Antimicrobials Flashcards
What do coordinate or global regulatory circuits do?
control the expression of genes encoding multiple virulence factors in some bacteria
What is quorum sensing?
a signaling system between bacterial cells that regulates the transcription of multiple genes
What is quorum sensing dependent on?
the production of one or more diffusable signal molecules called autoinducers or pheromones which enable a bacterium to monitor its own population density
Quorum sensing is an example of _____ _____ _____ in single-celled prokaryotic organisms.
coordinated multicellular behavior
What is quorum sensing used to regulate?
diverse physiological processes such as production of virulence determinants, swarming, bioluminescence and antibiotic synthesis
What are defensins?
antibacterial polypeptides that are the major effector mechanism of the natural immune system
What are some cell types tat produce defensins?
epithelial cells of the intestine, respiratory tract, mammary gland, skin, kidney, eye, and tongue, and granulocytes
What is the function of defensins?
they behave as amphiphiles that bind to the target cell membrane and form a pore or channel, attack fungi and eukaryotic cells, and stimulate wound healing by inducing synthesis of other compounds
What does the activation of toll-like receptors result in?
the production of inflammatory mediators and other products
What is the role of toll-like receptors on immune cells?
they signal that bacteria are attacking the cell
What defense mechanisms does the skin have?
mechanical barrier of dry, nonliving tissue, fatty acids, lysozyme, and normal flora
What are the defense mechanisms of mucous membranes?
mucus, cilia, phagocytic cells, saliva, stomach acid, proteolytic enzymes, flushing action of urine, tears, etc., and normal flora
What is iL1s role as a defense mechanism?
it induces fever and attracts and activates phagocytes
Normal tissues with a ___ ___ ____ are a very _____ environment for bacteria.
good blood supply, hostile
What are killed bacterins made from?
bacteria grown in culture that are then killed
How is an autogenous bacterin made?
a bacterial isolate is obtained from a diseased herd, then the isolate was used to make a bacterin for immunization of new animals coming into the same herd
What organisms are difficult to make a bacterin from?
organisms that have capsules composed of polysaccharides or organisms with polysaccharide outer layers
What is used to make a modified live vaccine?
living organisms
What is the advantage of modified live vaccines?
living pathogens are more likely to express antigens that are important in a good immune response
What are the types of genetically engineered vaccines?
Gal E, Aro A, carrier
What are Gal E vaccines?
galactose epimerase-less mutants - cell wall deficient organisms that do not survive host immune responses well
What are Aro A vaccines?
aromatic pathway mutants - these organisms are unable to synthesize PABA and thus folic acid, and subsequently DNA
What is a carrier vaccine?
an avirulent organism into which genes for antigens of other bacteria or viruses have been cloned
What is a toxoid?
an immunizing product derived from a toxin whereby the toxic portion has been inactivated but the immunogenicity has been preserved
How are toxoids made?
you use a toxin and inactivate it with formaldehyde
When are toxoids useful?
when toxins play a major role in the production of disease and where antibody against the toxin is protective
What are adjuvants used for?
they are added to bacterial vaccines to enhance the efficacy of a product
How do adjuvants work?
by slowing down the absorption of the immunogen or by enhancing or modifying the interaction of the antigen with the immune system
What immunoglobulin production is stimulated by intradermal injection or introduction of protein antigens on mucosal surfaces?
IgA
What immunoglobulin production is stimulated by an intramuscular injection?
IgG
What are biological response modifiers?
agents that alter normal host defense mechanisms or immune response
What are the two modes of action for biological response modifiers?
