Exam IV: Antibiotics II

Question 1

Gram Negative Cocci and Rods

Answer 1

Gram-negative cocci:
Neisseria gonorrheae- purulent ophthalmia or gonorrhea
Neisseria meninngitidis- meningococcal meningitis

Gram negative rods
Pseudomonas aeruginosa: dangerous secondary infections of wounds, pneumonia, eye infections, UTI
Helicobacter pylori: associated with peptic ulcer
Haemophilus influenza: infantile meningitis, conjunctivitis, chronic bronchitis, infection of the ear and sinuses

Question 2

Beta Lactams

Answer 2

Composed of 4 different groups:
1. Penicillin 
2. Cephalosporins 
3. Carbapenems; imipenem, meropenem,ertapenem
4. Monobactams; aztreonam 
They all share the beta lactam ring
Also called cell wall antibiotics

Question 3

Penicillin Resistance

Answer 3

Beta lactamases: comes along and break beta lactam ring apart because the bacteria are resistant to the penicillin and now the penicillin no longer works

Question 4

Penicillin Resistance

Answer 4

Beta lactamases: comes along and chew beta lactam ring apart because the bacteria are resistant to the penicillin and now the penicillin no longer works

They break a bond in the beta lactam ring of penicillin to disable it, so bacteria with this enzyme can resist the effect of penicillin and other beta lactam antibiotics

Question 5

Penicillin G

Answer 5

Penicillin G: IM, IV, oral (poorly absorbed)
Gram + strept pneumonia
Gram – Neisseria
Gram + rods clostridium
Spirochetes Syphilis

Question 6

Benzathine Penicillin G

Answer 6

Benzathine Penicillin G
IM injection
allowing prolonged antibiotic action over 2–4 weeks after a single IM dose (slow release)

DO NOT give in IV = kills patient

Question 7

Benzathine Penicillin G

Answer 7

Benzathine Penicillin G
IM injection
allowing prolonged antibiotic action over 2–4 weeks after a single IM dose
Treatment of syphillis

DO NOT give IV = kills patient

Question 8

Procaine + Benzathine Penicillin G

Answer 8

Procaine + Benzathine penicillin G
IM injection
This combination is aimed at reducing the pain and discomfort associated with a large intramuscular injection of penicillin.

Question 9

Beta Lactamase Resistant Penicillin

Answer 9

Anti-staphylococcal penicillin
NAPH for staph (methicillin susceptible)
Lack activity to gram negative bacteria because of their hydrophobicity

Nafcillin: unipen Oral, IM, IV
Oxacillin: oral, IM, IV
Cloxocillin: cloxapen oral
Dicloxacillin: dynapen Oral

Question 10

Extended Spectrum Penicillins

Answer 10

Can diffuse through porin channels
Effective against gram + cocci and gram – cocci (N.gonorrhoeae and N. Meningitis)
Gram – rods (E.coli, H. influenza)

Ampicillin (IV to treat enterococcal infections and Listeria meningitis): omnipen, Principen Oral, IM, IV

Amoxicillin used to treat uncomplicated ear, nose, and throat infections: amoxil, Trimox Oral; cannot be IV

Ticarcillin covers pseudomonas and enterobacter- ticar IM and IV
Piperacillin same as ticarcillin but also covers Klebsiella and enterococci; IM, IV

Extended spectrum plus beta lactamase inhibitors
Amoxicillin plus clavulanate (Augmentin Oral)
Ampicillin plus sulbactam (Unasyn IM, IV)
Piperacillin plus tazobactam (Zosyn IV)
Ticarcillin plus clavulanate (Timentin IV)
*Beta lactamase inhibitor makes it possible for the other drug to work more effectively

Question 11

Penicillin G and V: Narrow vs. Broad Spectrum

Answer 11

Penicillin G and Penicillin V are narrow spectrum antibiotics
Demonstrating activity against mostly gram positive cocci, gram positive bacilli, as well as gram-negative cocci
Extended spectrum penicillin have greater activity against gram negative bacilli

Question 12

Penicillin Absorption and Excretion

Answer 12

The primary route of excretion is by the kidneys with limited liver metabolism
The beta lactam antibiotics produce time dependent killing of bacteria , therefore frequent dosing is required
Maximum killing is dosing at 3 to 4 times daily

Question 13

Penicillin’s Contraindications

Answer 13

Generally contraindicated is person allergic to them
However, people previously allergic could tolerate the drug without allergic manifestation on subsequent administration
Serum ½ life of penicillin IgE antibodies range from 10 to more than 1000 days
Therefore risk of recurrent penicillin allergy is higher in persons with long ½ life antibodies or repeated exposure to penicillin
Little data is available about the 60-80% of people not exhibiting allergy on re-exposure will re-acquire the IgE and react to the drug on third exposure
The best practice is to refrain from use of penicillin if someone has had an allergic reaction to the drug
Penicillin is also contra-indicated in persons taking coumadin but appears to be rare in occurrence

