Week 16: Antimicrobial drugs

Bactercidial

kills susceptible bacteria

• Ex: penicillin — disrupts cell wall

Bacteriostatic

inhibits bacterial growth or replication and then the immune system kills the bacteria

• Ex: inhibits synthesis and slows down replication

Gram positive bacteria

Thick peptidoglycan layer

• Ex: strep

Gram negative bacteria

has an outer membrane and a thin pepdidoglycan layer in the periplasmic space

• Ex: E. coli

Empiric antibiotic therapy

the use of abx before the identification of a microorganism that is causing an infection, or before knowing how that microorganism ill respond to abx

Broad spectrum antibiotic

Active against a wider number of bacterial types and may be used to treat a variety of infectious diseases

• especially useful when infecting agents is unknown

• Also kills good bacteria

• Ex: if someone comes in with sepsis and they don’t know what the cause is so they give the patient a strong broad spectrum bacteria

Narrow spectrum antibiotic

active against a select group of bacterial types — must know the exact bacteria to ensure that we know what is causing the illness

• Kills fewer good bacteria

Beta lactam

Antibiotics that share a beta lactam ring structure e.g. penicillins, carbapenems, and cephalosporin

Beta lactamase

An enzyme produced by some bacteria that cleaves beta lactam thereby inactivating the antibiotic.

Vancomycin Resistant Enterococci (VRE)

• Very hardy bacteria — very hard to treat

• Intrinsically resistant to many antibiotics

• Vancomycin usually the treatment of choice

• However acquired resistance has made strains resistant

• Not a problem for healthy people but can cause wound, urinary, and septicemia in very young, old, frail

• Healthy people without enterococci disease can be carriers

Methicillin-Resistant Staphylococcus Aureus (MRSA)

infection is caused by a strain of staph bacteria that's become resistant to the antibiotics commonly used to treat ordinary staph infections

• Methicillin is a penicillin derivative

Clostridium Difficile Infection (CDI)

Resistant to antibiotics and they start to take over. They produce a toxin that is harmful to the GI lining, which causes the symptoms.

• Diarrhea!

Antibiotics that inhibit cell wall synthesis

• Penicillin

• Cephalosporins: cephalexin

• Carbapenems: imipenem

• Vancomycin

Antibiotic that blocks bacterial Nucleic acid replication

Fluoroquinolones: ciprofloxacin

Antibiotics that block protein synthesis

• Aminoglycosides: gentamicin

• Tetracyclines: doxycyclin

• Macrolides: azithromycin

Antibiotics that inhibit synthesis of bacterial metabolites

Sulfonamide/trimethoprim

Abx drug resistance mechanisms (make more flashcards for this — this one has too much on it)

• They are not mutagenic and do not cause genetic changes that lead to drug resistance

• Mutations in bacteria arise through spontaneous mutation and conjugation and these events occur naturally and in the absence of antibiotics

• Antibiotics just produce favorable conditions for drug resistant organisms to emerge

• All antibiotics can promote the growth of drug-resistance organisms. Broad spectrum antibiotics are better at this because they kill off more competing organisms than narrow spectrum drugs.

Adverse effects of antibiotics in general

• Hypersensitivity rxns

• GI effects

• Superinfection

• Stevens-Johnson Syndrome

Hypersensitivity reactions assessment findings

• Rash

• Pruritus

• Urticaria

• Systemic anaphylaxis

GI effects assessment findings

• Nausea

• Abdominal pain

• Diarrhea

Superinfection

any infection that occurs d/t antibiotic therapy

• Ex: yeast infection developing d/t healthy bacteria dying — yeast isn’t “in check”

Superinfection assessment findings

• Sore or furry throat

• Vaginal itching or discharge

• Rectal itching

• Foul-smelling feces

Superinfection by C.diff assessment findings

• Fever

• Abdominal pain/cramps

• Large volume of diarrhea with blood and mucous

Stevens-Johnson Syndrome assessment findings

• Fever

• Rash

• Blisters on skin

• Sloughing of skin

• Possible heath d/t infection from loss of skin integrity

Beta Lactam antibiotics that inhibit bacterial CW synthesis (3)

• Penicillins: penicillin G

• Cephalosporins: cephalexin

• Carbapenems: imipenem

Penicillin MOA

Penicillin blocks transpeptidase using its beta-lactam ring, activating autolysins that break down the cell wall → bactericidal (mainly gram+)

Penicillin G uses via IM and IV administration

• Streptococcal species: pneumonia and meningitis

• Mainly gram + but some gram – bacteria

• Acid labile so administered IM or IV

• Excreted unchanged by the kidney

Penicillin G adverse effects

• Least toxic of all antibiotics and safest of all medications

• Penicillin ALLERGY

• Pain at IM injection site, nausea, vomiting.

