for tuberculosis treatment

Polymyxins

Membrane-disrupting antibiotics used against drug-resistant gram-negative rods

Colistin

Polymyxin used against Pseudomonas aeruginosa and Acinetobacter baumannii

Quinolones/Fluoroquinolones

Drugs that inhibit DNA gyrase and topoisomerase IV

Nalidixic acid

First synthetic quinolone

Ciprofloxacin

Fluoroquinolone used for UTIs, STIs, GI infections, respiratory infections, and osteomyelitis

Norfloxacin

Fluoroquinolone commonly used for UTIs

Levofloxacin

Fluoroquinolone used for pneumonia, bronchitis, and sinusitis

Sparfloxacin

Fluoroquinolone used for respiratory infections

Rifampin

Blocks RNA polymerase and is important for tuberculosis and leprosy treatment

Streptomycin

Aminoglycoside used for plague, tularemia, and tuberculosis

Gentamicin

Aminoglycoside used for gram-negative rod infections

Tobramycin

Aminoglycoside especially useful for Pseudomonas infections in cystic fibrosis patients

Amikacin

Aminoglycoside useful against gram-negative bacteria

Aminoglycosides

Protein synthesis inhibitors used against aerobic gram-negative rods

Tetracycline

Broad-spectrum protein synthesis inhibitor

Doxycycline

Tetracycline antibiotic with broad-spectrum activity

Tigecycline

Broad-spectrum tetracycline derivative

Tetracyclines side effects

GI disruption, tooth staining, and interference with fetal bone development

Chloramphenicol

Broad-spectrum bacteriostatic drug that can cause aplastic anemia

Erythromycin

Macrolide used for Mycoplasma pneumonia, Chlamydia, pertussis, and diphtheria

Clarithromycin

Macrolide used for respiratory, skin, and Helicobacter pylori infections

Azithromycin

Macrolide used for respiratory, skin, and Mycobacterium infections

Clindamycin

Macrolide-related antibiotic used for anaerobic infections and penicillin-resistant Staphylococcus

Macrolides

Protein synthesis inhibitors that bind the 50S ribosomal subunit

Trimethoprim

Sulfonamide-related drug that interferes with folic acid synthesis

Sulfamethoxazole

Sulfonamide that interferes with folic acid synthesis

Bactrim

Combination of trimethoprim and sulfamethoxazole

Co-trimoxazole

Combination therapy of trimethoprim and sulfamethoxazole

Sulfonamides

Drugs that block folic acid synthesis

Fosfomycin

Drug used as an alternative treatment for UTIs

Synercid

Combination of quinupristin and dalfopristin with synergistic effects

Daptomycin

Membrane-disrupting drug mainly active against gram-positive bacteria

Telithromycin

Macrolide-related drug used for resistant respiratory infections

Linezolid

Protein synthesis inhibitor useful for MRSA and VRE

Synergistic effect

Two drugs work better together than either drug alone

Antifungal drugs

Drugs used to treat fungal infections

Difficulty of treating fungal infections

Fungal cells are eukaryotic, making selective toxicity difficult because human cells are also eukaryotic

Classes of antifungal drugs

Macrolide polyenes, griseofulvin, synthetic azoles, flucytosine, and echinocandins

Amphotericin B

Most versatile and effective antifungal drug used to treat serious systemic fungal infections

Amphotericin B uses

Histoplasmosis, Cryptococcus, and other systemic fungal infections

Nystatin

Antifungal used topically or orally for candidiasis of the skin and mucous membranes

Griseofulvin

Antifungal used for dermatophyte infections of hair, skin, and nails

Dermatophyte infections

Fungal infections of hair, skin, and nails such as athlete's foot

Griseofulvin disadvantages

Can damage kidneys and liver and often requires long-term treatment

Synthetic azoles

Broad-spectrum antifungal drugs that inhibit ergosterol and fungal cell membrane synthesis

Ketoconazole

Synthetic azole antifungal

Fluconazole

Synthetic azole antifungal

Itraconazole

Synthetic azole antifungal

Clotrimazole

Synthetic azole antifungal

Flucytosine

Cytosine analog with antifungal properties often used with Amphotericin B

Flucytosine disadvantage

Many fungi are resistant to it

Caspofungin

Echinocandin antifungal that damages fungal cell walls

Echinocandins

Antifungal drugs that damage fungal cell walls and do not target human cells