Week 4: Infection for real this time Flashcards
What is the PROCESS of infection?
- Encounter
- Transmission
- Colonization
- Invasion or Penetration
- Dissemination
- Cellular or tissue damage
Two ways that an individual can ENCOUNTER or come in contact with microorganisms
- Endogenous microorganisms
- Exogenous microorganisms
Endogenous microorganisms
Organisms already present in the body and part of the normal microbiome
Naturally on us
Exogenous microorganisms
Are transmitted from an external environment.
Not naturally on us
Two ways transmission of microorganisms can occur:
- Direct Transmission/Contact
- Indirect Transmission
Direct Transmission/Contact Two Types
- Vertical Transmission
- Horizontal Transmission
Vertical Transmission
From mother to child across placenta, during delivery from birth canal or breast milk
Horizontal Transmission
From one person to another through exposure to blood and body fluids
Indirect Transmission
Occurs from contact with:
infected materials,
inhalation or droplet infection,
ingestion of contaminated food or water
or inoculation
Colonization
Colonization is the ability of a pathogenic microorganism to survive and multiply on or within the human environment.
Invasion or Penetration
Invasion or penetration is the ability of pathogens to cross surface barriers including the skin and mucous membranes.
What does Invasion or Penetration require?
Requires penetration or break in the integrity of the barrier
Dissemination
Dissemination or spread of infection can occur by direct extension through surrounding tissue or through the blood or lymphatic vessels.
Two ways Tissue damage can occur?
- Directly
- Indirectly
Direct Tissue Damage
Production of toxins
Indirect Tissue Damage
Indirect as a result of an immune response with inflammation, swelling, scarring or necrosis
What are the STAGES of infection?
- Incubation Period
- Prodromal Stage
- Invasion or Acute Illness Period
- Convalescence
Incubation Period- what is it?
The period from initial exposure of infectious agent and the onset of symptoms.
Incubation period- what happens?
The microorganisms have:
entered the individual,
undergone initial colonization
and begun multiplying but are insufficient numbers to cause symptoms
How long does incubation period typically last?
Several hours to years
Prodromal Stage
The occurrence of initial symptoms, which are often very mild
Pathogens continue to multiply during this stage
Invasion or acute illness period
The pathogen is multiplying rapidly, invading farther and affecting the tissues at the site of initial colonization as well as other areas
the immune and inflammatory responses have been triggered; symptoms may be specifically related to the pathogen or to the inflammatory response
Convalescence: most cases what happens?
In most instances, the individual’s immune and inflammatory systems successfully remove the infectious agent and symptoms decline
Convalescence: less cases what happens?
the disease may be fatal or enter a latency phase with resolution of symptoms until pathogen reactivation at a later time
When can an infectious disease be contagious?
During all stages of infection
What are a common cause of disease?
Bacteria
How does gram staining differentiate microorganisms?
Gram staining differentiates the microorganisms as gram-positive or gram-negative bacteria
Gram positive bacteria
Gram-positive bacteria have teichoic acid and peptidoglycan in their outer membranes causing them to appear dark purple on Gram stain.
Gram- negative bacteria
Gram-negative bacteria have a lipopolysaccharide (LPS) in the outer membrane causing them to appear light pink on Gram staining.
Viruses
Are obligatory intracellular microbes consisting of nucleic acid protected from the environment by a protein shell, the capsid
The viral life cycle is completely intracellular and involves what steps
- Attachment/binding
- Penetration
- Uncoating
- Replication
- Assembly
- Release
Attachment during viral life cycle
Attachment to a specific receptor on the target cell
Penetration phase during viral life cycle
(entrance into the cell by endocytosis or membrane fusion)
Uncoating Phase during viral life cycle
is the release of viral nucleic acid from the viral capsid by viral or host enzymes
Replication phase during the viral life cycle
Replication is the synthesis of viral proteins and messenger RNA (mRNA).
The viruses inject their DNA or RNA into the host nucleus and use host resources for viral reproduction.
Assembly phase during viral life cycle
Assembly is the formation of new virions.
Release phase in viral life cycle
Release or shedding of new virions is by lysis or budding from the cell membrane.
