Advanced Pharmacology Drugs for Bacterial Infections Handout Samples/Advanced... · 1 Unit 9 ©2014 Barkley & Associates Advanced Pharmacology Drugs for Bacterial Infections Thomas

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Unit 9 ©2014 Barkley & Associates

Advanced PharmacologyDrugs for Bacterial Infections

Thomas W. Barkley, Jr., PhD, ACNP‐BC, FAANPPresident, Barkley & Associates

www.NPcourses.comand

Professor of NursingDirector of Nurse Practitioner ProgramsCalifornia State University, Los Angeles

Robert Fellin, PharmD, BCPSFaculty, Barkley & Associates

Pharmacist, Cedars‐Sinai Medical CenterLos Angeles, CA


Pathogenicity and VirulencePathogen: organism capable of causing disease Viruses, bacteria, fungi, unicellular organisms, etc. To infect humans, pathogens must bypass a number of elaborate body

defenses Entrance may include broken skin, ingestion, inhalation or contact with

mucous membranes such as nasal, urinary or vaginal mucosaPathogenicity: ability of an organism to cause infection Only a few dozen pathogens cause disease in humansVirulence: microbe that can produce disease when present in minute numbersPathogens cause disease by one of two basic mechanisms:1. Invasiveness: ability to grow rapidly & cause damage by sheer number2. Production of toxins

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Describing/Classifying Bacteria1. Microscopic Evaluation: after crystal violet Gram stain is applied Gram positive bacteria: thick cell wall; retain purple color after

stainingo Staphylococcuso Streptococcio Enterococci

Gram negative bacteria: thin cell walls; does not retain violet staino Bacteroideso Escherichia colio Klebsiellao Pseudomonaso Salmonella


Describing/Classifying Bacteria

2. Cellular Shape Bacilli: rod shaped Cocci: spherical shaped Spirilla: spiral shaped

3. Ability to Use Oxygen Aerobic: bacteria that thrive on an oxygen-rich environment Anaerobic: those that thrive best without oxygen

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Actions of Anti-infective Drugs Bactericidal agents: kill bacteria

Bacteriostatic agents: slow the growth of bacteria

Bacterial cells are quite different from human cells

o Bacteria have cell walls

o Use different biochemical pathways

o Contain certain enzymes that human cells lack

Antibiotics exert selective toxicity on bacterial cells by targeting these differences

Thus, bacteria can either be killed or their growth severely hampered without major effects on human cells


Acquired Resistance Microorganisms have the ability to replicate rapidly

During cell division, bacteria make frequent errors in duplicating their genetic code (mutations)

Mutations occur spontaneously and randomly throughout the ribosomal chromosome

Although most mutations are harmful to the organism, mutations occasionally result in a bacterial cell that has reproductive advantages over its neighbors

The mutated bacterium may be able to survive in harsher conditions or perhaps grow faster than other cells

Mutations that are of particular importance to medicine are those that confer drug resistance to a microorganism

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Acquired Resistance Antibiotics promote the development of drug-resistant bacterial

strains

Killing populations of bacteria that are sensitive to the drug leaves behind those microbes that possess mutations that made them insensitive to the effects of the antibiotic

Drug-resistant bacteria are then free to grow, unrestrained by their neighbors that were killed by the antibiotic, and the patient develops an infection that is resistant to conventional drug therapy = acquired resistance


Acquired Resistance Inevitable consequence of antimicrobial usage is the selection of

resistant microorganisms

Overuse and inappropriate use of antibiotics has fueled a major increase in prevalence of multidrug-resistant pathogens

Bacteria become resistant, not patients

Application of infection control procedures and teaching methods of proper hygiene for prevent transmission

Prudent use of antibiotics is critical to future antibiotic efficacy

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STOP Antimicrobial Resistance Does my patient still need antibiotics?

Have I chosen the most appropriate agent?

What is the duration of therapy?

Can we switch to an oral antibiotic?

