Antimicrobial Overview June 2015 General Principles Aerobic Gram

Antimicrobial Overview June 2015

Laureen A. Klein, Pharm.D.

Rutgers, The State University of New Jersey

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General Principles

• Narrowest spectrum possible to avoid resistance • Wider spectrum (including multiple agents) – neutropenic fever, polymicrobial infection, synergism (two agents with different mechanisms of action), tuberculosis • Ensure compliance

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Aerobic Gram-Positive Bacteria

• Streptococcus • Staphylococcus • Enterococcus • Cornybacterium • Listeria

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Aerobic Gram-Negative Bacteria

• Enterobacteriaceae (E. coli, Klebsiella, Enterobacter, Citrobacter, Proteus, Serratia, Salmonella, Shigella, Morganella, Providencia) • Pseudomonas • Helicobacter • Haemophilus • Legionella • Moraxella • Neisseria

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Anaerobic Bacteria

• Gram-Positive • Gram-Negative • Peptococcus • Bacteroides • Peptostreptococcus • Fusobacterium • Clostridia • Propionibacterium acnes

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Atypicals

• Chlamydia • Chlamydophila • Rickettsiae • Mycoplasma • Spirochetes (Syphilis, Lyme disease) • Mycobacterium (tuberculosis, mycobacterium avium complex [MAC])

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Mechanisms of Action (MOA)

• Cell wall synthesis inhibitors – beta-lactams (penicillins, cephalosporins, monobactam, carbapenems), vancomycin, lipoglycopeptides, fosfomycin, bacitracin

• Protein synthesis inhibitors – macrolides, ketolides, aminoglycosides, tetracyclines, metronidazole , dalfopristin/quinupristin, oxazolidinones (linezolid, tedizolid), clindamycin

• Inhibition of enzymes – rifampin (RNA polymerase), fluoroquinolones (topoisomerase), sulfamethoxazole/ trimethoprim (folic acid)

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Penicillins

• MOA: beta-lactams; bind to penicillin binding protein to inhibit cell wall synthesis • Spectrum: gram-positives (S. pneumoniae & Staphylococcal resistance), gram-negatives, anaerobes • Most eliminated renally • Resistance: beta-lactamase, altered penicillin binding protein, altered penetration • AEs: hypersensitivity, GI, hematological, seizures, interstitial nephritis

PANCE/PANRE Review Course Natural Penicillins (Pen G, Pen VK [PO], Procaine [IM], Benzathine IM])

• Spectrum: Treponema pallidum, Streptococcal species (pyogenes, pneumoniae [resistance]), Enterococcus (combined with aminoglycoside), Neisseria meningitidis, Borrelia burgdorferi, anaerobes above diaphragm • Indications: syphilis and strep respiratory tract infections including S. pneumoniae and S. pyogenes

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Antistaphylococcal Penicillins (dicloxacillin, nafcillin, oxacillin, methicillin)

• Spectrum: staphylococcal and streptococcal infections only • Effective for penicillinase producing organisms • If methicillin resistant resistant to all beta-lactams except ceftaroline • Indications: sensitive staphylococcal infections, generally skin infections • Nafcillin has hepatobiliary elimination

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Amino Penicillins (ampicillin, amoxicillin)

• Spectrum: Streptococcal species, Enterococci, Listeria, Enterobacteriaceae, Borrelia burgdorferi, Helicobacter pylori • Indications: respiratory tract infections, Lyme, GI ulcers – H. pylori, endocarditis prophylaxis • Mononucleosis – maculopapular rash – no urticaria

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• Spectrum: extended gram-negative coverage including Pseudomonas aeruginosa • Indications: infections in hospitalized patients • Intravenous only – inpatient treatment

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Penicillin + Beta-lactamase Inhibitors

• Agents: oral - amoxicillin/clavulanate (Augmentin), IV - ampicillin/sulbactam (Unasyn), piperacillin/tazobactam (Zosyn), ticarcillin/clavulanate (Timentin) • Spectrum: extends spectrum to beta-lactamase producing organisms (eg, S. aureus, Haemophilus, Neisseria, Moraxella, Bacteroides, Enterobacteriaceae) • Indications: Augmentin - respiratory tract infections, animal bites, skin infections and Others - serious infections • AE: clavulanatediarrhea