Two basic Fungi Structures
- Single celled yeasts
- Multicellular molds
Infections caused by Fungi
Mycoses
Mycoses characteristics
Can be superficial, deep or opportunistic
Superficial mycoses
Occur on or near skin or mucous membranes and usually produce mild and superficial disease
Dermatophytes
Fungi that invade the skin, hair, or nails
Diseases that dermatophytes produce
The diseases they produce are called tineas (ringworm)
Examples of tineas
- Tinea pedis
- Tinea cruris
- Tinea capitis
Tinea pedis
feet ringworm
Tinea cruris
groin ringworm
Tinea capitis
scalp ringworm
What is the most common cause of fungal infections in humans?
Candida albicans
Candida albicans
Opportunistic yeast that is a commensal inhabitant in the normal microbiome of many healthy individuals.
Where does C. albicans reside in healthy individuals?
residing in the skin, gastrointestinal tract, mouth, and vagina.
When healthy people take antibiotic therapy, what can happen with their naturally occurring C. albicans?
Candida overgrowth may occur, resulting in localized infection, such as vaginitis or oropharyngeal infection (thrush)
In immunocompromised people (especially those with diminished neutrophil levels) what happens with the Candida?
disseminated infection may occur
What does disseminated candidiasis involve?
Disseminated candidiasis may involve deep infections of several internal organs
The mortality rate among individuals with septic or disseminated candidiasis is about 30%
Parasitic microorganisms
Establish a relationship in which the parasite benefits at the expense of the other species.
Examples of unicellular protozoa
Malaria
Amoeba
Flagellaes
Name for parasitic worms
Helminths
Example of Helminths
Flukes
Nematodes
Tapeworms
How are most protozoan parasites transmitted?
Many protozoan parasites are transmitted through vectors or ingested.
Two possible traits of Antibacterial antibiotics?
- Bactericidal
- Bacteriostatic
Bactericidal
bactericidal (kill the microorganism)
Bacteriostatic
inhibit growth until the microorganism is destroyed by the individual’s own protective mechanisms
Mechanisms of Action of Most Antibiotics
- Inhibition of the function or production of the cell wall/membrane
- Prevention of protein synthesis
- Blockage of DNA replication
- Interference with folic acid metabolism
Four Basic Actions of Antibiotic Resistance:
- Decrease the concentration of the drug at its site of action
- Inactivate the drug
- Alter the structure of drug target molecules
- Produce a drug antagonist
Beta-Lactamase
Produced by most S.aureus species
Prevents the action of penicillin on the microorganismal cell wall
Selective toxicity of a drug
is defined as the ability of a drug to injure a target cell or target organism without injuring other cells or organisms that are in intimate contact with the target.
selective toxicity indicates the ability of an antibiotic to kill or suppress microbial pathogens without causing injury to the host.
Three examples of how we achieve selective toxicity:
- Disruption of the Bacterial Cell Wall
- Inhibition of an Enzyme Unique to Bacteria
- Disruption of Bacterial Protein Synthesis
Two schemes to classify Antimicrobial Drugs:
- Narrow Spectrum Antibiotics
- Broad Spectrum Antibiotics
Narrow Spectrum Antibiotics
Narrow-spectrum antibiotics, are active against only a few species of microorganisms.
Broad Spectrum Antibiotics
Broad-spectrum antibiotics are active against a wide variety of microbes.
Which type of drugs are generally preferred? Narrow or broad spectrum?
Narrow spectrum
Classification of Antimicrobial Drugs by Susceptible Organisms
- Antibacterial Drugs
- Antifungal Drugs
- Antiviral Drugs
Classification by Mechanism of Action: Antimicrobial drugs fall into seven major groups based on mechanism of action.
Drugs that:
- Drugs that inhibit bacterial cell wall synthesis/ activate enzymes that disrupt cell wall
- Drugs that increase cell permeability
- Drugs that cause lethal inhibition of bacterial protein synthesis
- Drugs that cause nonlethal inhibition of protein synthesis
- Drugs that inhibit bacterial synthesis of DNA and RNA or disrupt DNA function
- Antimetabolites
- Drugs that suppress viral replication
Drugs that inhibit bacterial cell wall synthesis/ activate enzymes that disrupt cell wall- -How?
These drugs weaken the cell wall and promote bacterial lysis and death
Drugs that increase cell permeability- Why and effect?
