Bios 350 Exam 4

asymptomatic carrier

- Active carrier with no signs or symptoms

Pandemic

- An epidemic that occurs on a worldwide scale;

Minimum Inhibitory Concentration (MIC)

- Antibacterial dilution tests - the lowest concentration of drug that inhibits visible bacterial growth; - Determining these concentrations helps identify the correct drug for a particular pathogen. - The MIC is determined by examining the tubes to find the lowest drug concentration that inhibits visible growth; this is observed as turbidity; -

Selective toxicity

- Antimicrobial drugs selectively kill or inhibit the growth of microbial targets while causing minimal or no harm to the host - Most antimicrobials are antibacterial because the prokaryotic cell provides a greater variety of unique targets for selective toxicity, in comparison to fungi, parasites, and viruses

Why is treatment of fungal, protozoan, and helminth infections difficult?

- Are eukaryotic - cell similar to humans - difficult for selective toxicity -

Clinical Considerations in Prescribing Antimicrobial Drugs

- Bacteriostatic (reversible inhibition) vs bactericidal mechanisms: bactericidal is required in patients who are immunocompromised. - spectrum of activity - dosage - route of administration - Potential for side effects - potential interactions between drugs

Common source vs Propagated Spread of Infectious disease

- Common Source: single source for all of the individuals infected; - Propagated Spread: occurs through direct or indirect person-to-person contact; there is no single source for infection; each infected individual becomes a source for one or more subsequent infections;

communicable, contagious, and noncommunicable

- Communicable: capable of being spread from person to person through either direct or indirect mechanisms. - Contagious: easily spread from person to person; can vary in degree of contagiousness; - noncommunicable: is not spread from one person to another; infections come from soil or water or open skin wounds;

mortality

- Death

exoenzyme: proteases

- Degrades collagen in connective tissue to promote spread;

Minimum Bactericidal Concentration (MBC)

- Dilution test - the lowest drug concentration that kills ≥ 99.9% of the starting inoculum; - Determining these concentrations helps identify the correct drug for a particular pathogen. - Tubes with no visible growth are inoculated onto agar media without antibiotic and serum levels of an antibacterial should be at least three to five times above the MIC for treatment of an infection.

epidemic

- Diseases for which a larger than expected number of cases occurs in a short time within a geographic region; -Ex. Influenza

endemic

- Diseases that are constantly present (often at a low level) in a population within a particular geographic region; - Such as malaria in Brazil

Sporadic

- Diseases that are seen only occasionally, and usually without geographic concentration; Ex. tetanus, plague

Emerging vs. reemerging infection disease

- Emerging: is either new to the human population or has shown an increase in prevalence in the previous twenty years. - reemerging: is increasing in frequency after a previous period of decline.

Etiological agent

- Etiology: the study of the causes of disease; - Cause of the disease is the agent;

Exoenzyme: Hyaluronidase

- Exoenzymes in general: enable them to invade host cells and deeper tissues; - Degrades hyaluronic acid that cements cells together to promote spreading through tissues;

endotoxin vs exotoxins

- Exotoxins are protein molecules that are produced by a wide variety of living pathogenic bacteria. - Majority of exotoxins are produced by gram positive bacteria; - Endotoxins stimulate the general systemic inflammatory response; BUT exotoxins are more specific in their action and target; -Exotoxins are also denature more at higher temperatures; Endotoxins are more heat tolerant; -Only a small concentration of exotoxins are required for toxicity;

Synergistic drug interactions

- For the optimum treatment of some infections, two antibacterial drugs may be administered together - Ex. trimethoprim and sulfamethoxazole (Bactrim). - Provide a benefit to the patient

Dosage

- The amount of medication given during a certain time interval; - Factors that contribute to ensuring optimum therapeutic drug levels: mass of patient; metabolism of drugs; half life of drug; dose vs time dependency

stages of pathogenesis: invasion

- involves the dissemination of a pathogen throughout local tissues or the body. Pathogens may produce exoenzymes or toxins, which serve as virulence factors that allow them to colonize and damage host tissues as they spread deeper into the body. Virulence factors also protect pathogens from host immune defenses.

semisynthetic antimicrobials

- is a chemically modified derivative of a natural antibiotic. - The chemical modifications are generally designed to increase the range of bacteria targeted, increase stability, decrease toxicity, or confer other properties beneficial for treating infections;

synthetic antimicrobials

- is a drug that is developed from a chemical not found in nature. - The success of the sulfa drugs led to the discovery and production of additional important classes of synthetic antimicrobials, including the quinolines and oxazolidinones

