NARROW SPECTRUM PENICILLINS: PENICILLIN SENSITIVE(PEN G &PEN
V)
-Mechanism of Action: “Bactericidal”- Weakens the cell wall, causing bacteria to
... [Show More] take up excessive amounts of water and rupture.
Occurs by two actions simultaneously: inhibiting transpeptidases and activating autolysins which disrupts synthesis of the cell wall and promotes the active destruction resulting in cell lysis and death.
-Examples: Penicillin G (Prototype Drug), Penicillin V, Nafcillin, Oxacillin, Dicloxacillin, Ampicillin, Amoxicillin, Piperacillin
Penicillin G-
-First Penicillin Available and often referred to plainly as Penicillin
-Bactericidal for gram negative and gram positive bacteria
-Should be taken with medications whereas Penicillin V is stable in stomach acids.
-Side Effects: Allergic reactions, pain at IM injection sites, prolonged (but reversible) sensory and motor dysfunction if injected into peripheral nerves, and neurotoxicity (seizures, confusion, hallucinations- if levels too high)
.
-Life Span Considerations:
*Infants- Used safely in infants with bacterial infections including syphilis, meningitis, & group A streptococcus
*Children/Adolescents- Common drug used to treat bacterial infections in children.
*Pregnant- No well controlled studies but evidence suggests no 2nd or 3rd trimester fetal risk.
*Breastfeeding- Amoxicillin is safe. Data is lacking about transmission of other PCNs from mother to infant through breast milk.
*Older Adults- Doses should be adjusted in older adults with renal dysfunction.
Penicillin Allergy:
-Most common drug allergy to date with severity ranging from minor rash to anaphylaxis
-Can possibly display cross sensitivity to cephalosporins and should not be used if possible
-observed 30 minutes minimum post drug injection for adverse reactions
-For history of PCN allergy, a skin allergy test can be done to assess current risk by injecting a tiny amount of allergen ID (only to be done where epinephrine and respiratory support is available if needed)
Penicillin V-
• Stable in stomach acid (Pen G is not)
• Used for oral therapy, can be taken with meals
NARROW SPECTRUM PENICILLIN: PENICILLIN RESISTANT: (Nafcillin, Oxacillin,
Dicloxacillin)
-Treats S. aureus and S. epidermidis
Broad-Spectrum Penicillins (Ampicillin & Amoxicillin):
-Most common side effects are rash and diarrhea (rash usually 3-10 days post TX start).
-Therapy can be PO or IV and requires dosage adjustment for renal impairment
-Treats Haemophilus influenzae, E. Coli, proteus mirabilis, enterococci, and Neisseria gonorrhoeae
EXTENDED SPECTRUM PENICILLIN: (Piperacillin)
-Treats same diseases as broad spectrum PLUS: *pseudomonas aeruginosa*, enterobacter spp, proteus, bacteroides fragilis, klebsiella spp
-Can cause bleeding secondary to disrupting platelet function
-Usually administered IV
-Reduce dose in renal pt’s
Cephalosporins (Cephalexin)
-Bactericidal drug (similar to PCNs)
-Increases activity against gram-negative agents
-Increases ability to reach cerebral spinal fluid (CSF)-3rd,4th,5th generations
-no routine lab monitoring
-Administered IM or IV
-Take cultures to determine sensitivity and infecting organism
-Contraindicated in pt’s with severe allergic reaction to cephalosporins or penicillins
- CAN CAUSE C. DIFF INFECTION (tell pt. To monitor for frequent stools)
-Used to treat infants & neonates. Especially in otitis media and gonococcal and pneumococcal infections
-Adverse Effects: Maculopapular rash, bronchospasm, anaphylaxis
-Education: Patients should not consume alcohol
First generation: tx’s staphylococci or streptococci
Cefadroxil, Cefazolin, Cephalexin
Second generation: TX’s H. Influenza, Klebsiella, pneumococci, staphylococci
Cefaclor, Cefotetan, Cefoxitin, Cefurozime
Third generation: tx’s pseudomonas aeruginosa, Neisseria gonorrhoeae, Klebsiella, Serratia
Cefdinir, Cefotaxime, Cefpodoxime, Ceftazidime, Ceftriaxone
Fourth generation: Pseudomonas aeruginosa
Cefepine, Ceftolozane/tazobactam
Fifth generation: Methicillin resistant Staphylococcus aureus
Ceftaroline
Carbapenems (Imipenem)
-Patients on valproate for seizures not to give
-Avoid in renal impairment pts
-Adverse effects: N/V/D, seizures (rare), rashes, pruritus
Vancomycin
-Used for C. Diff infection
-Treats S. Aureus and S. epidermidis, and MRSA
-Monitor Vanco drug levels
-Use caution in pt’s with renal impairment
Telavancin
-Black Box Warning: when used to tx hospital acquire or ventilator-associated bacterial pneumonia with creatinine clearance of less thn 50 ml/min, increased chance of mortality. Not safe in pregnancy
Aztreonam
-Adverse effects: pain & thrombophlebitis at injection site
USES: -treats gram negative bacteria: E. Coli, salmonella, Shigella, Serratia, Klebsiellam Proteus, H. influenza, P. aeruginosa
Fosfomycin
-Single dose therapy in women with uncomplicated UTI
-Adverse effects: diarrhea, headache, vaginitis, nausea, abdominal pain, rhinitis, drowsiness, dizziness, rash
Tetracyclines (Tetracycline)
-Broad spectrum bacteriostatic
-Contraindication/Precautions:
- After the 4th month of pregnancy can stain deciduous teeth and stain permanent teeth of children ages of 4 month and 8 years
- If given to treat an STD, abstain from intercourse until med is finished.
