12 - Antibiotics Flashcards
(53 cards)
1
Q
What is Bacteria?
A
- Bacteria are single celled organisms that can be shaped as rods, spheres,
or spirals. - Bacteria occupy almost every
habitat on Earth, including
humans - Most bacteria are rendered harmless by our immune system and some even play beneficial roles.
- Some bacteria are pathogenic and cause diseases such as cholera, syphilis and tuberculosis.
- Before discovering antibiotics, bacterial infection was a major cause of morbidity and death
2
Q
Bacterial Pathogenicity
A
Bacteria have virulence factors that they use to cause infection
Virulence factors include:
→ Fimbriae and pilli
→ Flagella
→ Secretion of toxins and enzymes
→ Invasion
3
Q
1) Fimbriae and Pilli
A
- Fimbriae and pilli are hair like structures that project from the surface of bacterial
cells. - They allow bacteria to attach to certain sites in our body so they are not washed away
Ex.E.coli are known to cause
bladder infections.
→ E. coli produce fimbriae that attach to the urogenital tract
4
Q
2) Flagella
A
- Bacteria typically live in aqueous environments and need to move to sites where they can survive.
- The flagellum that bacteria possess allows them to “swim” through the watery environment of our body to the site where they may survive
5
Q
3) Toxins and Enzymes
A
- Some bacteria secrete toxins and/or enzymes.
- Secreted toxins can have a wide array of effects including nausea, vomiting, diarrhea, cramps, pain, fever, or even paralysis
- In some cases, bacterial toxins produced outside of our body can mediate toxic reactions if they gain entry to our body.
→ Ex. Food poisoning - bacteria can colonize the food and when we ingest it, we get symptom’s of poisoning - bacteria also release enzymes
→ Some of these enzymes can degrade tissue or breakdown antibodies, our defense against infection
6
Q
4) Invasion
A
- Some bacteria can invade (enter) our cells.
→ Ex. the bacteria that cause Salmonella invade cells of the intestine and cause severe diarrhea. - Bacteria that cause tuberculosis usually enter our body in the lungs and can “hide” inside cells making it impossible for our immune system to act on them.
7
Q
Gram Staining of Bacteria
A
- Gram staining is a technique used to classify bacteria as either gram positive or gram negative.
Importance: the gram stain tells
us about the cell wall structure
of bacteria - the amount of peptidoglycan
→ important in determining which
antibiotic we use.
- Gram positive cells have a thick peptidoglycan wall that stains
PURPLE - Gram negative cells have a thin peptidoglycan layer and stain PINK
8
Q
Gram Positive vs. Gram Negative Bacteria
A
Gram Positive
- THICK peptidoglycan layer
- surface protein is techoic acid
→ techoic acids: surface antigen that provides rigidity to cell wall
Does NOT have
- outer cell membrane
- porins (few exceptions)
- LPS’s
Gram Negative
- THIN peptidoglycan layer
- No techoic acids
- Has Lipopolysaccharides
→ structural component of outer membrane and major surface antigen
- has outer cell membrane
→ protects bacteria from bile salts and detergents
- presence of porins
→ proteins that allow sugar, ions, and amino acids to enter bacteria
9
Q
Signs of Infection
A
- typical signs of infections include fever, overall malaise, local redness, and swelling
- Other signs of infection include increased respiratory rate and
tachycardia. - In some cases patients may not have a fever
→ Ex. newborn babies may have an immature hypothalamus or the
elderly may have decreased hypothalamic function. The
hypothalamus regulates body temperature. - There may be other signs of infection depending on the location of the
infection
→ Ex. patients with a UTI feel the
frequent need to urinate
10
Q
Selective Toxicity
A
The treatment of a bacterial infection is critically dependent on the ability
to produce selective toxicity.
* Selective toxicity means the therapy is able to destroy the bacteria without
harming the host (i.e. human cells).
* Selective toxicity is produced by targeting differences between the cellular
chemistry of bacteria and humans.
* Antibiotic therapy produces selective toxicity by:
o Disrupting the bacterial cell wall (human cells do not have a cell
wall).
o Targeting enzymes that are unique to bacteria.
o Disrupting bacterial protein synthesis (bacterial and human
ribosomes are different).
11
Q
Types of Infection
A
1) Bacterial Meningitis - Brain
2) Eye infections - eye
3) Ottis Media - ear
4) Sinusitis - sinus
5) Pneumonia - lungs
6) Upper resp tract Infection - nose, sinus, throat, larynx
7) Gastritis - stomach
8) Food Poisoning - GI tract (stomach, intestine)
9) Skin Infections - skin
10) STD’s - genitals, rectum, throat
11) UTI’s - bladder, urethra
12
Q
Selective Toxicity
A
- The treatment of a bacterial infection is dependent on the ability
to produce selective toxicity.
