-Enterococci

-Pseudomonas

-Enterobacter

-Cephalosporins

-Vancomycin

-Aminoglycosides

-Sulfonamides

-Amphotericin B

-Tetracyclines

-Isoniazid

-Erythromycin

-Clindamycin

-Sulfonamides

-Amphotericin B

-Aminoglycosides

-Vancomycin

-Minocycline

-Ethambutol

-Isoniazid

-Antivirals

-Chloramphenicol

-Sulfonamides

Superinfection most likely cause

Most common superinfection

-Broad spectrum antibiotics

-Intestinal Candidiasis

-Clindamycin

-Clostridium difficile

Macrolide

-Action

-Resistance

-50S, inhibit translocation

-Methyltransferase alteration

Chloramphenicol

-Action

-Resistance

-50S, inhibit transpeptidation

-Inactivating acetyltransferase

Aminoglycosides

-Action

-Resistance

-30S, blocks initiation and causes premature termination

-Acetyl, phosphoryl, or adenylyl conjugation

Tetracyclines

-Action

-Resistance

-30S, prevent tRNA binding

-Pumped out

Fluoroquinolones

-Action

-Resistance

-Inhibit topoisomerase

-Pump out

Rifampin

-Action

-Resistance

-Inhibits RNA polymerase

-Change in enzyme

Sulfonamides

-Action

-Resistance

-Inhibition of bacterial folic acid synthesis--> inconsequentil to humans

-Dec sensitivity of target enzymes, increased PABA formation, use of exogenous folate

Beta lactam

-Action

-Resistance

-Inhibition of bacterial cell wall synthesis

-Penicillinase, change of porins

Vancomycin

-Action

-Resistance

-Inhibition of peptidogylcan chain elongation

-Change in pentapeptide

-Naficillin

-Cloxacillin

-Oxacillin

Clostridium difficile DOC

(pseudomembranous colitis DOC)

-Rifampin

-Streptomycin

-Tetracycline

-Erythromycin

-Glycopeptides sterically inhibit the addition of subunits to peptidoglycan backbone

-Beta-lactams prevent the cross-linking reaction transpeptidation

-Antagonistic

-Protein synthesis inhibitors prevent teh action of cell wall synthesis inhibitors

-Natural penicillin

-GOOD G+ coverage

-Some G- and anaerobic coverage

-Eliminated by kidney= short-acting

Naficillin (parenteral)

Cloxacillin (oral)

Oxacillin (oral)

-Penicillinase resistant penicillin

-Less G+ coverage

-Some G- coverage

-DOC for penicillinase Staph

-Hepatic metabolism: CYP450 competition?

-NOT very acid stable

Ampicillin

Amoxicillin

-Extended spectrum penicillins

-Low G+

-Extended G-

-Anaerobic coverage

-Acid resistant= ORAL

-Susceptible to penicillinase (combine with penicillinase inhibitor)

-Kidney

EXCEPT for penicillinase resistant penicillins

Piperacillin

Ticarcillin

Mezlocillin

Carbenicillin

-Antispeudomonal penicillin

-Same coverage as extended spec, but used for pseudomonas coverage

-Susceptible to penicillinase (combine with penicillinase inhibitor)