o Food decreases absorption
· Complications
o GI discomfort (cramping, nausea, diarrhea, and esophageal ulceration)
§ Taking Doxycycline and Minocycline with meals will with GI discomfort BUT food will reduce absorption.
§ Avoid taking at bedtime to reduce the risk of esophageal ulceration.
o Yellow/Brown tooth discoloration, Hypoplasia of tooth enamel, Effects on bones
§ Avoid in children younger than 8 and women who are pregnant.
§ Can suppress the growth of long bones in premature infants.
o Hepatoxicity (lethargy, jaundice)
§ Avoid high daily doses IV.
§ Fatty infiltration of the liver
o Photosensitivity (exaggerated sunburn)
§ Use sunscreen with an SPF 30 or higher.
o Superinfection of the Bowel
§ C-diff associated diarrhea AKA antibiotic-associated pseudomembranous colitis. D/C med immediately
§ Yeast infections of the mouth, pharynx, vagina
o Dizziness. Lightheadedness (Minocycline)
o Renal Toxicity
· Contraindication/Precautions
o After the 4th month of pregnancy can stain deciduous teeth and stain permanent teeth of children ages of 4 month and 8 years
o If given to treat an STD, abstain from intercourse until med is finished.
· Interactions
o Interaction with milk products, calcium, iron supplements, laxatives containing magnesium and antacids causes formation of nonabsorbable chelates, thus reducing the absorption of tetracyclines.
§ Administer 1 hour BEFORE or 2 hours ingestion of chelating agents.
o Increase the risk of digoxin toxicity and increase INR by altering Vitamin K -producing flora in the gut.
o Decrease efficacy of oral contraceptives – use alternative form of birth control.
Life Stage Patient Care Concerns
Children/adolescents Tetracyclines should not be used in children younger than 8 years because they may cause permanent discoloration of the teeth.
Pregnant women Animal studies reveal that tetracyclines can cause fetal harm in pregnancy. Thus, this class of drugs should be avoided in pregnant women.
Breastfeeding women Use of tetracyclines during tooth development can cause permanent staining. Tetracyclines should be avoided by breastfeeding women.
Older adults Tetracyclines can interact with drugs, including digoxin. In the older adult who takes many medications, check for interactions.
Macrolides (Erythromycin)
· Uses
o Treatment of choice for Corynebacterium diphtheria and may be used as an alternative to Penicillin G in patients with PCN allergy.
o Treats chlamydial infections, pneumonia d/t Mycoplasma pneumonia, & streptococcal infections
o Fidaxomicin is a narrow spectrum macrolide that treats C.diff.
· Complications (S/E)
o GI Discomfort is the most common (nausea, vomiting, epigastric pain)
o Prolonged QT interval
§ Torsade’s de Pointes – dysrhythmia and sudden death.
o Ototoxicity with HIGH-dose therapy
§ Report hearing loss, vertigo, and tinnitus.
· Contraindications/Precautions
o Liver Disease and QT Prolongation are contraindications.
§ Avoid if patient has congenital QT prolongation and those taking class IA or III antidysrhythmic drugs.
§ avoided by patients taking CYP3A4 inhibitors CCB, azole antifungals, HIV protease inhibitors and nefazodone.
· Interactions
o Erythromycin prevents binging of chloramphenicol and clindamycin – antagonizing their antibacterial effects.
o Erythromycin inhibits the metabolism of antihistamines, theophylline, carbamazepine, warfarin, and digoxin which can lead to TOXICITY.
§ Monitor liver function if taken longer than 2 weeks.
§ Monitor PT/INR
• Minimizing Adverse Effects: Avoid use in patients with QT prolongation. GI disturbances can be reduced by administering with meals.