Get help from the experts (infectious disease MD/NP/Rx)

WASH YOUR HANDS


General Approach to Manage Infections Establish Presence of Infection

o Signs and symptoms: increased WBC, fever, infiltrates on chest x-ray, erythema, pus, secretions

Establish Severity of Infection

o Age of patient, immune status, comorbidities

Establish Site of Infection

o Respiratory, skin, blood, IV line, urine

Determine Likely Pathogen

o Based on site and/or patient factors

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Antibiotic Selection Broad-spectrum antibiotics: antibacterials effective against many

different species of pathogens

Narrow-spectrum antibiotics: antibacterials effective against only one or a restricted group of microorganisms

Optimally, laboratory tests should identify the specific pathogen prior to initiating anti-infective therapy

o Urine, stool, blood, spinal fluid, sputum, purulent drainage, etc.

Culture and sensitivity: process of growing the pathogen and identifying the most effective antibiotic to treat


Natural PenicillinsAgents: Penicillin G, Penicillin V (Pen V, Pen-VK)

MOA: Binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis

Spectrum: Against gram positive, less active against gram negative, limited anaerobic activity

Adverse

Effects:

Hypersensitivity reactions, rash, phlebitis, diarrhea, GI upset, sodium/potassium overload, renal dysfunction, C. difficile, seizures, fever, thrombocytopenia

Comments: Anaphylaxis: 0.04% to 2%Streptococcal, meningococcal infections and neurosyphilisUsed infrequently due to resistanceShould be given 1-2 hours before or after meals

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Anti-Staphylococcal PenicillinsAgents: nafcillin (Nafcil), dicloxacillin (Dynapen), oxacillin


Spectrum: Beta-lactamase producing Staph (usually limited to treatment of these bacteria); less active than natural penicillins against gram positive, no gram negative or anaerobic activity

Adverse

Effects:


Comments: Anaphylaxis: 0.04% to 2%DOC for MSSA infectionsEmpirical use has decreased due to resistance


Amino-PenicillinsAgents: amoxicillin (Amoxil, Trimox), ampicillin (Principen)


Spectrum: Active against many gram negative rods and have the same activity as natural penicillins against gram positive bacteria

Adverse

Effects:


Comments: Anaphylaxis: 0.04% to 2%Adjust dose in renal impairmentAmpicillin: enterococcus infectionsAmoxicillin: CAP, UTI, sinusitis, otitis

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PCN with Beta-Lactamase InhibitorAgents: amoxicillin/clavulanic acid (Augmentin), ampicillin/sulbactam

(Unasyn), piperacillin/tazobactam (Zosyn), ticarcillin/clavulanic acid (Timentin)


Spectrum: Extended-spectrum; active against anaerobes in addition to gram negative and gram positive bacteria

AdverseEffects:


Comments: Anaphylaxis: 0.04% to 2%Pip/tazo: diabetic foot infection, HAPAmp/sulb: animal/human bites, pyelonephritisTicar/clav: second line for Stenotrophomonas


Anti-Pseudomonal Penicillins

Agents: piperacillin (Pipracil), ticarcillin (Ticar)


Spectrum: Active against anaerobes, some gram positive, gram negative as well as Pseudomonas

Adverse

Effects:


Comments: Anaphylaxis: 0.04% to 2%Adjust dose for renal impairmentPiperacillin: on drug shortage listRarely used if availableRequires frequent dosing (q4h)

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First-generation CephalosporinsAgents: cefazolin (Ancef), cephalexin (Keflex), cefadroxil (Duricef)


Spectrum: Very active against gram positive cocci, inactive against enterococci and MRSA; limited activity against gram negative (E. coli, Klebsiella, & Proteus)

Adverse

Effects:

Phlebitis, diarrhea, allergic reactions, rash, C. difficile, seizures, fever, thrombocytopenia

Comments: Cross-reactivity with PCN allergy: 10%Adjust dose for renal impairmentDOC for antibiotic prophylaxis, cellulitisNot for CNS infections


