Exam 2 lecture 5 Flashcards
What drugs are discussed in miscellaneous antibiotics
Tetracyclines (tetracycline, doxycycline, minocycline)
Tetracycline analogs (tigacycline, arabacycline)
Sulfonamides (sulfamethoxazole trimethoprim)
Lincosamides (clindamycin), metronidazole
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
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
DIfference between MOA of tetracyclines and analogs and aminoglycosides?
Aminoglycosides bind to 30S but also other sites. And it is irreversible
Tetracycline- reversible
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
Are analogs affected by major tetracycline resistance mechanisms
No
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
What are the antibiotics that cover atypical bacteria
Tetracyclines, macrolides and fluoroquinolones
What is special about tetracyclines? Name target organism?
Treats atypicals
legionella, chlamydophilia, chlamydia, mycioplasma
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
mnemonic to remember gram negative aerobes
EEACKSS
enterobacter, Ecoli, AAcenitobactter, citrobacter, klebsiella, serratis, stenotrophomonas
Does tetracycline analog treat proteus spp or pseudomonas aeruginosa
No
What does tetracycline analog show enhanced activity against
Gram negative aerobes (EEACKSS) and anaerobes
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
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
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)
Why was minocycline IV developed
Acinetobacter
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
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
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
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
What does dihydropteroate synthase produce? Dihydrofolate reductase
dihydropteroate synthase produce dihydropteroic acid from PABA
Dihydrofolate reductase converts dihydrofolic acid to tetrahydrofolic acid
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
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
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)
No
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
NO
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