-Used in conjunction with aminoglycosides to prevent resistance

-Acid sensitive= NO ORAL

Cluvanic acid

Sulbactam

Tazobactam

-Penicillinase inhibitors

-Not ALL penicillinases are sensitive to these drugs

-MRSAs are resistant

Highest hypersensitivity drugs

Lowest sensitivity drugs

-Penicillin, sulfas, and cephalosporins

-Aminoglycosides and tetracyclines

Ampicillin rash

Amoxicillin rash

-Generalized dull red, maculopapular rash

-Appears 3-14 days after tx

-Usually seen in kids with infectious mononucleosis (EBV) during tx

-NOT ALLERGIC

-Does NOT preclude future penicillin tx

-Tissue irritation

-Excess Na and K--> cardiac/renal toxicity

-Soft frothy stools and diarrhea

-Superinfection

   >Mainly from extended spectrum

-Jarisch-Herxheimer rxn

-If resistant to penicillin, resistant to monobactam

-Safe is patients with penicillin allergy

-Monocyclic beta-lactam ring

-G- rods

-NOT active against G+ and anaerobes

-Ertapenem

-2nd gen ceph

-Glycopeptide: inhibits elongation of peptidoglycan chain

-Only effective against G+ bacteria

-Bactericidal

-Useful in treating G+ infections in penicillin allergy patients

-OTOTOXIC and NEPHROTOXIC

-"Red man" syndrome

-HUGE G- coverage, NO seizures

-Good CNS penetration

-Less G+

-Pseudomonas

-Enterobacteriaceae (even penicillinase producers)

-Huge G- and G+

-Good CNS penetration

-More resistant to beta-lactamases

-Inc ability to penetrate bacterial cells outer membrane

-Antipseudomonal

-Co-trimoxazole

-Second or third generation Ceph

-Step 1: sulfamethoxazole acts as PABA antagonist--> non-consequential to humans

-Step 2: trimethoprim prevents the reduction of dihydrofolate to tetrahydrofolate--> has potential bone marrow side effects

-Oral, parenterally, topical

-Liver acetylation and renal excretion

-Acetylated sulfonamides are insoluble--> crystalluria (kidney damage)

-Cause kernicterus in nursing infant--> jaundice accumulation and brain damage

-Stevens-Johnson Syndrome

-Sulfonamide

-Active against both methicillin susceptible and methicillin resistant strains

-Sulfonamide

-G+ and G- coverage

-Recurrent UTI

-BONE MARROW, GI, and HAIR effects

-Sulfonamide

-Topical used in tx of infections caused by 2nd and 3rd degree burns

Erythromycin

-Mechanism

-Resistance

-50S, interferes with the formation of initiation complex

-Pump out, methylase; most G- organisms are resistant

-Pts allergic to penicillin--> has similar coverage

-Pts with kindey failure: hepatic metabolism and fecal elimination

-Gastric acid destroys erythromycin, so they are modified for ORAL use

-Heptaic metabolism and fecal elimination--> not effective against UTI

-Elevated hepatic enzymes and jaundice

-QT prolongation--> torsade de pointes

-GREATEST GI disturbances

-Clarithromycin

-Azithromycin

-Good lung penetration: primarily used for respiratory infections

-Liver metabolism

-LEAST DIARRHEA CAUSING

-Similar drug interactions to erythromycin

-Once a day dose: reaches higher intracellular concentrations

-Similar coverage as erythromycin

-FOOD DEC bioavailability

-NO liver metabolism--> NO P450 interaction

-Less GI disturbances than erythro, but more than clarithro

-Good against erythromycin and penicillin resistant pneumococci

-ORAL

-Hepatic metabolism--> SERIOUS hepatotoxicity

-Good bone penetration

-Primary prophylaxis

-Anaerobic G- and G+

-Causes pseudomembranous colitis

Dalfopristin

Quinupristin

-Vancomycin resistant organisms (Staph and Enterococci)

-Complicated skin infections (Staph)

-P450 inhibitor

-GI distrubances

-Interfere with translation

-MAO inhibitor

-Vancomycin/methicillin resistant staph

-Does not interefere with P450--> use when dalfopristin and quinupristin are contraindicated

-Side effects similar to MAOI side effects

Imipenem

Meropenem

Ertapenem

-Must be given with cilastatin to be effective

-HUGE anaerobic coverage (enterobacter)

-SEIZURES

-Gram - enteric bacteria and UTI

-Parenteral administration

-Poor CNS penetration UNLESS high levels of inflammation

-Ototoxicity

-Nephrotoxicity: due to renal accumulation and elimination

-GI upset

-Neurmuscular weakness

-Drinking water (AIDS pts)

-Paromomycin

-Enterococci: penicillin and aminoglycoside

-Pseudomonas: piperacillin and aminoglycoside; 3rd/4th gen ceph and aminoglycoside