Selective toxicity: the therapy is able to destroy the bacteria without
harming the host (i.e. human cells).
- Selective toxicity is produced by targeting differences between the cellular chemistry of bacteria and humans.
- Antibiotic therapy produces selective toxicity by:
→ Disrupting the bacterial cell wall (human cells do not have a cell
wall).
→ Targeting enzymes that are unique to bacteria.
→ Disrupting bacterial protein synthesis (bacterial and human
ribosomes are different)
13
Q
What has to be Considered when selecting an antibiotic?
A
- Has the infectious bacteria been identified?
- Bacterial sensitivity to the antibiotic?
- Can the antibiotic access the site of infection?
- Is the patient able to battle the infection?
14
Q
1) Identification of the Bacteria
A
- bacteria are identified prior to selecting treatment
- gram stain is a rapid test that provides information on the structural
features of the bacteria. - culturing the bacteria to properly identify it will provide the best
basis for selection of the therapy - In some cases, cultures are not possible or reliable for identifying the
bacteria
→ Ex. 1 - cultures are rarely taken from children who have an ear infection because they are difficult to obtain.
→ Ex. 2 - samples from patients with lower respiratory infections may contain several species of bacteria.
15
Q
2) Bacterial Sensitivity to the Antibiotic
A
- Antibiotics can be bacteriostatic or bactericidal.
Bacteriostatic
→ Stops the growth and replication of bacteria = stops the spread of infection.
→ they do not kill the bacteria, they rely on the body’s immune system to attack and remove the bacteria
Bactericidal
→ Drugs kill the bacteria.
- Microbiologists can culture bacteria and determine the minimum inhibitory
concentration (MIC) and the minimum bactericidal concentration (MBC) of
antibiotic drugs
16
Q
Testing for MIC and MBC
A
Minimum inhibitory concentration (MIC): concentration of antibiotic that is required to stop bacteria from replicating
Minimum bactericidal concentration (MBC): minimum concentration that is required to kill bacteria
17
Q
3) Penetration to the Site of Action
A
- Some infections are difficult for antibiotics to penetrate
- These infections require careful selection of antibiotics that are able to penetrate to the site of action.
→ Meningitis
→ Urinary Tract Infections
→ Osteomyelitis
→ Abscesses
→ Otitis Media
18
Q
Meningitis
A
- An infection of the meninges: the membranes that cover the brain and spinal cord.
- Bacterial meningitis is rare but
is much more serious than viral
meningitis (i.e. life threatening). - Many antibiotics are unable to
penetrate the meninges - Therefore, effective treatment requires an antibiotic that penetrates the meninges and effectively eradicates the bacteria
19
Q
Urinary Tract Infections (UTIs)
A
- UTI’s occur when bacteria enter
any part of the urinary system. - The most common type is
an infection of the bladder caused
during catheterization. - Effective treatment of UTIs requires an antibiotic that enters the urinary system
→ drugs are often metabolized before entering the urinary system; important to have a drug ACTIVE in the urine that is not completely metabolized
20
Q
Osteomyelitis
A
- Osteomyelitis is an infection
of the bone. - Very few antibiotics are able
to enter the bone, making
treatment options limited. - Treatment of osteomyelitis
usually requires antibiotics
for 4 – 6 weeks
21
Q
Abscesses
A
- Skin abscesses occur when
pus or other infected material
collect under the skin - Abscesses are difficult to treat
with antibiotics because they are poorly perfused with blood
→ just bec the antibiotic is in blood, doe snot mean it will reach the abscess since it has poor perfusion
22
Q
Otitis Media
A
Otitis media: an infection of the middle ear and more referred to as an ear infection.
- Anybody can get an ear infection, but they are much more common in children.
- Many antibiotics do not penetrate the inner ear and are therefore not effective in treatment
23
Q
4) Ability of the Patient to Battle Infection
A
- The immunological state of the patient is a critical determinant in the selection of an antibiotic.
- Bactericidal antibiotics kill bacteria and can be used effectively in patients with compromised immune function.
- Bacteriostatic antibiotics only decrease the ability of bacteria to multiply, and therefore require the actions of the immune system to kill the bacteria.
