Microbio 10-12

Identify six (6) modes of action of antimicrobial drugs and recognize their cellular targets

Inhibit cell wall biosynthesis- Penicillin binding proteins, peptidoglycan subunits, and peptidoglycan subunit transport; Inhibit biosynthesis of proteins- 30S ribosomal subunit and 50S ribosomal subunit; Disrupt membranes- Lipopolysaccharide, inner and outer membranes; Inhibit nucleic acid synthesis- RNA & DNA; Antimetabolites- Folic acid synthesis enzyme and mycolic acid synthesis enzyme

Imidazoles

Inhibit ergosterol synthesis | Fungal skin infections and vaginal yeast infections

Polyenes

Inhibit ergosterol synthesis | Systemic yeast infections, oral thrush, and cryptococcal meningitis

Quinolones

Inhibit heme detoxification | Malaria

Benzimidazoles

Inhibit microtubule formation, reducing glucose uptake | helminths

Fluoroquinolones

Inhibit nucleic acid synthesis | Broad spectrum against gram-positive and gram-negative bacteria

Rifamycin

Inhibit nucleic acid synthesis | Narrow spectrum with activity against gram-positive and limited numbers of gram-negative bacteria. Also active against Mycobacterium tuberculosis

Enfuvirtide

Inhibition of membrane fusion | HIV

Ritonavir

Inhibition of protease | HIV

Diphtheria Exotoxin

Inhibition of protein synthesis, causing cellular death

Botulinum Neurotoxin

Inhibits release of the neurotransmitter acetylcholine from neurons, resulting in flaccid paralysis

Tetanus Neurotoxin

Inhibits the release of inhibitory neurotransmitters in the central nervous system, causing spastic paralysis

Semisynthetic Antimicrobial

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.

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

Synthetic Antimicrobial

a drug that is developed from a chemical not found in nature.

Antigenic Shift

a major change in spike proteins due to gene reassortment. This reassortment for antigenic shift occurs typically when two different influenza viruses infect the same host.

Cross-resistance

a single resistance mechanism confers resistance to multiple antimicrobial drugs.

Kinases

allow pathogens trapped in the clot to escape and spread,

Etests

alternative method used to determine MIC. A combination of the Kirby-Bauer disk diffusion test and dilution methods.

M Protein

alters the surface of Streptococcus and inhibits phagocytosis by blocking the binding of the complement molecules that assist phagocytes in ingesting bacterial pathogens.

active carrier

an infected individual who can transmit the disease to others. An active carrier may or may not exhibit signs or symptoms of infection.

Artemisinin

Produces damaging reactive oxygen species | Malaria

Proteases in host immune system evasion

Proteases combat antibody-mediated killing and clearance by attacking and digesting the antibody molecules

Streptolysin

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

Identify the endotoxin and recognize how our body responds to it

The lipopolysaccharide (LPS), Lipid A, found on the outer membrane of gram-negative bacteria. Lipid A triggers the immune system's inflammatory response. If the endotoxin concentration is low, the inflammatory response may provide the host an effective defense against infection; if high, can cause an excessive inflammatory response, leading to a severe drop in blood pressure, multi-organ failure, and death.

Target overproduction

The microbe may overproduce the target enzyme such that there is a sufficient amount of antimicrobial-free enzyme to carry out the proper enzymatic reaction

Identify the body's portals of exit and recognize how their secretions and excretions help transmit pathogens

The most common portals of exit include the skin and the respiratory, urogenital, and gastrointestinal tracts. Secretions and excretions can transport pathogens out of other portals of exit. Feces, urine, semen, vaginal secretions, tears, sweat, and shed skin cells can all serve as vehicles for a pathogen to leave the body.

Lethal Dose LD50

The number of pathogenic cells, virions, or amount of toxin required to kill 50% of infected animals.

Incidence

The number or proportion of new cases in a period of time.

Prevalence

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

Identify why the treatment of fungal, protozoan, and helminth infections is difficult

Their eukaryotic cells are very similar to human cells, making it more difficult to develop drugs with selective toxicity.

Disease

any condition in which the normal structure or functions of the body are damaged or impaired.

Infectious

any disease caused by the direct effect of a pathogen

Communicable

are capable of being spread from person to person through either direct or indirect mechanisms

Contagious

are easily spread from person to person. Not all contagious diseases are equally so; the degree to which a disease is contagious usually depends on how the pathogen is transmitted

Oseltamivir (Tamiflu)

block the activity of influenza virus neuraminidase, preventing the release of the virus from infected cells | Flu

Opportunistic

can only cause disease in situations that compromise the host's defenses, such as the body's protective barriers, immune system, or normal microbiota.