• Renal abnormalities with large doses

• Neurotoxicities (seizures, confusion, hallucinations) if blood concentration too high

How long should you monitor penicillin after giving?

20 minutes

If you have a sensitivity to _____, you should not take penicillin because…

• cephalosporins

• it is another beta-lactam antibiotic — rxn to abx is d/t the beta-lactam structure

• can be given if the patient only has a mild rash, but if they have anaphylaxis they need to avoid it

Bacterial resistance to penicillin

• Some bacteria can produce beta-lactamase (penicillinase)

• Cleaves the beta-lactam ring of penicillin rendering it inactive

Cephalosporin prototype name

Cephalexin

Cephalosporins MOA

• Beta-lactam abx

• Bactercidial

Benefits of later generations of cephalosporins

can get into the CSF easier

• can treat meningococcal infections bc it gets into CSF

Cephalosporin adverse effects

• GI: Abdominal pain, N/V

• Suprainfections: C. diff

• Alcohol intolerance

• IV and IM: abscess formation

• Nephrotoxicity

Cephalosporin monitoring

• RF

• Thrombophlebitis — rotate injection sites

• Cross allergy with penicillin

What should you do if cephalosporin is causing GI upset?

take with food

Carbapenems prototype name

Imipenem

Carbapenems MOA

Carbapenems indications

• Very broad spectrum, gram + and gram – organisms.

• Treating mixed and serious infections, including CNS infections*

Administration of Imipenem (Carbapenems)

IM and IV

• Imipenem is only given IV or IM

Carbapenems adverse effects

Generally well tolerated

• Hypersensitivity reactions

• Superinfections

• Seizures with renal dysfunction (rare) — bc excreted by kidneys

Carbapenems drug interactions

• Penicillin

• Cephalosporins

• Valproic acid

Vancomycin MOA

disrupts CW by binding to peptidoglycan precursors

• no Beta lactam ring

Vancomycin uses

Serious infections only with gram+ bacteria

• C.diff. and MRSA

Vancomycin adverse effects

• Major toxicity is renal failure.

• Otoxicity (rare, and reversible)

• Vancomycin Infusion Syndrome

• Thrombophlebitis

• Immune-mediated thrombocytopenia (rare)

What do you do when you get Vancomycin Infusion Syndrome?

A reaction does NOT mean that you stop vancomycin — you need to slow down the administration and administer antihistamines

To monitor during vancomycin administration

kidney and auditory function

Aminoglycosides prototype name

Gentamicin

• IV and IM

Where do Aminoglycosides accumulate?

Kidney and inner ear

• contributes to adverse effects

Aminoglycocides dose age

varies between patient — need to monitor each patient’s peak and troughs

Aminoglycosides adverse effects

• Nephrotoxicity: usually reversible.

• Irreversible ototoxicity (high trough levels for long periods)

• Vestibular effects: impaired balance, headache

• Neuromuscular blockade: flaccid paralysis, resp. depression

• GI: Anorexia, nausea, vomiting, diarrhea

Primary indicator of aminoglycoside toxicity

elevated TROUGH

How long after aminoglycoside administration should you check the peak?

30 mins after med given

Things to monitor when administering Aminoglycosides

• check 8th cranial nerve function (hearing and balance)

  • Report tinnitus

  • Vertigo

  • Nystagmus

  • Ataxia

  • HA

• Check RF (BUN, creatinine, CrCl)

• Encourage fluids

Tetracycline prototype name

doxycycline

Tetracycline adverse effects

• Gastrointestinal irritation

• Effect on bone and teeth- don’t give to pregnant, or breastfeeding women or children younger than 8y/o

• Superinfection

• Hepatotoxicity

• Renal toxicity

• Photosensitivity

Remembering adverse effects for tetracycline

“Terrible for teeth and tongue, tough on the tummy, toxic to liver and kidneys, teratogenic, and take sunscreen wherever you go!”

