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What are the characteristics of ideal antimicrobial drugs?
Toxic to the microbe but non toxic to the host, microbicidal not microbistatic, relatively soluble and functions even when highly diluted in body fluids, remains potent long enough to act and is not broken down or excreted prematurely, does not lead to the development of antimicrobial resistance, complements or assists the activities of the host’s defenses, remains active in tissues and body fluids, readily delivered to the site of infection, does not disrupt the host’s health by causing allergies or predisposing the host to other infections
What are antimicrobials?
an all inclusive term for any antimicrobial drug regardless of its origin
What are antibiotics?
substances produced by the natural metabolic process of some microorganisms that can inhibit or destroy other microorganisms, a lot of the times being produced by molds or bacteria
What is the difference between antimicrobials and antibiotics?
the main difference is antimicrobials can be made to kill anything and antibiotics are made to kill bacteria
What is a broad spectrum antimicrobial and when would it be used?
antimicrobial that works on a large number of species, it’s good for killing a lot of microbes but can also kill good bacteria leading to things like oral flush in your mouth
What is a narrow spectrum antimicrobial and when would it be used?
inhibitory to a limited range of bacteria, good for killing a specific kind of microorganism
What is colonization?
the establishment of a microbial population on or within a host without causing apparent disease symptoms
What is infection?
growth of organisms in the body
What is disease?
harm to the body via an infection
What is mutualism?
both parties benefit, example would be protozoans and termites since the protozoans secrete digestive enzymes for the termites, example would be lichens since it’s between fungi and algae or cyanobacterium
What is commensalism?
one member benefits and the other is neither helped or harmed, example would be most of the flora in our bodies since we provide protection and they don’t bother us
What is parasitism?
one member benefits at the expense of the other, often disease causing organisms
What is neutralism?
two organisms coexist but neither has any effect on the other, positive or negative
What could cause a commensal organism to become a pathogen?
If someone has a depressed immune system (could be caused by AIDS, organ transplant, severe burns, wounds) that could allow nonpathogens to become pathogens if they’re opportunistic
What is opportunism?
the ability of microorganisms, like certain bacteria, viruses, or fungi, to cause disease when they take advantage of a host's weakened immune system
What are the steps of opportunism?
Finding a portal of entry
Attaching firmly and Negotiating the Microbiome
Surviving Host defenses
Causing Damage (disease)
Exiting host
What is an infectious dose?
minimum number of pathogenic microorganisms to establish infection
What does virulence mean, and what does high vs low virulence mean?
the degree to which a pathogen can cause disease in its host. High virulence means more harmful and more symptoms, low virulence means less harm and less symptoms
Is a high infectious dose more virulent than a low infectious dose?
no a low infectious dose means they need less of the organism to cause an infection, so the low infectious dose would be more virulent
What is the lethal dose (LD50)? Is a low or high LD50 more virulent?
the dose of pathogenic organisms to kill 50% of an animal’s population. A low LD50 is more virulent since less of the pathogens are required to kill 50% of the population
What is the difference between signs and symptoms?
signs are objective, something someone else can see or measure like a rash or fever. symptoms are subjective, something the patient is feeling but no one else can see or measure like headaches or nausea
What is a syndrome?
disease can be identified by signs and symptoms
What are reservoirs and what are examples of living vs nonliving reservoirs?
sites where microbes survive and potentially multiply. Living are humans animals or plants, nonliving are soil and water
What are the ways of transmission of infectious agents and what are examples?
direct which is contact (kissing, sneezing, coughing), animal bites, or can be transplacental. indirect which is through vehicles (doorknobs, eating utensils, toys), airborne (shaking bedsheets, sweeping, mopping), aerosols which are suspensions of water particles and fine dust that can cause disease, and vectors (mosquitoes, ticks, flies)
What is the difference between endotoxins and exotoxins?
