Pharmacology - Jacobs Cards Flashcards
Clostridium difficile (C. diff.) secretes toxin A, which has what type of enzyme activity?
Glycosyltransferase (adds a surar onto Rho signaling protein, compromising intestinal barrier)
What toxin does Clostridium perfringens secrete that causes GI symptoms (diarrhea)?
Clostridium perfringens enterotoxin (CPE)
Is Borrelia burgdorferi (Lyme disease) a rod, sphere, or spirochete?
Spirochete
Is Treponema pallidum (syphilis) a rod, sphere, or spirochete?
Spirochete
How do tetracyclines work?
Inhibit protein synthesis (30S)
How do aminoglycosides work?
Inhibit protein synthesis (30S)
How do macrolides work?
Inhibit protein synthesis (50S)
How does clindamycin work?
Inhibits protein synthesis (50S)
How does linezolid work?
Inhibits protein synthesis (50S)
How does lefamulin work?
Inhibits protein synthesis (50S)
How do fluoroquinolones work?
Inhibit bacterial topoisomerases (DNA Gyrase and Topoisomerase IV)
How does sulfamethoxazole work?
Antifolate (Inhibits dihydropteroate synthetase, DHPS)
How does trimethoprim work?
Antifolate (inhibits dihydrofolate reductase, DHFR)
What is the generic name for the fixed 1:5 combination of trimethoprim (TMP) and sulfamethoxazole (SMZ)?
co-trimoxazole
What is the brand name for co-trimoxazole?
Bactrim
Why are sulfamethoxazole and trimethoprim used together (as co-trimoxazole)?
They are synergistic.
What type of fetal defect can occur if pregnant women take co-trimoxazole (TMP-SMZ)?
Neural tube defects
Why can co-trimoxazole cause hyperkalemia?
Trimethoprim resmbles the K+ sparing diuretic, triamterene (aldosterone antagonist)
How does polymyxin B work?
Forms holes in bacterial membranes
How does metronidazole work?
Bacterial enzymes use it to generate reactive oxygen species.
How does nitrofurantoin work?
Bacterial enzymes use it to generate reactive oxygen species.
How does vancomycin work?
Inhibits cell wall biosynthesis
How does bacitracin work?
Inhibits cell wall biosynthesis
Define the abbreviation VRE
Vancomycin-Resistant Enterococci
Define the abbreviation MRSA
Methicillin-Resistant Staphylococcus aureus
Why do penicillins (e.g. ampicillin) improve Gram POS coverage for aminoglycosides (e.g. gentimicin)?
Penicillins weaken the cell wall, which allows penetration of aminoglycosides
Which antibiotic class binds to negatively-charged phospholipids in the proximal tubule, and its high concentration there causes tubular necrosis (renal damage)?
Aminoglycosides
What antibiotic complexes with uromodulin in renal casts in thick ascending limb?
Vancomycin
What renal enzyme converts imipenem to a toxic metabolite that causes kidney damage?
DHP-1 (dihydropyrimidinase-1)
WHat DHP-1 inhibitor is co-administered with imipenem, to prevent renal injury?
Cilastatin
What is the main step in bacterial cell wall synthesis that penicillins inhibit?
Transpeptidase reaction
What is the main step in bacterial cell wall synthesis that vancomycin inhibits?
Transglycosylase reaction
What is the step in bacterial cell wall biosynthesis that bacitracin inhibits?
Phosphatase (dephosphorylation of C55-isoprenyl pyrophosphate)
Are antistaphylococcal penicillins effective against MRSA?
No
Renal transporter that secretes penicillin into tubular lumen.
Organic anion transporter (OAT)
Why does probenecid increase the half-life of penicillins?
Probenecid inhibits organic anion transporter (OAT)
Define the abbreviation KPC
Klebsiella pneumoniae carbapenemase
What drug classes does KPC cleave?
Penicillins, Cephalosporins, Carbapenems, and Monobactams (aztreonam)
What drug classes do metallo-beta-lactamases cleave?
Penicillins, Cephalosporins, Carbapenems, and Monobactams (aztreonam)
Define the abbreviation NDM-1
New Delhi Metallo-beta-lactamase 1
What drug classes to extended-spectrum beta lactamases cleave?
Penicillins and Cephalosporins
Is ceftolozane/tazobactam effective against KPC-producing Gram NEG pathogens?
No
Does the beta-lactamase inhibitor tazobactam inhibit penicillinases and ESBLs?
Yes
Does tazobactam inhibit NDM-1
No, there are no beta lactamase inhibitors that cover NDM-1 (yet)
If ceftazidime/avibactam effective against KPC-producing Gram NEG pathogens?
Yes (but there is emerging resistance)
What is the % cross-reactivity in hypersensitivity cases between penicillins and cephalsporins?
About 10%
Which carbapenem has the best CNS access (e.g. for treating Pseudomonas or Neisseria)?
Meropenem
Are carbapenems effective against CRE?
No, CRE is Carbapenem-Resistant Enterobacteriaceae
Are carbapenems effective against ESBL-producing Gram NEG bacteria?
Yes, ESBLs cleave penicillins, cephalosporins, and monobactams (aztreonam), but not carbapenems.
Do carbapenems cover B. fragilis?
Yes
Does piperacillin-tazobactam (Zosyn) cover B. fragilis?
Yes
Is meropenem/vaborbactam (Vabomere) effective against NDM-1?
No, there are no clinically useful metallo-beta-lactamase inhibitors available (yet)
Is aztreonam a beta lactam?