Primary

cause disease in a host regardless of the host's resident microbiota or immune system.

Noninfectious

caused by a wide variety of factors, including genetics, the environment, or immune system dysfunction.

Local

confined to a small area of the body, typically near the portal of entry.

passive carrier

contaminated with the pathogen and can mechanically transmit it to another host; however, a passive carrier is not infected.

Target modification

Because antimicrobial drugs have very specific targets, structural changes to those targets can prevent drug binding, rendering the drug ineffective.

Antigenic Variation

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

Enzymatic bypass

the bacterial cell may develop a bypass that circumvents the need for the functional target enzyme.

Latent Diseases

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

Primary/Secondary

the initial infection caused by one pathogen, can lead to a secondary infection by another pathogen.

Broad-Spectrum Antimicrobial

targets a wide variety of bacterial pathogens. Frequently used as empiric therapy to cover a wide range of potential pathogens while waiting on the lab identification of the infecting pathogen.

Narrow-Spectrum Antimicrobial

targets only specific subsets of bacterial pathogens. Most effective when the pathogen causing an infection has been identified.

Minimum Inhibitory Concentration (MIC)

the lowest concentration of drug that inhibits visible bacterial growth. determined by examining the tubes to find the lowest drug concentration that inhibits visible growth; this is observed as turbidity (cloudiness) in the broth.

Minimum Bactericidal Concentration (MBC)

the lowest drug concentration that kills ≥99.9% of the starting inoculum. Tubes with no visible growth are then inoculated onto agar media without antibiotics to determine the MBC.

Infectious Dose ID50

the number of pathogen cells or virions required to cause active infection in 50% of inoculated animals.

Antigenic Drift

the result of point mutations causing slight changes in the spike proteins hemagglutinin (H) and neuraminidase (N).

Infection

the successful colonization of a host by a microorganism. Infections can lead to disease.

Mode of Action

the way in which a drug affects microbes at the cellular level

Common Source

there is a single source for all of the individuals infected. Types of common source spread include point source spread, continuous common source spread, and intermittent common source spread. In point source spread of infectious disease, the source operates for a short time period—less than the incubation period of the pathogen. In continuous common source spread, the infection occurs for an extended period of time, longer than the incubation period. Finally, with intermittent common source spread, infections occur for a period, stop, and then begin again.

Zoonotic Disease

transmitted from animals to humans

Dorothy Hodgkin

used X-rays to analyze the structure of a variety of natural products and determined the structure of penicillin. Once the structure was understood, scientists could modify it to produce a variety of semisynthetic penicillins.

Natural Antibiotic

used to destroy unwanted bacteria, but it is not made out of synthetic materials

Identify why selective toxicity with regard to viral infection is almost impossible to achieve

viruses replicate within human host cells, making it difficult to develop drugs that are selectively toxic to viruses or virus-infected cells.

Hyaluronidase

degrades the glycoside hyaluronan, which acts as an intercellular cement between adjacent cells in connective tissue. This allows the pathogen to pass through the tissue layers at the portal of entry and disseminate elsewhere in the body

Recognize the importance of virulence factors

determine the extent and severity of disease they may cause. When genes encoding virulence factors are inactivated, virulence in the pathogen is diminished.

Period of Decline

during which the number of pathogen particles begins to decrease, and the signs and symptoms of illness begin to decline. However, during the decline period, patients may become susceptible to developing secondary infections because their immune systems have been weakened by the primary infection.

Period of Illness

during which the signs and symptoms of disease are most obvious and severe

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.

Helminths

glycans, proteases, and other things that allow them to gain entry to host tissues.

Protozoa

have virulence factors and pathogenic mechanisms analogous to prokaryotic and viral pathogens, including adhesins, toxins, antigenic variation, and the ability to survive inside phagocytic vesicles.

Mechanisms of Drug Resistance

include drug modification or inactivation, prevention of cellular uptake or efflux, target modification, target overproduction or enzymatic bypass, and target mimicry.

Focal

localized pathogen, or the toxins it produces, can spread to a secondary location.

Chronic Diseases

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

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.