- enhance the ability of the host to overcome bacterial virulence factors
- overcome immunosupression
What are endogenous biological response modifiers?
those that are produced normally by the host - may be produced as recombinant proteins and administered
What are some examples of endogenous biological response modifiers?
interleukin I, interleukin II, interferon, and granulocyte-macrophage-colony-stimulating factor (GM-CSF)
What is interleukin I?
a cytokine produced mainly by mononuclear phagocytes
What is interleukin II?
a glycoprotein secreted by T-lymphocytes after antigen and IL1 stimulation
What is interleukin II required for?
the production for the proliferation of activated T-cells, natural killer cells, and other cytotoxic effector cells
What are the types of interferon?
alpha, beta, and gamma
What is GM-CSF?
a major cytokine for hemopoiesis
What does GM-CSF enhance?
eosinophil chemotaxis, maturation of macrophages and dendritic cells, granulocyte activation, adjuvant effect, and inhibition of apoptosis
What does GM-CSF regulate?
immune responses based on development and maturation of antigen-presenting cells
GM-CSF skews the immune system toward a ____ _________.
Th1 response
What are exogenous biological response modifiers?
those that are not produced by the host but whose mechanisms of action include the induction of endogenous biological response modifiers and alteration of the biological response of the host
What are some examples of exogenous biological response modifiers?
components of mycobacteria C. parvum, C. granulosum, and Lactobacillus casei Coley treatment Listeria monocytogenes + GM-CSF gut flora Toxoplasma gondii LPS monophosphoryl lipid a
What is a bacteriostatic antimicrobial agent?
an agent if it merely inhibits the growth of bacteria
What are some examples of bacteriostatic antimicrobial agents?
tetracycline, sulfonamides, and chloramphenicol
What is a bactericidal antimicrobial agent?
agents that usually rapidly kill the target organism
What are some examples of bactericidal antimicrobial agents?
penicillin, streptomysin, cephlasporins, polymyxin, and neomycin
When a bacterial pathogen is isolated from a diseased animal or human what two questions need to be answered?
- What is the identity of the pathogen?
2. What antimicrobial drugs could be used to treat the infection?
What is the minimum inhibitory concentration (MIC)?
the minimum concentration of the drug necessary to inhibit the growth of the organism
What are breakpoints?
known MIC values that have been empirically determined for a given antimicrobial with a given pathogen in a given animal species
What is minimum bactericidal concentration (MBC)
a test use to give a better indication of the usefulness of antimicrobials that are bactericidal rather than bacteriostatic
What is the spectrum of an antimicrobial agent determined by?
how wide a variety of bacteria are affected by it
How do bacteria develop resistance to antimicrobials?
- transfer of this genetic material to other bacteria
- high replication rate
- alteration of a ribosomal binding site
What can the transfer of genetic material into bacteria be mediated by?
any of the mechanisms of genetic exchange such as the transfer of R-plasmids, transposons, and integrons, infection with a bacteriophage etc.
What are the groups of antimicrobial agents?
inhibition of growth by analogues, inhibition of cell wall synthesis, cell membrane inhibitors, inhibitors of DNA synthesis, inhibitors of the 30S ribosomal subunit, inhibitors of the 50S ribosomal subunit, and inhibitors of protein assembly
What antimicrobials are in the ‘inhibition of growth by analogues’ group?
sulfonamides, sulfones, and para aminosalicyclic acid
How do sulfa drugs work?
they are analogues of PABA and compete with it in the pathway for folic acid synthesis - in sufficient concentration, the sulfa drug will competitively inhibit this pathway and prevent the growth of bacteria
What species are sulfonamides banned in and why?
food animals because they are known to precipitate in the kidney
What are sulfonamides given in combination with?
trimethoprim
What does trimethoprim do?
inhibits the same folic acid synthetic pathway but does so by acting on dihydrofolate reductase
What is a commonly used trimethoprim-sulfa combination product?
tribrissen
What antimicrobials are in the ‘inhibition of cell wall synthesis’?
beta lactams (penicillins), semisynthetic penicillins, cephalosporins, bacitracin, vancomycin, and bambermycin
What do beta lactams do?
they bind to the transpeptidase enzyme and become irreversibly bound and thus incativated - cross-bridging cannot occur
What is beta lactams mechanism of action?
to kill actively growing cells by weakening the peptidoglycan to the point that the bacterium cant undergo normal cell division and bursts
Is penicillin more active against gram positive or gram negative bacteria?
