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What are the first groups of drugs used as antibiotics? And what antibiotics are commonly used?
Commonly used: sulfadiazine, sulfamethoxazole, and sulfisoxazole.
What is another name for Bactrim?
What is the mechanism of action for Sulfonamides?
- Sulfonamides acts as a bacteriostatic ABT by inhibiting the growth of organisms by preventing bacterial synthesis of folic acid production.
- Sulfonamides don't actually destroy bacteria but inhibits their growth.
- Does not affect human cells or other bacteria but rather bacteria that synthesize their own folic acid.
Define bacteriostatic antibiotic?
Antibiotics that do not actually kill bacteria but rather inhibit their growth.
Describe the indications for Sulfonamides (especially Sulfamethoxazole/Trimethoprim)
Sulfonamides is a broad spectrum antibiotics and works well against gram-positive and gram-negative organisms.
Sulfametahoxazole/Trimethoprim is commonly used for the TX of UTIs because they achieve a very high conc. in the kidneys, where they are also eliminated through.
What are other indications for Sulfamethoxazole/Trimethoprim?
- Also used for growths by organisms such as: Enterobacter species, E.Coli, Klebsiella spp., Proteus mirabilis, Proteus vulgarism, and S. aureus.
- Also used for respiratory infections.
- Also used as a prophylaxis and TX of opportunistic infections of clients with HIV infection, esp. Pneumocystis jirovecii (common cause of HIV pneumonia).
What are the contraindications for Sulfonamides?
- Allergy to Sulfonamides (sulfa-allergy)
- Pregnant women at term
- infants younger than 2 months.
What are adverse effects of Sulfonamides?
- Blood: agranulocytosis, aplastic anemia, hemolytic anemia, thrombocytopenia
- GI: N/V, diarrhea, pancreatitis, hepatotoxicity
- Integ: epidermal necrolysis, exfoliative dermatitis, Steven-Johnson syndrome, photosensitivity to exposure to sunlight
- Other: convulsion, crystalluria, toxic nephrosis, headache, peripheral neuritis, urticaria, cough, pulmonary infiltrates.
What are beta-lactam?
It's a class of ABT that function to inhibit the synthesis of bacterial peptidoglycan cell wall.
What are the four subclasses of Beta-lactams?
What are bacteriocidal antibiotics?
Antibiotics that kill bacteria
What are the four subgroups/classifications of Penicillins?
- Natural penicillin
- Penicillinase-resistance penicillins
- extended-spectrum penicillins
What are the different generic drug names of the subclass Natural penicillins?
- penicillin G (available in injectable form for IV or IM use)
- penicillin V (available in PO form;tablet or liquid)
What are the different generic drug names of the subclass penicillinase-resistant penicillins?
- These are ABT that are stable against hydrolysis by most staphylococcal penicillinases, which are enzymes that normally break down the natural penicillins.
What are the different generic drug names of subclass aminopenicillins?
- These are ABT that have an amino group attached to the basic penicillin structure that enhances their activity against gram-negative bacteria compared to natural penicillins.
What are the different generic drug names of the subclass extended-spectrum penicillins?
- These ABT have a wider spectra of activity than other PCN.
- Rarely used by alone. Usually used with other drugs.
What are the different kinds of penicillin-beta-lactamase inhibitor combinations?
- amipicillin/sulbactam (Unasyn)
- amoxicillin/clavulanic acid (Augmentin)
- ticarcillin/clavulanic acid (Timentin)
- piperacillin/tazobactam (Zosyn)
- First introduced in 1940 from molded bread and fruit.
- Kills a wide variety of bacteria
- Produce bacterial capable of destroying penicillins; the enzyme beta-lactamases. This decreases the effectiveness of penicillins, hence the creation of clavulanic acid, tazobactam, and sulfactam.
What is the mechanism of action of penicillins?
- Penicillin enter the bacteria via the cell wall
- Inside the cell, they bind to penicillin-binding protein
- Once bound, normal cell synthesis is disrupted
- Resulting in bacteria dying from cell lysis.
- Penicillins does not affect other cells in the body.
What are the indications for penicillins?
- Penicillins are used to prevent and treat infections caused by gram-positive bacteria such as:
- Streptococcus spp.
- Enterococcus spp.
- Staphylococcus spp.
What are some contraindications for penicillins?
- The only usual contraindication for penicillins is known drug allergy.