Drugs increase the permeability of cell membranes, causing leakage of intracellular material
Drugs that cause lethal inhibition of bacterial protein synthesis- How?
We don’t know why inhibition = cell death
Drugs that cause nonlethal inhibition of protein synthesis-HOW
Inhibit bacterial protein synthesis.
These agents only slow microbial growth- not kill
Drugs that inhibit bacterial synthesis of DNA and RNA or disrupt DNA function- How?
These drugs inhibit synthesis of DNA or RNA by binding directly to nucleic acids or by interacting with enzymes required for nucleic acid synthesis.
They may also bind with DNA and disrupt its function.
Antimetabolites- how do they work on harming microbes?
These drugs disrupt specific biochemical reactions.
The result is either a decrease in the synthesis of essential cell constituents or synthesis of nonfunctional analogs of normal metabolites.
Drugs that suppress viral replication- how?
Most of these drugs inhibit specific enzymes
Microbes have four basic mechanisms for resisting drugs
- Decrease the concentration of a drug at its site of action
- Alter the structure of drug target molecules
- Produce a drug antagonist
- Cause drug inactivation
How do microbes acquire mechanisms of resistance?
- Spontaneous Mutation
- Conjugation
Spontaneous Mutation
Spontaneous mutations produce random changes in a microbe’s DNA.
How many drugs does spontaneous mutation confer resistance?
Spontaneous mutations confer resistance to only one drug.
Conjugation
Conjugation is a process by which extrachromosomal DNA is transferred from one bacterium to another.
Where does conjugation primarily occur?
Conjugation takes place primarily among gram-negative bacteria.
Difference between Spontaneous Mutation and Conjugation?
In contrast to spontaneous mutation, conjugation frequently confers multiple drug resistance.
Causes of Antibiotic Resistance?
- Lack of compliance with drug regimen
- Overuse of antibiotics
Superinfection/Suprainfection
A superinfection is defined as a new infection that appears during the course of treatment for a primary infection.
When do new infections (or superinfections) develop?
New infections develop when antibiotics eliminate the inhibitory influence of normal flora, thereby allowing a second infectious agent to flourish.
Common example of suprainfection?
Development of vaginal Candida infection in a female treated with a broad spectrum antibiotic for a UTI
Priniciple Adverse Effects of Penicillins:
Allergic reactions
The penicillins have what in their structure and are therefore known as what?
Penicillins have beta- lactam ring in their structures and are known as beta-lactam antibiotics
What is included in the beta-lactam family?
- Cephalosporins
- Carbapenems
- Azetreonam
All the beta-lactam antibiotics share the same mechanism of action which is?
Disruption of the bacterial cell wall
Penicillins weaken cell wall by two actions:
- Inhibition of transpeptidases
- disinhibition (activation) of autolysins
The molecular targets of the penicillins (transpeptidases, autolysins, other bacterial enzymes) are collectively known as?
Penicillin-binding proteins (PBPs)
These molecules are names because penicillins must bind to them to produce antibacterial effects
Penicillinase (Beta-Lactamases)
Beta-lactamases are enzymes that cleave the beta-lactam ring and thereby render penicillins and other beta-lactam antibiotics inactive
Classification of Penicillins: Four major categories
- Narrow spectrum penicillins that are penicillinase sensitive (will be inactivated by penicillinase)
- Narrow spectrum penicillins that are penicillinase resistant
- Broad spectrum penicillins
- Extended spectrum penicillins
Examples of Narrow Spectrum Penicillins: Penicillinase sensitive
- Penicillin G
- Penicillin V
Example of Narrow-spectrum Penicillins: penicillinase resistant
- Nafcillin
- Oxacillin
- Dicloxacillin
Examples of Broad-spectrum penicillins (aminopenicillins)
- Ampicillin
- Amoxicillin
Examples of Extended-spectrum penicillin
Piperacillin
How is Penicillin G (Benzylpenicillin) administered?
IV or IM
Types of Allergic Reactions of Penicillins:
- Immediate
- Accelerated
- Delayed
Immediate Penicillin Allergic Reaction occur when?
Immediate Reactions occur within 2 to 30 minutes after drug administration
Accelerated Penicillin Allergic Reaction occur when?
