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ANTIBIOTICS All Antibiotics against simple bacteria = Inhibits Bacteria Cell Wall (Peptidoglycan) Exception: DAPTOMYCIN & POLYMYXIN

inhibit Cell Membrane

All Antifungals = Inhibit fungal Cell Membrane Exception: CAPSOFUNGIN & MICAFUNGIN inhibit Cell Wall BacteriaStatic prevent bacteria increase in concentration (arrest growth) rate bacteria dead = rate bacteria growth Chloramphenicol (2nd line in meningitis in infants, 1st is Vancomycin) Clindamycin Lincosamide Macrolides (ACE Azithromycin, Clarithromycin, Erythromycin) Tetracycline TMP (Trimethoprim)

BacteriaCidal (use it in immunocompromised pts: transplant, chemo, HIV, babys) kill all bacteria rate bacteria dead > rate of bacteria growth Aminoglycosides (GNATS Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin) Carbapenem Cephalosporin Cycloserine (2nd line TB) Fluoroquinolones PCN (penicillins) Vancomycin

Bacterial Infection Rx Common Rule Gram (-) Mild Cephalosporins

Gram (+) PCN Cephalosporins

Moderate 3rd Gen Cephalosporins Ceftriaxone (cross BBB to CSF for adults) Cefotaxime (cross BBB to CSF for kids) Ceftazidime (anti-Pseudo) Cefoperazone (anti-Pseudo) Cefixime Ceftizoxime Severe Gentamycin Fluoroquinolones Vancomycin

Fungal Infection Rx Common Rule Mild Nystatin Swish & Swallow for oral candidiasis (thrush) Topical form Moderate -azole (PO) Fluconazole Ketoconazole MOA Inhibit fungal sterol (ergosterol) synthesis, via inhibiting P450 enzyme Itraconazole that converts lanosterol to ergosterol. Miconazole Clotrimazole Severe Amphotericin B (IV) / Flucytosine Extended Rx: x10 days IV (once you get better) switch to PO azole x 10 weeks Note: PO must be high potency: Fluconazole or Itraconazole

Viral Infection Rx Common Rule Mild Supportive Moderate Supportive Severe Acyclovir (IV) used for brain Foscarnet & Ganciclovir CMV If coming in contact w a flue < 96hrs, to reduce severity &/or duration treat w/ Oseltamivir (Tamiflu)

Cell Wall Inhibitors (CWI) PCN, -lactam drugs Cephalosporins Anti-Fungal: Caspofungin, Micafungin) Vancomycin Cycloserine (2nd line TB) MOA: Binding to specific penicillin-binding proteins (PBPs/NAM) located inside the bacterial cell wall, thereby inhibiting the final stage of cell wall synthesis and leading to autolysis of the bacteria by autolysins. PCN contains -lactam ring which binds to PBP SE: Allergic Anaphylactic (severe Allergy: acute Epinephrine (IM), chronic avoid use of PCN) Interstitial nephritis (AIN) See Eosinophilic Casts in the urine, Eosinophilia GI upset Diarrhea NOTE: DONT GIVE Cephalosporins to patients w/ PCN allergy) Doxy and Erythromycin to Syphilis patients who are allergic to PCNs

PCN for Pseudomonas: CT MAP Make sure to give Clavulonic Acid to inactivate -lactamase Carbenicillin Ticarcillin Mezlocillin Azlocillin Piperacillin Gentamicin (Aminoglycoside) (IV) Gram (-) Aztreonam (Monolactam) (see pg 9 for further details)

PCN for Staph aureus: Not OCD Nafcillin Oxacillin Cloxacillin Dicloxacillin Extended spectrum PCN Amoxicillin (PO) Ampicillin (PO, IV, IM used for Listeria)