Influenza viral virulence: antigenic shift

- is a major change in spike proteins due to gene reassortment; - occurs typically when two different influenza viruses infect the same host.

active carrier

- is an infected individual who can transmit the disease to others. - may transmit the disease during the incubation period (before they show signs and symptoms) or the period of convalescence (after symptoms have subsided)

Role of the CDC

- is charged with protecting the public from disease and injury. - monitors diseases on the notifiable diseases list; -Publishes the Morbidity and Mortality Weekly Report (MMWR).

local infection

- is confined to a small area of the body, typically near the portal of entry. - Ex. boil on skin at entry point; urinary tract infection confined to bladder;

Host Immune system evasion: antigenic variation

- is the alteration of surface proteins so that a pathogen is no longer recognized by the host's immune system; -

Prevalence

- is the number, or proportion, of individuals with a particular illness in a given population at a point in time.

Influenza viral virulence: antigenic drift

- is the result of point mutations causing slight changes in the spike proteins hemagglutinin (H) and neuraminidase (N). - Small antigenic changes over time;

Role of WHO

- monitors and reports infectious diseases - also develops and implements strategies for their control and prevention.

Host Immune system evasion: M protein

- on the fimbriae of certain bacteria - inhibits phagocytosis by blocking the binding of the complement molecules that assist phagocytes in ingesting bacterial pathogens. Works by altering binding surface; -

Drug resistance

- overuse - misuse -subtherapeutic dosing - Patient noncompliance with the recommended course of treatment

Antagonistic drug interactions

- produce harmful effects - can occur between two antimicrobials or between antimicrobials and non-antimicrobials being used to treat other conditions. - cause loss of drug activity - Ex. Antacids + antimicrobials absorbed in the acidic environment of the stomach

Virulence factors

- produced by individual pathogens, which determine the extent and severity of disease they may cause; - encoded in genes

Host Immune system evasion: Proteases

- protect against phagocytosis. - combat antibody-mediated killing and clearance by attacking and digesting the antibody molecules

Genomic changes that can cause drug resistance

- selection for chromosomal mutations that confer resistance which can be transferred vertically; - Horizontal transfer of plasmids carrying resistive genes; Transposons

stages of pathogenesis: infection

- successful multiplication of the pathogen leads to infection.

Broad-spectrum antimicrobial

- targets a wide variety of bacterial pathogens, including both gram-positive and gram-negative species, and is frequently used as empiric therapy to cover a wide range of potential pathogens while waiting on the laboratory identification of the infecting pathogen - used in polymicrobic infections - Used as prophylactic prevention of infections with surgery/invasive procedures.

Narrow-spectrum antimicrobial

- targets only specific subsets of bacterial pathogens; - Ex. only target gram positive or gram negative

Routes of administration for antimicrobial drugs

- the method used to introduce a drug into the body, is also an important consideration for drug therapy - Orally: absorbed from GI tract into bloodstream - Topical: antifungal creams - parenteral route: intravenous or intramuscular injection - For most drugs, the plasma levels achieved by intravenous administration is substantially higher and peaks faster than levels achieved by oral or intramuscular administration

Body's portals of exit

- the skin and the respiratory, urogenital, and gastrointestinal tracts. - mouth: coughing and sneezing - urogenital: semen, feces, urine, etc. - Skin: shedding skin cells, sweat -

Zoonotic disease

- transmitted from animals to humans

Host Immune system evasion: Kinases

- trigger the conversion of plasminogen to plasmin, which is involved in the digestion of fibrin clots. By digesting a clot, ----- allow pathogens trapped in the clot to escape and spread;

Polymixins

-Mode of action: target the bacterial membrane; are lipophilic with detergent-like properties and interact with the lipopolysaccharide component of the outer membrane of gram-negative bacteria, ultimately disrupting both their outer and inner membranes and killing the bacterial cells. - Microbes they are used against: gram negative; multi resistant bacteria

Risk associated with broad-spectrum antimicrobials

-Risk is that they will target a wide variety of normal microbiota; -Superinfection: Secondary infection

Signs vs symptoms

-Signs: are objective and measurable, and can be directly observed by a clinician. Vital signs, which are used to measure the body's basic functions, include body temperature (normally 37 °C [98.6 °F]), heart rate (normally 60-100 beats per minute), breathing rate (normally 12-18 breaths per minute), and blood pressure (normally between 90/60 and 120/80 mm Hg) - Symptoms: are subjective; are felt by patient; loss of appetite, pain, etc.

