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Bacterial Functions in Human Body: Gut Microbiota's Impact on Brain, Behavior, and Asthma, Exams of Pharmacology

University of Westminster Pharmacology

Various functions of bacteria in the human body, including carbohydrate fermentation, production of bacteriosins, and the role of cdt in c. Diff infections. It also covers the impact of gut microbiota on brain, behavior, and mood, as well as the causes and effects of functional gi disorders, particularly irritable bowel syndrome (ibs) and asthma.

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2023/2024

Available from 03/28/2024

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Upenn Nursing Patho,Pharm Exam 3

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Microbe - ANS>> A living thing that is too small to be seen by the naked eye; require a

microscope to see them; includes many different life forms including bacteria, archea

(often live in extreme environments), fungi, protists, viruses, and microscopic animals

Microbiome - ANS>> The totality of microbes, their genetic information, and the milieu

in which they interact; typically consist of environmental or biological niches containing

complex communities of microbes; including gut and tongue microbiomes

Microbiota - ANS>> The microbial organisms that make up a specified microbiome;

composition of the microbiota in a community can vary substantially between

environmental sites, among host niches and between health and disease; not just

bacteria, but often focused on bacteria

Where are microbiota found? - ANS>> Skin and hair

Conjunctiva

Nares

Airways

Oral cavity

Entire GI tract

Urogenital tract

Metagenome - ANS>> The genetic information of a complex population, typically from

microbes in an environmental or host niche sample, that is made up of the genomes of

many individual organims

-The human microbial metagenome (all of our micorbes' genes) can be considered a

counterpart to the human genome (all of our human genes)

Commensalism - ANS>> A type of symbiotic relationship between two different

organisms in which one species benefits and the other is unaffected

Commensal bacteria - ANS>> Term that is used to indicate normal/expected

microbiota in different environments of the body

Describe the usual relationship between humans and microbiota - ANS>>

Interdependent and mutualistic

How do mutualistic "friendly" bacteria become pathogenic - ANS>> Growth becomes

uncontrolled or occurs in the wrong anatomical place

Phylotype - ANS>> Microbial group defined by 16S rRNA sequence similarity (16S

rRNA is a component of the 30S small subunit of prokaryotic ribosomes)

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Upenn Nursing Patho,Pharm Exam 3

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Microbe - ANS>> A living thing that is too small to be seen by the naked eye; require a microscope to see them; includes many different life forms including bacteria, archea (often live in extreme environments), fungi, protists, viruses, and microscopic animals Microbiome - ANS>> The totality of microbes, their genetic information, and the milieu in which they interact; typically consist of environmental or biological niches containing complex communities of microbes; including gut and tongue microbiomes Microbiota - ANS>> The microbial organisms that make up a specified microbiome; composition of the microbiota in a community can vary substantially between environmental sites, among host niches and between health and disease; not just bacteria, but often focused on bacteria Where are microbiota found? - ANS>> Skin and hair Conjunctiva Nares Airways Oral cavity Entire GI tract Urogenital tract Metagenome - ANS>> The genetic information of a complex population, typically from microbes in an environmental or host niche sample, that is made up of the genomes of many individual organims

The human microbial metagenome (all of our micorbes' genes) can be considered a counterpart to the human genome (all of our human genes) Commensalism - ANS>> A type of symbiotic relationship between two different organisms in which one species benefits and the other is unaffected Commensal bacteria - ANS>> Term that is used to indicate normal/expected microbiota in different environments of the body Describe the usual relationship between humans and microbiota - ANS>> Interdependent and mutualistic How do mutualistic "friendly" bacteria become pathogenic - ANS>> Growth becomes uncontrolled or occurs in the wrong anatomical place Phylotype - ANS>> Microbial group defined by 16S rRNA sequence similarity (16S rRNA is a component of the 30S small subunit of prokaryotic ribosomes)