Infant meningitis (0-3mon of life) 1. GBS (Strep agalactiae group B) 2. E. coli 3. Lysteria (add ampicillin) Rx: Infant Vancomycin + Cefotaxime + Ampicillin Adults Vancomycin + Ceftriaxone Elderly Vancomycin + Ceftriaxone Bacteria that has -lactamase: 1. Staph aureus 2. Strep pyogenes 3. Pseudomonas 4. Anaerobes (polymixed: brain, mouth, GI, vagina) 5. Clostridium Overcome bacteria -lactamase producer by: giving a combination of PCN & -lactamase inhibitor (Tazobactam, Sulbactam, Clavulonic Acid) Staph aureus resistant to Traditional PCN Nafcillin DOC for osteomylitis (IV) Oxacillin (PO) Cloxacillin (PO) Dicloxacillin (PO) MRSA Rx: Vancomycin (IV) measure trough & peak levels Treat VRSA w/ Linezolid inhibits 50/30 initiation Daptomycin cell membrane disrupter Daptomycin is a lipopeptide antibiotic with activity limited to Gram (+) organism, including MRSA. Itcauses depolarization of bacterial cellular membrane & inhibition of DNA, RNA & protein synthesis. Daptomycin is a/w CPK levels & an increased incidence of myopathy. Daptomycin also binds to & is inactivated by pulmonary surfactant, thus it is not effective in treating pneumonias.

CWI 1st Gen Cephalosporins Gram (+) & PEcK Proteus E coli Klebsiella Cefazolin Cephalexin Cephalothin Cephapirin Cephradine Cefazolin Cefadroxil

CWI 2nd Gen Cephalosporins Gram (+) & HEN PEcKS H. influenza Enterobacter Neisseria sp Proteus E coli Klebsiella Serratia m Cefaclor (MC used) Cefoxitin AntiAnaerobe Cefotetan AntiAnaerobe Cefuroxime Cefamandole Cefonicid CWI 4th Gen Cephalosporins More Gram (-) and Anti-Pseudomonas Cefepime

CWI 3rd Gen Cephalosporins More Gram (-) and Anti-Pseudomonas Ceftriaxone cross BBB to CSF for adults. Has the longest t1/2 for meningitis & gonorrhea Cefotaxime cross BBB to CSF for kids Cefozopran Ceftazidime anti-Pseudo Cefpirome Cefoperazone anti-Pseudo Cefixime Ceftizoxime Toxicity: Hypersensitivity reactions, Vit K deficiency Cross-hypersensitivity w/ penicillins occurs (Cautious in pts. who had anaphylactic shock w/ penicillins) Nephrotoxicity of aminoglycosides (GNATS) Disulfiram-like reaction w/ ethanol Under normal metabolism, alcohol is broken down in the liver by the enzyme alcohol dehydrogenase to acetaldehyde, which is then converted by the enzyme acetaldehyde dehydrogenase to the harmless acetic acid. Disulfiram blocks this reaction at the intermediate stage by blocking the enzyme acetaldehyde dehydrogenase Symptoms include flushing of the skin, accelerated heart rate, shortness of breath, nausea, vomiting, throbbing headache, visual disturbance, mental confusion, postural syncope, and circulatory collapse. Disulfiram like reaction caused by: Disulfiram Metronidazole Cephalosporins Procarbazine Rx Hodgkins lymphoma, also inhibits MAO thus increasing the effects of sympathomimetics, TCAs, and tyramine. CYP450 Cephalosporins Does Not cover LAMBB Listeria Atypical pneumonia Mycobacterium Rx: R x RIPE (Rifampin, INH, Pyrazinamide, Ethambutol) Note Ethambutol Carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
(can cause optic neuritis, central scotoma)

Bordetella pertussis + Brucellosis (undulant fever goes up & down, Rx: Erythromycin, Doxycycline)

Atypical pneumonias: Chlamydia pneumoniae/psittaci Mycoplasma pneumonia Legionella pneumophila can cause hyponatremia, hyperkalemia Rx: Macrolides ACE Azithromycin, Clarithromycin, Erythromycin (Block protein synthesis by blocking translocation at 50S Toxicity: Prolonged QT interval (esp. erythromycin) GI, acute cholestatic hepatitis (only w/ erythromycin estolate), eosinophilia, skin rashes. Azithromycin safe in pregnancy

Vancomycin DOC Serious empiric (MRSA) Gram (+) only: MRSA, Clostridium difficile MOA Inhibits CW mucopeptide formation by binding D-ala D-ala portion of cell wall precursos. Bactericidal SE NOT Nephrotoxicity (interstitial nephritis eosinophil casts in the urine) Ototoxicity Thrombophlebitis, Allergy anaphylactic (Rx anaphylaxis w/ IM Epinephrine) Red Man Syndrome d/t release of histamine, therefore (pretreat w/ antihistamines and SLOW infusion of the medication) Vancomycin Resistant Enterococcus, Intermediate Staph aureus, or VRSA Rx: Linezolid or Daptomycin Note: Vancomycin can also be given ORALLY (PO) to treat severe PMN, Clostridium difficile, because its not absorbed in GI.