Dorothy Hodgkin (1910-1994)

-Studied crystallography - determined structure of penicillin -This then allowed other scientists to produce semisynthetic drugs

Multiple drug resistant microbes (MDRs)

-Superbugs - carry one or more resistance mechanism(s), making them resistant to multiple antimicrobials.

Significance of healthcare-associated (nosocomial) infections (HAIs)

-infections acquired in health care facilities are called nosocomial; - Significant because higher rates of transmission are prevalent in these places;

4 steps of Koch's postulates

1. The suspected pathogen must be found in every case of disease and not be found in healthy individuals. (false) 2. The suspected pathogen can be isolated and grown in pure culture. (false) 3. A healthy test subject infected with the suspected pathogen must develop the same signs and symptoms of disease as seen in postulate 1. 4. The pathogen must be re-isolated from the new host and must be identical to the pathogen from postulate 2.

focal infection

a localized pathogen, or the toxins it produces, can spread to a secondary location.- Ex. infection site is in the gums but then pathogen enters bloodstream.

superinfection

an infection on top of another infection - develops when the antibacterial intended for the preexisting infection kills the protective microbiota, allowing another pathogen resistant to the antibacterial to proliferate and cause a secondary infection

primary/secondary infection

an initial infection is complicated by a second one in the same or a different location and caused by a different microbe.

natural antibiotics

Produced by microbes in nature, inhibit growth of competing bacteria - Ex. Penicillin

Epidemiology

concerns the geographical distribution and timing of infectious disease occurrences and how they are transmitted and maintained in nature, with the goal of recognizing and controlling outbreaks.

duration of latent diseases

the causal pathogen goes dormant for extended periods of time with no active replication. -

Chemotherapy

the use of chemicals or drugs to treat a disease;

mode of action

the way the agent kills or inhibits growth - At the cellular level

Vehicle

transmission of pathogens through vehicles such as water, food, and air. -Airborne: droplet transmission across long distances is considered vehicle transmission. - Waterborne: - Foodborne:

duration of chronic diseases

pathologic changes can occur over longer time spans (e.g., months, years, or a lifetime).

Duration of acute disease

pathologic changes occur over a relatively short time (e.g., hours, days, or a few weeks) and involve a rapid onset of disease conditions;

characteristics of the 5 periods of disease

- Incubation: no signs and symptoms; pathogen begins multiplying; can be one day to months to years from chronic diseases; -Prodromal: the pathogen continues to multiply and the host begins to experience general signs and symptoms of illness; - illness: signs and symptoms of disease are most obvious and severe. - decline: the number of pathogen particles begins to decrease, and the signs and symptoms of illness begin to decline. May be susceptible to developing secondary infections; - convalescence: the patient generally returns to normal functions, although some diseases may inflict permanent damage that the body cannot fully repair.

6 modes of action of antimicrobial drugs + cellular targets

- Inhibits cell wall biosynthesis: Penicillin-binding proteins and peptidoglycan subunit; - Inhibits biosynthesis of proteins: 30s and 50s ribosomal subunit; - Disrupt membranes: Lipopolysaccharide, inner and outer membranes; - inhibit nucleic acid synthesis: RNA and DNA; - Antimetabolites: Folic acid synthesis enzyme and Mycolic acid synthesis enzyme; - Mycobacterial adenosine triphosphate (ATP) synthase inhibitor: Mycobacterial ATP synthase

Incidence

- Is the number or proportion of new cases in a period of time. - For a chronic disease like HIV infection, prevalence will generally be higher than incidence because it represents the cumulative number of new cases over many years minus the number of cases that are no longer active

Vector

- Mechanical: an animal that carries a pathogen from one host to another without being infected itself; Ex. fly transferring feces to fruit which we eat and get sick from; - Biological: transmits the pathogen from one host to another; through animal bites or scratches;

Olsetamivir (Tamiflu)

- Mode of action: Neuraminidase inhibitors - Viruses inhibited: influenza,

Enfuvirtide

- Mode of action: Prevent the merging of the viral envelope with the host cell membrane; - Viruses inhibited: HIV

Ritonavir

- Mode of action: Protease inhibition; block the processing of viral proteins and prevent viral maturation. - Viruses inhibited: Hep. C, HIV

Etravirine

- Mode of action: Reverse transcriptase inhibition; This is as non-nucleoside noncompetitive inhibitors - Viruses inhibited: HIV

Polyoxins

- Mode of action: Target chitin synthesis -Microbes used against: Treats fungi that cause yeast infections and Valley fever (Coccidioidomycosis)

Nitroimidazoles

- Mode of action: become activated and introduce DNA strand breakage, interfering with DNA replication in target cells. Unfortunately, metronidazole is associated with carcinogenesis (the development of cancer) in humans. -Microbes used against: Protozoans: Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis.

