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.