-Bone marrow depression: dose dependent

-Inhibition of mitochondrial ribosomes: dose dependent

-Agranulocytosis: NON-dose dependent= FATAL

-STATIC

-G-, Tyhpoid fever, meningitis, eye infections, Rickettsia

-Hepatic metabolism and elimination

-CNS and eye penetration

-NOT A DOC for any organism due to toxic effects

Tetracyclines

-Absorption

-Metabolilsm/excretion

-Oral--> chelates with Ca, Fe, and Al

-Deposit in bone and teeth

-Fecal excretion primarily

-GI: due to broad spectrum--> resistant organisms energe

-Bone and teeth chelation= NO PREGNANCY

-Liver damage

-Photosensitization

-Allergy

-Fluoroquinolones

-Tetracyclines

-Tetracyclines: Ca, Fe, Al

-Fluoroquinoloes: antacids containing Mg

-G+ and G-; Pseudomonas and MRSA

-Lipid soluble--> extensive distribution

-Liver metabolism

-Urine excretion (UTI tx)

-TENDON RUPTURE
-Cartilage erosion

-NO PREGNANCY

-Levofloxacin

-Moxifloxacin

-Antituberculotic agent

-Inhibits mycolic acid synthesis

-Peripheral neuritis

-Hepatotoxicity

-Hemolysis

-Antituberculotic agent

-RNA polymerase inhibitor

-Nephritis

-Liver dysfxn

-Thrombocytopenia

-Antituberculotic agent

-Arabinogalactan synthesis inhibitor

-Visual toxicity: R/G color blindness

-Systemic can be used as topical

-Topical CANNOT be used as systemic

Amphotericin B

-Mechanism

Amphotericin B

-Administration

-Toxicity

-Coverage

-SYSTEMIC

-Parenteral

-Nephrotoxic: inc BUN and serum creatinine levels, some hepatotoxicity

-DOC for all fungal species except

   >Aspergillus

   >Combined with FLUCYTOSINE for Cryptococcus

Flucytosine

-Mechanism

-Uses

-SEs

-Fungal DNA antagonist: 5-fluorouracil--> anticancer

-Combined with Amphotericin B for cryptococcus infections

-Bone marrow depression, GI distrubances, alopecia

-AZOLES: inhibit ergosterol synthesis

-Amphotericin B: ergosterol interaction

AZOLES ANTAGONIZE AMPHOTERICIN B

Ketoconazole

-Administration

-Uses

-SEs

-ORAL

-When amphotericin B is not well tolerated (kidney failure)

-Inhibits CYP3A4

-Inhibits adrenal and testicular formation

-Gynecomastia

Fluconazole

-Administration

-Uses

-Adverse effects

-ORAL or IV

-CNS penetration--> used for fungal meningitis

-LESS toxic than amphotericin B and flucytosine

-Better tolerated than ketoconazole--> NO CYP3A inhibition

   >No testicular or adrenal problems

Echinocandins (-fungin)

-Mechanism

-Uses

-Inhibit D-glucan synthesis: inhibit cell wall synthesis

-Useful in pts with resistant aspergillosis and candidiasis

-NO nephrotoxicity

Griseofluvin

-Mechanism

-Administration

-Uses

-Toxicity

-Destroys mitotic spindle fibers

-Oral admin, but TOPICAl effect

   >Will become incorporated into keratin after months of administration

-Used for ringworm of skin, hair, and nails

-GI upset, bone marrow damage

Nystatin

-Administration

-Absorption

-Uses

-Topical or oral

-NO GI ABSORPTION

-Candidiasis in mouth, skin, GI tract, vagina

-USE for intestinal candidiasis superinfection

Terbinafine

-Administration

-Toxicity

-Topical and ORAL

-Oral= hepatotoxicity

Acyclovir and valacyclovir

-Uses

-Mechanism

-SEs

-HSV1and2, VZV

-Guanosine antagonist; must be phosphorylated by viral thymidine kinase--> non-toxic to human cells