Benzimidazoles

- Mode of action: bind to helminthic β-tubulin, preventing microtubule formation. Microtubules in the intestinal cells of the worms seem to be particularly affected, leading to a reduction in glucose uptake; -Microbes used against: Helminthic and also protozoans, fungi, and viruses. No specific example given in book.

Ivermectin

- Mode of action: binds to glutamate-gated chloride channels specific to invertebrates including helminths, blocking neuronal transmission and causing starvation, paralysis, and death of the worms; -Microbes used against: roundworm disease, onchoceriasis (river blindness caused by Onchocerca volvulus) and strongyloidiasis (caused by the worm Strongyloides stercoralis or S. fuelleborni); Also lice and bed bugs.

Polyenes

- Mode of action: class of antifungal agents naturally produced by certain actinomycete soil bacteria and are structurally related to macrolides. large, lipophilic molecules bind to ergosterol in fungal cytoplasmic membranes, thus creating pores -Microbes used against: Candida; Pathogens that cause systemic fungal infections like aspergillosis, cryptococcal meningitis, histoplasmosis, blastomycosis, and candidiasis.

Acyclovir

- Mode of action: function by inhibiting nucleic acid biosynthesis. - Viruses inhibited: herpes; chicken pox; shingles; Epstein Barr, cytomegalovirus;

Quinolones

- Mode of action: interfere with heme detoxification, which is necessary for the parasite's effective breakdown of hemoglobin into amino acids inside red blood cells. -Microbes used against: malaria; amebiasis typically caused by Entamoeba histolytica

AZT

- Mode of action: reverse transcriptase inhibitors block the early step of converting viral RNA genome into DNA; This is a nucleoside analog inhibitor; - Viruses inhibited: HIV

Imidazole

- Mode of action: synthetic fungicides that disrupt ergosterol biosynthesis; -Microbes used against: dermatophytes of the genera Trichophyton, Epidermophyton, and Microsporum; Also Candida and malassezia;

Praziquantel

- Mode of action: unclear, but it appears to cause the influx of calcium into the worm, resulting in intense spasm and paralysis of the worm. -Microbes used against: Schistosomiasis (blood flukes from Schistosoma class)

Alexander Fleming (1928)

- Observed the contaminating mold growth on old plates of staphylococci. He identified a strain of Penicillium notatum that inhibited the growth of staphylococci; - Penicillin became the first natural antibiotic

Host Immune system evasion: Mycolic acid

- Produced by acid-fast bacterium Mycobacterium tuberculosis; - enables the bacterium to resist some of the killing mechanisms within the phagolysosome when it is engulfed by phagocytes in the lung.

Artemisinin

- Semisynthetic - Mode of action: Exact mode unknown; appear to act as prodrugs that are metabolized by target cells to produce reactive oxygen species (ROS) that damage target cells. -Microbes used against: Malaria causing pagothens;

Virulence factors used by Fungi (eukaryotic pathogens)

- Similar to the bacterial virulence factors - Candida use proteases and phospholipases; - Cryptococcus: capsules - mycotixins: exotoxins

exotoxins: superantigens

- Stimulates excessive activation of immune system cells and release of cytokines (chemical mediators) from immune system cells. Life-threatening fever, inflammation, and shock are the result.