Question 14

Penicillin Allergy Crossover

Answer 14

Penicillin allergy… is the patient allergic to cephlasporin too because similar structure?
10% crossover for allergy, however it is probably 1%
The more similar the R group to the penicillin, the more likely they will react to it (1st cephalosporin)
2nd generation ones are a bit better, but the 3rd and 4th generation cephalosporins = no allergic reaction
Penicillin = type 1 allergic reaction and produces IgE (has a half life of 3 years)… if given penicillin in 1952 and broke out/reaction and then given in 1956, then they probably won’t react to it… but the best practice is to refrain from using penicillin if patient had previous reaction

Question 15

Cephalosporin Generations: Bacterial Resistance

Answer 15

First generation; very sensitive to the beta lactamases
Second to fourth generation: more resistant to beta lactamases
3rd and 4th generations mostly used for hospital bugs

Question 16

Cephalosporin Resistance Mechanism

Answer 16

Changes in drug target of penicillin binding proteins - methicillin-resistant Staphyloccocus aureus
Efflux pumps – MexAB-OprM efflux pump in Pseudomonas aeruginosa
Decreased permeability of cell wall – less common for cephalosporins

Alteration of drug itself by hydrolysis by beta-lactamases
Numbers and types of beta-lactamases increasing
Can be chromosomally or extra-chromosomally (more easily transmitted to other organisms) mediated

Resistance to one cephalosporin can result in resistance to others depending on mechanism
Resistance to cephalosporins can confer resistance to other beta-lactam drugs like penicillins as well

Question 17

Spectrum Changes of 2nd and 3rd Cephalosporins

Answer 17

Spectrum changes from first to third generation
First Generation: Better Gram Positive Cocci coverage
Third Generation: Better Gram Negative Rod coverage

Question 18

First Generation Cephalosporins

Answer 18

Prototype Drugs are CEFAZOLIN (for IV use) and CEPHALEXIN (oral use).
1. Staph. aureus - not effective against methicillin-resistant Staph. aureus & epidermidis
2. Streptococci - excellent activity versus Streptococcus sp.; not effective against penicillin-resistant Strep. pneumoniae
3. Other Gm + bacteria - excellent activity except for Enterococcus sp.
4. Moderate activity against gram negative bacteria.
Caution: resistance may occur in all cases.

Susceptible organisms include:
E. coli
Proteus (indole + Proteus sp. (many strains resistant))
Haemophilus influenzae (some strains resistant)
Neisseria sp. (some gonococci resistant)

Question 19

Second Generation Cephalosporins

Answer 19

Expanded activity against gram negative bacilli. Still have excellent activity against gram positive (Staph. and Strep.) bacteria.

Activity for Gram negative bacteria:
Neisseria sp. (some gonococci resistant)
H. influenzae (including some ampicillin-resistant strains)
Moraxella catarrhalis (some resistance esp. to cefaclor)
E. coli
Proteus (indole + Proteus (some strains resistant))
Morganella morganii (some strains resistant)
Klebsiella pneumoniae
Serratia sp. (many strains resistant)

Anaerobic infections - CEFOXITIN & CEFOTETAN only
Moderate activity against Bacteroides fragilis group.
Good activity for other Bacteroides sp., Peptostreptococcus, Fusobacterium,
Clostridium sp.
Abdominal surgery: give cefoxitin because lots of anaerobes growing there

Question 20

Third Generation Cephalosporins

Answer 20

Further expansion of Gram negative spectrum to include hard to treat organisms such as Enterobacter, Serratia, and Pseudomonas (ceftazidime only)
In addition to better Gram negative spectrum, this group has improved pharmacokinetic properties (longer half-lives) that allow once daily dosing with some agents
In general, activity toward Gram + bacteria is reduced.
These are specialty antibiotics that should be reserved for specific uses

Enterobacteriaciae that are almost always sensitive (>95% sensitive)
E. coli
Proteus mirabilis (indole –)
Proteus vulgaris (indole +)
Klebsiella pneumoniae

Combination therapy: if patient has gram positive bacteria with pseudomonas (remember don’t want two drugs that work via the same mechanism) so want to give 3rd generation cephalosporins and azithromycin

Question 21

Fourth Generation Cephalosporin

Answer 21

Cefepime 4th generation do cover the above bacteria and:
Pseudomonas
Bacteroides
Klebsiella
Enterobacteriaceae

Question 22

Cephalosporin Absorption

Answer 22

Oral cephalosporins are generally well absorbed
Cephalosporins are hydrophilic and widely distributed in extra-cellular fluid
Time dependent agents without significant post antibiotic effect
Serum and tissue concentrations should remain above organism’s MIC for at least 60% of the dosing interval to prevent organism regrowth

