Exam 2 lecture 5 Flashcards by Matti Daniel

What drugs are discussed in miscellaneous antibiotics

Tetracyclines (tetracycline, doxycycline, minocycline)
Tetracycline analogs (tigacycline, arabacycline)
Sulfonamides (sulfamethoxazole trimethoprim)
Lincosamides (clindamycin), metronidazole

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What are tetracycline drugs used? What are tetracycline analogs? Why did analogs come out?

Tetracyclines- tetracycline, doxycycline, minocycline and demeclocycline

Tetracycline analogs- Tigecycline, ervacycline and omadacycline

analogs have structural modifications to improve spectrum of activity

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MOA of tetracyclines and analogs? Static or cidal?

Inhibit bacterial protein synthesis by reversibly binding to the 30S ribosomal subunit

Typically bacteriostatic but may be cidal

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DIfference between MOA of tetracyclines and analogs and aminoglycosides?

Aminoglycosides bind to 30S but also other sites. And it is irreversible

Tetracycline- reversible

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Mechanism of resistance of tetracycline and analogs? Is cross resistance observed between tetracyclines?

Efflux decreases accumulation of tetracycline within bacteria
Ribosomal protection decreases access of tetracycline to ribosome

Cross resistance is observed between tetracyclines, except for minocycline

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Are analogs affected by major tetracycline resistance mechanisms

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Tetracycline spectrum of activity? Which are the most active? Target organism

Gram positive Aerobes

Minocyclin and doxycycline most active

MSSA* target organism

strep pneumoniae

Gram negative aerobes (no enterobacterales)
H. influenzae, H ducreyi, campylobacter and helicobacter

Miscellaneous bacteria
Legionella* (target organism), chlamydophila, chlamydia, mycoplasma, ureaplasma

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What are the antibiotics that cover atypical bacteria

Tetracyclines, macrolides and fluoroquinolones

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What is special about tetracyclines? Name target organism?

Treats atypicals

legionella, chlamydophilia, chlamydia, mycioplasma

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What is the spectrum of activity of tetracycline analogs? target organsims?

Gram positive aerobes
(group strep, viridians strep)
VSE and VRE
MSSA* and MRSA* (target organisms)

gram negative
EEACKSS

Anaerobes
Bacteroides spp

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mnemonic to remember gram negative aerobes

EEACKSS
enterobacter, Ecoli, AAcenitobactter, citrobacter, klebsiella, serratis, stenotrophomonas

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Does tetracycline analog treat proteus spp or pseudomonas aeruginosa

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What does tetracycline analog show enhanced activity against

Gram negative aerobes (EEACKSS) and anaerobes

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What is absorption of tetracycline impaired by? Explain the distributiion of tetracyclines in body

Di and tri valent cations (EXAM)

Good penetration into prostate. Absorbed best on an empty stomach

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Explain the elimiination of tetracyclines? when do we give dosage adjustments?

demeclo and tetra excreted unchanged in urine.

Doxy, mino and tetra analogs excreted non renally

Adjust tigecycline and eravacycline with liver disease, NOT renally

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Clinical use of tetracyclines and tetracycline analogs

-Outpatient community acquired pneumonia (doxy)

-Chlamydia infections- nongonococcal urethritis (doxy)

-Acinetobacter (minocycline)

-Polymicrobial infections such as complicated skin and intraabdominal infections (tet analogs)

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Why was minocycline IV developed

Acinetobacter

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adverse effects of tetracycline/tigecycline?

GI side effects (N/V) (most notable with tigecycline even though it is IV)

Photosensitivity

CI in pregnancy

Patient has to sit up after taking it

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Which antibiotics interact with divalent and trivalent cations leading to impaired absorption? Is azithromycin interacting with them?

fluoroquinolones and oral tetracyclines

No azithro does not interact

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Which antibiotic does NOT have activity against atypical bacteria
azithro, levofloxacin, amox-clav, doxy, moxi

Amox clav

B lactam have no effect on atypicals

Quinolone or macrolide or tetracycline need to be used

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MOA of TMP SMX? Cidal or static

sulfamethoxazole trimethoprim produce sequential blockade of microbial folic acid synthesis

SMX inhibite dihydropteroate and TMP inhibits dihydrofolate reductase

Alone they are static, combo they are cidal

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What does dihydropteroate synthase produce? Dihydrofolate reductase

dihydropteroate synthase produce dihydropteroic acid from PABA

Dihydrofolate reductase converts dihydrofolic acid to tetrahydrofolic acid

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Mechanism of resistance to TMS-SMX

develops more slowly to combination compared to either agent alone

mediated by point mutations and altered production or sensitivity of dihydrofolate reductase

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Spectrum of activity of TMP-SMX

only active against aerobes (never anaerobes)

Gram positive- staph aureus* (target organism) (MRSA, MSSA)

Gram negative- stenotrophomonas maltophilia NOT Pseudomonas
HENPEACKSSSS mnemonic
Other- pneumocystitis

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Name the gram negative bacteria TMP-SMX act on

Haemophilus spp Enterobacter N. Gonorrhea Proteus mirabillis E coli Acinetobacter Citrobacter Klebsiella Serattia Salmonella Stenotrophomonas HENPEACKSSSS

Does TMP SMX cover pseudomonas? (exam)

What is the drug of choice for tx and prophylaxis pneumocystis pneumonia infection in AIDS pts (EXAM)

TMP SMX

Explain the distribution of TMP SMX? What percent is protein bound

Good distibution, includes urine and prostate Penetrates CSF SMXSMX is 70% protein bound

Elimination of TMX- SMX? Are dose adjustments reuqired?