Accelerated reactions occur within 1 to 72hours
Delayed Penicillin Reactions occur when?
Delayed reactions occur within days to weeks.
Immediate and Accelerated Allergic Reactions to Penicillin are mediated by what?
Immunoglobulin E (IgE) antibodies
Anaphylaxis when taking penicillin leads to what?
- Laryngeal edema
- Bronchoconstriction
- Severe Hypotension
Anaphylactic reactions occur more frequently with what drug?
penicillins
Difference between Penicillin G and Penicillin V:
Penicillin V is stable in stomach acid, whereas penicillin G is not.
Which Penicillin can be taken orally? G or V?
Because of its acid stability, penicillin V has replaced penicillin G for oral therapy.
Beta-Lactamase Inhibitor
Beta-lactamase inhibitors are drugs that inhibit bacterial beta-lactamases.
How to extend the antimicrobial spectrum of the penicillin?
By combining a beta-lactamase inhibitor with a penicillinase-sensitive penicillin, we can extend the antimicrobial spectrum of the penicillin.
What are the combo of penicillins and beta-lactamase inhibitors that are available? There are three
- Ampicillin/sulbactam [Unasyn]
- Amoxicillin/clavulanate [Augmentin]
- Piperacillin/tazobactam [Zosyn]
What is the most widely used group of antibiotics?
Cephalosporins
Common Cephalosporin characteristics:
Are Beta-lactam antibiotics
Similar in structure and function to penicillins
Bactericidal
Low toxicity
How are cephalosporins grouped?
The cephalosporins can be grouped into five “generations” based on the order of their introduction to clinical use.
When progressing from first generation agents to fifth generation agents, what should we know about the cephalosporins?
As we progress from first-generation agents to fifth-generation agents, there is
(1) increasing activity against gram-negative bacteria and anaerobes,
(2) increasing resistance to destruction by beta lactamases, and
(3) increasing ability to reach the cerebrospinal fluid (CSF).
Because of poor absorption, how should Cephalosporins be administered?
Because of poor absorption from the gastrointestinal (GI) tract, many cephalosporins must be administered parenterally (intramuscularly [IM] or intravenously [IV]).
Adverse Effects to Cephalosporins:
- Allergic reactions
- Bleeding
Drug interactions with Cephalosporin:
Alcohol + Cephalosporin
Drugs that promote bleed + Cephalosporin
Calcium + Ceftriaxone (3rd gen)
Alcohol + Cephalosporin what happens?
induces a state of alcohol intolerance.
If a patient taking these drugs were to ingest alcohol, a disulfiram-like reaction could occur.
Drugs that promote bleed + Cephalosporin
more bleeding!
Characteristics about Carbapenems
- are beta lactam antibiotics
-very broad antimicrobial spectrum
- not active against MRSA
Four drugs in Carbapenems:
- Imipenem,
- Meropenem
- Ertapenem.
- Doripenem
Prototype Carbapenem
Imipenem
Imipenem- what spectrum; route of administration?
Extremely broad spectrum
IV only
Principle indications for Vancomycin
C.diff infection
MRSA infection
Treatment of serious infections with suspectible organisms in pts allergic to penicillins
Major toxicity of Vancomycin and adverse effects:
Renal failure
Ototoxicity- usually reversible and is rare
How to minimize risk of adverse effects of vancomycin?
Monitor drug serum level- peaks and troughs
infuse vancomycin slowly
What drug is a cell wall synthesis inhibitor and does not contain a beta-lactam ring?
Vancomycin
What happens when vancomycin is rapidly infused?
Rapid infusion of vancomycin can cause flushing, rash, pruritus, urticaria, tachycardia, and hypotension.
How to avoid rapid infusion effects of vancomycin?
infusing slowly, over 60 minutes or more
Azetreon belongs to a class of beta-lactam antibiotics known as?
Monobactams
Mechanism of action for Aztreonam
Aztreonam binds to PBP3.
Drug inhibits cell wall synthesis and thereby promotes cell lysis and death
Antimicrobial Spectrum and Therapeutic Use of Aztreonam a (Monobactam):
Narrow antimicrobial spectrum
Only active against gram negative aerobic bacteria
How is Aztreonam administered and why?