→ Patients with compromised immune function may not respond to
bacteriostatic antibiotics
Bacteriostatic antibiotics should not be used in ppl with compromised immune function such as:
→ AIDS
→ Organ transplantation
→ Cancer chemotherapy
and also elderly patients
24
Q
Potential Complications of Antibiotic Therapy
A
Common complications which include:
→ Resistance
→ Allergy
→ Serum sickness
→ Superinfection
→ Destruction of normal bacterial flora
→ Bone marrow toxicity
25
1) Resistance
- Antibiotic resistance refers to bacteria that did respond to an antibiotic and
have lost sensitivity over time.
- Antibiotic resistance is a concern in medicine as over 70% of bacteria associated with hospital infections show some resistance to at least one antibiotic that was once effective in treating them
- Antibiotic resistance can be acquired by 3 mechanisms:
1. Reduction of the drug at the site of the target.
2. Increased drug inactivation.
3. Alteration of the bacterial target.
26
How Antibiotic Resistance is Acquired
1. Reduction of the drug at the site of the target
- Over time, some bacteria will decrease the uptake of some
antibiotics.
- Similarly, some bacteria increase the expression of efflux pumps and
therefore bacteria more effectively extrude antibiotics
→ limit exposure of antibiotic inside cell
- The combination of decreased uptake and increased efflux results in decreased drug that is able to access its
bacterial target
- bacteria can evolve and divide rapidly
→ bacteria with increased expression of efflux pumps are the ones that survive and replicate
27
How Antibiotic Resistance is Acquired
2. Increased drug inactivation
- Some bacteria have evolved to produce increased amounts of enzymes that inactivate antibiotics.
Ex. some bacteria produce an enzyme called beta lactamase, which degrades all antibiotics that have a beta lactam ring in their structure (i.e. penicillins and cephalosporins)
→ penicillin are susceptible to this
28
How Antibiotic Resistance is Acquired
3. Alteration of the bacterial target
- Like most drugs, antibiotics act on targets to produce their effect
- Over time, bacteria evolves mutations in the target that make the antibiotic ineffective
→ streptomycin acts on ribosome to inhibit protein synthesis in bacteria
→ overtime, some bacteria can mutate their ribosome to disable the drug to bind to the ribosome - the drug is now ineffective
Ex. a mutation in bacterial ribosomes renders some antibiotics ineffective, as
the antibiotics are not able to
bind to the target
29
How to Prevent Resistance
Strategies to prevent resistance include:
1. Prevent infection
→ Vaccinate where appropriate
→ get catheters out if possible
2. Diagnose and treat infection effectively
→ Many patients with a cold (a virus) expect their doctor to give antibiotics, despite the fact that they are not effective against viruses!
3. Use antibiotics wisely
→ Only use antibiotics when necessary
4. Prevent transmission
→ Isolate the pathogen and prevent its spread.
→ wash hands before and after you touch any patient
30
2) Allergy
- The most common antibiotic allergy is penicillin.
Signs of allergy include:
→ Urticaria (hives)
→ Anxiety
→ Swelling of hands, feet, throat
→ Difficulty breathing
→ Hypotension
- Most fatal antibiotic allergic reactions occur within 20 minutes of dosing.
- Most allergic reactions experienced by patients are not true immune
mediated allergies
→ These patients experience symptoms such as vomiting, diarrhea and non-specific rash.
- If patient is having an allergic reaction you should stop the antibiotic
immediately and monitor vital signs
→ Patients may require treatment with
diphenhydramine (an antihistamine) and an epipen (epinephrine, a
vasoconstrictor; which counteracts effects mediated during an allergic rxn)
31
3) Serum Sickness
- Serum sickness is similar to an allergy but it typically develops 7-21 days
after antibiotic exposure.
- During serum sickness, the body’s immune system improperly identifies a
drug or drug-protein complex as harmful.
- The body then produces an immune reaction, which produces inflammation and other symptoms such as fever, hives, rash, joint pain, itching, angioedema and enlarged lymph nodes.
Treatment of serum sickness:
→ antihistamine (for itching),
→ analgesics (for pain)
→ corticosteroids (for inflammation).
32
4) Superinfection
- Superinfection is a special type of resistance.
- Superinfection is a new type of infection that develops during the course of antibiotic therapy.
- Broad spectrum antibiotics kill both pathogenic bacteria and normal
bacterial flora
→ Destruction of normal bacterial flora can allow new (super) bacteria to flourish and cause 2ndary infection
- Since superinfections are caused by drug-resistant bacteria, they are
difficult to treat.
33
5) Destruction of Normal Bacterial Flora
- In addition to superinfection, destruction of normal bacterial flora can have the following consequences:
- Intestinal bacteria synthesize vitamin K
→ Patients taking anticoagulant
(warfarin) require vitamin K and are
at increased risk of bleeding side
effects when vitamin K is low.
