Antibiotics and Antifungals

Pharmacology

Penicillin

Penicillin

MOA: weaken cell wall -> bacteria takes up excessive water and rupture: bactericidal

• broad spectrum

• resistance (old drug)

A/E: allergic reaction, N/V, rash, diarrhea

Combinations:

• augmentin (amoxicillin + clavulanate)

• zosyn (pipercillin + tazobactam)

Allergy:

• mild (rash & itchy) = give cephalosporin

• anaphylaxis (SOB, wheezing, tachycardia) = give vancomycin or epinephrine

Penicillin G

• narrow spectrum

• bactericidal

• least toxic (safest)

• IM lasts 30 days

DOC: pneumonia, pharyngitis, endocarditis, gas gangrene, tetanus, anthrax, meningitis, syphilis

Amoxicillin

• broad spectrum

• targets: E. coli, Salmonella, Shigella, H. influenzae

• low dose for renal impairment

DOC: ear infection

A/E: rash and diarrhea

Nafcillin

• narrow spectrum

• routes: IV, IM

DOC: IV penicillin

Cephalosporins

MOA: disrupts cell wall synthesis, cause cell lysis, & binds to PBPs

• broad spectrum (similar to penicillin)

• resistance

A/E: N/V & diarrhea

• bleeding tendencies (interact w/ Vit K)

• thrombophlebitis

• hypersensitivity rash

AVOID!!! Probenecid, alcohol, and other drugs that increase bleeding

Classifications:

• 1st: (Cephalexin) prophylaxis against infx in surgery

• 2nd: (Cefoxitin) rare for active infx

• 3rd: (Cefotaxime), (Ceftriaxone - DOC: gonorrhea), (Ceftazidime - DOC: pseudomonas aeruginosa) able to penetrate CSF

• 4th: (Cefepime - can be given for sepsis, MRSA, VRE, H. pylori) treat hospital pneumonias

• 5th: (Ceftaroline) associated with MRSA

Vancomycin

MOA: inhibits cell wall synthesis

• broad spectrum

• bactericidal

Uses: severe infections ONLY (MRSA & C. diff)

TOXIC to KIDNEYS

• low dose bc of renal impairment

• prior to 4th dose, TEST BLOOD

• give for anaphylactic rxn from penicillin

Routes: IV, can be PO

A/E:

• ototoxicity (rare, reversible, balance issues, ear ringing

• "Red Man" syndrome (red, itchy, tachycardia, irritable) SLOW IV infusion for at least an hr

Tetracyclines

MOA: inhibit protein synthsis

• broad spectrum (narrow - rare infx: rocky mountain spotted fever)

Food Drug Interaction:

• AVOID! calcium, iron, magnesium, aluminum, zinc

A/E:

• effects bone and teeth

• hepatotoxicity and nephrotoxicity

• photosensitivity

DOC & Uses:

• acne

• rickets

• lyme disease

• anthrax

• pregnant, breastfeeding, and < 8yo should NOT take this

Macrolides

MOA: inhibits protein synthesis & broad spectrum

• alternative for penicillin

Erythromycin (Macrolide)

• bacteriostatic, can be bactericidal

• Routes: PO or IV

DOC & Uses: Bordetella pertussis (whooping cough)

Interaction: theophylline, bipolar meds, warfarin

A/E: upper gastric pain (GI), prolonged QT & sudden cardiac death, superinfx, transient hearing loss

Clindamycin (Marcrolide)

• promote severe CDAD (report diarrhea ASAP -> sepsis)

• can target vaginosis

• Routes: PO, IM, IV, topical

A/E:

• CDAD for pseudomembranous colitis

• Hepatotoxicity

• Blood Dyscrasias

Linezolid

MOA: bacteriostatic protein synthesis inhibitor

• active against multi drug resistant (MRSA & VRE)

• do NOT give to cancer pts

• Route: IV & PO

A/E: prolonged therapy

• N/V, diarrhea

• headache

• myelosuppressin

• optic neuropathy (reversible)

• peripheral neuropathy (irreversible)

Interactions: monoamine oxidase inhibitors (MAOIs) and selectice serotonin reuptake inhibitors (SSRIs)

Aminoglycosides

MOA: disrupts protein synthesis (bactericidal), narrow spectrum

• Route: PO (absorbed erratically in GI; prophylactic)

• Uses: aerobic gram negative

Interactions: AVOID all nephro/ototoxic drugs and MSK relaxants

DOC: reversal (antidote) w/ IV infusion of calcium salt/gluconate

A/E:

• nephrotoxocity & ototoxicity

• neuromuscular blockade

• blood dyscrasia

• do NOT take if pregnant or meningitis

• peak = 30 min after IM or IV infusion

• trough = divided (sample before next dose), once daily (sample 1 hr before next dose)

Gentamicin (Aminoglycoside)

DOC: resistance (weaker of the 2)

Routes: IV, IM, intrathecal (spine)

Uses: treat serious infections by aerobic gram negative

• P. aeruginosa

• E. coli

Amikacin (Aminoglycoside)

DOC: when gentamicin resistant (expensive - stronger of the 2)

• active against broadest spectrum of gram negative

Sulfonamide

MOA: suppress bacterial growth by inhibiting tetrahydrafolic acid

• broad spectrum

• common allergy

• microbial resistance

DOC: UTI

Uses:

• nocardiosis

• ulcerative colitis

• chlamydia trachomatis

A/E:

• hypersensitivity rxn

• steven johnson syndrome

• hematologic effects

• kernicterus

• renal damage

Interactions: do NOT take if baby, breastfeeding, or pregnant

Bactrim (Sulfonamide Combination T+S)

MOA: inhibits sequential steps in bacterial folic acid synthesis

DOC: UTI

Uses:

• otitis media

• bronchitis

• pneumonia

Route: PO & IV

A/E:

• hyperkalemia

• hypersensitivity rxn (steven johnson syndrome)

• blood dyscrasias

• kernicterus

Silver Sulfadiazine (Sulfonamide)

MOA: suppress bacterial colonization w/ 2nd & 3rd degree burns

Route: topical

• give meds prior to application

• AVOID face

A/E: skin discoloration (blue, green, grey)

Nitrofurantoin

• urinary tract antiseptics

• low conc. = bacteriostatic

• high conc. = bactericidal

Uses: lower UTIs & prophylaxis

DOC: uncomplicated acute cystitis

A/E: (brown urine is normal)

• pulmonary rxn (SOB, chills, fever, cough)

• peripheral neuropathy (irreversible)

• birth defects

Fluroquinolones

MOA: disrupts DNA replication & cell division (bacteriostatic)

• broad spectrum

• Route: PO

Uses: resistant acute cystitis, acute bacterial prostatis, last resort

A/E: achilles tendon rupture & exacerbate myasthenia gravis

AVOID!!!

• age < 18 & 60+

• taking glucocorticoids

• undergone transplant

• sun/UV

Ciprofloxacin (Fluoroquinolone)

MOA: inhibits bacterial DNA gyrase & topoisomerase II

DOC: anthrax

Uses:

• infx = respiratory, UTIs, GI, bones, joints, skin, & soft tissue

• resistance = S. aureus, serratia marcescens, campylobacter jejuni, etc.

Drug & Food Interactions:

• increase drug levels: theophylline, warfarin, tinidazole

• decrease absorption: aluminum & magnesium antacids, iron & zinc salts, calcium (milk/dairy)

A/E:

• abdominal pain

• tendon rupture

• phototoxic

• restlessness, confusion, seizures

• candida infx

• risk for C. diff

Metronidazole (Fluoroquinolone)

• metallic taste

• does NOT fall in azole class

• must AVOID alcohol

DOC: mild to moderate C. diff

Uses: protozoal infx, H. pylori, C. diff

A/E: neurotoxicity, allergy (hypersensitivity rxn), superinfx

Amphotericin B

MOA: binds to fungal cell membrane, increases permeability

• broad spectrum

Uses: highly toxic, progressive & potentially fatal infx

Route: IV (test dose, check for precipitate, assess for phlebitis)

DOC: systemic mycoses

A/E:

• infusion rxn (fever, chills, rigors)

• nephrotoxicity (BUN & Creatinine)

• hypokalemia (monitor K)

• myelosuppressin

• elimination very long (1 yr)

• protect kidneys (1L bolus prior & lots of fluids)

Interactions: AVOID!!! nephrotoxic drugs (vancomycin, aminoglycosides), hydrocortisone, K sparing diuretics

Azole

MOA: inhibits ergosterol synthesis, increases permeability & leakage of cellular components

• broad spectrum

Uses: lower toxicity (safer & less effective than Amp B)

• monitor AST, ALT, & bilirubin

Route: PO

A/E: N/V/D, headache, rash

Itraconazole (Azole)

DOC: blastomycosis, histoplasmosis, paracoccidiomycosis, sporotrichosis

PSI Hey Baby

A/E: abdominal pain, edema, cardiosuppressin (serious)

Ketoconazole (Azole)

Uses: active against most fungi systemic mycoses & superficial infx

A/E:

• constipation (give w/ food)

• fatal hepatic necrosis

• sex hormone effects

• photophobia

KETO give FOOD

Interactions: inhibits CYP34A, increases other drug levels (warfarin, phenytoin, etc.)

Fluconazole (Azole)

• number 1 azole & prophylactic antifungal

A/E: 1st trimester birth defects (cleft lip, frontal bowing, etc.

Uses: blastomycosis, histoplasmosis, meningitis, vaginal, candida infx

Interactions: inhibits CYP34A, increase other drug levels (warfarin, phenytoin, etc.)

Clotrimazole (Azole)

MOA: binds to fungal cell membrane, increase permeability

DOC: dermatophytic infx & candidiasis of skin, mouth, & vagina

Routes: topical - try before PO ketoconazole bc of toxicity

A/E:

• oral: GI distress (N/V)

• topical: stinging, erythema, edema, urticaria (hives), pruritis (itchy), & peeling

• intravaginal: burning sensation & lower abd cramps

Nystatin

MOA: binds to fungal cell membrane, increase permeability

Routes:

• PO (swish & swallow)

• topical (powder in skin folds, cream everywhere else)

SWISH & SWALLOW cause youre NaSTY

DOC: intestinal condidiasis (skin, mouth, esophagus, vagina)

A/E:

• oral (N/V/D)

• topical (local irritation)