Influenza viral virulence: Adhesions

- Use adhesion to adhere to host cells. - interact with specific receptors; Influenza adheres to hemagglutinin; -Attachment site: Sialic acid of respiratory and intestinal cells;

Direct Contact

- Vertical: when pathogens are transmitted from mother to child during pregnancy, birth, or breastfeeding. - Horizontal: agent is transmitted by physical contact between two individuals; - Aerosol Droplet: refers to droplet transmission of a pathogen to a new host over distances of one meter or less.

systemic infection

- When an infection becomes disseminated throughout the body - Ex. respiratory infections may spread through the body and cause skin lesions

Recognize how septicemia can lead to shock and death

- When bacteria are both present and multiplying in the blood; can lead to drop in blood pressure (shock) that prevents cells and organs from receiving oxygen and nutrients; -inflammatory reaction can be severe and cause loss of fluid that causes organs to shut down

Macrobroth dilution test

- a dilution series of the drug in broth is made in test tubes and the same number of cells of a test bacterial strain is added to each tube; - are interpreted as the lowest concentration that inhibits visible growth

Selman Waksman (1940s)

- a prominent soil microbiologist at Rutgers University - discovered several antimicrobials, including actinomycin, streptomycin, and neomycin. The discoveries of these antimicrobials stemmed from Waksman's study of fungi and the Actinobacteria, including soil bacteria in the genus Streptomyces, known for their natural production of a wide variety of antimicrobials

Cross-resistance

- a single resistance mechanism confers resistance to multiple antimicrobial drugs. - Ex. having an efflux pump that can export multiple antimicrobial drugs is a common way for microbes to be resistant to multiple drugs by using a single resistance mechanism.

Virulence factors used by protozoa (eukaryotic pathogens)

- adhesins, toxins, antigenic variation, and the ability to survive inside phagocytic vesicles. -

Host Immune system evasion: capsules

- are used in adhesion but also aid in immune evasion by preventing ingestion by phagocytes. - makes the bacterial cell much larger, making it harder for immune cells to engulf the pathogen

toxin

- biological poisons that assist in their ability to invade and cause damage to tissues.

median infectious dose (ID50) vs median lethal dose (LD50)

- both are typically determined experimentally using animal models. - The ID50 is the number of pathogen cells or virions required to cause active infection in 50% of inoculated animals; - The LD50 is the number of pathogenic cells, virions, or amount of toxin required to kill 50% of infected animals.

reservoir

- can be living organisms or nonliving sites. Nonliving reservoirs can include soil and water in the environment. - Can naturally contain the pathogen or be contaminated;

Etests

- can be used to determine the MIC of an antibiotic. - is a combination of the Kirby-Bauer disk diffusion test and dilution methods; - Because the rate of drug diffusion is directly related to concentration, an elliptical zone of inhibition is observed with this test; - To interpret the results, the intersection of the elliptical zone with the gradient on the drug-containing strip indicates the MIC. -

primary pathogen

- can cause disease in a host regardless of the host's resident microbiota or immune system;

opportunistic pathogens

- can only cause disease in situations that compromise the host's defenses, such as the body's protective barriers, immune system, or normal microbiota; - . Individuals susceptible to opportunistic infections include the very young, the elderly, women who are pregnant, patients undergoing chemotherapy, people with immunodeficiencies

stages of pathogenesis: adhesion

- capability of pathogenic microbes to attach to the cells of the body using adhesion factors, and different pathogens use various mechanisms to adhere to the cells of host tissues. - adhesins on the surface of pathogens help it bind to receptors on host cells

Current strategies for antimicrobial discovery

- check large numbers of soils and microbial products for antimicrobial activity by using high-throughput screening methods - iChip: investigate the antimicrobial-producing capabilities of soil microbes that are difficult to grow by standard cultivation techniques in the laboratory; - combinatorial chemistry: a method for making a very large number of related compounds from simple precursors, and testing them for antimicrobial activity. - development of compounds that inhibit resistance mechanisms and restore the activity of older drugs, such as the strategy described earlier for β-lactamase inhibitors like clavulanic acid; - developing inhibitors of virulence factor production and function could be a very important avenue.

Virulence factors used by helminths (eukaryotic pathogens)

- depend heavily on virulence factors that allow them to gain entry to host tissues; -proteases

Gerhard Domagk (1930s)

- discovered the antibacterial activity of a synthetic dye, prontosil, that could treat streptococcal and staphylococcal infections in mice - Also worked with sulfanilamide, the active breakdown product of prontosil in the body; This was used to make Sulfanilamide the first synthetic antimicrobial drug

stages of pathogenesis: Exposure

- encounter - from food, objects we touch, etc. -pathogen must enter through a portal of entry;

Host Immune system evasion: coagulase

- exploits the natural mechanism of blood clotting to evade the immune system - if bacteria release coagulase into the bloodstream, the fibrinogen-to-fibrin cascade is triggered in the absence of blood vessel damage. The resulting clot coats the bacteria in fibrin, protecting the bacteria from exposure to phagocytic immune cells circulating in the bloodstream.