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Cephalosporins

• MOA: beta-lactams, inhibit cell wall synthesis • Spectrum: gram-positive, gram-negative •1st, 2nd, 3rd, 4th, 5th generation • Mostly renal elimination • AEs: hypersensitivity (cross -sensitivity with penicillin), GI, hematologic, serum sickness • Drug interactions: some have decreased absorption with decreased GI acidity

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First Generation Cephalosporins

• Oral: cephalexin (Keflex), cephradine (Velosef), cefadroxil (Duricef) • Parenteral: cefazolin (Ancef, Kefzol) • Spectrum: gram-positives (staph and strep), limited gram- negatives, oral anaerobes • Indications: alternative for staphylococcal (MSSA) and streptococcal infections, surgical prophylaxis

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Second Generation Cephalosporins

• Oral: cefaclor (Ceclor), cefprozil (Cefzil), cefuroxime (Ceftin) • Parenteral: cefuroxime (Zinacef), cefoxitin (Mefoxin), cefotetan (Cefotan) • Spectrum: MSSA, S pneumoniae, S pyogenes, H influenzae, Proteus, Moraxella catarrhalis, Borrelia burgorferi – less gram-positive and more gram-negative than first generation – anaerobes – some cover B. fragilus (cefoxitin, cefotetan) • Indications: respiratory tract infections, UTIs, Lyme, skin infections, surgical prophylaxis

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Second Generation Cephalosporins

• Cefaclor – serum sickness

• Methylthiotetrazole (MTT) side chain – cefotetan - hypothrombinaemia, alcohol intolerance (flushing, tachycardia, N/V, hypotension, dyspnea)

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Third Generation Cephalosporins

• Oral: cefixime (Suprax), cefpodoxime (Vantin), cefdinir (Omnicef), ceftibuten (Cedax), cefditoren (Spectracef) • Parenteral: ceftriaxone – IV and IM (Rocephin), ceftazidime (Fortaz or Tazicef), cefotaxime (Claforan) • Spectrum: less gram-positive and more gram-negative (H influenzae, E coli, Moraxella catarrhalis, Proteus, Klebsiella) than first and second generation, ceftriaxone – Borrelia burgdorferi – P. aeruginosa: ceftazidime • Indications: respiratory tract infections, UTIs, meningitis (ceftriaxone, cefotaxime), gonorrhea (ceftriaxone + azithromycin or doxycycline) • Ceftriaxone has hepatobiliary elimination

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Fourth/Fifth Generation Cephalosporins

• Cefepime (Maxepime) – parenteral – gram-positive and gram-negative activity – increased stability to beta-lactamases and activity against Pseudomonas aeruginosa

• Ceftaroline (Teflaro)- parenteral – gram-positive and gram-negative activity – activity against MRSA and resistant S. pneumoniae – no activity against Pseudomonas aeruginosa or extended spectrum beta-lactamases

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Cephalosporin + Beta-lactamase Inhibitors

• Agents: ceftazidime and avibactam (Avycaz), ceftolozane + tazobactam (Zerbaxa) • Spectrum = ceftazidime gram-negative coverage + coverage for beta-lactamase producing organisms – includes Pseudomonas aeruginosa • Indications: Complicated intra-abdominal infections and urinary tract infections • AEs: GI effects

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Third Generation Cephalosporins

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Monobactam

• Aztreonam (Azactam)– parenteral • MOA: inhibits cell wall synthesis • Spectrum: aerobic gram-negative only including Pseudomonas aeruginosa • Indications: alternative agent • AEs: limited risk of cross-reactivity, GI

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Carbapenems

• Agents: imipenem (Primaxin), meropenem (Merrem), ertapenem (Invanz), doripenem (Doribax) – all parenteral • MOA: inhibits cell wall synthesis • Spectrum: very broad, includes gram-positives, gram- negatives, anaerobes – Ertapenem has narrower spectrum – no Pseudomonas – Coverage includes extended spectrum beta-lactamase (ESBL) producing organisms • AEs: hypersensitivity (cross-reactivity with penicillins), GI, seizures, hypotension

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Fluoroquinolones

• norfloxacin (Noroxin) • ciprofloxacin (Cipro) • ofloxacin (Floxin) • levofloxacin (Levaquin) • gemifloxacin (Factive) • moxifloxacin (Avelox)

