Module 16 - Antibiotics Flashcards

Question

Increased drug inactivation.

Answer 1

Some bacteria have evolved to produce increased amounts of enzymes that inactivate antibiotics. For example, 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).

Answer 2

Like most drugs, antibiotics act on targets to produce their effect. Over time, bacteria may evolve mutations in the target that make the antibiotic ineffective. In the example, a mutation in bacterial ribosomes renders some antibiotics ineffective, as the antibiotics are not able to bind to the target.

Answer 3

1. Prevent infection – Vaccinate where appropriate, get catheters out if possible. 2. Diagnose and treat infection effectively – Many patients who have the common 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. This can be as simple as washing your hands. As a rule you should wash your hands before and after you touch any patient.

Answer 4

Allergy is a significant concern for some patients. 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.

Answer 5

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 includes antihistamine (for itching), analgesics (for pain), and corticosteroids (for inflammation).

Answer 6

Superinfection is an example of 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 bacteria to flourish. Since superinfections are caused by drug-resistant bacteria, they are difficult to treat.

Answer 7

* In addition to superinfection, destruction of normal bacterial flora can have the following consequences: Intestinal bacteria synthesize vitamin K. Patients taking the 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 and have devastating consequences to drug therapy (i.e. contraceptive failure with oral contraceptive drugs).

Answer 8

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 be educated to look out for symptoms such as sore throat, bruising, and fatigue as they are signs of bone marrow toxicity.

Answer 9

Fleming was doing work on bacteria called 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. The discovery of penicillin was a serendipitous observation!

Answer 10

The bacterial cell wall is composed of a peptidoglycan layer. Transpeptidases are enzymes that function to 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.

Answer 11

Penicillins inhibit transpeptidases and activate autolysins. Therefore, penicillins disrupt cell wall synthesis and promote cell wall destruction. The net result is bacteria take up excess water and die (lyse). Thus, penicillins are considered bactericidal and are only effective against actively growing and dividing bacteria. Penicillins are much more effective against gram positive bacteria because they do not have an outer membrane

Answer 12

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.

Answer 13

Narrow spectrum penicillins Narrow spectrum penicillinase resistant penicillins Broad spectrum penicillins Extended spectrum penicillins

Answer 14

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.

Answer 15

These antibiotics have an altered side chain that makes them not susceptible to inactivation by beta lactamase enzymes. Effective in treating penicillinase producing Staphylococci. Less effective versus non-penicillinase producing bacteria. Not effective in treating abscesses or penetrating into bone. Some bacteria have emerged that are resistant to this class of drug (i.e. MRSA).

Answer 16

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. They are readily inactivated by beta lactamases.

Answer 17

These drugs are effective against gram positive and gram negative bacteria. In addition, they are 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.

Answer 18

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 As we move from 1st generation to 4th generation, the drugs tend to increase in terms of 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%) so cephalosporins are a suitable alternative for patients allergic to penicillins

Answer 19

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. Rather, vancomycin binds to precursors of cell wall synthesis to block the transglycosylation step in cross bridge synthesis. Vancomycin may cause ototoxicity, and rapid infusion may cause “red person syndrome” (flushing, rash, itching, hypotension).

Answer 20

Are protein synthesis inhibitors. They act by binding to the 30S ribosomal subunit of bacteria, and therefore prevent the addition of amino acids to the peptide chain. 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.

Answer 21

Are protein synthesis inhibitors. They act by blocking the 50S ribosomal subunit of bacteria, and therefore block the addition of amino acids to the peptide chain. Macrolide antibiotics have a broad spectrum and are bacteriostatic. Adverse effects may include GI upset and QT interval prolongation

Answer 22

Are 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 include may include reversible myelosuppression.

Answer 23

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 include irreversible ototoxicity and reversible nephrotoxicity.

Answer 24

Unlike humans who obtain folic acid from our diet, survival of bacteria is critically dependent on the synthesis of folic acid to incorporate into DNA. Sulfonamides and trimethoprim act at different stages to block the synthesis of folic acid. Often these drugs are given in combination and result in bactericidal action. The most common use for this combination is for the treatment of UTIs. The primary adverse effect associated with this therapy is hypersensitivity reactions such as fever and photosensitivity. There is a small risk of severe hypersensitivity reaction called Stevens-Johnson Syndrome

Answer 25

Act by inhibiting DNA replication. They inhibit two 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 primarily include GI symptoms (nausea, vomiting, diarrhea).

Answer 26

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. Adverse effects of isoniazid include peripheral neuropathy and hepatotoxicity.