Question 23

Carbapenems

Answer 23

Differ from penicillin by a replacement of the sulfur by a methylene group in the 5 member ring

Drugs are:
Imipenem, meropenem, and ertapenem
Imipenem is combined with cilastin to reduce the renal metabolism of imipenem
Ertapenum- once daily dosing, but doesn’t cover pseudomonas

The carbapenems have a wide antibacterial spectrum
They are not hydrolyzed by most beta lactamases

ALL IV medication… not taken orally because will not be absorbed

Question 24

Carbapenems: Spectrum of Drug Activity

Answer 24

Spectrum of activity drug of choice:
Campylobacter fetus
Citrobacter freundii
Enterobacter
Acinetobacter
Serratia marcescens

Alternate choice:
Methicillin susceptible staph aureus, penicillin resistant strept pneumoniae, clostridium perfringens, E. coli, klebsiella pneumoniae, proteus mirabilis, indole positive proteus, pseudomonas aeruginosa

Question 25

Monobactum

Answer 25

Aztreonam: lacks the thiazolidine ring of penicillin Does not bind to PBPs of gram positive or anaerobic organisms Its spectrum is limited to aerobic gram negative species Enterbacteriaceae, klebsiella pneumoniae, proteus mirabilis, yersinia enterocolitica, salmonella, shigella, neisseria, haemophilus, and pseudomonas aeruginosa Excellent for patients with a penicillin allergy

Question 26

Macrolide Mechanism of Action

Answer 26

Macrolides inhibits RNA-dependent protein synthesis by reversibly binding to the 50S ribosomal subunits of susceptible microorganisms. Prevent elongation of the protein Drugs Include: azithromycin, clarithromycin, erythromycin

Question 27

Macrolide Spectrum of Activity

Answer 27

Generally, macrolides are active against gram-positive cocci (mainly staphylococci and streptococci) and bacilli, and to lesser-extent gram-negative cocci With the exception of Bordetella pertussis, Campylobacter, Chlamydia, Helicobacter, and Legionella species, gram-negative bacilli are generally resistant to the macrolides. Macrolides are also active against mycobacteria, mycoplasma, ureaplasma, spirochetes, and other organisms. Erythromycin has activity against gram-positive cocci and some gram-negative organisms (eg. B.pertussis, M. pneumoniae, L. pneumophilia). Make sure you treat the baby with erythromycin eye ointment for chlamydia because it can cause blindness

Question 28

Macrolide Comparison of Side Effects

Answer 28

Azithromycin and clarithromycin have improved tolerability and fewer gastrointestinal side effects than erythromycin Erythromycin has been associated with QT prolongation and ventricular arrhythmias, including ventricular tachycardia and torsades de pointes Symptoms of hepatitis, hepatic dysfunction and/or abnormal liver function test results may occur with erythromycin

Question 29

Macrolides: Dosing Regiment and Interactions

Answer 29

Azithromycin has much lower potential for interactions than erythromycin and clarithromycin. Newer macrolides have advantages over erythromycin in dosing regimen

Question 30

Macrolides: Gram Positive Activity

Answer 30

The gram-positive activity of clarithromycin is superior to that of erythromycin and azithromycin, especially against Streptococcus pyogenes and Streptococcus pneumoniae

Question 31

Macrolides: Gram Negative Activity and STDs

Answer 31

Azithromycin offers increased gram-negative coverage over erythromycin and clarithromycin A unique feature of azithromycin is an excellent activity against sexually transmitted pathogens, especially Chlamydia trachomatis. And more active against H. Influenza than clarithromycin Like clarithromycin, azithromycin also has good activity against Legionella and Mycoplasma species.

Question 32

Clindamycin

Answer 32

Clindamycin inhibits bacterial protein synthesis by binding to bacterial 50S ribosomal subunits. It may be bacteriostatic or bactericidal depending on the organism and drug concentration Used for bacterial vaginosis

Question 33

Clindamycin Absorption

Answer 33

Rapidly absorbed after oral administration Clindamycin does not penetrate the blood brain barrier

Question 34

Metronidazole Mechanism of Action

Answer 34

After diffusing into the organism, interacts with DNA to cause loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis and cell death in susceptible organisms Metronidazole is one of the mainstay drugs for the treatment of anaerobic infections and the treatment of choice for most patients with mild to moderate Drug of choice for clostridium difficile-associated diarrhea. It is approved by the US Food and Drug Administration (FDA) for the treatment of anaerobic and protozoal infections

Question 35

Metronidazole Spectrum of Activity

Answer 35

Is active against a broad array of anaerobes, protozoa, and microaerophilic bacteria Metronidazole exerts potent bactericidal activity against Bacteroides spp, Clostridium spp, Prevotella spp, Porphyromonas spp, Fusobacterium spp, and Bilophila wadsworthia. Metronidazole is also active against anaerobic protozoa such as T. vaginalis, E. histolytica, Giardia lamblia, Blastocystis hominis, and Balantidium coli.