Interactions with Tetracyclines

• Chelation?: iron, vitamin C, milk products, Mg containing laxatives, most antacids, anything with metal causes chelation

  • Affects absorption of tetracycline

  • Take on empty stomach — 1 hr before meals or 2 hrs after meals and a full glass of water (NEVER with vitamins or milk)

• Oral contraceptive efficacy can be decreased by tetracycline

Macrolides prototype name

Azithromycin

Macrolides type of med

Broad spectrum

• similar to penicillin, so it’s often used as a replacement for people with penicillin allergy

Macrolides adverse effects

Generally tolerable

• GI

• QT prolongs action and sudden cardiac death if given with CYP3A4 inhibitors

• Superinfection

• Hepatotoxicity

• Hearing loss in elderly

Macrolides drug interactions

• Major inhibitor of CYP3A4

• Other QT prolonging drugs — increases risk

Macrolides patient education (break this up)

• TRY to take oral med 1 h before or 2-3 h after meals with full glass of water; if GI upset can take with food

• Monitor liver function AST(SGOT, ALT (SGPT)

• Can be used in patients with compromised renal function because it is primarily excreted in the bile

• Monitor EKG in pt’s with known prolonged QT

Prototype name for drugs that block folic acid synthesis

Trimethoprium / sulfamethoxazole (Bactrim)

Where is Trimethoprium / sulfamethoxazole metabolized and excreted?

• Metabolized by liver

• Excreted by kidneys

Trimethoprium / sulfamethoxazole interactions

• Cross hypersensitivity with other sulfur-based drugs

• Thiazide and loop diuretics

• Sulfonylureas used to treat diabetes – use of both can intensify effect of sulfonylureas and promote hypoglycemia

Trimethoprium / sulfamethoxazole (Bactrim) adverse effects

• Kernicterus — brain damage in newborns d/t extremely high bilirubin

• Blood dyscrasias, including hemolytic anemia (immune mediated)

• Hepatotoxicity

• Hyperkalemia

• Hypoglycemia

• Hyponatremia

Class of drug that blocks bacterial nucleic synthesis

fluoroquinolone

Prototype name of fluoroquinolone

Ciprofloxacin (Cipro)

Fluoroquinolone adverse effects*

• Tendon rupture – especially Achilles tendon- Black box warning

• Phototoxicity – severe sunburn

• GI symptoms

Azoles use

broad spectrum antifungal that can be used for many fungal infections

Azole prototype name

Fluconazole (Diflucan)

Fluconazole Administration methods

• Oral

• IV

• Topical

Fluconazole MOA

Inhibits synthesis of ergosterol, a component of the fungal cytoplasmic membrane, leading to increased membrane permeability and leakage of cellular components

Fluconazole adverse effects (typically for systemic administration — IV)

• GI

• HA

• Cardiac suppression — decrease in ventricular EF

• Liver injury

Fluconazole drug interactions

• Cytochrome p450 inhibitor

• Drugs that reduce gastric acidity — take 1 hour before or 2 hours after Fluconazole

• NO PPIs d/t long duration of action

Antiviral therapy

Antivirals are limited because viruses rely on host cell machinery, making it hard to stop replication without harming the host; drugs work by targeting viral-specific reproductive processes.

Acyclovir (Zovirax) use

Only active against members of the herpes family

• Herpes simplex virus

• Varicella-zoster virus (VZV)

Acyclovir (Zovirax) MOA

Inhibits viral replication of herpes virus

Acyclovir (Zovirax) side effects

• GI: N/V and diarrhea

• HA/vertigo

Neuraminidase inhibitors prototype name

Oseltamivir (Tamiflu)

Oseltamivir (Tamiflu) use

• Treatment fir influenza A and B — within 2 days of symptom onset

• Flu prophylaxis — within 48 hours of exposure

• Patients >1 y/o

Oseltamivir (Tamiflu) adverse effects

• HA

• N/V