body's portals of entry

- eye - nose -mouth -ear - placenta - vagina -anus - broken skin - insect bite -needle - any mucosal surface; e include the mucous membranes of the respiratory tract, the gastrointestinal tract, and the genitourinary tract; -

iatrogenic and nosocomial

- iatrogenic: Diseases that are contracted as the result of a medical procedure; can occur after procedures involving wound treatments, catheterization, or surgery if the wound or surgical site becomes contaminated. - nosocomial: Diseases acquired in hospital settings; from the bed sheets or from medical equipment;

Infectious vs noninfectious disease

- infectious disease is ant disease caused by the direct effect of a pathogen; - Noninfectious: caused by a wide variety factors, including genetics, the environment, or immune system dysfunction;

Kirby-Bauer Disk Diffusion Susceptibility test (include term zone of inhibition)

- used as a starting point for determining the susceptibility of specific microbes to various antimicrobial drugs. - As the bacterial inoculum grows, antibiotic diffuses from the circular disk into the agar and interacts with the growing bacteria. - Antimicrobial activity is observed as a clear circular zone of inhibition; - provides only limited information on susceptibility and resistance to the drugs tested. - cannot distinguish between bacteriostatic and bactericidal activities, and differences in zone sizes cannot be used to compare drug potencies or efficacies.

Why is selective toxicity with regard to viral infection almost impossible?

- viruses are obligate intracellular pathogens that use the host's cellular machinery to replicate. - Simple, consisting of nucleic acid, a protein coat, viral enzymes, and, sometimes, a lipid envelope.

Indirect contact

-Fomite: inanimate objects that become contaminated by pathogens;

infection vs disease

-Infection: is the successful colonization of a host by a microorganism. - infection leads to disease; -Disease: causes signs and symptoms resulting in a deviation from the normal structure or functioning of the host.

exotoxins: cholera enterotoxin

-Intracellular targeting toxins - Activation of adenylate cyclase in intestinal cells, causing increased levels of cyclic adenosine monophosphate (cAMP) and secretion of fluids and electrolytes out of cell, causing diarrhea;

exotoxins: diphtheria exotoxin

-Intracellular targeting toxins - Inhibition of protein synthesis, causing cellular death;

exotoxins: Botulinum neurotoxin

-Intracellular targeting toxins - Inhibits release of the neurotransmitter acetylcholine from neurons, resulting in flaccid paralysis;

exotoxins: tetanus neurotoxin

-Intracellular- targeting toxins - Inhibits the release of inhibitory neurotransmitters in the central nervous system, causing spastic paralysis;

exotoxins: streptolysin

-Membrane disrupting - Proteins that assemble into pores in cell membranes, disrupting their function and killing the cell;

exotoxins: phospholipases

-Membrane disrupting - degrade cell membrane phospholipids, disrupting membrane function and killing the cell;

Fluoroquinolones

-Mode of action: Inhibits the activity of DNA gyrase and blocks DNA replication, killing the cell - Microbes they are used against: broad spectrum of gram negative and gram positive

Tetracyclines

-Mode of action: bind to the 30S subunit, and inhibit protein synthesis by blocking the association of tRNAs with the ribosome during translation; bacteriostatic; - Microbes they are used against: gram positive and gram negative

Bacitracin

-Mode of action: blocks the activity of a specific cell-membrane molecule that is responsible for the movement of peptidoglycan precursors from the cytoplasm to the exterior of the cell, ultimately preventing their incorporation into the cell wall. - Microbes they are used against: staphylococcus, Streptococcus, other gram positive;

Macrolides

-Mode of action: broad-spectrum, bacteriostatic drugs that block elongation of proteins by inhibiting peptide bond formation between specific combinations of amino acids. Work through binding to the 50S subunit of bacterial ribosomes. Bacteriostatic. - Microbes they are used against: gram positive and some gram negative; broad spectrum

Antimetabolites (sulfonamides, trimethoprim)

-Mode of action: competitive inhibitors for bacterial metabolic enzymes; inhibits the enzyme involved in production of dihydrofolic acid; bacteriostatic - Microbes they are used against: gram positive and negative; broad spectrum