Beta-lactams

penicillins, cephalosporins: Inhibit cell wall biosynthesis | Narrow-spectrum against gram-positive and a few gram-negative bacteria (Cephalosporins: similar to penicillin but with increased gram-negative spectrum)

Noncommunicable

not spread from one person to another

Signs

objective and measurable, and can be directly observed by a clinician.

Prodromal Period

occurs after the incubation period. During this phase, the pathogen continues to multiply and the host begins to experience general signs and symptoms of illness, which typically result from activation of the immune system, such as fever, pain, soreness, swelling, or inflammation. Usually, such signs and symptoms are too general to indicate a particular disease.

Incubation Period

occurs in an acute disease after the initial entry of the pathogen into the host. During this time the pathogen begins multiplying in the host, however there are insufficient numbers of cells/viruses present to cause signs and symptoms of disease. Incubation periods can vary from a day or two in acute disease to months or years in chronic disease, depending upon the pathogen. Factors involved in determining the length of the incubation period are diverse, and can include strength of the pathogen, strength of the host immune defenses, site of infection, type of infection, and the size infectious dose received. During this incubation period, the patient is unaware that a disease is beginning to develop.

Propagated Source

occurs through direct or indirect person-to-person contact. With propagated spread, there is no single source for infection; each infected individual becomes a source for one or more subsequent infections. With propagated spread, unless the spread is stopped immediately, infections occur for longer than the incubation period.

Vertical Contact

occurs when pathogens are transmitted from mother to child during pregnancy, birth, or breastfeeding

Antagonistic Interaction

produce harmful effects

Fungi

produce virulence factors that are similar to the bacterial virulence factors; adhesins, proteases, exoenzymes, capsule production, mycotoxins

Polyoxins

produced antifungals that target chitin synthesis | control fungi for agricultural purposes

Target mimicry

production of proteins that bind and sequester drugs, preventing the drugs from binding to their target.

Synergistic Interaction

provide a benefit to the patient

Syndrome

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

Cholera Enterotoxin

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

asymptomatic carrier

Active carriers who do not present signs or symptoms of disease despite infection

Identify the difference between emerging and reemerging infection diseases

An emerging infectious disease is either new to the human population or has shown an increase in prevalence in the previous twenty years. Whether the disease is new or conditions have changed to cause an increase in frequency, its status as emerging implies the need to apply resources to understand and control its growing impact. A reemerging infectious disease is a disease that is increasing in frequency after a previous period of decline. Its reemergence may be a result of changing conditions or old prevention regimes that are no longer working.

Pandemic

An epidemic that occurs on a worldwide scale

Sulfonamides, trimethoprim

Antimetabolites | Broad spectrum against gram-positive and gram-negative bacteria

Ivermectin

Block neuronal transmission, causing paralysis and starvation | Roundworm

Identify the role of the Centers for Disease Control and Prevention (CDC) in the U.S.

CDC. The CDC carries out international monitoring and public health efforts, mainly in the service of protecting US public health in an increasingly connected world.

Vancomycin

Inhibit cell wall biosynthesis | Narrow spectrum against gram-positive bacteria only, including multidrug-resistant strains

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

Identify the role of the World Health Organization (WHO)

Coordinate international public health issues. In addition to monitoring and reporting on infectious disease, WHO also develops and implements strategies for their control and prevention. WHO maintains a global alert and response system that coordinates information from member nations. In the event of a public health emergency or epidemic, it provides logistical support and coordinates international response to the emergency.

Identify the current strategies for antimicrobial discovery

Current research into the development of antimicrobial drugs involves the use of high-throughput screening and combinatorial chemistry technologies. New technologies are being developed to discover novel antibiotics from soil microorganisms that cannot be cultured by standard laboratory methods. Additional strategies include searching for antibiotics from sources other than soil, identifying new antibacterial targets, using combinatorial chemistry to develop novel drugs, developing drugs that inhibit resistance mechanisms, and developing drugs that target virulence factors and hold infections in check.

Paul Ehrlich

Discovered/synthesized a chemical compound capable of killing infectious microbes without harming the patient by screening 600+ arsenic-containing compounds, until he found compound 606. Discovered a chemotherapeutic way to treat syphilis

Mortality

Death

Proteases in host cell invasion

Degrades collagen in connective tissue to promote spread

Selman Waksman

Discovered several antimicrobials, including actinomycin, streptomycin, and neomycin, stemming from his study of fungi and the Actinobacteria.