Page | 2 Dysbiosis - ANS>> Disturbed homeostasis of the microbiota composition

major cause: antibiotics and other drugs
Relationship is bi-directional: meds and other factors, including disease, can cause dysbiosis, but dysbiosis can cause disease
Cause and effect not always clear Positive effects of gut microbiome for body - ANS>> - Protect against pathogens
Train/Stimulate immune function
Supply nutrients, energy, vitamins, and SCFA Negative factors affecting the gut microbiome - ANS>> - Inflammation (local>systemic)
Oxidative stress
Increase in Gram negative bacteria
Infection (opportunistic/pathogenic)
Altered metabolite production Causes of dramatic microbiome change early in life - ANS>> - diet changes
many and complex environmental exposures Hygiene Hypothesis - ANS>> The idea that being exposed to animals, microbes, etc. early in life "trains" the immune system to respond better, and more appropriately, to pathogens and allergens later
Possible connection to allergy/atopy Prebiotcs - ANS>> food ingredients resistant to digestion (think fiber), fermented by gut microbiota, with a selective effect on the microbiota and consequent beneficial effects on host's health
Stimulate growth or activity of certain types of bacteria Probiotc - ANS>> live micro-organisms which, when consumed in adequate amounts, confer a health benefit on the host
Must meet identification criteria, safety assessment, and efficacy assessment to qualify Culture-independent methods to analyze microbiota - ANS>> - Sequencing target genes
Metabolomics
Shotgun metagenomic sequencing
Proteomics Metabolomics - ANS>> characterizing small molecule metabolites that result from biological and biochemical processes in which microbiota are involved Shotgun metagenomic sequencing - ANS>> All DNA is sequenced, yielding data on taxonomic properties, and well as data on function(s) of bacteria

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Producing bacteria also produce agents that give them resistance to their own bacteriocins
2 way communication with immune system
Role in controlling inflammation and promoting it How does gut microbiome help "train" immune system - ANS>> - Distinguish between self and non-self
Distinguish between friendly and pathogenic bacteria
Promote anti-inflammatory activity of regulatory T cells (a subset of CD4-expressing T cells that prevent the overactive or inappropriately-activated function of Th1 cells
Promotes production of anti-inflammatory products such as defensins or IgA, prevent pathogen bacteria entry into tissue IgA (Immunoglobulin A) - ANS>> Antibody class that plays and critical role in immune function in the mucous membranes
frequently found in dimeric form (2 antibody units together) known as "secretory IgA"
- Secretes anti-proteolytic compunds that protect immunoglobulin from the harsh GI tract environment and also protects from secretions of microbiota Defensins - ANS>> Antimicrobial peptides found in gut lumen What are the anti-inflammatory cytokines found in the gut epithelium? - ANS>> IL- 10 and TCFB (transforming growth factor-beta) Connection between gut bacteria and various conditions/diseases - ANS>> They're implicated Findings of the burgeoning study of human microbiota - ANS>> There are many more associations than there are direct causations
correlation doesn't equal causation C.diff (description and steps of infection) - ANS>> - Gram +, spore-forming, anaerobic bacillus that infects colon
May be present in small numbers in colon but spores usually ingested via fecal-oral route
Most common healthcare associated infection
Example of dysbiosis
Steps 1.) antibiotic therapy 2.) disruption of colonic microbiota 3.) c. diff exposure and colonization 4.) release of toxin A ("enterotoxin") and toxin B ("cytotoxin") 5.) mucosal injury and inflammation Pathophysiology of C.Diff - ANS>> - Spread via fecal-oral route

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Once ingested spores germinate to vegetative state in small intesting then travel to colon where they attach to the colonic epithelium and reproduce
Can severely injure the colonic mucosal layer
Injury to colon caused by release of exotoxins by bacteria that attach to the colonic membrane (toxin A and B)
Toxins cause colonic epithelial cell necrosis, apoptosis, and disruption of cellular tight junctions Toxin A - ANS>> Causes inflammation leading to intestinal secretion and mucosal injury Toxin B - ANS>> 10xs more potent than toxin A, causes much more damage to colonic mucosa "Hypervirulent" strain of C.diff - ANS>> - Associated with emergence of newer antibiotics class, fluroroquinolones
Produces third toxin, CDT
Produces more toxin A and B
Lower cure rates and higher recurrence rates
More severe disease and worse outcomes including death CDT (C. difficile transferase) - ANS>> - Modifies host cell cytoskeleton leading to cell collapse and death
Gains entry to cell by binding to surface receptor that moves the toxin past the membrane and into the cytoplasm Major risk factor for C. diff infection - ANS>> Recent antibiotic use Major route of C. diff infection in hospitals - ANS>> Healthcare workers' hands
Wash hands!
Alcohol-based sanitizers are ineffective About how long does it take for c. diff spores to enter vegetative state once introduced to GI tract? - ANS>> 6 hours Signs and Symptoms of C. diff - ANS>> - At least 3 watery, unformed bowel movements per day
- Diarrhea is cardinal symptom
Abdominal pain
Nausea
Fever
Leukocytosis Colitis - ANS>> inflamed and painful colon
sign of c. diff infection

