Antimicrobial Therapy Flashcards
Antimicrobial agent vs Antimicrobial drug
An antimicrobial is an agent that kills all microorganisms (i.e. fungi, bacteria etc) or stops their growth.
Antibiotic- A drug used to treat bacterial infections.
Antimicrobial agent
- suppress growth and multiplication
- kill organism
Natural Antibiotic - drug
Penicillin derived from fungi
Antibiotics can also be derived from other bacteria e.g. aminoglycosides and carbapenems
Bacillus polymyxa– Polymixin, Penicillium notatum– Penicillin
-Cephalosporium acremonium–> Cephalosporin
-Streptomyces venezuelae–> Chloramphenicol
Semi Synthetic
ampicillin, amoxicillin, methicillin
Synthetic
Sulphonamides, Quinolones
Selective Toxicity
Cause greater harm to microorganisms than to host
Chemotherapeutic index = lowest dose toxic to patient divided by dose typically used for therapy
-it selectively kills or inhibits the growth of microbial targets while causing minimal damage to host.
Classification - range of activity
Narrow spectrum - active towards fewer m.o.s (macrolides, polymyxin)
Narrow broad spectrum - active towards gram +ve and gram -ve (beta lactam)
Moderate spectrum - active towards Gram +ve bacteria and some systemic and UTI causing
Gram -ve bacteria. (Aminoglycosides, Sulfonamide)
Broad spectrum - active against Gram +ve and Gram -ve except Pseudomonas and Mycobacteria (Chloramphenicol, Tetracycline)
Anti-mycobacterial antibiotics: Ethambutol, Rifampicin, Isoniazid, Pyrazinamide-Treats TB
Broad spectrum is good first treatment of infection (T/F)
False; Can cause resistance to bacteria or destroy normal flora
Bacteriostatic vs Bactericidal
Bacteriostatic: Antibiotics that stops or inhibits the growth of bacteria i.e. no bacteria multiplication or
generation of new bacteria but they do not kill bacteria e.g. tetracycline, chloramphenicol – slow acting
• Bactericidal: Antibiotics that actually kill bacteria by any mechanism depending on the antibiotic used,
e.g. aminoglycosides – fast acting via killing
Lag, log, stationary, death phases
Lag+log phase - organism is maximally multiplying
Stationary - no deaths no new bacteria
Death- of bacteria
What phase do antimicrobials work at?
Log phase
Synergistic - Drug combinations
Action of one drug enhances the activity of another
Antagonistic - Drug combinations
Activity of one drug interferes with the action of another
Additive - Drug combinations
Neither synergistic or antagonistic
Indifference - Drug combinations
Each drug works no better or no worse alone or in combination
Prophylaxis therapy
– no organisms identified but used as a precautionary measure (used for prevention of infection)
Empirical therapy
– initial – infecting organism not identified – single broad spectrum agent (treat until you know what you are treating)
Definitive therapy
– microorganism identified – a narrow –spectrum low toxicity regiment to complete the course of treatment (definite diagnosis)
PK vs PD
Pharmacokinetics (PK) refers to the movement of drugs through the body, whereas pharmacodynamics (what body does to drug)
(PD) refers to the body’s biological response to drugs. (what drug does to body)
By graphing drug concentration versus time, you can get some ballpark estimates of the drug’s basic PK properties (T/F)
True
The maximum concentration the drug attains
Cmax
Time at which this maximum occurs
Tmax
Classification of Antimicrobial Agents against organisms
Antibacterial •Antiviral •Antifungal •Antiprotozoan •Anthelmintic
β lactam antibiotics: chemical composition classification
Penicillin, cephalosporin, carbapenem, monbactam - -Beta lactam rings present with side chains
Tetracycline group of antibiotics: chemical composition classification
- Aminoglycosides: streptomycin, neomycin, kanamycin, amikacin, gentamicin
- Polypeptide: polymixin, bacitracin
- Glycopeptides: vancomycin, teicoplanin
Beta lactam - no activity
No activity against LAME Listeria Atypicals (Mycoplasma/Chlamydia) MRSA Enterococci
The side structures determine what the beta lactam is active against (T/F)
True
Another example of extending side chain antibiotic
Carabpanems - commonly used for the treatment of
severe or high-risk bacterial infections.
Clavanic acid - base of structure.