*Oral and parenteral agents *Renal and hepatic elimination

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Fluoroquinolones

• MOA: bind to and inhibit topoisomerases II & IV • Good tissue penetration • Spectrum: gram-positives (issues of resistance), gram- negatives (cipro & levo - P. aeruginosa, gonorrhea resistance), atyp icals ( chlamy dia , my cop lasma), some have anaerobic coverage – moxifloxacin • Resistance: modified DNA gyrase • Concentration-dependent efficacy and post-antibiotic effect • Indications: respiratory tract infections, skin infections (newer agents), UTIs, anthrax, GI infections (Salmonella, Shigella, Traveler’s diarrhea)

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Fluoroquinolones - Adverse Events

•GI • CNS – headache, peripheral neuropathy • Cartilage toxicity (no peds) • Tendinitis and tendon rupture – black box warning • Phot osensiti vity it • QT prolongation • Hypo/hyperglycemia •Rash • Exacerbation of myasthenia gravis • Increased liver function tests

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Fluoroquinolones - Drug Interactions

• Divalent/trivalent cations - chelation • Drugs affecting QT interval • Drugs affecting blood glucose • Theophylline • Warfarin

9 PANCE/PANRE Review Course Macrolides • Agents: erythromycin, clarithromycin (Biaxin), azithromycin (Zithromax) • oral/parenteral • MOA: inhibit protein synthesis • Spectrum: – gram-pp,ositives, including Stappyhylococcus aureus , S pneumonia , and S pyogenes, C&E>A, some staphylococcal and pneumococcal resistance – some gram-negatives including H. pylori, H influenzae, Moraxella catarrhalis, Legionella, A>C>E, none have activity against Pseudomonas or Enterobacteriaceae) – atypicals (mycoplasma, Chlamydophila pneumonia, Chlamydia trachomatis, Treponema pallidum) • Indications: respiratory tract infections (CAP), GI ulcers (clarithro), MAC (azithro & clarithro), chlamydia STDs, skin infections

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Macrolides

• Azithromycin half-life = 2-4 days • Hepatic elimination • AEs: GI (stimulates GI motility), ototoxicity, prolong QT, cholestatic jaundice (erythro), metallic taste (clarithromycin), phlebitis (erythro) • Drug Interactions: inhibit cytochrome P450

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Ketolides (telithromycin - Ketek)

• MOA: protein synthesis inhibitor • Spectrum: gram-positive, gram-negatives, atypicals, some anaerobes • AEs: hepatic dysfunction (contraindicated in peds), contraindicated in patients with myastenia gravis, GI, vision problems, QT prolongation • Drug Interactions: inhibits cytochrome P450

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Tetracyclines (tetracycline, doxycycline, minocycline)

• MOA: protein synthesis inhibitors • Spectrum: Propionibacterium acnes, H. pylori, Rickettsia, Chlamydia, Mycoplasma, Borrelia burfdorferi, Treponema pallidum, community-acquired MRSA, Streptococcus pneumoniae (resistance issues) • Indications: acne, respiratory tract infections (including community-acquired pneumonia), Lyme, GI ulcers (tetracycline), Rocky Mountain Spotted Fever, chlamydia, community-acquired MRSA • Mostly hepatic elimination

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• AEs: photosensitivity, deposition in teeth and bones (no peds & pregnancy), GI, vestibular reactions (minocycline), hepatotoxicity • Drug Interactions: chelation with divalent and trivalent cations, oral contraceptives, warfarin

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Glycylcyclines (tigecycline-Tygacil)

• Parenteral • MOA: protein synthesis inhibitor • Spectrum: gram-positive (including MRSA), gram-negatives, anaerobes, atypicals • Indications: alternative agent • AEs: GI, photosensitivity, tooth discoloration (no peds or pregnancy)

11 PANCE/PANRE Review Course Aminoglycosides (gentamicin, tobramycin, amikacin) • Parenteral • MOA: protein synthesis inhibitors • Spectrum: aerobic gram-positives and gram-negatives (P. aeruginosa) • Concentration dependent efficacy and post -antibiotic effect • Indications: generally gram-negative infections in hospital • Synergy with beta-lactams • AEs: nephrotoxicity, ototoxicity, neuromuscular blockade (myasthenia gravis) • Renally excreted • Monitor serum concentrations