Clindamycin
o Drug of choice for severe Group A Streptococcal infection and for gas gangrene
o Widely used and as an alternative to penicillin
· Complications
o *CDAD, formerly known as antibiotic-associated pseudomembranous colitis is the MOST SEVERE toxicity
§ Symptoms may develop 4-6 weeks AFTER withdrawal.
§ Drugs that decrease bowel motility (opioids, anticholinergics) may WORSEN symptoms and should NOT be used.
o Erosive Esophagitis
· Black BOX Warning
o Clindamycin can cause fatal Clostridium difficile diarrhea. Patients should promptly report nay diarrhea.
· Interactions
o May decrease oral contraceptive activity.
Linezolid
· Uses
o 5 Approved indications
§ Infections caused by VRE
§ Hospital Acquired pneumonia caused by S. Aureus (Methicillin—susceptible & methicillin-resistant strain or S. pneumoniae (penicillin-susceptible strain only)
§ Community-associated pneumonia (CAP) caused by S. pneumonia (penicillin- susceptible strains only)
§ Complicated skin and skin structure infections caused by S. aureus (Methicillin
—susceptible & methicillin-resistant strains), Streptococcus pyogenes, or Streptococcus agalactia.
§ Uncomplicated skin and skin structure infections caused by S.
aureus (Methicillin—susceptible & methicillin-resistant strains) or S. pyogenes. To delay the emergence of resistance Linezolid should generally BE RESERVED for infections caused by VRE or MRSA
o Aerobic and facilitative gram-positive bacteria
o It is NOT active against gram-bacteria.
· Complications
o *Most common are diarrhea, nausea, and headache.
o Oral suspension contains phenylalanine and must NOT be used by patients with phenylketonuria.
o May cause reversible myelosuppression – manifesting as anemia, Leukopenia thrombocytopenia or even pancytopenia – (Draw CBC weekly)
o *Rare, prolonged therapy has been associated with neuropathy.
· Interactions
o Weak inhibitor of Monoamine Oxidase (MAO) > risk for hypertensive crisis.
§ MAO inhibitors can cause severe hypertension if combined with indirect-acting sympathomimetics (epinephrine, pseudoephedrine, methylphenidate, cocaine) or with foods that contain large amounts of tyramine.
o Combining linezolid with a selective serotonin reuptake inhibitor (SSRI) (Paroxetine, duloxetine) can increase the risk for serotonin syndrome.
Tedizolid
· Uses
o Skin and soft tissue infections caused by MRSA, Streptococcus and Enterococcus
Aminoglycosides (Gentamicin, Tobramycin, Amikacin)
· Uses
o Gentamicin: Bacterial infections caused by aerobic gram-negative bacilli:
Pseudomonas aeruginosa Enterobacteriaceae
o Kanamycin: Bacterial infections caused by gram-negative bacilli—not to be used for Serratia and Pseudomonas, as these bacteria are now resistant
o Neomycin: Topical infection Prevention in minor cuts Ocular bacterial infections
o Amikacin: Bacterial infections caused by gram-negative bacilli
o Tobramycin: Bacterial infections caused by aerobic gram-negative bacilli:
Pseudomonas aeruginosa Enterobacteriaceae
o Streptomycin: Used in combination with other drugs to treat tuberculosis; also used to treat tularemia and plague
-Oral or IV
· Complications
o Ototoxicity
§ Cochlear damage (hearing loss), vestibular damage (loss of balance) is largely IRREVERSIBLE.
§ *First sign of impending COCHLEAR damage is high-pitched tinnitus.
· (Amikacin & Kanamycin) = auditory
§ *First sign of VESTIBULAR damage is headache. Followed by nausea, unsteadiness, dizziness, and vertigo.
· (Gentamycin & Tobramycin) = vestibular
§ AUDIOMETRIC testing is needed.
o Nephrotoxicity
§ Correlates with:
· The total cumulative dose of aminoglycosides
· High Trough levels
§ Usually manifest as acute tubular necrosis. Prominent symptoms are proteinuria, casts in the urine, production of dilute urine and elevations in serum creatinine and blood urea nitrogen (BUN)
§ Cells of the proximal tubule REGENERATE, injury to the kidneys usually REVERSES.
· Contraindications/Precautions
o cautious in patients with kidney impairment, hearing loss and myasthenia gravis.
o if taking ethacrynic acid (increases the risk for ototoxicity), amphotericin B, cephalosporins, vancomycin (increases the risk for nephrotoxicity) and neuromuscular blocking agents (tubocurarine).