Gerhard Domagk

Discovered the antibacterial activity of a synthetic dye, prontosil, that could treat streptococcal and staphylococcal infections in mice. Also worked with sulfanilamide, the first synthetic antimicrobial created, serving as the foundation for the chemical development of a family of sulfa drugs.

Nosocomial

Diseases acquired in hospital settings

Epidemic

Diseases for which a larger than expected number of cases occurs in a short time within a geographic region

Endemic

Diseases that are constantly present (often at a low level) in a population within a particular geographic region

Iatrogenic

Diseases that are contracted as the result of a medical procedure

Sporadic

Diseases that are seen only occasionally, and usually without geographic concentration

Polymyxins

Disrupt membranes | Narrow spectrum against gram-negative bacteria, including multidrug-resistant strains

Define dosage and identify the factors that contribute to ensuring optimum therapeutic drug levels

Dosage- The amount of medication given during a certain time interval. Factors- In children, dose is based upon the patient's mass. For adults and children 12 years of age and older, there is a standard dose regardless of the patient's mass. Additional considerations include how drugs are metabolized and eliminated from the body, as well as factors specific to the drugs themselves that influence appropriate dose and time interval between doses.

Period of Convalescence

During this stage, the patient generally returns to normal functions, although some diseases may inflict permanent damage that the body cannot fully repair.

Airborne Vehicle

Dust and fine particles known as aerosols, which can float in the air, can carry pathogens and facilitate the airborne transmission of disease. inhalation of these particles can lead to a serious and sometimes fatal respiratory infection

Identify how exposure to an antimicrobial drug can lead to drug resistant populations

Exposure to an antimicrobial compound can select for chromosomal mutations conferring resistance, which can be transferred vertically to subsequent microbial generations and become predominant in a microbial population that is repeatedly exposed to the antimicrobial.

Identify the stages of pathogenesis and recognize the process by which they occur

Exposure: An encounter with a potential pathogen | For a pathogen to cause disease, it needs access into host tissue. An anatomic site through which pathogens can pass into host tissue is called a portal of entry. These are locations where the host cells are in direct contact with the external environment. Adhesion: the capability of pathogenic microbes to attach to the cells of the body using adhesion factors | Molecules called adhesins are found on the surface of pathogens and bind to specific receptors on host cells. Adhesins are present on the fimbriae and flagella of bacteria, the cilia of protozoa, and the capsids or membranes of viruses. Invasion: 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 Infection: successful multiplication of the pathogen

Mechanical Vector

Facilitated by a mechanical vector, an animal that carries a pathogen from one host to another without being infected itself

Foodborne Vehicle

Food contaminated through poor handling or storage can lead to foodborne transmission of disease

Identify two genomic changes that can cause drug resistance

Horizontal gene transfer and transposons

Bacitracin

Inhibit cell wall biosynthesis | Broad-spectrum against gram-positive and gram-negative bacteria

Fomite Contact

Inanimate objects that aid in disease transmission, like doorknobs

Praziquantel

Induce calcium influx | Schistosomiasis

Recognize the significance of healthcare-associated (nosocomial) infections (HAIs)

Infections acquired in health-care facilities. HAIs are often connected with surgery or other invasive procedures that provide the pathogen with access to the portal of infection.

Nitroimidazoles

Inhibit DNA synthesis | Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis

Aminoglycosides

Inhibit biosynthesis of proteins | Broad spectrum

Macrolides

Inhibit biosynthesis of proteins | Broad spectrum

Tetracyclines

Inhibit biosynthesis of proteins | Broad spectrum

Define Drug Resistance and identify list the factors that contribute to it

Microbes evolve in order to overcome the antimicrobial compounds produced by other microorganisms. Several important factors can accelerate the evolution of drug resistance. These include the overuse and misuse of antimicrobials, inappropriate use of antimicrobials, subtherapeutic dosing, and patient noncompliance with the recommended course of treatment.

Cellular uptake prevention or efflux

Microbes may develop resistance mechanisms that involve inhibiting the accumulation of an antimicrobial drug, which then prevents the drug from reaching its cellular target.