It is not absorbed by the GI tract so must be administered parenterally (IM or IV)
Adverse effect of Aztreonam
Similar to other beta-lactam antibiotics
Drugs that are Bacteriostatic Inhibitors of Protein Synthesis:
- Tetracycline
- Macrolides
- Clindamycin
- Linezolid
What spectrum type of drug are Tetracyclines?
The tetracyclines are broad-spectrum antibiotics.
Four types of Tetracyclines:
- tetracycline,
- demeclocycline,
- doxycycline
- minocycline
Disorders that Tetracyclines are first line drugs are:
- Treatments of infectious disease
- Treatment of acne
- Treatment of Peptic Ulcer Disease
- Mycoplasma pneumoniae
- Lyme Disease
- Anthrax
How is Tetracylines effected by food intake?
Absorption of three agents (tetracycline, demeclocycline, and doxycycline) is reduced by food, whereas absorption of minocycline is not.
Why should tetracylines NOT be given with calcium, iron, magnesium, aluminum and zinc?
The tetracyclines form insoluble chelates with calcium, iron, magnesium, aluminum, and zinc. The result is decreased absorption.
Tetracyclines should NOT be given with what?
Tetracyclines should not be administered together with:
(1) calcium supplements,
(2) milk products (because they contain calcium),
(3) iron supplements,
(4) magnesium-containing laxatives, and
(5) most antacids (because they contain magnesium, aluminum, or both).
Adverse Effects of Tetracyclines:
- Tetracyclines irritate the GI tract.
- Diarrhea may result from superinfection of the bowel (in addition to nonspecific irritation), it is important that the cause of diarrhea be determined.
- Tetracyclines bind to calcium in developing teeth, resulting in yellow or brown discoloration;
- When taken after the fourth month of gestation, tetracyclines can cause staining of deciduous teeth of the infant.
- Photosensitivity
Are Macrolides narrow or broad spectrum?
Macrolides are broad spectrum antibiotics that inhibit bacterial protein synthesis.
What is the oldest member of the Macrolide family?
Erythromycin
What are the members of the macrolide family?
- Erthyromycin
- Clairithromycin
- Azithromycin
What kind of bacteria are Erythromycin used for?
The drug is active against most gram positive and gram negative
What is a treatment of choice for people allergic to Penicillin G?
Erythromycin
What illnesses specifically is Erythromycin used for?
Whooping cough
acute diphtheria
Corynebacterium diphtheria
chlamydial infections
M. pneumoniae.
Streptococcus pyogenes
Adverse Effects of Erythromycin (a Macrolide)
Erythromycin is generally free of serious toxicity and is considered one of our safest antibiotics.
- the drug does carry a very small risk of sudden cardiac death from QT prolongation.
- Gastrointestinal disturbances (epigastric pain, nausea, vomiting, diarrhea) are the most common side effects.
- Superinfections, thrombophlebitis, transient hearing loss
Drug interactions of Erythromycin
Erythromycin can increase the plasma levels and half-lives of several drugs, thereby posing a risk of toxicity.
Mechanism of action of Clindamycin
Inhibits protein synthesis
Antimicrobial Spectrum of Clindamycin
Clindamycin is active against most anaerobic bacteria (gram positive and gram negative) and most gram-positive aerobes.
Uses for Clindamycins:
- Because of its efficacy against gram-positive cocci, clindamycin has been used widely as an alternative to penicillin.
- The drug is employed primarily for anaerobic infections outside the CNS (it does not cross the blood-brain barrier).
Adverse Effects of Clindamycin
- Clostridioides difficile–Associated Diarrhea
- Hepatic toxicity
- Blood dyscrasis
- Diarrhea
- Hypersensitivity
Linezolid- why is it important?
The drug is important because it has activity against multidrug-resistant gram-positive pathogens, including vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA)
to delay the emergence of resistance, linezolid should generally be reserved for infections caused by VRE or MRSA, even though it has other approved uses
Linezolid is primarily used against what kind of bacteria?
Active against aerobic and facultative gram positive bacteria
It is a bacteriostatic inhibitor of protein synthesis
What drug inhibits bacteria by inhibiting protein synthesis and causing cell death?
Aminoglycosides- they are bacteriocidal
Aminoglycosides: narrow or broad spectrum? What kind of bacteria are they used for?
