MIC301 Exam 4

antimicrobial

drug against microbes

• kill or inhibit microbial growth to prevent pathogenic action

• categorized by the type of pathogen they target

Alexander Fleming

• discovered first antibiotic: penicillin

• S. aureus were unable to grow near mold “zone of inhibition”

antimicrobial criteria

1. effective against microbes

2. sufficiently nontoxic to host

3. able to be purified in high amounts

broad-spectrum

term used to describe a drug that is effective against a board range of microbes

narrow-spectrum

term used to describe antimicrobials that target a limited range of microbes

• effective mainly against one group/subgroup

• preferred because there is less disruption to normal microbiota

• require definitive identification of pathogen

limited-spectrum

term used to describe drug that is effective against a single organism/disease

empiric therapy

medical treatment based on clinical experience/observation with a broad-spectrum drug initiation while waiting for culture or ID results

naturally occurring antimicrobials

substances produced by microorganism that inhibit other living microorganisms

synthetic antimicrobials

drugs manufactured by chemical processes

semisynthetic antimicrobials

chemical modification of naturally occurring antibiotics

therapeutic index

ratio of toxic dose to the therapeutic dose

• estimates the margin of safety where the drug is effective but not toxic

hepatotoxic

toxic to liver

• antimicrobial drugs may cause liver injury

• most commonly citd reason for discontinuing drug development or removing a drug from the market

nephrotoxic

toxic to kidneys

• antimicrobials are a leading cause of drug associated kidney damage

oral administration

preferred route of antimicrobials

• easiest, convenient, inexpensive

• drug must be stable in acidic environment of stomach and sufficiently absorbed in the intestine but not irritating GI mucosa

parental administration

any route not involving the intestines (usually via injection or infusion)

• rapid absorption and faster onset of drug action

• utilizes needles/intravenous lines

prophylaxis therapy

antibiotics used to prevent infection

• broad therapy antibiotics

• eg pre-surgery

pathogen-directed therapy

organism is known but susceptibility is unknown

• narrow spectrum antibiotic

susceptibility-guided therapy

organism is known and susceptibility is known

• goal

• narrow spectrum antibotics

bacteriostatic

• inhibit bacterial growth

• target bacterial protein synthesis and metabolic pathways

• patient’s own immune system kills off bacterial and leads to recovery

• reversible

• MIC

bactericidal

• kills bacteria

• targets bacterial cell walls, cell membranes, nucleic acids

• does not rely on patient immune system

• may cause massive and fatal bacterial toxin release

• irreversible

• MBC

antiviral drugs

• do not destroy target pathogen

• inhibit viral development to treat active infection

• difficult to design safe and effective drugs that won’t harm host

• goal - target/disable essential virus-specific proteins

antifungal drug targets

• mycoses

• interfere with nucleic acid synthesis

• interfere with cell wall synthesis = lysis

• interfere with cell membrane stability and structure

antiparasitic drugs

• difficult to develop due to complex life cycles of eukaryotic parasites

• often target intracellular components (may function to stun or kill)

• limited by toxicity

antibiotic susceptibility testing

• determine organism causing specific infection and which antimicrobials will inhibit the growth of the infecting microbe

• identify and report drug resistance

• samples include blood, urine, CSF, stool, etc…

agar diffusion tests

• determine basic antimicrobial susceptibility profile

• relatively inexpensive

• ex) kirby-bauer disk diffusion and epsilometer test

kirby-bauer test

1. drug-infused disks are placed on inoculated agar surface

2. plates incubated to allow for bacterial growth and drug diffusion from disc

3. zone of inhibition appears if bacteria are prevented from growing

E-test

1. strips infused with drug gradient are placed on freshly inoculated aghar surface

2. plates are incubated to allow for bacterial growth and drug diffusion from the strip

3. an ellipse shaped inhibition zone intersects test strip at MIC of antibiotic

intrinsic resistance

natural resistance to antimicrobial drugs based on inherent microbial structure/function

ex) absence of target, low affinity target, low permeability, efflux mechanisms, inherent to physiology

acquired resistance

resistance acquired by genetic mutation or resistance genes

• resistance occurs when drug concentration levels within the cell are kept below the MIC