endotoxins are lipopolysaccharides in the outer membrane of gram negative bacteria that are released when the cell dies which cause an inflammatory response. exotoxins are proteins actively secreted by bacteria (gram positive or negative) that are very specific and can disrupt cell processes or destroy cells
What is the goal of antimicrobial treatment?
destroying the infectious agent without harming the host cells
What is selective toxicity?
the ability of a drug or agent to kill or inhibit a pathogen without harming the host organism
What structures or features of prokaryotes can be targeted by antimicrobials?
flagella, cell wall, cytoplasmic membrane, DNA/RNA polymerase, and stopping folic acid synthesis
What are the sources used to obtain antimicrobials?
they can be made from almost anything, so soil, bacteria, plants, animals, fungi, or even synthetic compounds made in a lab
What is the difference between microbicidal and microbiostatic?
microbicidal agents kill microorganisms, while microbiostatic agents inhibit their growth without killing them
What is disc diffusion (Kirby Bauer technique)?
there will be 2 discs on the plate and around the disc there will be no bacteria growing. This is because from the center of the disc there’s a drug that kills bacteria so the farther out the drug disperses the more bacteria it will kill
What is tube dilution method?
used to determine minimum inhibitory concentration (MIC) this is done by putting the same amount of bacteria in each tube but different amounts of the drug. The MIC is the the first tube or well with no growth, indicating the lowest concentration of drug that kills the cells
What is the zone of inhibition and what does a small vs large circle mean?
the circular area around an antibiotic that indicates inhibited or slowed microbial growth. A small circle means the microbe is more resistant to the antibiotic and a large circle means the microbe is less resistant to the antibiotic
What is therapeutic index and which is preferable, high or low?
the ratio of a toxic dose of a drug compared to MIC. this means a bigger therapeutic index is better because it’s a wider range between the effective and toxic doses, so bigger the number the better
What are penicillinases and what do they do?
bacterial enzymes that can break the beta lactam ring of penicillin, thereby inactivating the drug
What are the 5 major targets of antimicrobial agents?
cell wall synthesis, protein synthesis, nucleic acid replication and transcription, plasma membrane integrity, essential metabolic pathways
How do penicillins work?
inhibits the synthesis of bacterial cell walls by interfering with the linking of PPG
How do sulfonamides work?
inhibiting the synthesis of folic acid which is needed for bacterial growth and cell division
How are biofilm infections different than nonbiofilm infections and why are they harder to treat?
biofilm infections are made from a protective community of bacteria rather than free floating bacteria in nonbiofilm infections. This makes it harder for antimicrobials to penetrate into the biofilm and bacteria in a biofilm can sometimes express different genes than ones who aren't, plus some drugs like aminoglycosides can cause biofilms to grow faster
What are the targets of antifungal drugs?
cause fungal membranes to lose selective permeability, interfere with their sterol synthesis, inhibit cell wall synthesis, inhibit their DNA synthesis
What are the targets of antiprotozoal drugs?
interfere with metabolism and DNA and RNA synthesis, however can be very toxic to the host
What are the targets of antihelminthic drugs?
doesn’t get rid of adults but blocks reproduction, they can also paralyze by preventing glucose metabolism, disintegrate, and inhibit metabolism
Why are antifungal, antiprotozoal, and antihelminthic drugs more likely to be toxic to humans than antibacterial drugs?
because we’re all eukaryotes so the therapeutic index is way smaller
What are the 3 targets for antiviral drugs?
Inhibiting virus entry, inhibiting nucleic acid synthesis, inhibition of viral assembly/release. This does often kill the host cell however
How do microbes acquire antimicrobial resistance?
acquiring a gene that enables the bacterium to produce an enzyme that destroys or inactivates a drug or acquisition of a gene via horizontal gene transfer that enables a bacterium to produce a multi drug resistance pump
What are 5 structures or mechanisms that microbes use to resist antimicrobials?