gram positive
What is an example of a semisynthetic penicillin?
amoxicillin and cloxacillin
What is the difference between beta lactams and semisynthetic penicillins?
they have been engineered to have different properties such as the ability to withstand stomach acid and are more active against gram-negatives
What is the most important property of some of the semisynthetic penicillins?
their ability to resist breakdown by the penicillinase enzyme produced by many bacteria
What are suicide molecules?
molecules that bind to penicillinase enzymes thus preventing them from destroying the active beta lactam ring structure of penicillins such as amoxicillin
What are some examples of suicide molecules?
clavulanic acid and tazobactam
What is clavamox?
a combined product of amoxicillin and clavulanic acid
What is the structure of cephalosporins?
they have a nucleus that resembles the penicillin nucleus and have a similar mechanism of action
What are some examples of cephalosporins used in food animals?
ceftiofur (naxel, excenel, and excede)
What are some examples of cephalosporins used in small animal medicine?
cefodoxime (simplicef) and cefovecin (convenia)
What are the advantages of cephalosporins?
resistance to penicillinase to varying degrees
they are not as allergenic as penicillin
as a group, they have a broad spectrum of activity
What are older cephalosporins active against and what is an example?
cephalothin - active against most gram-positive bacteria but have limited activity against gram-negatives
What are older cephalosporins referred to as?
first generation cephalosporins
What are second generation cephalosporins active against?
most gram-positive bacteria but are also active against some gram-negatives
What are some examples of third generation cephalosporins?
ceftiofur (naxcel, excenel), cefovecin, and cefpodoxime
What are third generation cephalosporins active against?
gram-positives but are effective against most gram-negatives
What is the structure of third generation cephalosporins?
they are highly protein bound which protect the drug from elimination and covey a long plasma elimination half life
What is bacitracin?
a polypeptide isolated from B. subtilis that interacts with the bacterial cell membrane to prevent transfer of structural components
What type of antimicrobial agent is bacitracin and what type of bacteria does it affect?
bactericidal - gram positives
How is bacitracin given?
topically but it is highly toxic when given systematically
What drug is vancomycin similar to?
bacitracin
What is vancomycin used to treat?
serious staphylococcal infections in humans that are not responsive to other antimicrobials
What is bambermycin?
a complex of antimicrobial substances produced by Streptomyces bamberiensis with a trade name of flavomycin
What is bambermycin active against?
gram positive cell wall synthesis but has little activity against some of the normal flora such as lactobacillus
What antimicrobials are ‘cell membrane inhibitors’?
polymyxin and polyenes
Which polymyxins are in use?
B and E because the others are toxic
How do polymyxins work?
they bind to the outer surface of cell membranes and disrupt the structure and function of the phospholipid and lipopolysaccharide components
What are polymyxins active against?
gram-negatives
What infections are polymyxins used for?
severe Pseudomonas aeruginosa infections
How do polyenes work?
they selectively inhibit organisms whose cell membranes contain sterols and because of this are used to treat fungal infections
What are some common polyenes?
amphoteracin B, nystatin, and azoles
What is amphoteracin B used to treat?
systemic fungal infections but has a number of serious side effects such as nephrotoxicity
How is nystatin used?
it is too toxic to use systemically, but is commonly found in topical preparations
What are some examples of azoles?
ketoxonazole, miconazole, and clotrimizole
How do azoles work?
they interfere with the synthesis of ergosterol in the fungal cell membrane
How is Ketoconozole used?
systemically
How are triazoles (fluconazole) given?
orally
What drugs are ‘inhibitors of DNA synthesis’?
quinolones, metronidazole, novobiocin, carbadox
What do quinolones do?
selectively block DNA synthesis in susceptible bacteria by inhibiting DNA gyrase A - knwon as DNA gyrase inhibitors
Which quinolones are in widest use?
fluoroquinolones
Provide some examples of quinolones used in veterinary medicine.
enrofloxacin (baytril) and danofloxacin
What are some quinolones used in human medicine?
