Module 09: Inhibiting the Growth of Pathogens in Vivo Using Antimicrobial Agents Flashcards
This refers to the use of any chemical or drug to treat any disease or condition.
Chemotherapy
The chemicals (or drugs) used to treat diseases are referred to as ____________. By definition, this is any drug used to treat any condition or disease.
Chemotherapeutic Agents
This aided in the treatment of dysentery.
Ipecac
This was discovered to be effective in treating malaria.
Quinine extract of cinchona bark
The chemotherapeutic agents used to treat infectious diseases are collectively referred to as ____________. Thus, this is any chemical (or drug) used to treat an infectious disease, either by inhibiting or by killing pathogens in vivo.
Microbial Agents
Drugs used to treat bacterial diseases are called ______________.
Antibacterial agents
Drugs used to treat fungal diseases are called ___________.
Antifungal agents
Drugs used to treat protozoal diseases are called _____________.
Antiprotozoal agents
Drugs used to treat viral diseases are called ______________.
Antiviral agents
This is a substance produced by a microorganism that kills or inhibits the growth of other microorganisms.
Antibiotics (All antibiotics are antimicrobial agents but not all are antibiotics)
The chemotherapeutic agents used to treat infectious diseases are collectively referred to as ___________________.
Antimicrobial agents.
Antibiotics are produced by what?
Certain moulds and bacteria that live in soil which gives them a selective advantage for the available nutrients.
What are some examples of antibiotics formed from molds?
(1) Penicillin
(2) Cephalosporins
What are some examples of microorganisms formed from bacteria?
(1) Bacitracin
(2) Erythromycin
(3) Chloramphenicol
Antibiotics that have been chemically modified to kill a wider variety of pathogens or reduce side effects are called ________________.
Semisynthetic antibiotics (eg ampicillin, amoxicillin and nafcillin)
He is a Scottish bacteriologist, accidentally discovered the first antibiotic when he noticed that the growth of contaminant Penicillium notatum mould colonies on his culture plates was inhibiting the growth of Staphylococcus bacteria
Alexander Fleming
The discovery of penicillin by Alexander Fleming where manifested by?
(A) Colonies of Staphylococcus aureus are growing well in this area of the plate.
(B) Colonies are poorly developed in this area of the plate because of an antibiotic (penicillin) being produced by a colony of Penicillium notatum (a mould), shown at
C
An ideal antimicrobial agent should:
(1) Kill or inhibit the growth of pathogens
(2) Cause no damage to the host
(3) Cause no allergic reaction in the host
(4) Be stable when stored in solid or liquid form
(5) Remain in specific tissues in the body long enough to be effective
(6) Kill the pathogens before they mutate and become resistant to it
They purified penicillin and demonstrated its effectiveness in the treatment of various bacterial infections
Sir Howard Walter Florey and Ernst
Boris Chain,
This was discovered by Gerhard Domagk which as effective against streptococcal infections in mice.
Protonsil
Him and his colleagues isolated streptomycin (the first antituberculosis drug) and subsequently discovered antibiotics such as chloramphenicol, tetracycline, and erythromycin in soil samples.
Selman Waksman
This inhibits growth of bacteria, whereas bactericidal drugs kill bacteria.
Bacteriostatic drugs
The five most common mechanisms of action of antimicrobial agents are as follows:
(1) Inhibition of cell wall synthesis
(2) Damage to cell membranes
(3) Inhibition of nucleic acid synthesis (either DNA or RNA synthesis)
(4) Inhibition of protein synthesis
(5) Inhibition of enzyme activity
These drugs inhibit production of folic acid (a vitamin) in those bacteria that require p-aminobenzoic acid (PABA) to synthesize folic acid.
Sulfonamide drugs
Why are sulfa drugs considered as competitive inhibitors?
They inhibit growth of microorganisms by competing with an enzyme required to produce an essential metabolite.
Sulfa drugs are characterized to be what?
Bacteriostatic because they prevent growth
In most Gram-positive bacteria, how does penicillin interfere?
synthesis and cross-linking of peptidoglycan, a component of cell walls. By inhibiting cell wall synthesis, penicillin destroys the bacteria
This destroys gram positive bacteria.
Vasomycin
These only Gram-negative bacteria; they are referred to as narrow-spectrum antibiotics.