- It's very important for nurses to obtain an accurate health hx regarding the type of rxn to PCN.
What are some adverse effects of penicillins?
- Allergic reactions (occur in 0.7% p 4% of TX courses) such as: urticaria, pruritus, angioedema.
- Those allergic txn to penicillins also have an increased of allergic rxn to other beta-lactam ABT.
- Cross reactivity between penicillins and cephalosporins is between 1% to 4%.
- The most common adverse effects are GI: N/V, diarrhea, abdominal pain.
What drugs interacts with penicillins?
- MANY drugs interact with PCN.
- NSAIDs: it competes for protein binding, resulting in more free and active PCN (may be beneficial.
- Oral contraceptives: Mechanism is unknown, but may decrease the efficacy of the BC
- Warfarin: it reduces vit. K from gut flora, resulting in enhanced anticoagulant effect of warfarin.
What are Cephalosporins?
- Cephalosporins can destroy a broad spectrum of bacteria and the ability to kill a bacteria is directly related to the chemical changes made to their basic chemical cephalosporin structure.
- There are five generations:
- Frist generation
- Second generation
- Third generation
- Fourth generation
- Fifth generation
- Each generation is divided according to their antimicrobial activity.
What are First Generation Cephalosporins?
- First generation cephalosporins are active against gram-positive bacteria and have limited activity against gram-negative.
- Available in parenteral and oral forms.
- cefazolin (Ancef) IV or IM
- cephalexin (Keflex) PO
- Used for surgical prophylaxis and for susceptible staphylococcal infection.
What are Second generation Cephalosporins?
- Good gram-positive coverage
- Enhanced gram-negative coverage than first generation.
- cefoxitin (Mefoxin)
What is Cefoxitin (Mefoxin)
- second generation cephalosporin
- used prophylactically for abdominal and colorectal surgical procedures because it effectively kill intestinal bacteria, including anaerobes.
- Available in IV and IM
What is cefuroxime (Zinacef/Ceftin)?
- Two kinds: Cefuroxime sodium (Zinacef) & cefuroxime axetil (Ceftin)
- Zinacef only available in IM (parenteral) form
- Ceftin is only available in PO form but has little antibacterial activity until it is hydrolyzed in the liver to its active form.
What are third generation Cephalosporins?
- Most potent group against gram-negative bacteria
- Less active against gram-positive bacteria than first and second generation.
- ceftriaxone (Rocephin) - IM
- ceftazidime (Ceptaz, Fortaz, Tazidime) - IM
- cefotazime - IM
- cefpodoxime - PO
- ceftibuten - PO
- cefdinir - PO
- ceftizoxime - IM
What is Rocephin?
- Third generation cephalosporin.
- ONLY given once a day
- available in IV/IM form
- Has a long half life
- Primarily eliminated via the hepatic system
- Easily passes the meninges (therefore given for meningitis)
- Diffuses into the CSF to treat CNS infections.
What is ceftazidime?
- Third generation cephalosporin
- Available in IV or IM
- Excellent gram-negative coverage
- Used for difficult-to-treat infections such as psudomonas spp.
- Eliminated by renal instead of biliary route
- Excellent spectrum of coverage
- Resistance is limiting usefulness.
What are fourth generation cephalosporins?
- A broader spectrum of antibacterial activity against gram-positive bacteria in comparison to third generation.
- Used to treat uncomplicated UTIs, skin and skin structure infections, and pneumonia.
- Cefepime (Maxipime)
What are fourth generation cephalosporins?
- It had a broader spectrum of activity than current cephalosporins
- Newest cephalosporin
- Effective against a wide variety of organisms: MRSA and Pseudomonias spp.
- Available in IM form
- Not yet been marketed.
What are adverse effects of cephalosporins?
- Similar to PCN:
- mild diarrhea
- abdominal cramps
- Has a potential cross-sensitivity with PCN if allergies exist.
What are carbapenems?
- It's a subgroup of beta-lactams
- Broadest-spectrum antibacterial action
- Therefore, reserved for complicated body cavity and connective tissue infection in acutely ill patients.
- May cause drug-induced seizure activity, but can be reduced with proper dosage.
- Given parenterally.
- imipenem/cilastatin (Primaxin)
What is imipenem/cilastatin (Primaxin)?
- Effects by binding to penicillin-binding proteins, inhibiting bacterial cell wall synthesis.
