2015 ANTIMICROBIAL OVERVIEW -...

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Antimicrobial Overview June 2015

Rutgers, The State University of New Jersey

Laureen A. Klein, Pharm.D.

PANCE/PANRE Review Course

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


Aerobic Gram-Positive Bacteria

• Streptococcus

• Staphylococcus

• Enterococcus

• Cornybacterium

• ListeriaListeria

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Aerobic Gram-Negative Bacteria

• Enterobacteriaceae (E. coli, Klebsiella, Enterobacter, Citrobacter, Proteus, Serratia, Salmonella, Shigella, Morganella, Providencia)

• Pseudomonas• Helicobacter• Haemophilus• Haemophilus• Legionella• Moraxella• Neisseria


Anaerobic Bacteria

• Gram-Positive• Peptococcus

• Peptostreptococcus

• Clostridia

• Propionibacterium acnes

• Gram-Negative• Bacteroides

• Fusobacterium

• Propionibacterium acnes


Atypicals

• Chlamydia

• Chlamydophila

• Rickettsiae

• Mycoplasma

• Spirochetes (Syphilis, Lyme disease)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 metronidazoleaminoglycosides, tetracyclines, metronidazole, dalfopristin/quinupristin, oxazolidinones (linezolid, tedizolid), clindamycin

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


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


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 resistantresistant to all beta lactams• If methicillin resistant resistant to all beta-lactams

except ceftaroline• Indications: sensitive staphylococcal infections, generally

skin infections• Nafcillin has hepatobiliary elimination


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


Extended-Spectrum Penicillins(piperacillin, ticarcillin)

• Spectrum: extended gram-negative coverage including Pseudomonas aeruginosa

• Indications: infections in hospitalized patients

• Intravenous only – inpatient treatment y p

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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: clavulanatediarrhea


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,AEs: hypersensitivity (cross sensitivity with penicillin), GI, hematologic, serum sickness

• Drug interactions: some have decreased absorption with decreased GI acidity


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• 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


Second Generation Cephalosporins

• Cefaclor – serum sickness

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


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


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


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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Monobactam

• Aztreonam (Azactam)– parenteral

• MOA: inhibits cell wall synthesis

• Spectrum: aerobic gram-negative only including Pseudomonas aeruginosa

• Indications: alternative agentg

• AEs: limited risk of cross-reactivity, GI


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– Ertapenem has narrower spectrum – no Pseudomonas– Coverage includes extended spectrum beta-lactamase (ESBL)

producing organisms

• AEs: hypersensitivity (cross-reactivity with penicillins), GI, seizures, hypotension


Fluoroquinolones

• norfloxacin (Noroxin)

• ciprofloxacin (Cipro)

• ofloxacin (Floxin)

• levofloxacin (Levaquin)

• gemifloxacin (Factive)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), atypicals (chlamydia, mycoplasma), some have ), yp ( y , y p ),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)


Fluoroquinolones - Adverse Events

• GI

• CNS – headache, peripheral neuropathy

• Cartilage toxicity (no peds)

• Tendinitis and tendon rupture – black box warning

Ph t iti it• Photosensitivity

• QT prolongation

• Hypo/hyperglycemia

• Rash

• Exacerbation of myasthenia gravis

• Increased liver function tests


Fluoroquinolones - Drug Interactions

• Divalent/trivalent cations - chelation

• Drugs affecting QT interval

• Drugs affecting blood glucose

• Theophylline

• WarfarinWarfarin

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Macrolides• Agents: erythromycin, clarithromycin (Biaxin), azithromycin

(Zithromax)

• oral/parenteral

• MOA: inhibit protein synthesis

• Spectrum: – gram-positives, including Staphylococcus aureus, S pneumonia, g p , g p y , p ,

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


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


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 prolongationproblems, 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)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


Tetracyclines

• 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


Glycylcyclines (tigecycline-Tygacil)

• Parenteral

• MOA: protein synthesis inhibitor

• Spectrum: gram-positive (including MRSA), gram-negatives, anaerobes, atypicals

• Indications: alternative agentg

• AEs: GI, photosensitivity, tooth discoloration (no peds or pregnancy)

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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• 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


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


Metronidazole (Flagyl)Tinidazole (Tindamax)

• Oral/parenteral

• Spectrum: anaerobes (Bacteroides, C. difficile) and parasites (Trichomonas, Giardia, Entamoeba), H. pylori