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Sulfonamides

• MOA: inhibit folic acid synthesis • Spectrum: gram-positive (Staphylococcus aureus, Streptococcus pneumoniae) and gram-negative (H. influenzae, Moraxella catarrhalis, E coli, Proteus) Pneumocystic jiroveci • Indications: trimethoprim/sulfamethoxazole (TMP/SMX [Bactrim, Septra]): respiratory tract infections, UTIs, PCP, community-acquired MRSA • AEs: GI, hypersensitivity (includes Stevens Johnson Syndrome), bone marrow suppression, photosensitivity • DIs: oral contraceptives, warfarin, sulfonylureas

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Metronidazole (Flagyl) Tinidazole (Tindamax)

• Oral/parenteral • Spectrum: anaerobes (Bacteroides, C. difficile) and parasites (Trichomonas, Giardia, Entamoeba), H. pylori • IditiGIiftiIndications: GI infections, gynecol liliftiogical infections, trichomoniasis • Hepatic elimination • AEs: metallic taste, GI, CNS, dark urine • Drug Interactions: warfarin • Alcohol intolerance (flushing, tachycardia, N/V, hypotension, dyspnea)

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Fidaxomicin (Dificid)

•Oral • MOA: inhibits protein synthesis • Spectrum: Clostridium difficile • Not systemically absorbed • AEs: nausea, vomiting

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Clindamycin

• MOA: inhibit protein synthesis • Spectrum: gram positive and anaerobes • MRSA – community-acquired • Hepatic elimination • Alternative agent in penicillin allergic patients • AEs: GI – pseudomembranous colitis

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Rifampin

• MOA: inhibits RNA synthesis • Indications: TB, eradication of nasal carriage of H. flu, Meninogococcus, Staphylococcus, additional agent for resistant infections • Hepatic elimination • AEs: orange-red body fluids, hepatotoxicity, GI, flu-like symptoms • Drug Interactions: induces cytochrome P450

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Methicillin-Resistant Staphylococcus aureus (MRSA)

• Vancomycin • Linezolid (Zyvox) and Tedizolid (Sivextro) - oral • Dalfprostin/quinupristin (Synercid) • Daptomycin (Cubicin) • Lipoglycopeptides: telavancin (Vibativ), oritavancin (Orbactiv), dalbavancin (Dalvance) • Others: tigecycline, ceftaroline • Community: clindamycin, tetracycline , trimethoprim/sulfamethoxazole- oral

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Vancomycin

• Inhibits cell wall synthesis – binds to peptidoglycan precursor and prevents cross-linking of peptidoglycan strands (different than beta-lactams) • Parenteral: MRSA – drug of choice, also other staph and strep infections and Enterococcus faecalis • Oral – not absorbed - C. difficile treatment • Renal excretion • AEs: red man’s syndrome, thrombophlebitis, nephrotoxicity, ototoxicity • Monitor serum concentrations – trough concentrations – 10-20 mg/L

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Oxazolidinones

• Linezolid (Zyvox) and Tedizolid (Sivextro) • Oral/Parenteral • Inhibit protein synthesis • MRSA, enterococci, streptococci • AEs: myelosuppression (monitor CBC), GI, headache, neuropaththy • Drug interactions: – Linezolid inhibits monoamine oxidase (MAO) – avoid tyramine (aged cheese, sausage, beer), selective seretonin reuptake inhibitors (SSRIs), pseudoephedrine, tricyclic antidepressants, bupropion, sumatriptin, beta2 agonists, sympathomimetics, tryptophan, ginseng, dopamine, dobutamine, sibutramine

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Lipoglycopeptides • Telavancin (Vibativ), Oritavancin (Orbactiv), Dalbavancin (Dalvance) • All parenteral only • Vancomycin derivatives • Spectrum: MRSA, streptococci, enterococci • Dalbavancin – 2 doses one week apart • Oritavancin – single dose • AEs: nausea, vomiting, headache, diarrhea, infusion reactions – taste disturbances, QT prolongation, foamy urine, and nephrotoxicity with telavancin • DIs - CYP450 - oritavancin - warfarin (CYP2D6) • Coagulation test interference: telavancin and oritavancin

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Methicillin-Resistant Staphylococcus aureus (MRSA)

• Dalfprostin/quinupristin (Synercid) – IV – AEs: arthralgias, rash, hyperbilirubinemia, N/V, headache – Inhibits CYP450

• Daptomycin (Cubicin) – IV – AEs: increased CPK (monitor weekly), GI, CNS

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UTIs

• Nitrofurantoin •Fosfomycin • Methenamine • All have some GI effects

• Generally recommended treatment for uncomplicated UTI is trimethoprim/sulfamethoxazole