The aminoglycosides are antibiotics used primarily against aerobic gram-negative bacilli.
Narrow spectrum
Most commonly employed Aminoglycosides
- Gentamicin
- Tobramycin
- Amikacin
How are Aminoglycosides administered and why?
Not absorbed in the GI so must be administered parenterally to treat systemic infections
Adverse Effects of Aminoglycosides:
Nephrotoxicity
Ototoxicity
Hypersensitivity reactions
Neuromuscular blockade
How does ototoxicity occur with use of Aminoglycosides?
The risk of ototoxicity is related primarily to excessive trough levels of drug rather than to excessive peak levels.
When trough levels remain persistently elevated, aminoglycosides are unable to diffuse out of inner ear cells, and hence the cells are exposed to the drug continuously for an extended time. It is this prolonged exposure, rather than brief exposure to high levels, that underlies cellular injury.
Aminoglycoside-Induced Neuromuscular Blockade:
Aminoglycosides can inhibit neuromuscular transmission, causing flaccid paralysis and potentially fatal respiratory depression.
How to treat neuromuscular blockade caused by Aminoglycosides?
Reversal with IV infusion of a calcium salt (ex; calcium gluconate)
How to monitor serum drug levels?
How monitoring is done depends on the dosing schedule employed (once daily dosing or the use of dividing doses)
When once daily dosing is employed for drugs, what do we measure?
When once-daily dosing is employed, we need to measure only trough levels.
When drawing blood samples for aminoglycoside levels, how to measure PEAK level?
Samples of peak levels should be taken 30 minutes after giving an IM injection or after completing a 30 minute IV infusion
When drawing for aminoglycoside levels, what is sampling for trough levels dependent on?
Sampling for trough levels depends on the dosing schedule.
For patients receiving divided doses of aminoglycosides, when should trough samples be taken?
For patients receiving divided doses, trough samples should be taken just before the next dose.
For patients receiving once daily doses of aminoglycosides, when should trough samples be taken?
For patients receiving once-daily doses, a single sample can be drawn 1hour before the next dose. The value should be very low, preferably close to zero.
What were the first drugs available for the systemic treatment of bacterial infections?
Sulfonamides
Primary use of Sulfonamides
UTI
How do sulfonamides suppress bacterial growth?
Sulfonamides suppress bacterial growth by inhibiting synthesis of tetrahydrofolate, a derivative of folate.
Purpose of folate in all cells?
Folate is required by all cells to make DNA, RNA, and proteins;
What step in folate synthesis does sulfonamide block?
Sulfonamides block the step in which PABA is combined with pteridine to form dihydropteroic acid. Because of their structural similarity to PABA, sulfonamides act as competitive inhibitors of this reaction.
Adverse effects of Sulfonamides
- Hypersensitivity reactions
- Blood dyscrasias
- Kernicterus
- Renal damage from crystalluria
Hypersensitivity Reactions from Sulfonamides- most severe?
The most severe hypersensitivity response to sulfonamides is Stevens-Johnson syndrome, a rare reaction with a mortality rate of about 25%.
Hematologic Effects of Sulfonamides:
Sulfonamides can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Adverse Effect of Kernicterus from using Sulfonamides
Kernicterus is a disorder in newborns caused by the deposition of bilirubin in the brain.
Renal damage from Sulfonamides
Because of their low solubility, older sulfonamides tended to come out of solution in the urine, forming crystalline aggregates in the kidneys, ureters, and bladder. These aggregates cause irritation and obstruction, sometimes resulting in anuria and even death.
Silver Sulfadiazine and Mafenide
These sulfonamides are employed to suppress bacterial colonization in patients with second- and third-degree burns.
Difference between application of Silver sulfadiazine and mafenide?
Local application of mafenide is painful,
Application of silver sulfadiazine is pain free.
What drug is similar to sulfonamides in that it suppresses synthesis of tetrahydrofolate- needed for bacteria to make folate?
Trimethoprim
What is Trimethoprim’s mechanism of action?
Trimethoprim inhibits dihydrofolate reductase, the enzyme that converts dihydrofolate to its active form: tetrahydrofolate
Trimethoprim/Sulfamethoxazole (TMP/SMZ):
The antimicrobial effects of TMP/SMZ result from inhibiting consecutive steps in the synthesis of tetrahydrofolate.