Page | 7 Roles of SCFA in immune system - ANS>> - enhanced ROS burst

more phagocytosis
induction of apoptosis
modulation of recruitment
cytokine production Roles of SCFA in metabolism and inflammation - ANS>> Obesity can shift balance of gut micobiota species causing an imbalance of SCFA that play out metabolic roles with insulin sensitivity, fatty oxidation, LPS inflammation, and lipogenesis Most common strains of bacteria used as probiotics - ANS>> Bifidobacterium and Lactobacillus Characteristics of probiotics - ANS>> - low pH adaptation
bile tolerance
adhesion Functions of probiotics - ANS>> - promotion of dietary nutrient digestion and uptake
strengthening of intestinal barrier function
modulation of host immune response
enhancement of antagonism towards pathogens Effects of probiotics - ANS>> - prevention/treatment of GI disorders + food allergies and intolerance
reduction of cholesterol levels (lowers BP) Major MOA of probiotics - ANS>> - Enhance and repair epithelial barrier
Increase adhesion to intestinal mucosa which inhibits pathogen adhesion
Competitive exclusion of pathogenic microorganisms
Production of anti-microbial subatnces
Promote digestion and uptake of dietary nutrients
Modulates immune system
- interact with epithelial and dendritic cells (DCs) and with monocytes/macrophages and lymphocytes
- helps DCs and naive T-helper cells mature, influence development of anti- inflammatory regulatory T cells True or False: The short-term use of probiotics appears to be safe and effective in everyone, even those who are immunocromprised or severely debilitated - ANS>> False, The short-term use of probiotics appears to be safe and effective in patients who are not immunocompromised or severely debilitated Therapeutic uses of probiotics in infants - ANS>> NEC Therapeutic uses of probiotics in children - ANS>> - Acute infectious diarrhea

Page | 8

- AAD

Lactose maldigestion Therapeutic uses of probiotics in adults (including elderly) - ANS>> - AAD
Lactose maldigestion
Pouchitis Describe brain-gut communication - ANS>> - 2 way communication between ENS and CNS
disturbance in microbiome can lead to disturbance in CS and vice-versa Influence of CNS on intestinal microbiota - ANS>> Perturbation of your normal habitat via stress induced changes in gastrointestinal:
physiology
epithelial function
mucin production
EE cell function
motility Release of neurotransmitters Influence of gut microbiota on brain, behavior, and mood - ANS>> - activation of neural pathways to brain
activation of mucosal immune response
production of metabolites that directly affect CNS Functional GI disorder - ANS>> - comprises symptoms arising in the mid or lower GI tract that are not attributable to anatomical or biochemical defects
symptoms: abdominal pain, early satiety, nausea, bloating, distension, and various symptoms of disordered defecation 3 most common functional GI disorders - ANS>> - irritable bowel syndrome (IBS)
constipation
functional dyspepsia Irritable bowel syndrome (IBS) - ANS>> - Most common functional GI disorder
chronic or recurrent symptoms of lower abdominal pain related to bowel movements, change in bowel habits (diarrhea, constipation, or alternating), a sense of incomplete rectal evacuation, passage of mucus with stool, and abdominal bloating/distension
known to sometimes occur as a post-infectious problem
emotional stress is one trigger for an IBS exacerbation
"good evidence" that microbiota perturbance is implicated in the etiology of IBS Impact of probiotics on IBS symptoms - ANS>> Some probtiotics help some patients with some symptoms of IBS
degree of "help" varies

Page | 10 Factors that modulate the impact of bacterial invasion by microorganisms - ANS>> - intrinsic virulence

quantity of microorganisms that penetrate the host
host's immune response (e.g. resistance to infection) Formula for infection risk - ANS>> (inoculum x virulence)/host resistance (+ or - )
not a strict mathematical formula
top= organism factors
bottom= host factors
- include age, sex, integrity of host immune system, and any host comorbidities Chain of transmission for infection - ANS>> - Infectious agent
Reservior: human, animal, insect, soil, food, water, fomites
Portal of exit: nasal mucosa and oral mucosa
Mode of transmission: insect bite, nasal droplets, semen
Portal of entry: nasal mucosa, oral mucosa, skin abrasion, and skin puncture
Susceptible victim: malnourished, unimmunized, and immune compromised Nosocomial infection - ANS>> accquired during the course of stay in hospital, nursing home, or other health care facility
e.g. pneumonia, UTI, and c. diff Main factors that contribute to nasocomial infections - ANS>> - microorganisms in the hospital
a compromised host
chain of transmission Stages of infection - ANS>> - incubation: between exposure and symptoms
prodrome: non-specific symptoms; often a feeling of malaise, may have fever, headache, fatigue, and/or other non-specific symptoms
illness: overt s/sx of infection
recovery: return toward homeostasis *Chronic carrier state is possible in some infections When is an infection the most communicable? - ANS>> from transition from incubation to prodomal period until halfway through the illness periods Community acquired pneumonia (CAP) - ANS>> acquired outside of hospital or extended-care facilities Hospital-acquired pneumonia (HAP) - ANS>> acquired in the hospital; diagnosis made> 48 hrs after admission; increased risk for MDR Ventilator associated pneumonia (VAP) - ANS>> diagnosis made 48-72 hrs after endotracheal intubation