Decreased permeability of plasma membrane does not allow antibiotic to enter
Altered receptor sites do not allow antibiotics to fit
Antibiotics removed from cell via pumps
Antibiotics broken down by newly synthesized enzymes
Metabolic pathways are shut down or an alternative pathways are used which occurs via mutation of original enzymes
What are superbugs and why should we be concerned about them?
microbes that have developed a resistance to one or more antimicrobials. This is concerning because they often can’t be treated and when they reproduce their offspring have the same resistance.
What are some new antimicrobial strategies we can use?
Combine β-lactam antibiotic with a specific inhibitor of β-lactamases. The inhibitor binds irreversibly with the β-lactamase and prevents its action. The drug can enter the cell and inhibit cell wall synthesis.
Bacteriophages: target specific strains of a bacteria while leaving normal microflora alone
RNA interference: small pieces of RNA interfere with the expression of genes
Defense peptides: break holes into membranes
CRISPR: make cuts in genes so they can’t function anymore
What are some undesirable side effects of antimicrobial therapy?
Resistant organisms will be unaffected, the patient could be allergic to the agent, some drugs cause toxic effects to the host, broad spectrum antibiotics can destroy the natural microflora of the GI tract which are supposed to be helpful
What is a superinfection and how does it occur?
When you take something like penicillin to get rid of a pathogen, but then once so many of those organisms are killed of that means that organisms that were once competing with those pathogens are competing with nobody anymore so they multiply like crazy since they’re not suppressed anymore
How do we acquire our microbiome?
Some colonization before birth, colonization during birth, 8-12 hours after birth, and there are microbes present in breast milk with 600 species and it has sugars that the baby can’t digest. Also babies putting things in their mouth gives them microbes as well.
What are the sites that normal microbiota are found in humans?
skin, mouth, respiratory tract, gastrointestinal tract, urinary tract, reproductive tract
What influences our microbiome and how can we change it?
age, diet, genetics, and environment. We can change it by eating more probiotic + prebiotic rich foods, exercising, and only using antibiotics when necessary
How is the human microbiome project changing the understanding of normal biota?
we are finding many different microbes in places we didn’t expect. As well as discovering everyone's microbiome is different
What are the benefits of having a microbiome and what does our microbiome do for us?
a microbiome allows our bodies to harvest nutrients we wouldn’t be able to on our own (however this also means the nutrient value of food is dependent on the individual’s microbiota and how well those microbiota can harvest nutrients). Our microbiome also can protect us by teaching our bodies what is a good vs bad microbe, help with structure by fortifying barriers, and help with metabolic functions like synthesizing vitamins
What is fecal bacteriotherapy and what can it help with?
healthy donor poop is put into the gastrointestinal tract of the patient so the patient has healthy bacteria in their system to fight whatever disease (often c. dif) in their gastrointestinal tract
What is quorum sensing and how can it be used to prevent disease?
a method of communication that bacteria use to coordinate action, like sending out signals to all release at the same time to increase virulence. By disrupting this communication, we can stop bacteria from working together thereby inhibiting their ability to cause infections
How do viruses attach to host cells?
they have special receptors that attach to the host cell and make their way inside, very specific
How do microbes establish infection?
entering the body, adhesion which is attaching to host cells and not being washed away, avoiding host defenses and phagocytosis because of capsules, and periodically changing their appearance so antibodies don’t recognize them
What are the offensive strategies microbes use to cause disease?
toxins (endo and exo) and enzymes that can trigger a harmful host response, and both of these can prevent phagocytosis and change the gene expression of the host
What are the 3 kinds of exotoxins and what do they do?
cytotoxins destroy cells, neurotoxins interfere with nerve impulses, enterotoxins affect the GI tract
What is the difference between toxins and enzymes in microbial disease?
toxins are poisons that directly damage host cells or disrupt their functions, while enzymes are catalysts that break down host tissues to help the microbe feed or spread
What is an injurious host response and how does it affect disease progression of an infection?
Host’s excessive or inappropriate response to a microorganism so it’s not just the microbe, it’s interplay between host and invader which can delay recovery time or make the disease even worse
What is the chain of infection and why is it important?