• 3 main types: alter drug target, inactive drug, reduce drug concentrations inside cell

superbug

strains of bacteria, viruses, parasites, and fungi that are resistant to antimicrobials commonly used to treat the infections they cause

superinfections

result when superbugs emerge from the initial infection resistant to the treatment and become the primary cause of a second infection

antimicrobial stewardship

coordinated program that promotes the appropriate use of antimicrobials to improve patient outcomes, reduce and combat microbial resistance, and decrease the spread of infections caused by mutlidrug resistant organisms

upper respiratory tract

mouth, nasal passages, paranasal sinuses, pharynx, epiglottis

• warm, humidify, filter air

lower respiratory tract

larynx, trachea, bronchi, bronchioles, lungs, alveoli

• directs air to lungs

sinusitis

a. infectious agents and inhaled allergens can aggravate and inflame sinuses and nasal passages

b. sinus congestion - mucus accumulates in hollow chambers, puts pressure on surrounds structures

mostly caused by viruses and inhaled allergens, NOT bacteria

mucociliary escalator

ciliated mucous membranes lining lower respiratory tract

• trap inhaled debris and sweep it toward the mouth to prevent it from entering the lungs

alveolar macrophages

reside in alveoli of the lungs

clear out debris and pathogens not trapped by mucociliary escalator

laryngitis

• inflammation of the larynx

• can cause temporary voice loss due to swelling of the vocal cords

croup

laryngotracheobronchitis

• combined inflammation of larynx, trachea, bronchi, bronchioles

• viruses cause most cases

• characterized by barking cough and respiratory stridor (wheezing)

common symptoms of respiratory infections

cough, stridor, dyspnea, fatigue, sneezing, sore throat, fever

ARI etiologic agent

serovars of rhinoviruses and coronaviruses (also parainfluenza, adenoviruses, nonpolio-type enteroviruses)

ARI transmission

highly communicable

spread through person contact, respiratory droplets, formites

ARI symptoms

runny nose, sore throat, coughing, sneezing, fatigue, body aches, loss of appetite, low grade fever, thickened/discolored mucus

ARI

acute respiratory infection

• normally infects adults 3x per year and children 6x per year

• antibiotics will not cure but may be prescribe if symptoms persist >10 days

RSV

respiratory syncytial virus

• common severe respiratory virus that can lead to bronchiolitis

• infections most common in winter

• disease often severe in infants, elderly, immunocompromised

• leading cause of acute respiratory lower tract infection in children under 5

RSV etiological agent

enveloped single-stranded RNA virus

(pneumoviridae family)

RSV transmission

respiratory aerosols

direct contact with eyes or nose

influenza etiological agent

enveloped single stranded 8-segmented RNA virus

influenza mechanism of disease

most strains bind ciliated cells in upper respiratory tract

some strains can directly affect lungs

influenza complications

secondary bacterial infections

pneumonia

can be deadly in people with pre-existing conditions

influenza type a

• moderate to severe illness

• all ages

• avian and mammalian

• pandemic

influenza type b

mild to moderate disease

all ages, primarily children

epidemics

influenza type c

rare in humans; no epidemics

hemagglutinin

glycoprotein spikes on surface that attach and invade target cells in respiratory tract

neuraminidase

glycoprotein on surface of influenza virus that helps newly formed viral particles escape the host cell

Covid etiological agent

SARS-CoV2 virus

enveloped

single stranded RNA genome

spike proteins

Covid mechanism of disease

1. spreads via respiratory droplets or aerosols

2. binds to ACE2 on host cells

3. symptoms can develop within 2 to 14 days

4. degree of severity varies

5. kills patients due to sudden and marked reduction in blood oxygen (ARDS)

streptococcus genus

gram-positive cocci; grow in chains or diplococci

often found as normal flora of the upper respiratory tract and skin

some strains cause diseases (dental carries, endocarditis, pharyngitis)

strep throat etiological agent

group A streptococcus S. pyogenes

beta-hemolytic

scarlet fever etiological agent

lysogenized S. pyogenes strains acquire ability to produce erythrogenic toxin

ET toxin over stimulates inflammatory response and dilates capillaries

scarlet fever symptoms

red sandpaper-like rash

reddened tongue that resembles surface of strawberry

most common in children under 10

streptococcus pyogenes virulence factors

1. hyaluronic acid capsule (resemble human connective tissue)

2. M protein (adhesion to host cells avoid phagocytosis)

3. exotoxins/enzymes (damage cell membranes, inactivate immune response, fever and rash)

streptococcus pyogenes complications

otitis, sinusitis, invasive pneumonia, autoimmune sequelae

streptococcus pyogenes diagnosis

rapid strep test for bacterial antigenes

culture that identifies S. pyogenes

streptococcus pyogene treatment

antibotics

• penicillin based drugs

pertussis etiological agent

(whooping cough)

• bordetella pertussis - gram negative, coccobacillus, aerobic, motile, encapsulated

pertussis stages

1. catarrhal - non specific cold-like symptoms develop 1 week after infection

2. paroxysmal - peak coughing; worsen symptoms due to progressively thickened mucus and inflamed, exotoxin damaged respiratory epithelium

