Chapter 10 Flashcards
Characteristics of ideal antimicrobial drugs
- toxic to microbe but not host
- microbicidal
- does not lead to resistance
- readily delivered to site of infection
- remains potent long enough/not broken down/excreted prematurely
- remains active in tissues and body fluids
- does not disrupt host’s health by causing allergies and superinfection
- relatively soluble
use of a drug to prevent infection of a person at risk
prophylaxis
the use of drugs to control infection
antimicrobial chemotherapy
all-inclusive term for any antimicrobial drug, regardless of its origin
antimicrobials
substances produced by the natural metabolic processes of some microorganisms that can inhibit or destroy other microorganisms; generally the term is used for drugs targeting bacteria and not other types of microbes
antibiotics
drugs that are chemically modified in the lab after being isolated from natural resources
semisynthetic drugs
drugs produced entirely by chemical reactions
synthetic drugs
narrow spectrum drugs
target specific microbes
broad spectrum
target variety of microbes (gram pos and gram neg)
but can cause resistance
antibiotics are originally metabolic products of _______ and _______
bacteria and fungi
produced by microbes in order to reduce competition for nutrients and space in their habitat
antibiotics
what bacteria genera and mold genera have the greatest number of antibiotics
Streptomyces and Bacillus
Penicillium and Cephalosporium
before antimicrobial therapy begins, what three factors need to be considered?
- identity of microbe causing infection
- degree of the microbes susceptibility (sensitivity) to various drugs
- overall medical condition of the patient
drug sensitivity testing
involve exposing a pure culture of the microbe to several different drugs and observing the effects of the drug on growth
Kirby-Bauer technique
an agar diffusion test that provides useful data on antimicrobial susceptibility
- The surface of a plate of special medium is spread with test bacterium
- Small discs containing premeasured amounts of antimicrobial are dispensed onto the bacterial lawn
- After incubation the zone of inhibition surrounding the discs is measured and compared
E-Test
provides additional information on drug effectiveness
Zone of inhibition
roughly speaking, the larger the size of the zone, the greater the bacterium’s sensitivity to the drug
Tube dilution tests
the antimicrobial is diluted serially in tubes of broth
each tube is then inoculated with a small uniform sample of pure culture, incubated, and then examined for growth (turbidity)
the smallest concentration (highest dilution) of a drug that visibly INHIBITS growth is called the
minimum inhibitory concentration (MIC)
defined as a ration of the dose of the drug that is toxic to humans compared to its minimum effective (therapeutic) dose.
therapeutic index
does a smaller therapeutic index indicate more of a risk or less?
MORE RISKY
what should the physician consider before prescribing antimicrobials?
- preexisting medical conditions
- allergies
- underlying liver/kidney disease (depends where the drug is metabolized/excreted)
- infants, elderly, (gastro /organ absorption) and pregnant women (placental barrier) require special precautions
- other drugs currently taking
alcohol and cephalosporins have drug _____
interactions
what are the goals of antimicrobial drugs
disrupt cell processes, disrupt structures of bacteria, fungi, and protozoa, or to inhibit virus replication
drugs should kill or inhibit microbial cells without simultaneously damaging host tissues
selectively toxic
example of drugs with excellent selective toxicity
those that block the synthesis of the cell wall in bacteria e.g. penicillins
-they have low toxicity and few direct effects on human cells b/c human cells lack the chemical peptidoglycan
What are the five categories based on what metabolic targets antimicrobial drugs affect?