Page | 11 Healthcare associated pneumonia (HCAP) - ANS>> diagnosis made while in the community or < 48 hrs after hospitalization, for someone with any of the following risk factors:

hospitalized in an acute care hospital for > 48 hrs within 90 days of the diagnosis
resided in a nursing home or long-term care facility
received recent IV antibiotic therapy, chemotherapy, or wound care within 30 days preceding the diagnosis
attend a hospital outpatient clinic or hemodialysis clinic Most common causative bacteria in CAP - ANS>> S. pneumoniae About 25% of cases of CAP are caused by what? - ANS>> Viruses with or without bacterial co-infection About how many cases of CAP have an unidentified infectious agent - ANS>> up to 50% Correlation between hospitalization and multi-drug resistant form of bacterial pneumonia - ANS>> The longer the stay the greater the risk Risk factors for pneumonia - ANS>> - younger (< 2 years old) or older (65+ years old)
smoker
lung disease
hospitalization
immobility and/or depressed cough reflex
dysphagia
immunocompromised
flu and respiratory syncytial virus (RSV)
alcoholism
IV drug abusers
malnourishment
inhalation of chemicals and other lung irritants Types of pneumonia - ANS>> - bacterial: most common; may be primary cause, or secondary to viral infection, or co-exist with viral infection
viral: flu, RSV, Human metapneumovirus (HMPV), and others
aspiration: inhale food, drink, vomit, or saliva into airway; PNA caused by oropharyngeal or GI tract bacteria > risk of dysphagia or sedated; may be mix of bacteria, both aerobes and anaerobes
chemical: inhalation of liquid, gases, or small particles; more properly called pneumonitis, although may lead to actual infection, depending on what was inhaled Typical vs Atypical pneumonia - ANS>> - not well-defined but still used clinically
Typical: typical s/sx associated with S. pneumoniae

Page | 13

common in respiratory tract
O antigen: outermost portion of bacteria's surface covering
H antigen: slender threadlike structure that's part of the flagella Describe virulence of S. pneumoniae - ANS>> able to avoid phagocytosis and may become invasive, moving into the blood or cross the BBB Effects of S. pneumoniae - ANS>> - induces vascular permeability - > edema - > migration of inflammatory cells, mediators
activates inflammatory cascade, including release of IL-1, IL-6, and TNF-alpha from macrophages Secretions of S. pneumoniae - ANS>> - proteins for adhesion to mucosa in upper airways and lungs (where it can multiply)
proteins that lyse and destroy ciliated cells
protease that inhibit IgA, prevents it from being attached to mucus
hydrogen peroxide - > damage to host cells How do bacteria make it to the lungs to cause bacterial pneumonia - ANS>> - inhalation (most common route)
aspiration
hematogenous (bloodstream, least common) How are bacteria able to cause pneumonia - ANS>> evade defense mechanisms and/or overhwhelm alveolar macrophages' ability to phagocytose them as they multiply rapidly Effects of inflammatory response set in motion by alveolar macrophages - ANS>> - IL- 6 and TNF-alpha initiate fever
other cytokines released by macrophages attract neutrophils which kill bacteria via ROS, enzymes, and antimicrobial proteins (neutrophil ROS, in excess, can cause lung damage)
neutrophils also extrude a meshwork containing antimicrobial proteins that trap and kill bacteria, known as neutrophil extracellular traps (NETs)
inflammatory mediators released by macrophages and recruited neutrophils create an alveolar capillary leak
alveolar air spaces fill with exudative fluid and debris causing a decrease in gas exchange What causes the clinical manifestations of pneumonia - ANS>> The inflammatory response, not the proliferation of the bacteria Clinical manifestations of pneumonia - ANS>> - s/sx: fever, chills, dyspnea, productive cough, and pleuritic chest pain
physical exam: tachypnea, tachycardia, dullness to percussion, diminished breath sounds, inspiratory crackles, tactile fremitus, and egophony