Drug Induced Pseudomembranous Colitis (PMN) CCAAA Cephalosporins Clindamycin Amoxicillin Ampicillin Any antibiotics Why do you get PMN after antibiotic therapy? Because the antibiotic wipes out the NATURAL flora of the gut, allowing overgrowth of Clostridium dificile, an anaerobe Rx: Mild PMN Immediately discontinue the antibiotic Severe PMN Metronidazole first, if not available, then Vancomycin (PO) liquid/crystal

Anti-Fungal Pathway

SQUALENE

Terbinafine (-)


LANOSTEROL

-azoles (-) Amphotericin B (-) Nystatin

ERGOSTEROL

Anti-Fungal All systemic and serious fungus infections Ampho B (IV) and Flucytosine (IV) All local infections -azole (Fluconazole, Ketoconazole, Itraconazole, Miconazole, Clotrimazole) Derm infections -azole, Griseofulvin (PO, or IV), Terbinafine (PO) Candida infections Nystatin (swish & swallow), -azole, & if its systemic candida infection treat with Ampho B (IV) + Flucytosine (IV)

Amphotericin B DOC Big Gun for serious fungal infections (systemic, or focal important organs: Brain, Heart, Kidney) MOA Binds to ergosterol (ergosterol is unique to fungi) of cell membrane, forming membrane pores. Commonly used w/ Flucytosine (Inhibits DNA synthesis by conversion to 5-Fluorouracil) in systemic infections, to lower the Ampho B dosage. SE Electrolyte imbalance (Serious HYPOKALEMIA can cause weakness & arrhythmias- vent. fib) Hypo K, -Ca, -Mg, -PO4, -Na 1st sign of Kidney not functioning Hyper K in Late stage of kidney failure. Anemia IV phlebitis Note: Hydration reduces nephrotoxicity Liposomal amphotericin reduces toxicity (lipid based form)

Azoles Flucanazole, Itraconazole, Ketoconazole, Clotrimazole, Micronazole MOA Inhibits fungal ergosterol, structurally similar to imdazole. Inhibits P450 enzyme that converts lanosterol to ergosterol SE Inhibits P450 enzymes in liver (therefore liver dysfunction) = Gynecomastia (b/c you need P450 to break down estrogen). Check LFTs in long term use Potency: Remember that you need to use high potency for the extended treatment Flucanazole (High Potency) DOC for cryptococcal meningitis in AIDS pts. (b/c it can cross BBB) Ketonazole (Low Potency) Clotrimazole (Candida) Miconazole (Candida) Terconazole Itranazole (High Potency) Voriconazole

Metronidazole MOA selectively absorbed by ANAEROBIC bacteria and sensitive protozoa. Forms free radical toxic metabolites in the bacterial cell that damage DNA Is non, enzymatically reduced by reacting w/ reduced ferredoxin, which is generated by pyruvate oxidoreductase, causing toxic products to anaerobic cells into bacterial DNA cell death Inhibits DNA gyrase/topoisomerase II Note: Metronidazole is CONTRAINDICATED in Pregnant women (especially during 1st trimester) and in breast feeding patients. SE Disulfiram like reaction when taken w/ alcohol (b/c it inhibits acetyldehyde dehydrogenase Treats GET GAP Giardia Entamoeba histolytica Trichomonas vaginalis Gardnerella vaginallis Anaerobes (Bacteroides, Clostridium) *Anaerobic infection (abscess) below the diaphragm PMC (Clostridium difficile) PUD (H. Pylori) CMP Clarithromycin Metronidazole PPI (Omeprazole)

H. Pylori Rx: CAP Clarithromycin Amoxicillin PPI (Omeprazole)

OR

If the above fail then: Rx: [PPI (Omeprazole + Bismuth + Metronidazole + Tetracycline] 4 x per day