I di ti GI i f ti l i l i f ti• Indications: GI infections, gynecological infections, trichomoniasis


• 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, vomitingAEs: nausea, vomiting


Clindamycin

• MOA: inhibit protein synthesis

• Spectrum: gram positive and anaerobes

• MRSA – community-acquired


• Alternative agent in penicillin allergic patientsAlternative agent in penicillin allergic patients

• AEs: GI – pseudomembranous colitis


Rifampin

• MOA: inhibits RNA synthesis

• Indications: TB, eradication of nasal carriage of H. flu, Meninogococcus, Staphylococcus, additional agent for resistant infections


• 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


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 treatmentOral not absorbed C. difficile treatment• Renal excretion• AEs: red man’s syndrome, thrombophlebitis, nephrotoxicity,

ototoxicity• Monitor serum concentrations – trough concentrations –

10-20 mg/L


Oxazolidinones

• Linezolid (Zyvox) and Tedizolid (Sivextro)• Oral/Parenteral• Inhibit protein synthesis• MRSA, enterococci, streptococci• AEs: myelosuppression (monitor CBC), GI, headache,

thneuropathy• 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• 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


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


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 infectionacyclovir• Severe infectionacyclovir• AEs: GI, headache


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 HAOseltamivir 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)


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


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


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 reactions, insomnia, asthenia, irritability, fatigue, s eac o s, so a, as e a, ab y, a 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 suppressiondecreases absorption)


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• Terbinafine (Lamisil) – dermatophyte infections• Flucytosine – only as part of combination therapy• Echinocandins: caspofungin (Cancidas), micafungin

(Mycamine), anidulafungin (Eraxis) – candida and aspergillosis


Antifungals – Adverse Events

• Amphotericin: nephrotoxicity, electrolyte disorders, anemia, flu-like symptoms

• Azoles: hepatotoxicity, QT prolongation, ketoconazole-decreased cortisol & testosterone, voriconazole-vision

• Terbinafine: hepatotoxicityTerbinafine: 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


Bugs and Drugs

• Methicillin sensitive Staphylococcus aureus (MSSA): penicillinase-resistant penicillin (eg, nafcillin, dicloxacillin), first-generation cephalosporin

• MRSA serious: vancomycin

• MRSA outpatient: clindamycin, tetracycline, linezolid p y , y ,

• Streptococcus pyogenes: penicillin or amoxicillin, first generation cephalosporin

– penicillin allergic – clindamycin or macrolide

• Streptococcus pneumoniae – outpatient infections –penicillin V, amoxicillin, cephalosporins, macrolides


Bugs and Drugs

• Haemophilus influenzae and Moraxella catarrhalis: second or third generation cephalosporin, amoxicillin + clavulanic acid

• Pseudomonas aeruginosa –

– Oral: ciprofloxacin and levofloxacinp

– 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: azithromycin and doxycycliney y y y

• 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


Antibiotic Adverse Events Highlights

• Photosensitivity – SMP/TMX, tetracyclines, fluoroquinolones, tigecycline, hepatitis C treatments

• Rash – multiple agents (fluoroquinolones*)

• QT prolongation – macrolides, fluoroquinolones, telithromycin lipoglycopeptidestelithromycin, lipoglycopeptides

• Infusion reactions – vancomycin, lipoglycopeptides

• Nephrotoxicity – vancomycin, aminoglycocides, amphotericin, penicillins, tetracycline (outdated), foscarnet, cidofovir

• Hepatotoxicity – antifungals

• Ototoxicity – aminoglycosides, minocycline (vestibular), amphotericin


Adverse Events Highlights

• Seizures – penicillin, fluoroquinolones, carbapenems

• Mononucleosis – erythematous rash – amoxicillin

• Bone marrow suppression –sulfamethoxazole/trimethoprim, linezolid, ganciclovir, foscarnet interferon flucytosinefoscarnet, 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 - tetracyclinesp y

• Contraindicated in pediatrics and pregnant women-tetracyclines, fluoroquinolones, tigecycline, telithromycin

• Contraindicated in neonates: sulfa agents

• Teratogen - ribavirin


Drug Interactions Highlights

• Macrolides, dalfopristin/quinupristin, telithromycin , azole antifungals – inhibit cytochrome P450

• Rifampin – induces cytochrome P450

• Fluoroquinolones and tetracyclines – chelated by divalent d t i l t tiand trivalent cations

• 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)


Thank you!Thank you!

2015 ANTIMICROBIAL OVERVIEW -...

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