Page | 14

other: inflitrate on CXR; proper specimen, gram stain, culture, and susceptibility; leukocytosis with PMNs predominating, low O2 sat
extra-pulmonary s/sx (most common in atypical pathogens) Polymorphonuclear cells (PMN) - ANS>> granulocytes, neutrophils are the dominant type Inflitrate - ANS>> any substance or type of cell that occurs within or spreads as through the interstices (interstitium and/or alveoli) of the lung, that is foreign to the lung, or accumulates in greater than normal quantity within it CURB-65 criteria - ANS>> how to determine whether inpatient or outpatient treatment is needed for CAP Most common causative pathogen in uncomplicated UTIs - ANS>> E. coli Cystitis - ANS>> lower UTI; infection contained to bladder and/or urethra Pyelonephritis - ANS>> upper UTI; infection above bladder, i.e., in the kidneys, ureters, and peri-renal tissue What are upper UTIs usually results of? - ANS>> Bladder bacteria from lower UTI ascending into the ureters and kidneys
why a person may have both an upper and lower UTI Complicated UTI - ANS>> - can be upper or lower
associated with an underlying condition that increases the risk of therapy failure Uncomplicated UTI - ANS>> - can be upper or lower
healthy nonpregnant adults with no risk factors for treatment failure Urinary stasis' impact on UTI risk - ANS>> - gives bacteria time to attach and multiply
caused by decreased fluid intake and "holding it" too long Vesicoureteral reflux - ANS>> - ureterovesical junction(UVJ) fails to function as a one- way valve, allowing urine and bacteria to reflux back to the kidney
causes chronic infections and high pressure can cause kidney scarring
typically diagnosed in children Normal defense mechanisms of the urinary tract - ANS>> - urination "flushes" out bacteria before they are able to adhere to the bladder wall
lower urinary pH is intolerable to most bacteria
proteins secreted by kidneys prevent bacterial adherence
in females, vaginal lactobacilli kill uropathogens
in males, prostatic secretions are bactericidal
secretory IgA

Page | 16 Continuing ascent up the ureter to the kidney is the pathway for what? - ANS>> Pyelonephritis Pathophysiological steps of lower UTI - ANS>> Bacteria: 1.) ascend urethra 2.) attach to bladder epithelium 3.) invade epithelium 4.) replicate 5.) bacterial toxins and proteases cause exfoliation of cells 6.) note the inflammatory response, as well as the possibility of bacterial persistence in the epithelium What can cause acute kidney injury (AKI)? - ANS>> bacteria continuing their ascention up the urethra and into the kidney(s) Steps in how a lower UTI progresses to pyelonephritis (upper UTI) - ANS>> 1.) Colonization

pathogen colonizes the periurethral area and ascends through the urethra towards bladder 2.) Uroepithelium penetration
fimbriae allow bladder epithelial cell attachment and penetration
following penetration, bacteria continue to replicate and may form biofilms 3.) Ascension
once sufficient bacterial colonization occurs, bacteria may ascend up on the ureter towards the kidney
fimbria may aid in ascension
bacterial toxins may also play a role in inhibiting peristalsis (reducing urine flow) 4.) Pyelonephritis
infection of the renal parenchyma causes an inflammtory response called pyelonephritis
while infection of renal parenchyma is usually the result of bacterial ascension, it can also occur from hematogenous spread 5.) Acute kidney injury
if inflammation cascade continues, tubular obstruction and damage occur, leading to interstitial edema
- may lead to interstitial nephritis causing acute kidney injury (AKI) Clinical manifestations of lower UTI - ANS>> Signs/Symptoms
dysuria
urgency
frequency
nocturia
suprapubic heaviness or pain
gross hematuria Labs