- reserved for known or
suspected multidrug-resistant (MDR) bacterial infections
Antibiotic activity drugs
Macrolides - inhbits growth
Quinolones - inhibits/kills
Chloramphenicol - stops growth
Antimicrobial agent
Streptogramins (treats VRSA)
Slow spread of mycobacteria
Rifabutin
Antifungal
- Treats and prevents myosis Imidazoles belong to the class of azole antifungals, which includes ketoconazole, miconazole, and clotrimazole
Classification based on Mechanisms of Action Antimicrobials
- Inhibition of bacterial cell wall synthesis
- Inhibition of protein synthesis
- Inhibition of nucleic acid synthesis
- Inhibition of metabolic pathways
- Disruption of cell membrane permeability
- Inhibition of viral enzymes
Inhibition of bacterial cell wall synthesis
Cycloserine Vancomycin Bacitracin Penicillin Cephalosporin Monobactams Carapenems
Inhibition of protein synthesis
Chloramphenicol (binds to 50s portion; inhibits peptide bond formation)
Erythromycin
Tetracyclines (interferes with tRNA to rRNA attachment)
Streptomycin (changes shape of 30s; mRNA read incorrectly)
Disruption of cell membrane permeability
Polymyxin B
Azoles - antifungal agents
Inhibition of viral enzymes (producing metabolites)
Sulfanilamide
Trimethroprim
PBP - cell wall (Cephalosporin)
PBP produces folate which is responsible for the production of RNA and DNA
Result: Deformed cell wall
- Cephalosporins (Cephalexin, cefotaxime andvceftazidime)
Abx
Antibiotics
Antifungal agents (Polyenes)
Polyene (macrocyclic ring) consists of:
- Amphotericin B - polyene macrolide antibiotic produced by Streptomyces nodosus
- blocks microtubule that transports
nutrients
- Nystatin - obtained from Streptomyces noursei
- similar mechanism as Amp B
Echinocandins
- binds to fungal cell membrane (Ergosterol) and forms pores. This alters permeability & transport and
as a result, cell death occurs. Inhibits glucan biosynthesis
Heterocyclic benzofuran
- Early antifungal (Griseofulvin)
- Active against Dermatophytes: epidermophyt
on, trichophyton , microsporum - Interferes with mitosis
Antimetabolite
- Flucytosine
- Converted by fungal enzyme through steps and incorporated into fungal RNA leading to miscoding during mRNA,dna and protein synthesis
Allylamine
- Terbinafine
- Synthetic; orally active
- inhibits squalene (ergosterol biosynthesis); build up causes cell death
Azoles
- Disrupts synthesis of ergosterol
- Disrupts membrane structure and cell growth
Azoles - groups
Imidazoles - Clotrimazole, Econazole, Miconazole, Ketoconazole
Triazoles - Fluconazole, Itraconazole, Posaconazole, Voriconazole
Topical antifungal - Cicloporix
-Cicloporix
-active against Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Microsporum canis, Candida albicans, and Malassezia
furfur.
-Inhibits element transport in cells -> disrupting rna,dna,protein synthesis
Topical antifungal - Tolnaftate
- Distorts hypae; stunts mycelia growth
- active against Epidermophyton, Microsporum, and Malassezia furfur
Antiparasitic Agents - Antiprotozoal
Metronidazole; Nifurtimox, Atovaquone, Pentamidine, Benznidazole, Quinacrine, Dehydroemetine, Sodium
stibogluconate
Antihelmintic - Niclosamide
Niclosamide blocks glucose uptake by
intestinal tapeworms.
Antihelmintic - Mebendazole
• Mebendazole blocks glucose uptake by
nematodes. Albendazole is similar to
mebendazole.
Antihelmintic - Levamisole
• Levamisole paralyses the musculature of nematodes which lose anchorage and are expelled
Antihelmintic - Praziquantel
• Praziquantel paralyses both adult worms and larvae.
Antihelmintic - Thiabendazole
Thiabendazole inhibits cellular enzymes
Antihelmintic - Pyrantel
Pyrantel depolarises neuromuscular
junctions of susceptible nematodes
expelled in faeces.
Antihelmintic - Diethylcarbamazine
•Diethylcarbamazine kills microfilariae and adult worms.
Antihelmintic - Ivermectin
•Ivermectin kills microfilaria (early stage in the life cycle of certain parasitic nematodes)