-Rare SEs

-SAFE IN PREGNANCY

Docosanol

-Mechanism

-Uses

-Prevents fusion of host cell plasma membrane and HSV

-TOPICALLY for cold sores

Ganciclovir and valganciclovir

-Activation and spectrum

-Toxicity

-HSV: activated by thymidine kinase

-CMV: activated by kinase phosphotransferase

-INHIBITS DNA polymerase

-Neutropenia

Oseltamivir

-Spectrum

-Mech

-Administration/SEs

-Influenza A and B

-Neuraminidase inhibitor: inhibit release of virus from infected cell

-Orally--> nausea and vomiting

Zanamivir

-Spectrum

-Mech

-Administration/SEs

-Influenza A and B

-Neuraminidase inhibitor: inhibit release of virus from infected cell

-Intranasal/inhaler--> bronchospasm

Ribavirin

-Uses

-Toxicity

-Respiratory syncytial virus

-Combined with interferon alfa to treat hep c

-EXTREMELY teratogenic: pt or partern CANNOT use

-Anemia

Interferon alfa-2b

-Mech

-Uses

-Toxicity

-Inhibit viral protein synthesis and replication

-Inhibit penetration and uncoating

-Hepatitis C (with ribavirin)

-Neutropenia and anemia (with ribavirin)

-DEPRESSION and suicide

Zidovudine

-Mech

-Toxicity

-Reverse transcriptase inhibitor

-Anemia and neutropenia

-Lactic acidosis

-Hepatotoxicity

Lamivudine

-Uses

-Hep B DOC

-HIV reverse transcriptase inhibitor

-HIV adjunct becase it is tolerated so well

Didanosine

Zalcitabine

Stavudine

Toxicities

Peripheral neuropathy

Didanosine= pancreatitis

Efavirenz

-Mech

-Use

-Toxicity

-Directly binds to reverse transcriptase and inhibit is (non-nucleotide)

-DOC of initial HIV tx

-TERATOGENIC

Protease inhibitors -navir

-Mech

-Uses

-Met

-SEs

-Inhibits protease that makes mature infectious virions

-HIV tx in combination with reverse transcriptase inhibitors

-CYP3A4 metabolism

-Facial AND peripheral atrophy, buffalo hump, truncal obesity

-Hyperlipidemia, hypercholesterolemia, hyperglycemia

EnFUVirtide

-Mech

-SE

-Fusion inhibitor

-Injection site rxn

-Corticosteroids: moon face with peripheral atrophy

-Protease inhibitors: facial peripheral atrophy

Cyclosporine

-Mech

-Uses

-Toxicity

-T-cell inhibition by inhibiting calcineurin

-Transplant pts; autoimmune pts

-HTN, renal toxicity

-Gingival hyperplasia

MORE toxic than tacrolimus

Tacrolimus

-Mech

-Uses

-SEs

-T-cell inhibition by inhibiting calcineurin

-Transplant pts; autoimmune pts

-Rescue drug during rejection episode

-HTN, renal toxicity

-TREMOR and INSOMNIA

Mycophenolate mofetil

-Mech

-Uses

-SEs

-Selectively suppress B cells

-Prevent rejections

-CMV infections

-Skin rash

Azathioprine

-Mech

-Uses

-SEs

-6-mercaptopruine: inhibits de novo purine synthesis

-Prevents rejection

-ANTIPROLIFERATIVE: bone marrow suppression and FETAL toxicity

Cyclophosphamide

-Mech

-Uses

-SEs

-T and B cell suppression

-Can inhibit established immune response

-Hemorrhagic cystitis (MESNA= resolve)

-Bone marrow suppression

-TERATOGENIC

Methotrexate

-Mech

-Uses

-SEs

-Inhibits dihydrofolate reductase

-RA

-Bone marrow suppression

-TERATOGENIC

Thalidomide

-Mech

-Uses

-SEs

-TNF alpha suppression

-Prevention of graft-versus host reaction

-TERATOGENIC

-Exogenous T-cell specific antibodies

-Allergic phenomena

Interleukin-2

-Mechanism

-Uses

-SEs

-Stimulates immune system

-Metastatic renal cell carcinoma

-Malignant melanoma

-Severe hypotension

-Anemia, thrombocytopenia

Granulocyte colon-stimulating factor

-Uses

Mechlorethamine

-Mechanism

-Uses

-Alkylates DNA

-Hodgkins disease

-Leukemias