Both eliminated by kidney and liver Dose adjustment required in pts with CRCl<30

What are the clinical uses of TMP SMX

Acute, chronic or recurrent infections of UTI THE DRUG OF CHOICE for pneumocystitis pneumonia Skin infection due to CA-MRSA acute or chronic prostatitis Stenotrophomonas

Adverse effects of TMP SMX and what to monitor (EXAM)

HS rxn (rash) Leukopenia, thrombocytopenia Crystalluria, hyperkalemia, creatinine

TMP SMX pregnancy and drug inetarctions

NEVER USED IN LACTATING women pregant women at term Interacts with warfarin, increases anticoag effect

WHat is the most common dosage forms for TMO SMX, what to remember about dosing

double strength (DS) most common Includes 160 mg TMP and 800 mg SMX will be in 1:5 ratio

What are polymixin drug names? Why were they introduced? why has use of them increased

Polymyxin B and Colistin Introduced into clinical practice in 1950s for tx of infections due to gram negative bacteria Over past decades use increased due to emergence of MDR gram negative bacteria

MOA of polymyxins? Time or conc dependent? Cidal/static?

Cations that bind to anionic membrane of gram negative bacteria, causing displacement of Ca and Mg, induces permeability change Concentration dependent bactericidal

Resistance of polymyxins

Alterations of outer cell membrane

Spectrum of activity of polymixins? Target organism? (EXAM)

NO GRAM POSITIVE ACTIVITY AND NO ANAEROBES Gram negative aerobic bacilli only PEEACKSSS P. aeruginosa is target organism

What bacteria are covered by polymyxins

PEEACKSSS P aeruginosa E coli Enterobacter Acinetobacter Citrobacter Klebsiella Shigella Stenotropomonas Salmonella

Describe the elimination of polymyxin? dosage adjustment?

50% of CMS (colistin) (CMS) is eliminated unchanged by kidney Requires adjustment

clinical use of polymyxin? What bacteria is it used against

SInce they are so toxic only used for MRSA for gram negative bacteria such as acinetobacter baumannii and pseudomonas aeruginosa

adverse effects of polymyxin

Nephrotoxicity up to 43% Neurotoxicity

What is more nephrotoxic colistin or polymyxin C

Colistin Associated with serious adverse effects sp not often used

What are clindamycin and metronidazole the best for?

Clinda- best for Above diaphragm except for tx of brain abscess also covers gram positive aerobes. No gram negative coverage Metronidazole- best below diaphragm antibiotic, useful for CNS/CSF penetration.

MOA of clindamycin? Static/cidal?

Inhibitor of protein synthesis by binding exclusively to 50s reversibly is bacteriostatic, but may be bactericidal at high concentrations

Mechanism of resistance to clindamycin

Altered target sites (main)-alters 50s ribosomal binding site, confering high level resistance to macrolides NO EFFLUX

What gene encodes clindamycin altered target site

Erm

Clindamycin spectrum of activity

Gram positive aerobes MSSA* and CA-MRSA* target organism Group and viridians strep strep Pneumo (only PSSP) Anaerobes best activity against ADA (above diaphragm anaerobes) Bacteroides spp* target organism Peptostreptococcus Clostridium spp (NOT C DIFF) Other bacteria Toxoplasmosis malaria

What is one of the biggest inducer of C diff collitis

Clindamycin

Distribution of clindamycin? Elimination? HD removal?

Good tissue penetration including bone, minimal CSF penetration Elimination- metabolized by liver NOT removed during hemodialysis

Clinical use of clindamycin

Anaerobic infections OUTSIDE of the CNS Pulmonary SKin and soft tissue infection in pts with penicillin allergies, pts with infections for CA-MRSA

Adverse effects of clindamycin

C Diff collitis worst enducer GI issues

MOA of metronidazole? Bacteriostatic.cidal?

prodrug that inhibits DNA synthesis Bactericidal

Mechanism of resistance to metronidazole

Altered growth requirements- organism grows in higher local oxygen, decreasing activation of metronidazole Altered ferredoxin levels- leads to less activation of metronidazole

Spectrum of activity metronidazole (what does it not cover EXAM!!)

- metronidazole does not cover any aerobes (EXAM) -We need to add another antibiotic for polymicrobial infection Anaerobic bacteria (ADA)- peptostreptococcus spp BDA*- Bacteroides SPP (ALL)* and clostridium spp* (ALL) Anaerobic protozoa- trichomonasDoe

What is metronidazole good for (EXAM)

Second line for C diff

Does Metronidazole act against actino mycin and proprioni bacteria

Distribution of metronidazole

DOES penetrate CSF We dont even need IV, we can do oral

Clinical use of metronidazole

Metronidazole is an alternative agent for non severe C diff Anaerobic infections - intraabdominal, pelvic, infected diabetic foot and decubitus ulcer brain abscess Other- trichomonas, Giardia

Adverse effects of metronidazole? pregnancy?

Metallic taste in mouth (take with food), stomatitis Peripheral neuropathy Avoid during pregnancy and breast feeding

Metronidazole drug interactions

Warfarin- increase anticoag effect Alcohol- disulfram rxn

What drugs interact with warfarin

Metronidazole Trimethoprim sulfa Clarithromycin/erythromycin fluoroquinolones

What meds can not be used with pregnancy

Metronidazole Sulfonamides Fluoroquinolones Tetracyclines Telavancin

What drugs do you have to renally adjust

Vanc gent trimethoprim Cefazolin All B lactams except nafcillin

What drugs could cause nephrotoxicity

Nafcilllin Colistin TObramycin VAnco

Exam 2 lecture 5 Flashcards

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