- Indicated for TX of bone, joint, skin, and soft tissue infections; and many more.
- Cilastatin inhibits an enzyme that breaks down imipenem.
What are other antibiotic drugs of carbapenems?
- meropenem (Merrem)
- ertapenem (Invanz)
- doripenem (Doribax)
What are monobactams?
- It's a subgroup of beta-lactams
- It's synthetic beta-lactams antibiotics.
- Primarily active against aerobic gram-negative bacteria (E.coli, Klebsiella spa., Pseudomonas spp.)
- Parenteral use only
- Used for moderately to severe system infections and UTIs.
What are macrolides?
- It's a class of ABT.
- considered bacteriostatic, but in high concentrations may be bacteriocidal to some susceptible bacteria.
- Four main macrolide antibiotics:
- erythromycin (E-mycin, E.E.S., others)
- azithromycin (Zithromax)
- clarithromycin (Biaxin)
What is the mechanism of action for macrolides?
- Prevent protein synthesis within bacterial cells
- Considered bacteriostatic
- Bacterial will eventually die
- May be bactericidal in high concentrations.
What are the indications of macrolides?
- Step infections: streptococcus pyogenes (group A beta-hemolytic streptococci)
- Mild to moderate URI and LRI: Haemophilus influenzae
- Spirochetal infections: Syphilis and Lyme disease
- Gonorrhea, Chlamydia, and Mycoplasma
What are other indication for use of azithromycin and clarithomycin?
Recently approved for mycobacterium avium-intracelllar complex infection, which is an opportunistic infection associated with HIV/AIDS.
What are other indication for use of clarithromycin?
Recently approved for use in combination with omeprazole for TX of active ulcer disease associated with Helicobacter pylori infection.
What are adverse effects of macrolides?
- GI effects primarily with erythromycin: N/V, diarrhea, hepatotoxicity, flatulence, jaundice, anorexia.
- Newer drugs, azithromycin and clarithromycin have fewer GI adverse effects, longer duration of action, better efficacy, and better tissue penetration.
What are ketolides?
- It's a class of ABT.
- Better antibacterial coverage than macrolides
- Derived from erythromycin A.
- Active against gram-positive bacteria, including multi-drug resistance strains of S. pneumoniae
- Use is limited because it has been associated with sever liver damage.
- Telithromycin (Ketek)
What are Tetracyclines?
- Bacteriostatic drugs that inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome.
- Obtained from cultures Streptomyces.
- Is a natural and semisynthetic ABT
- Stops many function of essential bacteria
What does Tetracyclines bind to and what food should be avoided?
- Binds (chelate) to Ca2+ and Mg2+ and Al3+ ions to form insoluble compounds, therefore, should not be taken with:
- dairy products
- iron salts
- These reduces the oral absorption of tetracyclines.
Why shouldn't Tetracyclines be given to pregnant/lactating women and children under the age of 8 years?
It's not given because it causes discoloration of the teeth if it binds with the calcium in the teeth. This could also be considered as a contraindication.
What are the indications for Tetracycline?
- It's has a wide spectrum of activity:
- gram-negative/gram-positive organisms
- Lyme disease
- Demecocycline is also used to treat SIADH by inhibiting the action of ADH.
What are the different kinds of Tetracycline?
What are the adverse effects of Tetracycline?
- Strong affinity for calcium, causing:
- discoloration of permanent teeth and tooth enamel in fetuses and children or nursing infants if taken by the lactating mother.
- May retard fetal skeletal development if taken during pregnancy.
- Alters intestinal flora, leading to: superinfection (overgrowth of nonsusceptible organisms such as Candida), diarrhea, pseudomembranous colitis.
- May also cause:
- vaginal candidiasis
- gastric upset
- maculopapular rash
- other effects
- (1) infection occurring during antimicrobial treatment for another infection, resulting from overgrowth of an organism not susceptible to the ABT used.
- (2) a secondary microbial infection that occurs in addition to an earlier primary infection, often due to weakening of the patient's immune system function by the first infection.
What are aminoglycosides?
- Natural and semisynthetic ABT
- Produced from Streptomyces
- Has many route of administration but has a very poor PO oral absorption through the GI tract (no PO forms)
- Bactericidal; preventing protein synthesis
- It very potent ABT with serious toxicities requires therapeutic monitoring.
- Kills mostly gram-negative and some gram-positive.
What are the different kinds of aminoglycosides?