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Herpes Viruses

• acyclovir (Zovirax), famciclovir (Famvir), valacyclovir (Valtrex) • Herpes simplex (first episode, treatment/suppression of recurrences, decrease transmission) • Herpes zoster – varicella (speed healing, decrease pain & neuralgia) • Severe infectionacyclovir • AEs: GI, headache

PANCE/PANRE Review Course Influenza • Zanamivir (Relenza – inhaled), oseltamivir (Tamiflu - oral), peramivir (Rapivab - IV) – Influenza A and B treatment (w/in 2 d) and prevention – Influenza A resistance to oseltamivir – Zanamivir – bronchospasm – Oseltamivir – nausea, vomiting, HA – Peramivir – diarrhea

• Amantadine and rimantadine – Influenza A treatment and prevention (due to resistance issues not currently recommended) – AEs: GI, CNS (less with rimantadine)

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Cytomegalovirus (CMV)

• Ganciclovir (Cytovene), valganciclovir (PO, Valcyte) – bone marrow suppression • Foscarnet (Foscavir) –nephrotoxicity, electrolyte disorders, bone marrow suppression • Cidofovir (Vistide) – nephrotoxicity, neutropenia • Fomivirsen (Vitravene) – ocular toxicity

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Hepatitis B

• Preferred Agents: – Nucleos(t)ide analogues: (entecavir [Baraclude], tenofovir [Viread]) – Interferon, pegylated interferon

• Nonpreferred treatments: lamivudine, adefovir, telbivudine, emtricitabine

• All treatment decrease HBV DNA levels and have been associated with HBeAG loss/seroconversion, decreases in ALT, and improvements in liver histology

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Hepatitis B

• Nucleos(t)ide analogues (oral) – Greater and faster decline in HBV DNA levels than with interferon – Long-term treatment required – Resistance issues (low with tenofovir and entecavir) – Minimal side effects – HA, GI

• Interferon (SC) – 16 – 48 weeks treatment duration – AEs: many, including flu-like symptoms, bone marrow suppression, and psychiatric symptoms

PANCE/PANRE Review Course Hepatitis C – Initial Treatment - Directly acting antivirals • Genotype 1a – Ledipasvir/Sofosobuvir (Harvoni) – Ombitasvir/Paritaprevir/Ritonavir/ Dasabuvir (Viekira Pak) + Ribavirin – Simeprevir (Olysio) + Sofosobuvir (Sovlaldi) +/- ribavirin • Genotype 1b – Ledipasvir/Sofosobuvir (Harvoni) – Simeprevir (Olysio) + Sofosobuvir (Sovaladi) – Ombitasvir/Paritaprevir/Ritonavir/ Dasabuvir (Viekira Pak) +/- ribavirin • Genotype 2 – Sofosobuvir (Sovaldi) + ribavirin • Genotype 3 – Sofosobuvir (Sovaldi) + ribavirin

http://www.hcvguidelines.org

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Hepatitis C – Adverse events • Sofosobuvir (Sovaldi): fatigue, headache, nausea • Simeprevir (Olysio) + sofosobuvir (Sovaldi): fatigue, headache, nausea, insomnia, pruritus, rash, photosensitivity • Ombitasvir/paritaprevir/ritonavir/ dasabuvir (Viekira Pak): skin reac ti on s, in somni a, asth eni a, irrit abilit y, f ati gue, pruritus, nausea, increased bilirubin and LFTs, anemia (contraindications due to drug interactions) • Ledipasvir/sofosobuvir (Harvoni): fatigue, headache, nausea, diarrhea, insomnia • Ribavirin: anemia, teratogen

• Multiple drug interactions (CYP450, acid suppressiondecreases absorption)

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Antifungals

• Polyenes: amphotericin – wide spectrum • Azoles: ketoconazole (Nizoral), fluconazole (Diflucan), itraconazole (Sporonax), voriconazole (Vfend), posaconazole (Noxafil) – spectrum varies from one agent to the other • Terbinafine (Lamisil) – dermatophyte infections • Flucytosine – only as part of combination therapy • Echinocandins: caspofungin (Cancidas), micafungin (Mycamine), anidulafungin (Eraxis) – candida and aspergillosis

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Antifungals – Adverse Events