Second-generation CephalosporinsAgents: cefuroxime (Zinacef, Ceftin), cefoxitin (Mefoxin), cefotetan

(Cefotan), cefaclor (Ceclor), cefprozil (Cefzil), loracarbef (Lorabid)


Spectrum: Have extended gram negative coverage and some anaerobic coverage; less coverage against gram positive organisms than first generation

Adverse Effects:

Phlebitis, diarrhea, allergic reactions, rash, C. difficile, seizures, fever, thrombocytopenia, disulfiram reaction (cefotetan)

Comments: Cross-reactivity with PCN allergy: 10%DOC for antibiotic prophylaxis (GI procedures), CAP, abdominal and pelvic infectionsNot for CNS infections

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Third-generation CephalosporinsAgents: cefotaxime (Claforan), ceftriaxone (Rocephin), ceftazidime

(Fortaz), cefpodoxime (Vantin), cefixime (Suprax), cefdinir (Omnicef)


Spectrum: Most of these agents are active against gram positive but less than the first generation cephalosporins; major advantage is their expanded gram negative coverage

Adverse

Effects:


Comments: Cross-reactivity with PCN allergy: 10%DOC for CAP, UTI, meningitis, endocarditisCeftazidime effective vs. Pseudomonal infections


Fourth-generation CephalosporinsAgents: cefepime (Maxipime)


Spectrum: Broad spectrum; active against gram positive and gram negative including pseudomonas, but weakagainst anaerobes

AdverseEffects:


Comments: Cross-reactivity with PCN allergy: 10%Adjust dose for renal impairmentDOC for HAP, neutropenic fever, hospital acquired UTIGreat CNS penetrationCefepime + metronidazole = pip/tazo

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Fifth-generation CephalosporinsAgents: ceftaroline (Teflaro)


Spectrum: Broad spectrum; active against gram positive and gram negative bacteria

Adverse

Effects:


Comments: Cross-reactivity with PCN allergy: 10%Adjust dose for renal impairmentDOC for HAP, neutropenic feverCan be used for CAP, skin/soft tissue infectionsRole in therapy still to be definedGenerally not considered first line agent


MonobactamsAgents: aztreonam (Azactam)


Spectrum: Narrow spectrum; resistant to beta-lactamase producing organisms and are only active against gram negative organisms

Adverse Effects:

Phlebitis, rash, diarrhea, nausea, abnormal LFT’s

Comments: NO cross-reactivity with PCN allergy

No activity against gram positive or anaerobic organisms

Adjust dose for renal impairment

Primarily used as an alternative for PCN allergic patients

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CarbapenemsAgents: imipenem (Primaxin), meropenem (Merrem), doripenem (Doribax),

ertapenem (Invanz)

MOA: binds to receptors (penicillin-binding proteins) on the bacteria’s cell wall which results in cell lysis

Spectrum: extended spectrum antibiotic: gram negative, gram positive and anaerobic coverage

AdverseEffects:

hypersensitivity reactions, rash, phlebitis, renal dysfunction, C. difficile, seizures, fever, thrombocytopenia

Comments: Cross-reactivity with PCN allergy: thought to be fairly high (up to 40%)Not active vs. MRSA,VRE, atypical pathogens or StenotrophomonasErtapenem does NOT cover Pseudomonas, but does still cover ESBLShould NOT be used routinely


MacrolidesAgents: erythromycin, azithromycin (Zithromax), clarithromycin

(Biaxin), fidaxomicin (Dificid)MOA: Inhibit protein synthesis by reversibly binding to the 50S

ribosomal subunit of the bacteria resulting in cell deathSpectrum: Limited gram positive activity, little gram negative activity,

active against Chlamydia and MycoplasmaAdverseEffects:

GI intolerance: diarrhea, nausea, metallic taste (possibly less with azithromycin & clarithromycin), cholestatic hepatitis, rash