Rifamycin

-Mode of action: functions by blocking RNA polymerase activity in bacteria. The RNA polymerase enzymes in bacteria are structurally different from those in eukaryotes, providing for selective toxicity against bacterial cells. - Microbes they are used against: mycobacteria; gram negative

Vancomycin (glycopeptide)

-Mode of action: inhibits cell wall biosynthesis and is bactericidal; Does not directly inactivate penicillin binding proteins but it is very large and blocks the cell from incorporating cell wall subunits into N-acetylglucosamine and N- acetylmuramic acid (NAM-NAG) backbone of the peptidoglycan structure (transglycosylation). -Also blocks transpeptidation. - Microbes they are used against: bactericidal against gram-positive bacterial pathogens; not active against gram negative;

Aminoglycosides

-Mode of action: large, highly polar antibacterial drugs that bind to the 30S subunit of bacterial ribosomes, impairing the proofreading ability of the ribosomal complex; bactericidal - Microbes they are used against: aerobic gram negative bacteria and some gram positive;

Beta-lactams (penicillins and cephalosporins)

-Mode of action: s block the crosslinking of peptide chains during the biosynthesis of new peptidoglycan in the bacterial cell wall. They are able to block this process because the β-lactam structure is similar to the structure of the peptidoglycan subunit component that is recognized by the crosslinking transpeptidase enzyme, also known as a penicillin-binding protein (PBP). - Microbes they are used against: Penicillin is active against gram positive bacteria and Pasteurella multocida a gram negative pathogen. Cephalosporin is more affective against gram negative bacteria. Cephalosporin is effective against MRSA (methicillin restistant Staphyl aureus.

Syndrome

A specific group of signs and symptoms characteristic of a particular disease

endotoxin

A toxic component of the outer membrane of certain gram-negative bacteria that is released only when the bacteria die. - The lipopolysaccharide (LPS) found on the outer membrane of gram-negative bacteria; The lipid component of endotoxin, lipid A, is responsible for the toxic properties of the LPS molecule

Paul Ehrlich (1910)

Discovered first cure for syphilis which is caused by treponema pallidum,

How exposure to an antimicrobial drug can lead to drug resistant populations

Exposure could lead to chromosomal mutations that confer resistance in the microbe

Cellular uptake prevention or efflux

Mode of action: - inhibiting the accumulation of an antimicrobial drug by using efflux pumps to pump drug out of cell, which then prevents the drug from reaching its cellular target. -In Gram negative: can involve changes in outer membrane lipid composition, porin channel selectivity, and/or porin channel concentrations - many gram-positive and gram-negative pathogenic bacteria produce efflux pumps.

Drug modification or inactivation

Mode of action: - For aminoglycosides: through enzymatic transfer of chemical groups to the drug molecule, impairing the binding of the drug to its bacterial target. - For B-Lactams: bacterial resistance can involve the enzymatic hydrolysis of the β-lactam bond within the β-lactam ring of the drug molecule. - Inactivation of rifampin commonly occurs through glycosylation, phosphorylation, or adenosine diphosphate (ADP) ribosylation, and resistance to macrolides and lincosamides can also occur due to enzymatic inactivation of the drug or modification.

Enzymatic bypass

Mode of action: - bypass that circumvents the need for the functional target enzyme;

target mimicry

Mode of action: - involves the production of proteins that bind and sequester drugs, preventing the drugs from binding to their target.

Target overproduction

Mode of action: - overproduction of the target enzyme such that there is a sufficient amount of antimicrobial-free enzyme to carry out the proper enzymatic reaction.

target modification

Mode of action: - structural changes to those targets can prevent drug binding; - Through spontaneous mutations in the genes encoding antibacterial drug targets; - Ex. Genetic changes impacting the active site of penicillin-binding proteins (PBPs) can inhibit the binding of β-lactam drugs

Antimicrobial drugs

Target infectious microorganisms; work by destroying or interfering with microbial structures and enzymes, either killing microbial cells or inhibiting growth;

Virulence and pathogenicity

The ability of a microbial agent to cause disease; degree to which an organism is pathogenic is virulence;

Morbidity

The state of being diseased; - total morbidity is expressed in numbers of individuals without reference to the size of the population. - The morbidity rate can be expressed as the number of diseased individuals out of a standard number of individuals in the population, such as 100,000, or as a percent of the population.

Asymptomatic or subclinical

do not present any noticeable signs or symptoms.

Passive carrier

is contaminated with the pathogen and can mechanically transmit it to another host; - Is not infected though