- Intestinal bacteria metabolize some
drugs and contribute to the first pass effect
→ Destruction of normal intestinal flora can lead to increased blood drug levels and therefore toxicity
- Intestinal bacteria are involved in enterohepatic recycling of drugs.
→ Destruction of intestinal bacteria can
decrease enterohepatic recycling (i.e. can cause contraceptive failure with oral contraceptive drugs).
34
6) Bone Marrow Toxicity
- Bone marrow toxicity is a very rare but serious complication of
antibiotic therapy.
- Symptoms of bone marrow toxicity include aplastic anemia, thrombocytopenia, agranulocytosis and leukopenia.
- Patients should look out for symptoms such as sore throat, bruising, and fatigue as they are signs of bone marrow toxicity
35
Penicillins
- Penicillin was discovered in 1928 by
Scottish physician Sir Alexander Fleming.
- His discovery of penicillin is one
of the most influential discoveries in medicine
36
Discovery of Penicillin
- Fleming was doing work on bacteria staphylococci in his lab.
- He went on vacation for a month and when he returned, his plates were contaminated with mould.
- Fleming noticed that the mould killed the staphylococci in close proximity
→ he thought that something produced by the mould could kill bacteria
37
Penicillin and the Bacterial Cell Wall
- The bacterial cell wall is composed of a peptidoglycan layer.
- Transpeptidases are enzymes that form cross bridges between the peptidoglycan strands, therefore making the cell wall strong.
- Autolysins are bacterial enzymes that degrade the peptidoglycan cell wall.
- Together transpeptidases and autolysins are called penicillin binding
proteins (PBPs) and are the primary target of penicillin antibiotics
38
Penicillins – Mechanism of Action
- Penicillins inhibit transpeptidases and activate autolysins.
- penicillins disrupt synthesis of the cell wall and promote cell wall destruction.
- The net result is bacteria take up excess water and die (lyse).
- Penicillins are considered bactericidal and are only effective against
bacteria that are actively growing and dividing
- Penicillins are much more effective against gram positive bacteria
because they do not have an outer membrane and have thicker peptidoglycan layer
39
Penicillin Resistance
Penicillin resistance may be caused by:
1. Inability to reach its target
2. Inactivation
3. Mutation in PBPs that make them have low affinity for penicillins
(i.e. methicillin resistant Staphylococcus aureus, MRSA)
- The predominant mechanism of resistance is inactivation by enzymes
called beta lactamases
→ These enzymes target the beta lactam ring of penicillins rendering the drug inactive.
- We now have beta lactamase inhibitors, which block this enzyme and help avoid resistance.
40
Classes of Penicillins
1) Narrow spectrum penicillins
2) Narrow spectrum penicillinase resistant penicillins
3) Broad spectrum penicillins
4) Extended spectrum penicillins
41
1) Narrow Spectrum Penicillins
- Effective in treating gram positive bacteria.
- Some are destroyed by gastric acid so they must be administered IV or
IM
- Effective in the treatment of pneumonia and meningitis.
- Are generally considered to be safe.
- Drug allergy is the primary adverse
effect.
42
2) Narrow Spectrum Penicillinase Resistant Penicillins
- These antibiotics have an altered side chain that makes them not susceptible to inactivation by beta lactamase enzymes (aka penicillinases)
- Effective in treating penicillinase producing Staphylococci.
- Less effective versus non-penicillinase producing bacteria
- if you have a bacteria that does not produce penicillinases, just use a narrow spectrum penicillin (instead of this class)
- Not effective in treating abscesses or penetrating into bone.
- Some bacteria have emerged that are resistant to this class of drug (i.e.
MRSA).
43
3) Broad Spectrum Penicillins
Advantage: Effective against both gram positive and gram negative bacteria.
- Broader spectrum is due to their ability to penetrate the outer membrane of gram negative bacteria (narrow spectrum can not do this)
- They are readily inactivated by beta lactamases; therefore susceptible to resistance
44
4) Extended Spectrum Penicillins
- These drugs are effective against gram positive and gram negative
bacteria.
- also effective in treating patients infected with Pseudomonas aeruginosa, a bacteria that is resistant to all other penicillins.
- Extended spectrum penicillins are also susceptible to degradation by beta
lactamase enzymes.
45
Other Antibiotics - Cephalosporins
- Have the exact same mechanism of action as penicillins since they inhibit
transpeptidases and activate autolysins.
- Cephalosporins are bactericidal and can be separated into 4 generations:
→ 1st generation
→ 2nd generation
→ 3rd generation
→ 4th generation
- Cephalosporins directly kill bacteria
- As we move from 1st generation to 4th generation, the drugs tend to
increase in their activity against gram negative bacteria, increase resistance to the destruction by beta lactamases, and increase in their ability to penetrate the cerebrospinal fluid.