Therapeutic uses for TMP/SMZ:
The combination is especially valuable for:
UTIs,
otitis media,
bronchitis,
shigellosis, and
pneumonia caused by P. jiroveci and Pneumocystis pneumonia and
GI infection
Two urinary antiseptics are available: They are only used for UTIs
- Nitrofurantoin
- Methenamine
Drugs in Nitrofurantoin family?IGNORE THIS SLIDE I THINK ITS WRONG!
[Furadantin, Macrodantin, Macrobid]
What do Nitrofurantoin do at low concentrations?
Nitrofurantoin [Furadantin, Macrodantin, Macrobid] is a broad-spectrum antibacterial drug, producing bacteriostatic effects at low concentrations and bactericidal effects at high concentrations.
What do Nitrofurantoin do at high concentrations?
Nitrofurantoin [Furadantin, Macrodantin, Macrobid] is a broad-spectrum antibacterial drug, producing bacterioSTATIC effects at low concentrations and bacteriCIDAL effects at high concentrations.
Methenamine [Hiprex, Urex]- mechanism of action
Methenamine [Hiprex, Urex] is a prodrug that, under acidic conditions, breaks down into ammonia and formaldehyde.
The formaldehyde denatures bacterial proteins, causing cell death.
Tuberculosis is caused by what:
Tuberculosis is caused by Mycobacterium tuberculosis
How is M. tuberculosis transmitted?
Is transmitted from person to person by inhaling infected sputum that has been aerosolized, usually by coughing or sneezing.
Where is initial infection of M. tuberculosis?
Initial infection is in the lungs
What happens in most cases of M. tuberculosis?
In most cases, immunity to M. tuberculosis develops within a few weeks, and the infection is brought under complete control.
As a result, approximately 90% of individuals with primary infection never develop clinical or radiologic evidence of disease.
What happens if immune system fails to control primary infection of M. tuberculosis?
If the immune system fails to control the primary infection, clinical disease (tuberculosis) develops.
What happens to lungs when you have the clinical disease of Tb?
The result is necrosis and cavitation of lung tissue.
Lung tissue may also become caseous (cheese-like in appearance).
In the absence of treatment, tissue destruction progresses, and death may result.
First line drugs for Tb:
- Isoniazid (MH)
- Rifampin
- Rifapentine, rifabutin, pyrazinamide, ethambutol
Adverse Effects of Isoniazid
Hepatotoxicity
Peripheral neuropathy
Optic neuritis- bc drug crosses blood brain barrier
Anemia
How does using isoniazid result in peripheral neuropathy?
Peripheral neuropathy results from isoniazid-induced deficiency in pyridoxine (vitamin B6).
If peripheral neuropathy occurs, it can be reversed by administering pyridoxine (but much higher doses needed)
Adverse Effects of Rifampin
Hepatotoxicity- toxic to liver and can lead to hepatitis
Discoloration of Body Fluids- red orange color to urine, sweat, tears
GI disturbances
Second line Antituberculosis Drugs
levofloxacin and moxifloxacin
three injectable drugs (capreomycin, amikacin, streptomycin),
and three other drugs (PAS, ethionamide, and cycloserine).
kanamycin
Fluroquinolones- what spectrum and what use?
the fluoroquinolones are broad-spectrum agents that have multiple applications.
Benefits of Fluoroquinolones
Benefits derive from disrupting DNA replication and cell division.
How are Fluoroquinolones administered?
All of the systemic fluoroquinolones can be administered orally.
Prototype Fluoroquinolone
Ciprofloxacin
Side Effects of Fluoroquinolones
GI
CNS
Tendon Rupture* rare but a big deal I guess???
Phototoxicity
Candida infections
Increased risk of C.diff infection
Older pt issues
GI side effects taking Fluoroquinolones
Nausea/Vomiting, diarrhea, abdominal pain
CNS side effects of Fluoroquinolones
Dizziness, headache, restlessness, confusion, rarely seizures
Candida infections side effects of taking Fluoroquinolones
Pharynx and vagina
Effects of taking Fluoroquinolones in old people
Confusion
Somnolence
Psychosis
Visual disturbances
