Treatment of Bacterial Infections - Ch 87-93 Flashcards
What is Chemotherapy?
Drugs that are βselectively toxicβ to invading microorganisms that have minimal effect on host
Necrotizing fasciitis
βFlesh-eating diseaseβ
Caused by variety of bacteria
Infections
Invasion and multiplication of organisms
Infections may be caused by foreign bacteria or normal flora (e.g. in immunocompromized
patients)
Colonization of the body by normal flora
Not usually harmful, can help in controlling growth of potentially pathogenic organisms
What causes implications for the action of antibacterials?
Gram-positive or Gram-negative cell wall
What are antibacterial drugs?
Either kill or slow down the growth of bacteria
What are the 2 subgroups of antibacterial drugs?
Bactericidal
Bacteriostatic
Bactericidal
Drugs are directly lethal to bacteria at clinically
achievable concentrations
Bacteriostatic
Drugs can slow bacterial growth but do not cause
cell death
What is critical in helping the body control and eliminate infections?
Immune system
Host defences are especially important in what group of antibiotics?
Bacteriostatic
Superinfection
new microbes take over when antibacterials kill normal flora
- eg respiratory, genitourinary tract and GI tract
microbe resistant to drug action = difficult to treat
Opportunistic infections
Infections that would not normally harm an immunocompetent person
-Existing colonization becomes infections
-Can be viruses, fungi, bacteria or protozoa
Who is affected by opportunistic infections?
Immunocompromised patients
How many people die globally from antibacterial resistance?
5 million people
What enhances selection of mutant bacteria (resistance)?
Improper choice of antibiotics
The dose is too low
Dosing not continued for long enough
Improper use of antibacterial, e.g, to treat a viral infection
Prophylactic use of antibacterials, e.g. in animal feed
What host factors need to be taken into consideration when providing antibacterial therapy?
Host age, allergies, organ health, pregnancy, site of infection and personβs general health
What are allergic reactions?
Immune response
-GI upset is not an allergic reaction
What are the four common mechanisms of action of antibacterials?
- Disruption of critical metabolic reactions
- Interference with cell wall synthesis
- Interference with protein synthesis
- Interference with DNA replication
What mechanism of action do sulfonamides use?
Inhibit metabolism
What spectrum do Sulfonamides have?
Broad spectrum
(effective against gram-positive and gram-negative)
What type of antibacterial are sulfonamides?
Bacteriostatic
How do sulfonamides inhibit/disrupt metabolic reactions?
Prevent synthesis of folic acid
Examples of sulfonamides
Sulfamethoxazole
Sulfadiazine
What are sulfonamides combined with?
trimethoprim
e.g, co-trimoxazole
Bactrim or Septra for UTI and otitis media
Where do sulfonamides reach effective concentrations?
Urinary tract
What are other clinical uses of sulfonamides?
Upper respiratory tract infections
others e.g, malaria, chlamydia
If someone is allergic to 1 sulfa-drug does that allergy applie to other reivatives of sulfa-life drugs?
Yes
e.g, anti diabetic agents sulfonylureas
thiazide and loop diuretics (increase urine)
Can pregnant women take sulfonamides and why?
No it is linked to birth defects in the 1st trimester and close to end of pregancy may increase fetal bilirubin (kernicterus brain damage)
It is advised to take sulfonamides during breastfeeding?
No also infants less than 2 months should not ingest
What are some adverse effects of sulfonamides?
Integumentary allergies
Blood adverse effects
GI adverse effects
What are some adverse effects affecting the skin caused by sulfonamides?
Stevens-johnson syndrome
Photosensensitivty
What are some blood adverse effects caused by sulfonamides?
(bone marrow depression)
Agranulocytosis, thrombocytopenia, aplastic anemia
What are GI adverse effects caused by sulfonamides?
Nausea and vomiting
Who discovered Beta-lactam antibacterials?
Sir Alexander Fleming (1928)
-Discovered Staphylococcus aureus was destroyed by the mold Penicillium notatu β> penicillin
What percent of S. aureus is resistant to penicillin now?
95%
What mechanism of action do Beta-lactam antibacterials use?
Inhbit cell wall enzyme responsible for peptidoglycan synthesis
What kind of antibacterial are Beta-lactams?
Bactericidal
What are the 4 groups of Beta-lactam antibacterials?
Penicillins
Cephalosporins
Monobactams
Carbapenems
What do all Beta-lactam antibacterials have in common?
Beta-lactam ring in their structures
What groups of Beta-lactams are commonly used in Canada?
Penicillins
Cephalosporins
Carbapenems
What are the 2 min subgroups of penicillins?
Naturally occurring
Semi-synthetic
What are Naturally occurring penicillin sensitive to?
Beta-lactamase
What are semi-synthetic penicllin resistant to?
Beta-lactamase
What kind of spectrums do semi synthetic penicillin have?
Broad or extended
What are broad spectrum semi-synthetic penicillins called?
Aminopenicillins
What are extended semi-synthetic penicillins called?
Anti-pseudomonal penicillins
What are the 2 narrow-spectrum (natural) penicillins that are still commonly used?
Penicillin G and Penicillin V
Example of beta-lactamase-resistant penicillin?
Cloxacillin
Examples of aminopenicillins (broader-spectrum)
Amoxicillin (more acid-stable), ampicillin
Examples of anti-pseudomonal penicillins (extended-spectrum)
Ticarcillin, piperacillin
Anti-pseudomonal penicillins can even be used against which bacteria?
Pseudomonas aeruginoas
-affects mostly ill people e.g, immunocompromized, cystic fibrosis
Pseudomonas aeruginosas opportunistic infections?
Respiratory tract
Ears
Eyes
CNS
UTI
Endocarditis
Describe the mechanism of action of Penicillins
- Penicillins enter the bacteria
- Inside the cell they bind to penicillin- binding proteins
- Normal cell wall synthesis is disrupted
- Bacteria cells rupture
- Penicillins do not kill other cells in the body
What kind of antibacterial are penicillins?
Bactericidal
Depending on which type of penicllin, penicillins are active against most of which type of bacteria?
Most gram-positive
-Only some gram-negative
Why is there resistance to Penicillins?
Some bacteria produce enzymes capable of destroying penicillins
What enzyme do bacteria produce that causes resistance?
Beta-lactamases which splits the Beta-lactam ring
What is used in combination with penicillins?
Beta-lactamase inhibitors
(helps with resistance)
Examples of Beta-lactamase inhibitors
Clavulanic acid (amoxicillin + clavulanic acid)
Tazobactam (piperacillin + tazobactam)
How can Penicillins be administered?
PO, IM, IV
Penicillin G administration
IV or IM
Penicillin V administration
PO
Adverse effects of Penicillin
GI problems
-Nausea, vomiting, diarrhea, pain
(generally well tolerated)
Allergic reactions
What is the most common cause of drug allergy?
Penicillin