· Black BOX Waring
o Aminoglycoside> Neurotoxicity/Ototoxicity
§ Use of aminoglycosides is associated with irreversible ototoxicity. Neurotoxic symptoms: numbness, tingling, muscle twitching and seizures. This risk increases in patients on high doses or with prolonged use and in patients with preexisting renal impairment.
o Aminoglycoside >Nephrotoxicity
§ . This risk increases in patients using high does, with prolonged use and in patients with preexisting renal impairment.
o Aminoglycoside-Induced Neuromuscular Blockade
§ inhibit neuromuscular transmission, causing flaccid paralysis and potentially fatal respiratory depression. Most episodes of neuromuscular blockade have occurred after intraperitoneal or intrapleural instillation of aminoglycosides.
· Beneficial Drug Interactions
o Penicillin disrupts the cell wall and thereby facilitate access of aminoglycosides to their site of action.
o Cephalosporins & Vancomycin weaken the bacterial cell wall to enhance bacterial kill when used with aminoglycosides.
· Adverse Drug Interactions
o Risk for injury to the inner ears is increased by concurrent use of loop diuretics.
o Penicillin inactivates aminoglycosides when in the same IV solution.
· Monitoring Serum Drug Levels
o Once -A-Day-Dosing: It is only necessary to obtain blood sample for measuring trough levels .
o Divided Doses
§ Peak: 30 min AFTER administration of aminoglycoside IM or 30 min AFTER COMPLETION of an IV infusion
§ Trough: Right BEFORE the next dose
Patient-Centered Care Across the Life Span Aminoglycosides
Life Stage Patient Care Concerns
Infants treat bacterial infections in infants younger than 8 days. Dosing is based on weight and length of gestation.
Children/adolescents safe for use against bacterial infections
Pregnant women can harm the fetus.
Breastfeeding women Gentamicin is probably safe to use during lactation. There is limited information regarding its use in this way
Older adults Caution must be used regarding decreased renal function in the older adult
Summary of Key Prescribing Considerations Aminoglycosides
• Therapeutic Goal: Treatment of serious infections caused by gram-negative aerobic bacilli.
• Baseline Data: Blood and/or urine cultures.
• Monitoring: Aminoglycoside levels (peaks and troughs) and renal function must be monitored.
• Identifying High-Risk Patients: caution in patients with renal impairment, preexisting hearing impairment, and those receiving ototoxic and nephrotoxic drugs.
• Evaluating Therapeutic Effects: Patients must be monitored for indications of antimicrobial effects, including reduction in fever, pain, or inflammation.
• Minimizing Adverse Effects: Caution must be exercised when aminoglycosides are used in combination with other nephrotoxic or ototoxic drugs. Patients must be instructed to report symptoms of ototoxicity.
Sulfonamides
· Uses
o Broad spectrum of microbes comprising gram-positive cocci (including methicillin- resistant Staphylococcus aureus),
o Gram-negative bacilli, Listeria monocytogenes, actinomycetes (e.g., Nocardia), chlamydiae (e.g., Chlamydia trachomatis)
o Some protozoa (e.g., Toxoplasma species, plasmodia, Isospora belli)
o 2 fungi: Pneumocystis jirovecii (formerly thought to be Pneumocystis carinii) and Paracoccidioides brasiliensis.
o Sulfasalazine is used to treat Ulcerative Colitis.
*Their applications are now limited due to the introduction of bactericidal antibiotics that are less toxic than the sulfonamides, and the development of sulfonamide resistance. Today, UTI is the principal indication for these drugs.
· Complications
o Hypersensitivity Reactions
§ Stevens-Johnson Syndrome if the most severe- widespread lesions of the skin and mucous membranes
o Blood Dyscrasias
§ Hemolytic Anemia, agranulocytosis, leukopenia, thrombocytopenia, aplastic anemia
· Obtain blood samples for baseline and periodic CBC counts to detect disorders.
· Observe for bleeding, sore throat and pallor.
o Kernicterus
§ A disorder in newborns cause by deposition of bilirubin in the brain.
§ Because of the risk for kernicterus, sulfonamides should not be administered to infants younger than 2 months. In addition, sulfonamides should not be given to pregnant patients after 32 weeks of gestation or to those who are breastfeeding.
o Renal Damage
§ Older sulfonamides tended to come out of solution in the urine,
forming crystalline aggregates in the kidneys, ureters, and bladders. These aggregates cause irritation and obstruction, sometimes resulting in anuria and even death.
§ Sulfamethoxazole is the only intermediate-acting sulfonamide available. The risk for renal damage from crystalluria can be reduced by maintaining adequate hydration.
· Interactions
o Sulfonamides can intensify the effects of warfarin, phenytoin, and sulfonylurea-type oral hypoglycemics (glipizide, glyburide). These drugs may require a reduction in dosages to prevent toxicity. [Show Less]