Pathogen, Reservoir (source of pathogen), Transmission to new host, Portal of entry into susceptible host, Portal of exit from host, back to start. This is important becauseEach link in this chain is a target, so doing things like controlling mosquito populations reduces the reservoir, washing hands eliminates the mode of entry, covering your sneeze eliminates the mode of exit, and immunizing the population reduces susceptible hosts
What are portals of entry and exit for pathogens?
Entry: eyes, mouth, nose, skin, cuts
Exit: any hole in your body, cuts, nose, sneeze
What are the different kinds of carriers of a pathogen?
Active which are people who currently have the disease, Incubating which are people who have the disease but it hasn’t fully incubated yet, Healthy/Asymptomatic which are people who have no symptoms but they spread the disease, Chronic which are people who still have the disease even after they recover, and Passive which are most often health care workers who interact with disease all the time
What are direct and indirect modes of transmission of infectious agents?
Direct: contact (kissing, sneezing, coughing), animal bites, transplacental
Indirect: Vehicles (doorknobs, eating utensils, toys), airborne (shaking bedsheets, sweeping, mopping) Aerosols are suspensions of water particles and fine dust that can cause disease, vectors (mosquitoes, ticks, flies)
What are fomites and what are examples?
inanimate objects that can hold a germ. Doorknobs, keyboards, toys, surgical instruments, medical equipment, bedding
What is a zoonotic infection?
disease naturally occurs in animals but can be transmitted to humans
What are vectors and what’s the difference between a mechanical vector and a biological vector?
a living organism that transmits the disease to you indirectly
Mechanical - vectors that transmit passively, microbe doesn’t have to reproduce in the vector for it to stay alive
Biological- necessary component of the life cycle of the pathogen, and they are required for the multiplication and development of the microorganism
What are healthcare associated infections and what are the 3 most common types?
also called nosocomial, happens because people are already sick and then they’re exposed to more pathogens in the hospital. Healthcare personnel may be passive carriers due to improper hand washing or carelessness. 3 most common types are urinary tract infections, surgical sites, and respiratory.
What are Koch’s postulates used for and why are they not always effective?
used to show how a particular microbe causes a particular disease. Not always effective because sometimes there isn’t an animal model, it’s very difficult to obtain a pure culture of viruses, some organisms can’t be grown on laboratory media
What’s the difference between epidemiology and pathology?
Epidemiology: the study of how a disease affects a population, so determine the cause of an an outbreak and other public health concerns
Pathology: the study of how the disease affects the body
What did Hippocrates do for epidemiology?
understood certain disease were more prevalent near swampy areas, so people shouldn’t live there since they could get yellow fever and malaria
What did Jenner do for epidemiology?
cowpox and smallpox were related, which led to smallpox immunization
What did Semmelweis do for epidemiology?
reduced childbed fever by making doctors wash their hands between visits
What did Nightengale do for epidemiology?
cleanliness in war hospitals, statistical analysis showing that her methods worked to save lives
What did John Snow do for epidemiology?
most people affected with cholera lived in a small area and seemed to use the same water pipe, so he removed the pump handle so people had to use a different water source which helped reduce the spread. Another example later on was people were buying water from a certain manufacturer that was getting the water from a river infected with sewer water so a lot of people got the disease
What is an epidemic?
larger than normal number of cases of a disease in a certain period of time, doesn't have to be a huge amount of people but it just has to be more than normal
What are the different kinds of epidemics?
Sporadic: occasionally, irregular intervals
Endemic: continuously present in a population, like the common cold
Pandemic: more than one country at once
Point-Source: one single contaminated source in a short time like a potluck item
Common-Source: one single contaminated source over a long time like a contaminated water source
Propagated: person to person transfer like influenza, not just one source
What is herd immunity and why is it important?
Proportion of immunized or resistant individuals, higher herd immunity means less chance of an epidemic and a decrease in herd immunity can lead to epidemics
What are some epidemiology agencies and what do they do?