Page | 17

bacteriuria, pyuria
nitrate [+], leukocyte esterase [+] Clinical manifestations of upper UTI - ANS>> Signs/Symptoms
fever, chills
flank pain
nausea/vomitting
malaise
*with or without typical lower UTI s/sx PE
costovertebral (CVA) tenderness Labs
bacteriuria, pyuria, may have increased serum WBCs
nitrate [+], leukocyte esterase [+] Clinical manifestations of UTI in pediatric patients - ANS>> - infants and those under 2 y.o. may present with fever as sole manifestation of UTI
Children older than 2 y.o. often have same sx as adults, but will complain of abdominal pain
Previously-continent children may suddenly revert to bladder incontinence
pyuria on dipstick isn't present in about 10% of culture-positive pediatric UTIs; if dipstick is neg but UTI suspected send for culture and sensitivity Clinical manifestations of pneumonia and UTI in geriatric patients - ANS>> - may not present with any classic symptoms for either; may not even be febrile
very common cluster of s/sx for both in geriatric patients is a "change in mental status":
- confusion
- delirium
- lethargy
- sudden incontinence in a previously continent patient (esp. in UTI) Delirium - ANS>> - sudden onset
dramatic changes in cognition and behavior
can vary during the course of a day
reversible
in older adults can be brought on by infection, pain, other illness, or disorientation of the hospital setting Dementia - ANS>> - develops over years
progressive changes in cognition and behavior
won't vary in the course of a single day
not reversible

Page | 19 Two markers of septic shock - ANS>> 1.) persistent hypotension that requires vasopressors (such as norepinephrine) to maintain a MAP of at least 65 Hg 2.) serum lactate level greater than 2 mmol/L (18mg/dL) despite adequate volume resuscitation

may result in circulatory failure True or False: sepsis is a medical emergency - ANS>> True What's an important warning sign of sepsis? - ANS>> hypotension Signs and symptoms of sepsis - ANS>> - shivering or feeling very cold
fever
extreme pain or discomfort
diaphroesis or clammy skin
confusion or disorientation
SOB
tachycardia
hypotension ***Patient may go from okay to sick to very sick to critically-ill in a very short period of time, sometimes even just hours Rapid treatment of sepsis - ANS>> - increase MAP (fluids and vasopressors)
early broad-spectrum antibiotics until culprit pathogen is identified then you de-escalate or change antibiotic
in attempts to prevent organ failure which is unfortunately common and if the person survives may or may not be permanent Microorganisms - ANS>> bacteria, fungi, viruses, and others Antimicrobial - ANS>> any substance (natural or synthetic) able to suppress the growth of microorganisms or kill pathogenic microorganisms Antibiotics - ANS>> - originally: substance produced by one microoganism that selectively inhibits the growth of another
common meaning: any medication that kills or inhibits the growth of bacteria Antimicrobials - ANS>> agents that kill or suppress the growth of fungi, viruses, parasites, or protozoa Prophylactic antibacterial therapy - ANS>> - no s/sx, trying to avoid infection, used before risk of infection turns into a suspected infection
requires knowledge of the most likely pathogens
make best choice of antimicrobial that will reduce the pathogen at potential site of infection

Page | 20

in some cases given to those at risk for infection
use sparingly and carefully to avoid formation of antibiotic resistance
example: vaccines Empiric antibacterial therapy - ANS>> - clinical s/sx of infection, used when getting gram stain and micro culture of samples taken from suspected site of infection
requires knowledge of the most likely pathogens; infection is known and/or clinically apparent
make best choice of antimicrobial that will help eradicate the pathogen at the sight of infection; take host factors into account
based on common pathogens by site, known exposure, and/or use of broad spectrum drugs
site - > common pathogens - > appropriate drug Definitive antibacterial therapy - ANS>> - site of infection usually known; bacterial susceptibilities known; used once organism is identified and susceptibility is determined
data on pathogen(s) and susceptibility pattern(s) to antimicrobials is already known (culture and sensitivity, MIC determined)
narrow (de-escalate) from initial empiric therapy
follows definitive identification of organisms and their susceptibilities
uses narrow spectrum drugs Methods of measuring susceptibilities - ANS>> Qualitative methods
e.g. disk-diffusion Quantitative methods
e.g. serial dilution
minimum inhibitory concentration (MIC)
minimum bactericidal concentration (MBC) Minimum inhibitory concentration (MIC) - ANS>> drug concentration at which organism's growth is inhibited Minimum bactericidal concentration (MBC) - ANS>> drug concentration at which organism death occurs; will exceed MIC
test is much less common than MIC How susceptibilities are determined - ANS>> MIC values and clinically achievable drug concentrations at the site of infection Both factors must be taken into account Ideal properties for antibiotics - ANS>> Selective toxicity
affects bacteria and not host
affects the right bacteria without "collateral damage" to microbiota of gut, GU tract, etc

Bacterial Functions in Human Body: Gut Microbiota's Impact on Brain, Behavior, and Asthma, Exams of Pharmacology

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Upenn Nursing Patho,Pharm Exam 3

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