- Allergy is the most frequently reported adverse effect
- Cross reactivity of people with penicillin allergy is rare (< 1%)
→ cephalosporins are a good alternative for patients allergic to penicillins
46
Other Antibiotics - Vancomycin (drug name, not a class)
- Vancomycin is a potentially toxic drug that is used only to treat serious infections such as those caused by MRSA including osteomyelitis, meningitis, pneumonia, and septicemia.
- Vancomycin inhibits cell wall synthesis but not by binding to PBPs (penicillin binding proteins)
→ INSTEAD, it binds to precursors of cell wall synthesis to block the transglycosylation step in cross bridge synthesis
- Vancomycin may cause ototoxicity (hearing loss), and rapid infusion can cause “red person syndrome” (flushing, rash, itching, hypotension)
→ should be infused slowly overtime
47
Other Antibiotics - Tetracyclines
- protein synthesis inhibitors
- They act by binding to the 30S ribosomal subunit of bacteria, and prevent the addition of amino acids to the peptide chain
→ tetracycline blocks the elongation of bacterial protein which inhibits protein synthesis
- Tetracyclines are broad spectrum antibiotics that are bacteriostatic
- They are effective in treating bacteria that cause typhus fever, chlamydia,
and cholera.
Adverse effects include:
→ GI irritation
→ Photosensitivity – patients must avoid UV (A and B) light and
always wear sun block when outside.
→ Susceptible to superinfection
48
Other Antibiotics - Macrolide Antibiotics
- protein synthesis inhibitors
- They act by blocking the 50S ribosomal subunit of bacteria, and
block the addition of amino acids to the peptide chain (inhibit protein synthesis)
- Macrolide antibiotics have a broad spectrum and are bacteriostatic.
-Adverse effects:
→ GI upset
→ QT interval prolongation
49
Other Antibiotics - Oxazolidinones
- bacteriostatic protein synthesis inhibitors
- They act by binding to a specific region of the 50S ribosomal subunit to
inhibit protein synthesis
- Are narrow spectrum with activity only against gram positive bacteria
- They are important because they are effective in treating MRSA and
vancomycin resistant enterococci (VRE). → Use of oxazolidinones should be
reserved for MRSA and VRE.
Adverse effects
→ reversible myelosuppression (bone marrow toxicity)
50
Other Antibiotics - Aminoglycosides
- Are bacteriocidal, narrow spectrum (effective vs. gram negative), protein synthesis inhibitors
- They act by binding to the 30S
ribosomal subunit to prevent
protein synthesis
- Aminoglycosides are rapidly lethal to bacteria and the mechanism that accounts for this rapid lethality is unknown
Adverse effects
→ irreversible ototoxicity (ear)
→ reversible nephrotoxicity
51
Other Antibiotics - Sulfonamides and Trimethoprim
- Unlike humans who obtain folic acid from our diet, survival of bacteria is dependent on the synthesis of folic acid to incorporate into DNA
→ bacteria synthesizes folic acid
→ folate synthesis produces bacterial DNA
→ bc humans do not make folic acid, these drugs are selective for eradicating bacteria
- Sulfonamides compere with Paba in 1st step of folic acid synthesis
- Trimethoprim act at different stages to block the synthesis of folic acid
- These drugs are given in combination and result in bactericidal action
- The most common use for this
combination is for the treatment of UTIs
Adverse effect
→ hypersensitivity reactions (such as fever and photosensitivity)
→ small risk of severe hypersensitivity reaction: StevensJohnson Syndrome
52
Other Antibiotics - Fluoroquinolones
- Act by inhibiting DNA replication
- They inhibit 2 enzymes, DNA gyrase
and topoisomerase IV.
- Fluoroquinolones are bactericidal and broad spectrum.
- Fluoroquinolones are effective in the treatment of UTIs, osteomyelitis, and soft tissue infections.
Adverse effects
→ GI symptoms (nausea, vomiting, diarrhea).
53
Other Antibiotics - Isoniazid (drug name, not class)
- Isoniazid is the primary treatment for tuberculosis.
- It acts by inhibiting the synthesis of mycolic acid, a component unique to
the cell wall of tuberculosis-causing bacteria
- Since mycolic acid is a unique component to M. tuberculosis bacteria,
isoniazid is only effective in treating tuberculosis
→ no other bacteria used mycolic acid in bacterial synthesis
Adverse effects
→ peripheral neuropathy
→ hepatotoxicity