Identify the body's portals of entry and recognize their importance to the infection process

Mucosal surfaces are the most important portals of entry for microbes; these include the mucous membranes of the respiratory tract, the gastrointestinal tract, and the genitourinary tract. Although most mucosal surfaces are in the interior of the body, some are contiguous with the external skin at various body openings, including the eyes, nose, mouth, urethra, and anus. | Breached Skin | Parenteral Routes

Etravirine

Non-nucleoside noncompetitive inhibition | HIV

AZT

Nucleoside analog inhibition of nucleic acid synthesis | HIV

Acyclovir

Nucleoside analog inhibition of nucleic acid synthesis | Herpes

Biological Vector

Occurs when the pathogen reproduces within a biological vector that transmits the pathogen from one host to another

Horizontal Contact

Often, contact between mucous membranes is required for entry of the pathogen into the new host, although skin-to-skin contact can lead to mucous membrane contact if the new host subsequently touches a mucous membrane. Contact transmission may also be site-specific

Recognize how septicemia can lead to shock and death

Patients with septicemia are described as septic, which can lead to shock, a life-threatening decrease in blood pressure (systolic pressure <90 mm Hg) that prevents cells and organs from receiving enough oxygen and nutrients.

Phospholipases

Phospholipases that degrade cell membrane phospholipids, disrupting membrane function and killing the cell

Capsules

Prevents immune cells from being able to adhere and then phagocytose the cell. In addition, the capsule makes the bacterial cell much larger, making it harder for immune cells to engulf the pathogen

Chemotherapy

Refers to any use of chemicals or drugs to treat disease.

Reservoir

Reservoirs can be living organisms or nonliving sites. Nonliving reservoirs can include soil and water in the environment. For pathogens to persist over long periods of time they require reservoirs

Drug modification or inactivation

Resistance genes may code for enzymes that chemically modify an antimicrobial, thereby inactivating it, or destroy an antimicrobial through hydrolysis.

Identify the clinical considerations in prescribing antimicrobial drugs

Several factors including bacteriostatic vs. bactericidal mechanisms, spectrum of activity, dosage & route of administration, potential side effects, and potential interactions between drugs. Use of bacteriostatic or bactericidal drugs depends on the type of infection and immune status. A patient with strong immune defenses can use bacteriostatic /bactericidal drugs. An immunocompromised person must use a bactericidal drug

Identify the various routes of administration for antimicrobial drugs recognizing the plasma concentration as a function of time

Routes- Oral and parenteral route (injection). Plasma levels achieved by intravenous administration is substantially higher than levels achieved by oral or intramuscular administration, and this can also be an important consideration when choosing the route of administration for treating an infection

Symptoms

Subjective, meaning felt or experienced by the patient, but they cannot be clinically confirmed or objectively measured.

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.

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

The diameter of the zone of inhibition, measured in millimeters and compared to a standardized chart, determines the susceptibility or resistance of the bacterial pathogen to the drug.

Antimicrobial Drugs

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

Pathogenicity

The ability of a microbial agent to cause disease

Etiological Agent

The cause of the disease,

Virulence

The degree to which an organism is pathogenic

Morbidity

The state of being diseased

Identify the four steps of Koch's postulates

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

Recognize the risk associated with using broad-spectrum antimicrobials and identify how this could lead to a superinfection

They also target a broad spectrum of normal microbiota, increasing the risk of a superinfection. A superinfection develops when the antibacterial intended for the preexisting infection kills the protective microbiota

Asymptomatic or Subclinical

They do not present any noticeable signs or symptoms

Waterborne Vehicle

Water contamination through poor sanitation methods leads to waterborne transmission of disease

Aerosol Droplet Contact

When an individual coughs or sneezes, small droplets of mucus that may contain pathogens are ejected. Refers to droplet transmission of a pathogen to a new host over distances of one meter or less.

Systemic

When an infection becomes disseminated throughout the body

Mycolic Acid

When it is engulfed by phagocytes in the lung, the protective mycolic acid coat enables the bacteria to resist some of the killing mechanisms within the phagolysosome.

Define Toxin

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

Alexander Fleming

examined old plates of staphylococci and discovered that contaminating mold growth (penicillium notatum i.e. Penicillin) inhibited staphylococcal growth on one plate.

Adhesions

it allows the virus to bind to the sialic acid on the membrane of host respiratory and intestinal cells.

Selective Toxicity

it selectively kills or inhibits the growth of microbial targets while causing minimal or no harm to the host. Most antimicrobial drugs currently in clinical use are antibacterial because the prokaryotic cell provides a greater variety of unique targets for selective toxicity, in comparison to fungi, parasites, and viruses.

multiple drug resistant microbes (MDRs)

known as "superbugs" and carry one or more resistance mechanism(s), making them resistant to multiple antimicrobials.