CDC and WHO identify potential outbreaks using data from health care centers and agencies. IFDE identified 94 diseases for potential eradication
Why was smallpox “easy” to eradicate?
no natural vectors or biological vectors, duration of infectiousness is limited, characteristic rash, recovery means permanent immunity, one dose cheap stable vaccine, long lasting immunity from vaccination, permanent and recognizable scar from vaccination
What does it mean if a disease is notifiable vs reportable and what are examples?
Notifiable: need to know if the diseases appear or increase in frequency, helps reduce chances of epidemics
Reportable: high amounts of people being infected
examples would be smallpox, AIDS, measles etc
What is the difference between incidence and prevalence?
Prevalence: total number of existing cases in a given population
Incidence: number of new cases over a certain time period
What are the 3 components of the first line of defense?
physical barriers, chemical barriers, and microbiota barrier
How do normal microbiota contribute to the first line of defense?
outcompeting pathogens for nutrients and colonization sites, produce bacteriocins which it have a narrower range than and more potent than antibiotics, and our microbiomes also teach our immune system how to defend ourselves
How is the 3rd line of defense different than the first and second lines and are all 3 necessary when fighting a pathogen?
The third line of defense is adaptive and is made specifically for the specific microbe you are fighting, but three lines are not always needed for a good immune response
What are physical barriers and what are some examples?
protecting your body mostly on the outside, like skin, nose hairs, sebum, mucus membranes
What are some chemical defenses and where they are in the body?
compound in mucous membranes, saliva, ear wax, low pH of skin, antimicrobial chemical in semen, and acidic pH of the vaginal fluid
What is the mononuclear phagocyte system/reticuloendothelial system and how does it relate to innate immunity?
network of macrophages and monocytes that engulf damaged cells, pathogens, virus particles. Overall the system is loaded with different types of macrophages
What is the structure and function of the lymphatic system?
a network of vessels, nodes, and organs like the spleen and thymus that circulate a fluid called lymph. the primary function is to filter lymph and remove waste pathogens and dead cells, while also producing and maturing immune cells
What is the difference between specific and non specific immunity?
Nonspecific involves macrophages attacking a general array of targets, specific involves B and T cells attacking specific threats
What are the 4 steps of phagocytosis?
Chemotaxis: directed migration where phagocytic cells are attracted to a site by a chemical gradient and they follow the chemical as it gets stronger
Attachment: phagocyte attaches to the invader or foreign material. Capsules often mask ligands for attachment so complement or antibodies can opsonize the bacteria and allow the phagocyte to attach, also pattern recognition receptors (PPRs) like peptidoglycan and lipopolysaccharide can also be used to grab onto cells and pull them into the phagocytes.
Ingestion: the cell after being attached to the macrophage is surrounded by the arms of the macrophages and then they are surrounded and eaten
Digestion: a lysosome binds to the phagosome and a bunch of enzymes are used to digest the bacterial cell
What is the purpose of inflammation?
localize the infection, to prevent spread of pathogens, to destroy and detoxify pathogens, and to aid in repair and healing
What are the 4 steps of inflammation?
Injury/immediate reaction
Vascular reactions
Edema and pus formations
Resolution scar formation
How does edema assist in eliminating pathogens?
fluid dilutes toxic substances, then fibrin clot traps bad microbes making it easy for phagocytosis
How does the fever mechanism work?
stimulates white blood cells to deploy and destroy, reduces available free plasma iron, induces the production of interleukin I which causes proliferation and activation and maturation of lymphocytes. It also slows down the rate of growth of some pathogens and kills some pathogens outright
What are potential detrimental effects of fever?
prolonged high fevers, tachycardia, elevated respiratory rate (tachypnea), increased caloric demand, mild to severe dehydration, lowering of seizure threshold
How do different organisms attach to host cells?
bacteria use fimbriae, viruses use spike proteins, protozoa use specialized attachment organelles, fungi use cell wall diffusion