Comments: Many drug-drug interactionsDOC for atypical PNA coverageAzithromycin: MAC prophylaxis & treatment, chlamydial infectionsFidaxomicin: Clostridium difficile infection only

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Telithromycin (Ketek) MOA: Similar to that of macrolides, and is related to 50S-ribosomal

subunit binding with inhibition of bacterial protein synthesis

Spectrum: Similar to macrolides, with additional activity against multi-resistant S. pneumoniae (including erythromycin-resistant and penicillin-resistant strains), methicillin-resistant Staphylococcus aureus, H. influenzae, and enterococci

AdverseEffects:

Diarrhea, nausea, vomiting, dizziness, headache, abnormal vision, blurred vision, prolonged QTc interval, Torsade's de pointes, hepatotoxicity

Comments: Many drug-drug interactionsAdjust dose for renal impairmentFDA removed all labeled indications except CAP due to adverse effect profile


TetracyclinesAgents: tetracycline, doxycycline (Vibramycin), minocycline (Minocin)

MOA: Inhibits protein synthesis of bacteria (does not produce cell death, but halts cell reproduction)

Spectrum: Active against gram positive and gram negative as well as anaerobes, mycoplasma, rickettsia, chlamydia

AdverseEffects:

GI intolerance, stains and deforms teeth in children, vertigo, affects bone growth, phlebitis, photo-sensitivity, hepatotoxicity

Comments: Many drug-drug & drug-food (Ca, Fe) interactions DOC for atypical PNA coverage, acneDue to the emergence of resistance these agents have lost most of their usefulnessNOT for CNS infections

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Tetracyclines – continued Contraindicated in children < 8 years of age yellow-brown discoloration

of the teeth

Pregnancy category D effect linear skeletal growth of the fetus and child

Decrease the effectiveness of oral contraceptives

Toxic effects may occur if taken past the expiration date (do not save medication)

Do not take with milk products, Fe supplements, Mg-containing laxatives or antacids

o Wait 1-3 hours before taking antacids; Wait at least 2 hours before taking lipid-lowering drugs such as colestipol (Colestid) and cholestyramine (Questran)

May increase the risk of oral/perineal Candida (?)


AminoglycosidesAgents: gentamicin (Garamycin), tobramycin (Nebcin), amikacin

(Amikin), colistimethate (Colistin), streptomycin

MOA: Inhibits protein synthesis (irreversibly binds to 30S ribosomes) resulting in cell death

Spectrum: Active against gram negative organisms; given in combination with beta-lactam for gram positive synergy (never use alone for the treatment of gram positive infections)

Adverse Effects: Nephrotoxicity, ototoxicity, neuromuscular blockade

Comments: Dose adjusted to achieve therapeutic peak and troughPrimarily administered IV or IMNebulized therapy: tobramycin, amikacin, colistimethate

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SulfonamidesAgents: trimethoprim (Trimpex), trimethoprim/sulfamethoxazole (Bactrim,

Septra)

MOA: Inhibits the conversion of dihydrofolic acid in the bacteria halting reproduction

Spectrum: Inhibits gram positive and gram negative organisms; active against toxoplasma and PCP

Adverse Effects:

Pruritus, photosensitivity, GI intolerance, renal failure, hyperkalemia, bone marrow suppression, SJS

Comments: Combination of trimethoprim and sulfamethoxazole results in bacteria cell deathAdjust dose for renal impairmentPrimary use: UTI, MRSA skin infections, PCP treatment and prophylaxis


FluoroquinolonesAgents: ciprofloxacin (Cipro), levofloxacin (Levaquin), norfloxacin

(Noroxin), moxifloxacin (Avelox), ofloxacin (Floxin)MOA: Inhibits bacterial DNA resulting in cell death in susceptible

organisms Spectrum: Active against gram negative but less active against gram

positive; newer agents have enhanced activity against gram positive and anaerobic organisms

AdverseEffects:

GI intolerance, headache, dizziness, diarrhea, photosensitivity, insomnia, QTc prolongation, damage growing cartilage, tendonitis