• Amphotericin: nephrotoxicity, electrolyte disorders, anemia, flu-like symptoms • Azoles: hepatotoxicity, QT prolongation, ketoconazole- decreased cortisol & testosterone, voriconazole-vision • Terbinafine: hepatotoxicity • Echinocandins: histamine-mediated reactions, hepatotoxicity, GI, HA, fever, phlebitis, hypokalemia, bone marrow suppression • Griseofluvin: GI, HA, hepatotoxicity • Flucytosine: bone marrow suppression, GI, hepatitis

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Antifungals – Important Drug Interactions

• Azoles inhibit cytochrome P450 • Ketoconazole & itraconazole require GI acidity for absorption • Rifampin increases clearance of azoles

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Bugs and Drugs

• Methicillin sensitive Staphylococcus aureus (MSSA): penicillinase-resistant penicillin (eg, nafcillin, dicloxacillin), first-generation cephalosporin • MRSA serious: vancomycin • MRSA outppy,y,atient: clindamycin, tetracycline, linezolid • Streptococcus pyogenes: penicillin or amoxicillin, first generation cephalosporin – penicillin allergic – clindamycin or macrolide • Streptococcus pneumoniae – outpatient infections – penicillin V, amoxicillin, cephalosporins, macrolides

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Bugs and Drugs

• Haemophilus influenzae and Moraxella catarrhalis: second or third generation cephalosporin, amoxicillin + clavulanic acid • Pseudomonas aeruginosa – – Oral: ciprofloxacin and levofloxacin – Intravenous: ticarcillin, piperacillin, ceftazidime, cefepime, aztreonam, aminoglycosides, carbapenems (except ertapenem), ceftolozane + tazobactam

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Bugs and Drugs

• Neisseria gonorrhoeae: ceftriaxone + azithromycin or doxycycline • Neisseria meningitis: ceftriaxone, cefotaxime • Clostridium difficile: metronidazole, vancomycin, fidaxomicin • Chlamydia: azithromyyyycin and doxycycline • Mycoplasma pneumoniae: macrolide or tetracycline • Borrelia burgdorferia (Lyme): doxycycline, amoxicillin, cefuroxime axetil • Treponema pallidum (Syphilis): penicillin G, benzathine penicillin • Helicobacter pylori: proton pump inhibitor + clarithromycin + amoxicillin or metronidazole

PANCE/PANRE Review Course Antibiotic Adverse Events Highlights

• Photosensitivity – SMP/TMX, tetracyclines, fluoroquinolones, tigecycline, hepatitis C treatments • Rash – multiple agents (fluoroquinolones*) • QT prolongation – macrolides, fluoroquinolones, telithromycin, lipoglycopeptides • Infusion reactions – vancomycin, lipoglycopeptides • Nephrotoxicity – vancomycin, aminoglycocides, amphotericin, penicillins, tetracycline (outdated), foscarnet, cidofovir • Hepatotoxicity – antifungals • Ototoxicity – aminoglycosides, minocycline (vestibular), amphotericin

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Adverse Events Highlights

• Seizures – penicillin, fluoroquinolones, carbapenems • Mononucleosis – erythematous rash – amoxicillin • Bone marrow suppression – sulfamethoxazole/trimethoprim, linezolid, ganciclovir, foscarnet, interferon, flucytosine • Clostridium difficile infections – all (clindamycin*) • GI – multiple agents (clavulanate*)

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Adverse Events Highlights

• Taste disturbance – clarithromycin, metronidazole, tinidazole, telavancin • Tendonitis – fluoroquinolones • Orange-red fluids – rifampin • Discolored teeth and bone deposits - tetracyclines • Contraindicated in pediatrics and pregnant women- tetracyclines, fluoroquinolones, tigecycline, telithromycin • Contraindicated in neonates: sulfa agents • Teratogen - ribavirin

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Drug Interactions Highlights

• Macrolides, dalfopristin/quinupristin, telithromycin , azole antifungals – inhibit cytochrome P450 • Rifampin – induces cytochrome P450 • Fluoroquinolones and tetracyclines – chelated by divalent andtid triva len t ca tions • Linezolid – monoamine oxidase inhibitors • Alcohol – disulfuram reaction (headache, tachycardia, flushing, GI) - metronidazole, cefotetan • Hepatitis C and HIV treatments – multiple cytochrome P450 interactions • Decrease in GI acidity decreases absorption of some azoles and some antivirals (hepatitis C and HIV)

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