Colistin and Nalidixic acid
Antibiotics that are destructive to both Gram-positive and Gram-negative bacteria are called _____________.
Broad Spectrum Antibiotics (Ciproflaxin, Ceftriaxone, Tetracycline)
These agents agents should be used only in patients whose host defense mechanisms (see Chapters 15 and 16) are functioning properly (i.e., only in patients whose bodies are capable of killing the pathogen once its multiplication is stopped).
Bacteriostatic agents should be used in immunosuppressed patient and leukopenic patients
In this, sometimes one drug is not sufficient; two or more drugs may be used simultaneously, as in the treatment of tuberculosis
Multidrug therapy
This is when two antimicrobial agents are used together to produce a degree of pathogen killing that is greater than that achieved by either drug alone.
synergism
This is when two drugs actually work against each other. The extent of pathogen killing is less than that achieved by either drug alone.
Antagonism
These are referred to as ß-lactam drugs because their molecular structure includes a four-sided ring structure known as a ß-lactam ring
Penicillin
What does penicillin inhibit?
Synthesis of cell wall (have maximum effect on those that are dividing)
These are referred to as natural penicillin.
Penicillin G and penicillin V (have good effect on gram positive bacteria namely Streptococcus, anaerobic bacteria, spirochetes.
These are also β-lactam antibiotics and, like penicillin, are produced by molds. Also, like penicillin’s,
these interfere with cell wall synthesis and are bactericidal.
Cephalosporins
These cephalosporins are primarily against are active primarily against Gram-positive bacteria
First generation
These cephalosporins have increased activity against Gram-negative bacteria
Second generation
These cephalosporins have even greater activity against Gram negatives (including Pseudomonas aeruginosa)
Third generation
This is an example of a fourth-generation cephalosporin with activity against both Gram positives and Gram negatives, including P. aeruginosa.
Cefepime
This is a fifth-generation cephalosporin that has expanded activity against aerobic Gram positive cocci, including methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant
Staphylococcus epidermidis (MRSE).
Ceftaroline
These are among the most powerful antibacterial agents in use today. They also include a β-lactam ring (Fig. 9-4).
Carbapenems
What do carbapenems inhibit?
Cell wall synthesis and is effect among aerobic Gram positive, aerobic Gram negative, and anaerobes.
These are considered the “antibiotics of last resort” because of their activity against Gram negative bacteria that have developed resistance to many different antimicrobial agents.
Carbapenems (imipenem and meropenem)
If Klebsiella or Enterobacter spp. become resistant to the carbapenems, they are referred to as ______________
carbapenem-resistant
Enterobacteriaceae (CRE).
They also target the bacterial cell wall. They have excellent activity against most aerobic and anaerobic Gram-positive bacteria, but have no activity against most Gram-negative bacteria.
Glycopeptides (vancomycin)
Bacteria, especially enterococci, are becoming resistant to these drugs, and they have a number of toxic side effects. When enterococci become resistant to vancomycin, they are referred to as ____________________.
vancomycin-resistant enterococci (VRE).
These are broad-spectrum drugs that exert their effect by targeting bacterial ribosomes and thereby halting protein synthesis.
Tetracyclines
Tetracyclines are characterized as what?
Bacteriostatic
These are effective against a wide variety of bacteria, including chlamydia’s, mycoplasmas, rickettsia’s, Vibrio cholerae, and spirochetes, such as Borrelia spp. and Treponema pallidum.
Tetracyclines
These are bactericidal broad-spectrum drugs that also inhibit bacterial protein synthesis. The major factor that limits their use is their toxicity.
Aminoglycosides
These are effective against a wide variety of aerobic Gram-negative bacteria, but are ineffective against anaerobes. They are used to treat infections with members of the family Enterobacteriaceae
Aminoglycosides
These inhibit protein synthesis. These include erythromycin, clarithromycin, and azithromycin. They are effective against chlamydia’s, mycoplasmas, T. pallidum, H. influenzae, and Legionella spp.
Macrolides
Macrolides are?
(bacteriostatic at lower doses; bactericidal at higher doses
These are bactericidal drugs that inhibit DNA synthesis. The most commonly used against members of the family Enterobacteriaceae and P. aeruginosa.
Fluoroquinolone
These are broad-spectrum agents with activity against both Gram-positive and Gram-negative bacteria.