Comments: Adjust dose for renal impairmentNOT recommended for patients < 18 years of ageAvoid in pregnancyResistance rates are rising!! (>65%)

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Clindamycin (Cleocin)MOA: Inhibits protein synthesis (50S ribosomal subunit) halting

bacterial reproduction

Spectrum: Active against gram positive and anaerobic organisms only

Adverse

Effects:

Diarrhea (C. difficile), rash, phlebitis, blood dyscrasias, nausea, vomiting, diarrhea, dyspepsia

Comments: Alternative for PCN allergic patients

Can be used for MRSA (confirm with susceptibility)

Surgical prophylaxis for PCN allergic patients


Lincomycin (Lincocin)MOA: Inhibits protein synthesis (50S ribosomal subunit) halting

bacterial reproduction

Spectrum: Active against aerobic and anaerobic gram-positive bacteria, some anaerobic gram-negative bacteria

Adverse

Effects:

Diarrhea (c. difficile), colitis, diarrhea, pruritus, cardiac arrest, cardiac dysrhythmia

Comments: Reserved for serious infections where less toxic antimicrobial agents are inappropriate

Adjust dose in renal/hepatic dysfunction

Only FDA labeled for Staphylococcus aureus, Pneumococcal, Streptococcal infections

BBW: Clostridium difficile infection

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Metronidazole (Flagyl)MOA: causes the formation of toxic metabolites within the

bacterial cell resulting in cell death

Spectrum: active against gram negative anaerobic organisms only

Adverse

Effects:

GI intolerance, metallic taste, headache, peripheral neuropathy, phlebitis, taste disturbances, disulfiram-like reaction w/ EtOH

Comments: Primary uses: anaerobic infections (abscess), aspiration PNA, intra-abdominal infections, vaginitis (trichomonas infection, bacterial vaginosis), infectious diarrhea

DOC for C. difficile


Vancomycin (Vancocin)MOA: Inhibits bacterial cell wall synthesis resulting in cell death

Spectrum: Active against gram positive organisms

Adverse

Effects:

Phlebitis at injection site, “red-man syndrome”, fever, nephrotoxicity, rash

Comments: DOC for MRSA, VAP

Alternative for surgical prophylaxis in PCN allergic patients

Dose adjusted to achieve therapeutic trough


No activity against gram negative or anaerobes

Oral vancomycin for refractory C. difficile colitis

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Quinupristin/Dalfopristin (Synercid) MOA: Synergistic combination that irreversibly binds to separate sites

on the bacteria to inhibit protein synthesis

Spectrum: Active against gram positive organisms,NOT active against E. faecalis

AdverseEffects:

Phlebitis, arthralgias/myalgias, hyperbilirubinemia, nausea, diarrhea, rash

Comments: Drug of last resort!Primary use: VRE, VRSA, alternative to vancomycin for MRSAResistance can occur during treatmentSeveral drug-drug interactionsReduce dose in hepatic impairmentIncompatible with saline solutions


Linezolid (Zyvox) MOA: Inhibition of bacterial protein synthesis. Inhibition of protein

synthesis occurs at a very early stage resulting in a lack of cross-resistance with existing antimicrobials

Spectrum: Active against gram positive organisms

Adverse

Effects:

N/V/D, headache, dizziness, insomnia, rash, thrombocytopenia, myelosuppression (anemia, leukopenia, pancytopenia, and thrombocytopenia)

Comments: Should not be used routinely!