3. convalescent - pertusis symptoms gradully fade; secondary pneumonia possible

pertussis treatment

• early antibotic treatment

• supportive care (hospitalization may be required)

• vaccination most effective prevention method

tuberculosis etiological agent

mycobacterium tuberculosis

• acid fast bacilli

• mycolic acid in cll wall (think, hydrophobic, waxy, long fatty acids)

• pulmonary TB most common, extrapulmonary (infection outside respiratory tracrt)

tuberculosis transmission

transmitted via inhalated of contaminated air droplets

humans only known resevoirs

formerly known as white plague

can be active or latent

tubuerculosis symptoms

chronic, productive coughing (> 3 weeks)

• bloody sputum indicative of lung damage and invasive disease

• fever, night sweats, loss of appetite

• disease deadly in people with AIDS

mantoux tuberculin skin test

• intradermal injection of tuberculin purified protein derivative

• injection site evaluated in 48-72hr to measure skin rxn

• can not detect between active vs latent infection

tuberculosis treatment

curable with multi-drug antimicrobial therapy for several months

BCG vaccine and infection control

pneumonia

• inflammation and fluid accumulation in the lower respiratory tract, especially of the alveoli

• leading cause of death from an infectious agent in US

• very common HAI

bacterial pneumonia

high fever; cough produces thick yellow/green mucus/sputum

systemic symptoms intense

viral pneumonia

moderate fever, cough often dry, symptoms like headaches and fatigue more prominent

typical pneumonia

• sudden onset of severe pulmonary infection

• characterized by high fever, shaking chills, lobar lung consolidation

• caused by S. pneumoniae

atypical pneumonia

bacterial pneumonia that is not characterized by signs and symptoms as consolidation; not as severe

caused by abnormal bacterial

lack of response of typical antibiotics

pneumococcal pneumonia etiological agent

streptococcus pneumoniae

• gram positive

• encapsulated diplococcus

• alpha-hemolytic

• leading cause of typical pneumonia

typical pneumonia mechanism of disease

• transmitted person to person via respiratory droplets

• colonizes nasopharynx of a new host (biofilm)

• may spread to middle ear or lungs

polysaccharide capsule

virulence factor for streptococcus pneumoniae

• protective, antigenic, carbohydrate layer anchored cell surface

• protects against phagocytosis, antibiotics, environmental stressors

• basis of vaccines

pneumolysin

pneumoccal exotoxin that lysis cells and damages tissues

mycoplasma pneumoniae etiological agent

type of atypical pneumonia

• small self replicating organism

• lack cell wall - pleomorphic, intrinsic resistance to antibiotics, susceptible to desiccation

tightly associated with surface of human respiratory cells

evades immune response by localizing intracellularly

mycoplasma pneumoniae virulence factor

secreted hydrogen peroxide

• damages airway epithelial cells and cilia and responsible for persistant cough

“walking pneumonia” bc symptoms develop slowly and are mild

legionella pneumonia

gram-negative, motile coccobacilli

environemental resevoir - water

• facultative intracellular parasite (can live/reproduce inside or outside cells)

• invade amoebae in environment and macrophages in humans

• most severe atypical pneumonia

blastomycosis

dimorphic endemic fungus

• symptoms consistent with pneumonia

• noncommunicable

• saprophyte that thrives on decomposing plant matter in moist soil in mold form

• spores become airborne and may germinate into yeast

epidermis

outermost structure of skin

outer layer is tightly packed with dead cells

inner layer contain keratinocytes (waterproofing protein)

dermis

middle layer of skin composed of dermal fibroblasts, collagen fibers, immune cells

also contains blood vessels, nerves, hair follicles, sweat gland ducts, sebaceous glands

subcutaneous layer

made of fat cells, nerves, blood vessels

• not techically skin layer

melanin

part of skin defense mechanism

antimicrobial properties and protects from UV damage

perspiration

skin defense mechanism

• acidic pH

• high salt concentration

• washes away microbes

lysozyme

enzyme present in sweat

breaks down peptidoglycans

sebum

oily substance produced by sebaceous glands

contains low pH lipids and proteins that moisturize the skin

skin microbiome

normal microbiota reside in epidermis, sweat/sebaceous glands, hair follicles

many factors affect normal biota like occupation, age, cosmetics, hormones

primary lesion

associated with a specific disease process; useful for diagnosis of infections

secondary lesions

less obviously associated with a speific disease; may develop as secondary to primary or from scrating or allergic response

rash

widespread eruption of lesions may be symptomatic or asymptomatic

macule

flat discolored area of the skin; doesn’t alter texture or thickness

ex) freckles

papule

raised solid lesion; may be discolored; has distinct borders

pustule

raised lesion with pus below surface