- gentamicin (Garamycin) - commonly used
- neomycin (Neo-fradin) - available in oral and not IV. used for GI tract. Can also be given as an enema to decontaminate the GI tract before surgical procedures.
- tobramycin (Nebcin) - commonly used
- amikacin (Amikin) - commonly used
- streptomycin - still used for TB
What is the mechanism of action for aminoglycosides?
- Works similar to tetracyclines, in that it binds to ribosomes 30S and prevent the protein synthesis in the bacteria.
- Used synergistically with beta-lactams or vancomycins.
Why does the aminoglycosides have postantibiotics effect?
Because aminoglycosides works on the bacteria by gaining access to the ribosomes after the beta-lactams breaks down the cell wall.
What is postantibiotic effect?
a period of continued bacterial suppression that occurs after brief exposure to certain antibiotic drug classes, especially aminoglycosides and carbapenems.
What are the indications for aminoglycosides?
- Used to kill gram-negative bacteria: Pseudomonas spp., E.coli, Proteus spp., Klebsiella spp., and Serratia spp.
- Often used in combination with other ABT for synergistic effect.
- Used for certain gram-positive infections that are resistant to other ABT.
What are adverse effects of Aminoglycosides?
- Can cause serious toxicities:
- Nephrotoxicity (renal damage) evident by urinary casts, proteinuria, elevated BUN and serum creatinine levels. Usually reversible.
- Ototoxicity (renal impairment and vestibular impairment resulting from injury to cranial nerve VIII). Less common and is often not reversible
- Other adverse effects: headache, paresthesia, fever, superinfection, vertigo, skin rash, and dizziness
Toxicity to the kidneys, often drug induced or manifested as compromised renal function
Toxicity to ears, often drug induced and manifesting as varying degrees of hearing loss that is more likely to become permanent than nephrotoxicity.
When on Aminoglycosides, what should be closely monitored?
- Renal function (BUN/creatinine level, as well as urine output.
- Monitor therapeutic effect by checking peak & trough 5-7 days while on therapy.
When is peak and trough checked?
- Only when patient is on IV ABT TX.
- Trough is to be drawn 1 hour before next dose of IV ABT
- Peak is to be drawn 30 min after IV ABT administration is complete.
Why does aminoglycosides possibly cause superinfection?
Because it is broad spectrum ABT.
What are Quinolones?
- It is a class of ABT that is very potent bactericidal broad-spectrum ABT.
- Also called flouroquinolones
- Excellent oral absorption comparable to IV injection.
- Effective against gram-negative organisms and some gram-positive organisms.
What the different kinds of Quinolones?
- Ciprofloxacin (Cipro) - commonly used to treat with infection below the diaphragm Gram-neg
- norfloxacin (Noroxin) - bad oral absorption.
- levofloxacin (Levaquin) - commonly used
- moxifloxacin (Avelox) - commonly use.
- The last two are referred to as respiratory criminals to treat pneumonia.
What is the mechanism of action for Quinolones?
- Kills bacteria by altering their DNA, causing cell death.
- Does not affect human DNA.
What are the indications for Quinolones?
- Gram-negative bacteria such as pseudomonas
- Respiratory infections
- Bone and joint infections
- GI infection (salmonella)
- Skin and soft tissue infection
- Sexually transmitted diseases
- Used to treat complicated UTIs because have high conc in kidneys and effects gram-negative bacteria.
What are some adverse effects of Quinolones?
- CNS: headache, dizziness, fatigue, depression, restlessness, insomnia
- GI: N/V, diarrhea, constipation, thrush, increased liver function studies, others
- Cardiac: Prolonged QT interval - causes cardiac dysrhytmia when pt are taking disopyramide and amiodarones.
- Integ: rash, pruritus, urticaria, flushing, photosensitivity (with lomefloxacin)
- Others: fever, chills, blurred vision, and tinnitus.
What is the black box warning for quinolones?
- Increased risk for tendonitis and tendon rupture.
- Less common in short term tx, but rather longer term care in elderly patients, patients with renal failure, and those receiving concurrent glucocorticoid therapy.
What are some interactions with quinolones?
- Anticoagulant should be used with caution with quinolones becuase it affects the vit K synthesis by altering the intestinal flora.
- Nitrofurantoin (macrobid) also interact with quinolones.
What are symptoms of superinfection?
fever, perineal itching, unusual discharge, cough and lethargy