Levofloxacin and moxifloxacin
Antifungal agents work by:
(1) Binding in cell membrane sterols
(2) By interfering with sterol synthesis
(3) By blocking mitosis or nucleic synthesis
These antifungal agents have a mechanism of binding in cell membrane sterols
Nystatin and amphotericin B
These antifungal agents have a mechanism of interfering with sterole synthesis.
Fluconazole and miconazole; echinocandins)
These antifungal agents have a mechanism of blocking mitosis and nucleic acid synthesis.
Griseofulvin and 5-flucytosine
These are usually toxic to the host.
Antiprotozoal agents
Antiprotozoal agents work by:
(1) Interfering with DNA and RNA synthesis (chloroquine, pentamidine, and quinacrine)
(2) Interfering with protozoal metabolism
These antiprotozoal agents have the mechanism of interfering with protozoal metabolism
Metronidazole
These are the newest weapons in antimicrobial methodology. Difficult to develop these agents because viruses are produced within host cells.
Antiviral agents
Some drugs have been developed that are effective in certain viral infections, but not others; they work by inhibiting _____________within cells.
Viral Replication
These are (several antiviral drugs that are administered simultaneously) are being used to treat HIV infection.
Cocktails
These are microbes (mainly bacteria) that have become resistant to one or more antimicrobial agents. Infections caused by superbugs are difficult to treat!
Superbugs
If bacteria that were once susceptible to a particular drug
become resistant, this is called _____________.
Acquired resistance
Bacterial superbugs include?
(1) Methicillin-resistant Staphylococcus aureus (MRSA)
(2) Vancomycin-resistant Enterococcus spp. (VRE)
(3) Multidrug-resistant Mycobacterium tuberculosis
(MDRTB)
(5) Multidrug-resistant strains of Acinetobacter,
Burkholderia, Pseudomonas
(6) Neisseria gonorrhoeae
(7) Carbapenemase-producing Klebsiella pneumoniae (KPC
Some bacteria are naturally resistant because they lack the specific target site for the drug or the drug is unable to cross the organism’s cell wall or cell membrane and, thus, cannot reach its site of action. Resistance of this type is known as
Intrinsic resistance
Before a drug enters a bacterial cell, it must first bind to proteins on the surface of the cell; these proteins are called _______________.
Drug-binding sites
A chromosomal mutation that
affects the structure of a drug-binding site can prevent the drug from binding, resulting in _____________.
Drug resistance
Many bacteria have become resistant to penicillin because they have acquired the gene for ______________.
Penicillinase production during conjugation.
A plasmid that contains multiple genes for drug resistance is known as a ___________.
Resistance factor (R-factor).
Bacteria can also become resistant to drugs by developing the ability to produce _________________. An MDR pump enables the cell to pump drugs out before they can damage or kill the cell
Multidrug-resistance (MDR) pumps (also known as MDR transporters or efflux pumps).
–
Every penicillin, cephalosporin, and carbapenem molecule contains a double-ringed structure (referred to as a “house and garage”). The “garage” is known as the ____________.
β-lactam ring.
Some bacteria produce enzymes, ____________, that destroy this ring; when the β-lactam ring is destroyed, the drug no longer works
β-lactamases
Types of β-lactamases:
Penicillinases
Cephalosporinases
Carbapenemases
Drug companies have developed special drugs that combine a
β-lactam antibiotic with a β-lactamase inhibitor (e.g. piperacillin/tazobactam)
This is when drug therapy is initiated before laboratory results are available (i.e., before the pathogen is identified and/or before susceptibility test results are available).
Empiric Therapy
Reasons why antimicrobial agents should not be used indiscriminately:
(1) Organisms susceptible to the agent will die, but resistant ones will survive; this is known as selecting for resistant organisms.
(2) The patient may become allergic to the agent.
(3) Many agents are toxic to humans and some are very toxic.
(4) With prolonged use, a broad-spectrum antibiotic may destroy the normal flora, resulting in an overgrowth of bacteria known as a superinfection, such as Clostridium difficile-associated diarrhea.
Selecting for Drug-Resistant Organisms
A/ Indigenous microbiota of a patient before antibiotic therapy (S, susceptible; R, resistant).
B. After antibiotic therapy has been initiated.
C. Resistant organisms multiply and become the predominant organisms.