Question 36

Clavulanic Acid

Answer 36

Has the beta lactam ring and fools the bacteria so they destroy the beta lactam drugs attached to the other antibiotic so it leaves the other antibiotic active

Question 37

Metronidazole: Disulfiram Reaction

Answer 37

Drug interactions Ingestion of alcohol during metronidazole therapy (administered orally or vaginally) can result in a disulfiram-like reaction characterized by flushing, tachycardia, palpitations, nausea, and vomiting Doesn’t allow alcohol to be metabolized so if they drink they get very sick Patient will ask when they can drink again: can happen up to seven days after stopping the medication

Question 38

Tetracycline Structure

Answer 38

Tetracycline, minocycline, and doxycycline All the tetracyclines are derivatives of a four ringed nucleus and differ in structure Various derivatives exhibit somewhat different pharmacologic properties Differences in absorption, protein binding, metabolism, excretion and degree of activity against susceptible micro-organisms Doxycycline – treats mostly everything Tetracycline: has to be taken on an empty stomach

Question 39

Tetracycline: Mechanism of Action

Answer 39

``` The tetracyclines (tetracycline, doxycycline, demeclocycline, minocycline, etc.) block bacterial translation by binding reversibly to the 16S rRNA in the 30S subunit and distorting it in such a way that the anticodons of the charged tRNAs cannot align properly with the codons of the mRNA Tetracycline HAS TO get inside the bacteria to work ```

Question 40

Tetracycline

Answer 40

H. pylori: amoxicillin usually used but tetracycline can be used if patient allergic to amoxicillin Drug of choice for Lyme Disease Tetracycline: all of them will bind to the enamel of the teeth even if teeth are not grown in yet; if crosses placenta, bind to teeth and discolor them- look green; after 8 years old you will be able to take tetracycline since teeth are fully formed by then; teratogenic Doxycycline: given for chlamydia- use it 2x/day for 7 days so azithromycin is the drug of choice because less dosing

Question 41

Drug Classifications

Answer 41

Once drug is classified as C, D, and X= bad for baby A and B = studies done that show no birth defects; B is animal study C= complete studies are not really available and don’t know about them D and X- have proof that it harms the baby Use sunscreen with tetracyclines because subject to burns Tetracyclines: category D; not until 8 years old

Question 42

Floroquinolones

Answer 42

Quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription Quinolones can enter cells easily and therefore are often used to treat intracellular pathogens such as Legionella pneumophila and Mycoplasma pneumoniae

Question 43

First Generation Quinolones

Answer 43

Nalidixic Acid (NegGram) Enterobacteriaceae Oral administration Low serum and tissue drug concentrations, Narrow gram-negative Coverage uncomplicated urinary tract infections NOT for use in systemic infections

Question 44

Second Generation Quinolones

Answer 44

Norfloxacin: enterobacteriaceae; oral administration Gram negative coverage compared to first generation quinolones, limited gram positive coverage Uncomplicated urinary tract infections Not for use in systemic infections Cipro and leviquin can be oral or IV Better gram negative than first generation quinolones UTIs treated well, not systemic Cipro covers pseudomonas; in Cali bacteria are resistant to this drug

Question 45

Third Generation Quinolones

Answer 45

1st generation is only gram negative, but as generations go on mostly gram positive Levofloxacin and Moxifloxacin (opthalmic)and (systemic)

Question 46

Quinolones: Pharmacokinetics

Answer 46

Oral dosing equivalent to intravenous Tissue penetration: high tissue concentrations Stool and bile, prostate, lung, WBCs (neutrophils, macrophages), kidney and urine Low tissue concentrations (poor penetration) Poor cerebrospinal fluid penetration Excretion Renal excretion: most Fluoroquinolones; some hepatic excretion

Question 47

Quinolones: Adverse Effects

Answer 47

Tendinopathy (severe adverse event) (black box warning) Onset at approximately day 13 of therapy ``` Higher risk patients: Age over 60 Concurrent Corticosteroid use Athletes Transplant recipients ```

Question 48

Quinolones: Drug Interactions

Answer 48

Antiarrhythmics (risk QTc prolongation) NSAIDs (risk of Seizure) Increases level of other medications: Increased anticoagulation effect with Coumadin Increased Cyclosporine (also risks nephrotoxicity) Increased caffeine level Increased Theophylline levels Increased Riluzole levels (treats ALS) Chelates with cations (decreased Quinolone absorption): Avoid these agents within 2 hours of Quinolone Antacids containing Magnesium, Aluminum or Calcium Iron Sulfate, zinc, calcium, didanosine, sucralfate *Same with tetracyclines