Anti-Anaerobes 5 Regimesn anti-anaerobes (mixed flora, abscess, aspiration infection, B/M/GI/V): Clindamycin (Blocks peptide bond formation at 50S) Bacteroides fragilis, Clostridium Perfinges, in aspiration pneumonia or lung abscesses SE Pseudomembranous Colitis (above diaphragm) Metronidazole Cephalosporins: Cefoxitin and Cefotetan (both 2nd gen) PCN and Tazobactam, Sulbactam, or Clavulonic acid Imipenem Imipenem + Cilastatin, Meropenem MOA Imipenem is a broad-spectrum, -lactamase-resistant carbapenem. ALWAYS administer w/ cilastatin. Because renal dihydropeptidase I inhibits Imipenem, and cilastatin inhibits the renal dihydropeptidase I, therefore preventing the inactivation of the drug in the renal tubules. Covers Gram (+), Gram (-) and anaerobes = Wide spectrum and used in life-threatening infections or after other drugs failed, but not used often due to side effects Meropenem is not deactivated by renal dihydropeptidase I, and has reduced risk of seizures SE Seizures with high plasma levels, Skin rash, and GI Note: Wont cover MRSA, so you will need to add Vancomycin Fluoroquinolones Ciprofloxacin DOC for NON-pregnant pts, and Pyelonephritis Levofloxacin DOC for COPD pneumonia (Empiric therapy) Moxifloxacin Rarely Used d/t causing Torsades de pointes (variant of Ventricular fib to treat, defibrillate) Norfloxacin Ofloxacin Sparfloxacin Nalidixic acid (a quinolone) MOA Inhibit DNA gyrase (gopoisomerase II) Cant be taken w/ anti-acids CONTRAINDICATED IN PREGNANT WOMEN & IN CHILDREN (Because it can cause damage to cartilage. Can cause Tendinitis and Tendon rupture in adults. Make sure you tell them NO EXERCISE) SE Skin rashes, GI, Tendinitis and Tendon rupture.

Drugs that Induce Torsades de Pointes Moxifloxacin Erythromycin (macrolide) Amiodarone K+ channel blocker (Class III Anti-arrhythmic, also exhibits Class I properties). Can cause pulmonary fibrosis, hepatotoxicity, hypo- & hyperthyroidism (Monitor LFTs, TFTs, and PFTs) Quinidine 2nd line to treat Wolff Parkinson Dz (Note: 1st line for Wolff Parkinson is Procainamide) NOTE: Any drug that prolongs QT interval can cause Torsades de Pointes

Aztreonam (Anti-Pseudo) MOA monobactam, resistant to -lactamase. Inhibits cell wall synthesis via binding to PBP, syngergistic w/ aminoglycosides. Can be given to penicillin-allergic patients or to patients with renal insufficiency NO cross-sensitivity w/ penicillins or cephalosporins (HORRAAAYYYY)

Populations with high risk of Pseudo and Staph aureus Infections 1. Burn 2. Diabetes 3. Cystic Fibrosis 4. Neutropenia

Rifampin Induces P450 MOA Inhibits DNA-dependent RNA polymerase, therefore inhibiting transcription SE Red/orange body fluids (urine, tears warn the patient so they dont get scared) DOC TB (along with 3 other drugs in combination) RIPE Rifampin, INH, Pyrazinamide (effective in acidic pH of phagolysosomes, where macrophages swallow TB), Ethambutol ( carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase) Mono therapy DOC for prophylaxis for bacteria meningitis contact. Rifabutin used in HIV pts w/ TB Rifapentine Rifampicin

Drugs that cause Rhabdo/Myo lysis RIPS F Rifampin INH Prednisone (Steroids) Statins lipids Fibrates fats Aminoglycosides Buy AT 30s CELL at 50s Gentamicin Neomycin Amikacin DOES NOT cause nephrotoxicity (metabolized by liver, so cant be given to pts with liver failure, but if the pt has renal insufficiency, you can use this drug) Tobramycin Streptomycin Kanamycin