norfloxicin and ciprofloxicin
What species are fluroquinolones banned in?
food producing animals
What is metronidazole used against?
infections with anaerobic bacteria and some protozoa
What is metronidazole ineffective against?
aerobes and facultative anaerobes
What is novobiocin used for?
it is a bactericidal for a number of bacteria, especially gram positives
How does novobiocin work?
it inhibits DNA gyrase B which accounts for the differences in spectrum compared to quinolones
What is Novobiocin used for in bovine?
mastitis
What is carbadox used for?
swine feed at weaning to control bacterial enteritis and as a growth promoter
What does carbadox do?
it intercalates into bacterial DNA and causes mutations
How does rifampin work?
it selectively inhibits DNA-dependent RNA polymerase of bacteria
What is rifampin useful against?
gram-positives, mycobacteria, and rhodococcus equi
What drugs are in the ‘inhibitors of the 30S ribosomal unit’?
aminoglycosidic aminocyclitols, tetracyclines, and nitrofurans
What are some aminoglycosidic aminocyclitols?
streptomycin, neomycin, kanamucin, gentamicin, spectinomycin, amikacin, and tobramycin
How must aminoglycosidic aminocyclitols given?
parenterally or topically applied
Why must you be cautious when giving aminoglycosidic aminocyclitols to renal compomised animals parenterally?
because they can be nephrotoxic and ototoxic
What is a negative of aminoglycosidic aminocyclitols?
they can produce residues in tissues in food producing animals
What do tertracyclines do?
inhibit protein synthesis at the 30S ribosomal subunit
What are some examples of tetracyclines?
chlortetracycline, aureomycin, oxytetracycline, and doxycycline
What do nitrofurans do?
they inhibit protein synthesis by preferentially inhibiting the synthesis of inducible enzymes necessary for translation
What is nitrofurantion used for?
urinary tract infections
What is a common nitrofuran?
furacin
What drugs belong in the ‘inhibitors of the 50S ribosomal subunit’ group?
chloramphenicol, florfenicol, macrolides, erythromycin, lincomycin, tilmicosin, and tiamulin
How does chloramphenicol work?
it acts by binding to the 50S subunit, preventing fRNA from binding and thus inhibiting peptide bond formation
What are the side effects of chloramphenicol?
severe, fatal, aplastic anemia in humans
What species is chloramphenicol prohibited in?
food-producing animals
How is resistance to chloramphenical gotten?
through the high level production of chloramphenicol acetyltransferase or through changes in the permeability or the bacterial membrane that prevent the drug from reaching its target
What are some examples of florfenicol?
nuflor, nuflor gold and aquaflor
What is florfenicol used for?
bovine CNS and respiratory disease
What is erythromycin?
a macrolide antibiotic that attaches to the same site on the 50S ribosomal subunit as cloramphenicol
What shouldn’t erythromycin be combined with?
lincomycin because they compete with the same sites
How does resistance to erythromycin occur?
by genetic mutation resulting in structural alteration of the 50S ribosomal subunit
What is lincomycin?
a macrolide that is commonly used in feed in the US
What is an example of lincomycin?
clindamycin
What does lincomycin cause in horses?
severe, potentially fatal diarrhea
What species is tilmicosin used in?
cattle, sheep, and swine
What is tilmicosin used to treat?
respiratory disease
How is tilmicosin administered?
subcutaneously
What is tilmicosin toxic to?
humans, goats, and swine
What are some examples of tilmicosin?
Drazzin, zactran, and zuprevo
What is tiamulin used for?
fattening swine
How does tiamulin work?
it binds to the 50S ribosomal subunit and inhibits protein synthesis primarily in staphylococci, streptococci, and spirochetes
What is tiamulin not active against?
gram negative bacteria
What drugs belong in the ‘inhibitors of protein assembly’ group?
griseofulvin
What is griseofulvin used for?
the treatment of dermatophyte infections
How does griseofulvin work?
it acts by inhibiting mitosis and thereby preventing replication of actively growing fungi