- Inhibition of cell wall synthesis
- Inhibition of nucleic acid (RNA and DNA) structure and fx
- Inhibition of the ribosome in protein synthesis
- Interference with cytoplasmic membrane structure or fx
- Inhibition of folic acid synthesis
Drugs that target the cell wall
Penicillins
-natural form used to treat gram-pos cocci, some gram-neg bacteria (meningococci, syphilis, spirochetes)
Cephalosporins
- Cefazolin
- Cefaclor
- Cephalexin
Carbapenems
- Aztreonam (narrow-spectrum)
- Doripenem
- Imipenem
Miscellaneous (Vancomycin, Bacitracin, Isoniazid(tuberculosis), Fosfomycin tromethamine)
Drugs that target PROTEIN SYNTHESIS
Aminoglycosides
-Streptomycin (broad spectrum-gram neg rods, gram pos, bubonic plague, tuberculosis)
Tetracyclines
- block the attachment of tRNA on the A acceptor site and stop further protein synthesis
- tetracycline
Glyclycyclines
- Tigecycline
- effective against bacteria that have become resistant to Tetracyclines
Macrolides
- inhibit translocation of the subunit during translation (erythromycin)
- azithromycin, clarithromycin
- relatively broad spectrum, semisynthetic, AIDS treatment
Miscellaneous
- Linezolid
- Quinupristin + dalfopristin
Drugs that target FOLIC ACID SYNTHESIS
Sulfonamides
- interfere with folate metabolism by blocking enzymes required for synthesis of tetrahydrofolate
- Sulfamethoxazole, Silver sulfadiazine (burns, eye infections), Trimethoprim
Drugs that target DNA OR RNA
Fluoroquinolones
- inhibit DNA unwinding enzymes or helicases-> stopping DNA transcription
- Levofloxacin, Ciprofloxacin
Miscellaneous
-Rifampin
Drugs that target CYTOPLASMIC OR CELL MEMBRANES
Polymyxins (colistins)
- interact with membrane phospholipids distort cell surface and cause leakage of protein and nitrogen bases
- Polymyxin B
- Daptomycin (most active against gram-pos bacteria)
examples of gram neg bacteria
salmonellosis, plague, gonorrhea
List narrow spectrum penicillins
G (best drug choice when bacteria are sensitive; low cost; low toxicity)
V
Methicillin, nafcillin (poor absorption; growing resistance)
List broad spectrum penicillins
Ampicillin - work on gram-neg bacilli
Amoxicillin - work on gram-neg infections; good absorption
VERY BROAD:
Azlocillin, Mezlocillin, Ticarcillin - effective against Pseudomonas species; low toxicity compared with aminoglycosides
TRUE OR FALSE
Biofilm inhabitants are often affected by the same antimicrobials that work against them when they are free living.
FALSE
they are often unaffected by the same ones when they are in biofilms that would usually work when they are free living
Why can some antibiotics now work as well on biofilms?
cannot easily penetrate the sticky extracellular material surrounding biofilm
*b/c of the different phenotype expressed by biofilm bacteria (different genes are expressed and therefore there are different antibiotic susceptibility profiles than if the microbes were free living)
A lipopeptide that is effective in deep tissue infections with resistant bacteria
- has shown success in biofilm infection treatment
Daptomycin (Cubicin)
what is a risk because of the similarity between fungal and human cells?
often means that drugs toxic to fungal cells are also capable of harming human tissues
Macrolide polyenes
Agents used to treat fungal infections
ex: Amphotericin B
- bind to fungal membranes, causing loss of selective permeability
- can be used to treat skin, mucous, membrane lesions caused by Candida albicans
- injectable form of drug can be used to treat histoplasmosis and Cryptococcus meningitis
Azoles
Agents used to treat fungal infections
Ex: Ketoconazole. Fluconazole, Clotrimazole, Miconazole
- interferes with sterol synthesis in fungi
- Ketoconazole -> cutaneous mycoses, vaginal and oral candidiasis, systemic mycoses
Echinocandins
Agents used to treat fungal infections
Ex: Micafungin, caspofungin
- inhibit fungal cell wall synthesis
- used against Candida strains and aspergiollosis
Allylamines
Agents used to treat fungal infections
Ex: Terbinafine, naftifine
- inhibit enzyme critical for ergosterol synthesis
- used to treat ringworm and other cutaneous mycoses
principal tx for malaria for hundreds of years; extracted from the bark of the cinchona tree
-has since been replaced by synthesized quinolones (less toxicity)
Quinine
malaria parasite
Plasmodium
why is no single drug universally effective for malaria?
because there are several species of plasmodium, and many stages in its life cycle
Artemisinin
a drug which originates from a plant called sweet wormwood; is a staple for malaria tx
Metronidazole (Flagyl)
anti-protozoal drug
;effective in treating severe intestinal infections and hepatic disease caused by Entamoeba histolytica
;orally it can treat Giardia lamblia and Trichomonas vaginalis