Aminoglycosides MOA Inhibit formation of initiation complex and cause misreading of mRNA (so dont give it to pregnant pts). Requires O2 in order for it to be uptaken. So you cant use it for anaerobic infections SE Nephrotoxicity (especially when its combined with cephalosporins) = AIN, you will see eosinophilia and eosinophil casts in urine Ototoxicity (especially when used with LOOP diuretics) Teratogen (Another reason not to give to a pregnant pt)

Monitor trough and peak levels

Tetracyclines Buy AT 30S CELL at 50S Tetracycline used to treat acne, but causes photosensitivity Doxycycline Fecally eliminated, therefore can be used by pts with renal failure. (Doxycycline + Erythromycin is 2nd line for Chlamydia, Lyme Dz & Rickettsia Demeclocycline DOC for SIADH (small cell carcinoma of the lung) chronic use, it desensitizes ADH receptor in the collecting duct of the kidneys (Note: Lithium desensitizes ADH receptor as well) Minocycline Treats acne, and does not cause photosensitivity MOA Bind to 30S and prevent attachment of aminoacyl-tRNA (limited CNS penetration ) Must NOT be taken w/ milk or anti-acids. Divalent cations inhibit its absorption from the GI Absorbed with acids, make sure to advice your patient to take it on an empty stomach SE Bone, teeth DOC Lyme Dz (Borrelia burgdorferi), Chlamydia, Rickettsia. 2nd line for Syphillis (1st line for Syphillis is Penicilin)

3 Regimens for Syphillis Rx: 1. PCN 2. Doxycycline 3. Erythromycin (macrolide)

Atypical/Walking pneumonia caused by: 1. Chlamydia pneumoniae 2. Mycoplasma pneumonia 3. Legionella pneumonia

Macrolides ACE Azithromycin Clarithromycin Erythromycin MOA Inhibits translocation at 50S/23S ribosome subunit (inhibiting Peptidyl Transferase) Macrolides sterically block the progression of the growing peptide SE Erythromycin (Seizures, Torsades de Pointes)= prolonged QT interval, GI, acute cholestatic hepatitis (only w/ erythromycin estolate), eosinophilia, skin rashes. Azithromycin can be used in pregnant pts. DOC Atypical pneumonias

Linezolid MOA Inhibits peptidyl transferase of 50S/30S initiation in process of protein synthesis. Class of oxazolidinone DOC Vancomycin resistant bugs (Daptomycin can be used) Chloramphenicol MOA Inhibits 50S peptidyltransferase activity SE Aplastic anemia (not dose dependent), Gray baby syndrome (in premature infants because they lack liver UDP glucuronyl transferase) Leads to failure to thrive & vasomotor collapse = death used to treat meningitis (H influenza, N meningitides, Strep pneumo)

Microcytic Sideroblastic Anemia can be caused by: MCC = Alcohol Chloramphenicol INH Pyrazinamide Lead poisoning PABA/Folic Acid Pathway Inhibitors: Methotrexate MOA Inhibits dihydrofolate reductase inhibits the synthesis of DNA (S-phase), RNA, thymidylates, and proteins Indications Ectopic pregnancy, molar, rapidly dividing cancers SE Neutropenia (Rescue: Leukovorin = Folonic Acid)

SMX, sulfonamides PABA antimetabolites inhibit dihydropteroate synthetase. Gram(+) & (-) Nocardia, Chlamydia Triple sulfas or SMX for simple UTI. SE Hypersensitivity reactions, Hemolysisi if G6PD deficient, Nephrotoxicity (interstitial nephritis), photosensitivity

Trimethoprim MOA Inhibits bacterial dihydrofolate reductase. Used in combination w/ sulfonamides for UTI infections SE Megaloblastic anemia, leucopenia, granulocytopenia

Dapsone, acedapsone, aldesulfone DOC Prophylactic for infection in HIV, multiple myeloma, Leprae (acid-fast bacillus that likes cool temperatures, infects skin & superficial nerves) SE Hymolysis and methemoglobinemia

Infectious Endocarditis Native Valve Endocarditis =NVE (Nafcillin + Gentamycin) or (Vancomycin + Gentamycin) Prosthetic Valve Endocarditis = PVE (Nafcillin + Gentamycin + Rifampin) or (Vancomycin + Gentamycin + Rifampin)