Many drug-drug interactions

No dosage adjustment for hepatic or renal impairment

Primary use: VRE, VRSA, alternative to vancomycin for MRSA

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Daptomycin (Cubicin)MOA: Binds to bacterial cell membranes and causes cell death by

inducing depolarization of the membrane potential, leading to disruption of DNA, RNA and protein synthesis

Spectrum: Active against gram positive organisms; no gram negative activity

Adverse

Effects:

Diarrhea, vomiting, pain in throat, rhabdomyolysis, renal failure, myopathy, asthmatic pulmonary eosinophilia


Should NOT be used for pulmonary infections


Primarily used for vancomycin resistant infections (VRE, VRSA)


Tigecycline (Tygacil)

MOA: Binds to the 30s subunit on the ribosome and interferes with bacterial synthesis (bacteriostatic) glycylcycline, is a derivative of minocycline (tetracyclines)

Spectrum: Broad spectrum: active against gram positive, gram negative, anaerobes and atypical organisms

Adverse

Effects:

Abdominal pain, diarrhea, nausea, vomiting, headache, pancreatitis, elevated LFT’s, anaphylaxis


NO activity against Pseudomonas or Proteus

Adjust dose for hepatic impairment

Primarily reserved for multi-drug-resistant infections (MDR) infections

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Rifaximin (Xifaxan)

MOA: Inhibits bacterial RNA synthesis by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase

Spectrum: Narrow spectrum: active against Escherichia coli

Adverse

Effects:

Peripheral edema, abdominal pain, constipation, defecation urgency, flatulence, nausea, rectal tenesmus, vomiting, ascites,dizziness, headache, fatigue

Comments: Uses: Traveler's diarrhea, hepatic encephalopathyResistance is a concernHepatic encephalopathy: rifaximin may suppress gastrointestinal floraDo not use for infectious diarrhea due to pathogens other than Escherichia coli


Telavancin (Vibativ)MOA: Inhibits bacterial cell wall synthesis and disrupts membrane

barrier functionSpectrum: Narrow spectrum: active against gram positive organisms; NO

gram negative activityAdverseEffects:

Nausea, taste sense altered, vomiting, prolonged QT interval, acute renal failure, increased serum creatinine, hypersensitivity reaction

Comments: Not an agent of first choiceAdjust dose in renal impairmentAvoid use during pregnancy; women of childbearing potential should have a serum pregnancy test prior to administrationBBW: may increase mortality in patients with pre-existing moderate or severe renal impairmentREMS program: avoid exposure during pregnancy

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Urinary AntisepticsAgents: nitrofurantoin (Macrodantin, MacroBid)

MOA: Inactivates/alters bacterial ribosomal proteins and other macromolecules inhibiting the syntheses of bacterial DNA, RNA, cell wall and protein

Spectrum: active against the common gram positive urinary pathogens and has moderate activity against gram negative pathogens

Adverse

Effects:

GI intolerance, rash, peripheral neuropathy

Comments: Exert antimicrobial activity in the urine but have little or no systemic antibacterial effect

Limited to therapy & prevention of uncomplicated UTI’s

Contraindicated in renal impairment


Drugs for Tuberculosis

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Tuberculosis Caused by Mycobacterium tuberculosis

Typically invades the lungs, but may travel to any body system, particularly bone, via the blood or the lymphatic system

The body activates the immune system and attempts to isolate the pathogens by creating a wall around them

Slow-growing mycobacteria usually become dormant, existing inside cavities called tubercles

o May remain dormant (even during an entire lifetime) or reactivate

Two other types of human mycobacteria:

o Mycobacterium leprae – responsible for leprosy

o Mycobacterium avium complex (MAC) – infection in the lungs, commonly observed in AIDS patients; Azithromycin and Clarithromycin used to treat


Differences in TB Drug Therapy3 Differences in Treating TB vs. Other Infections:

1. Mycobacteria have a cell wall that is resistant to penetration by anti-infective drugs For medication to reach the organisms in tubercles, therapy must be for 6

to 12 months2. Pharmacotherapy requires at least three and sometimes four or more

antibiotics administered concurrently Mycobacterium grow slowly and resistance is common Using multiple drugs in different combinations for long periods of time

lowers the potential for resistance and increases the success of therapyo Two broad categories of antitubercular drugs:

First-line agents: safer and generally, the most effective Second-line agents: more toxic, less safe and reserved for when

resistance develops3. TB drugs are used extensively for chemoprophylaxis

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Antituberculosis DrugsAgent Isoniazid Rifampin Pyrazinamide

Drug interactions:

+ +++ -

Adverse Effects:

peripheral neuropathy, hepatitis, skin rashes, fever, arthralgia, hypersensitivity reactions

hepatitis, thrombocytopenia, renal failure, “flu-like” syndrome, cutaneous reactions

hepatitis, fever, skin rashes, arthralgia, GI upset, hyperuricemia

Monitoring: LFT’s LFT’s LFT’s

Comments: Supplement pyridoxine (B6)

Red/orange discoloration of body secretions



Antituberculosis DrugsAgent Ethambutol StreptomycinDrug interactions:

- +

Common

Adverse Effects:

optic neuritis, skin rashes, drug fever, hyperuricemia

vestibular and/or auditory or 8th

nerve dysfunction, renal dysfunction, skin rashes, neuromuscular blockade

Monitoring: Red-green color discrimination and visual acuity

Audiometric and neurologic examination; renal function

Use with caution in renal dysfunction

Comments: Adjust dose for renal impairment


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Antituberculosis DrugsSecond-Line Agents

Amikacin (Amikin)

Capreomycin (Capastat Sulfate)

Ciprofloxacin (Cipro)

Cycloserine (Seromycin)

Ethionamide (Trecator-SC)

Levofloxacin (Levaquin)

Rifabutin (Mycobutin)

Rifapentine (Priftin)


Antituberculosis DrugsAgent: bedaquiline (Sirturo)

MOA: Inhibits mycobacterial ATP synthase which is an enzyme required for the generation of energy

AdverseEffects:

Chest pain nausea, increased liver enzymes, arthralgia, headache, hemoptysis, prolonged QT interval

Comments: Approved only for MDR TB w/ 3 other agentsShould be used only when other effective treatment regimens cannot be offeredNot recommended for drug-sensitive tuberculosis, latent TB or for extra-pulmonary tuberculosisBBW: QT prolongation

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Treatment of TB (without HIV)Preferred Regimen Alternative Regimen Alternative Regimen

Initial PhaseDaily INH, RIF, PZA, and EMB* for 56 doses (8 weeks)

Initial PhaseDaily INH, RIF, PZA, and EMB* for 14 doses (2 weeks), then twice weekly for 12 doses(6 weeks)

Initial PhaseThrice-weekly INH, RIF, PZA, and EMB* for 24 doses(8 weeks)

Continuation PhaseDaily INH and RIF for 126 doses (18 weeks)

orTwice-weekly INH and RIF for 36 doses(18 weeks)

Continuation PhaseTwice-weekly INH and RIF for 36 doses(18 weeks)

Continuation PhaseThrice-weekly INH and RIF for 54 doses (18 weeks)

*EMB can be discontinued if drug susceptibility studies demonstrate susceptibility to first-line drugs


Treatment of Latent TBRegimen Duration in

MonthsComments

IsoniazidDAILY

9 Standard/regimen of choice Preferred for + HIV patients

IsoniazidDAILY

6 Should not be used in patients with fibrotic lesions on chest radiography, patients with HIV infection or children

Isoniazid and RifapentineONCE WEEKLY

3 Administered as DOTDoes not replace other recommended LTBI treatment

RifampinDAILY

4 Used when INH resistance is suspected; intolerant to INH

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Populations Who ShouldReceive ChemoprophylaxisSkin Reactions:

5 mm: HIV infected persons, contacts of known cases or chest film typical for TB

10 mm: Immigrants from high prevalence areas or those in high risk groups; healthcare workers

15 mm: For all other persons not in high risk groups


The End

Documents

Advanced Pharmacology Drugs for Bacterial Infections Handout Samples/Advanced... · 1 Unit 9 ©2014 Barkley & Associates Advanced Pharmacology Drugs for Bacterial Infections Thomas