No, it is a monobactam. It is rarely cross-reactive in patients that are hypersensitive to penicillins.
Is aztreonam broad-spectrum against Gram NEG or Gram POS?
Aztreonam is broad spectrum against Gram NEG bacteria; except: ESBL, KPC, and metallo-beta lactamase strains (e.g. NDM-1)
Are beta lactamase inhibitors (e.g. tazobactam) competitive or irreversible?
Competitive
What drug class does cefotetan belong to?
Cefamycins (but it is often classified as a Cephalosporin)
Is aztreonam effective against Pseudomonas?
Yes. Used against drug-resistant strains, and for pnenumonia prophylaxis in cystic fibrosis patients.
What IV antibiotic can cause red man syndrome (red, itchy skin caused by histamine release) if infused too quickly?
Vancomycin
Is vancomycin broad spectrum against Gram POS or Gram NEG bacteria?
Gram POS (Strep, Staph, and Enterococci, except VRE)
How is vancomycin administered for intestinal C. difficile-associated diarrhea (CDAD)?
Orally
How is vancomycin administered for systemic infections?
Intravenous
How is vancomycin eliminated?
Renally, as unchanged drug (caution: vancomycin accumulates in patients with renal failure!)
Is vancomycin effective against MRSA?
Yes
Name two organs that vancomycin is toxic to.
Ears (ototoxic) and kidneys (nephrotoxic)
How is bacitracin administered?
Topically
Is bacitracin a peptide or a small molecule drug?
Peptide
Why does bacitracin have a high incidence of contact dermatitis?
It is a peptide and elicits an immune response.
Does topical bacitracin give coverage against Gram POS or Gram NEG bacteria?
Gram POS
Name the aminoglycosides
amikacin gentamicin neomycin streptomycin tobramycin
Name the tetracyclines
doxycycline minocycline tetracycline demeclocycline (other broader-spectrum ones not listed)
Name the macrolides
azithromycin clarithromycin erythromycin fidaxomicin
Name the carbepenems
doripenem ertapenem imipenem/cilastatin meropenem
Name the aminopenicillins
amoxicillin ampicillin
Name the natural penicillins
Penicllin G Penicillin V
Name the beta lactamase inhibitors
Except for clavulanate, they end in -bactam:clavulanate sulbactam tazobactam avibactam relebactam vaborbactam
How is aztreonam administered?
Intravenously, except for Psudomonas prophylaxis in cystic fibrosis.
What pathogen are cefamicins (cefotetan) active against that cephalosporins are not?
Bacteroides fragilis (anaerobe)
What pathogen is the second-generation cephalosporins (e.g. cefuroxime) active against that the first-generation (e.g. cefazolin) is not?
Haemophilus influenzae
Which cephalosporin is active against MRSA?
ceftaroline (advanced gen cephalosporin - sometimes called fifth gen)
What cephalosporins that are active against Pseudomonas?
Ceftazidime (3rd gen) and Cefipime (4th gen) note: Cefipime/Avibactam and Ceftolozane/Tazobactam also cover Pseudomonas.
Is ceftriaxone active against gonorrhea (Neisseria gonorrhea)?
Yes. But gonorrhea is often concomitant with Chlamydia, so doxycycline or azithromycin is usually added for coverage.
Is ceftriaxone effective against Chlamydia?
No. If ceftriaxone is used for a mixed STD, you should add azithromycin or doxycycline to cover Chlamydia.
What can happen if too much penicillin is given intrathecally for a CNS infection (e.g. mixing up doses)?
Seizures
Does vancomycin have a broad or narrow therapeutic window?
Narrow (therapeutic index is small, risk of toxicity if levels not monitored)
Name two classes of antibiotics that cause photosensitivity.
Tetracyclines and Fluoroquinolones
What class of antibiotics deposit in bone, and can stain developing teeth in children?
Tetracyclines
Name two antibiotic classes that bind to multivalent cations - avoid taking with dairy, antacids, or supplements containing Ca2+, Mg2+, Al3+, or Fe3+.
Tetracyclines and Fluoroquinolones
What effect do multivalent cations (calcium, iron, aluminum, magnesium) have on tetracyclines and fluoroquinolones?
If taken together, they inhibit oral absorption of the antibiotic (wait 2 hours).
What oral tetracycline is taken for acne vulgaris?
Sarecycline
Are aminoglycosides more effective against Gram POS or Gram NEG pathogens?
Gram NEG (aerobes)
Why are aminoglycosides not effective (when used alone) against Gram POS organisms?
They cannot penetrate the thick cell wall.
Are aminoglycosides positively or negatively charged?
Positively charged
Name two drug classes that have a post-antibiotic effect (PAE) - continue inhibiting bacterial growth after levels drop.
Aminoglycosides and Fluoroquinolones
Name two drug classes that are most effective when high peak concentrations are reached (PK index: PEAK/MIC)
Aminoglycosides and Fluoroquinolones
Are aminoglycosides orally bioavailable?
No, if treating a systemic infection, you need to inject them.
Which macrolide is not absorbed in the GI tract?
Fidaxomycin - taken orall for C. diff.
Are macrolides effective against Gram POS pathogens?
Not reliably - there is a lot of Strep. resistance (note: azithromycin may fail treating some URIs due to Strep. pneumo. resistance).
Are macrolides effective against Enterobacteriaceae (e.g. E. coli, Klebsiella pneumoniae)?
Not against most. Azithromycin is effective against Shigella and Salmonella, but not others).
List drug regimens for H. pylori.
Triple therapy: clarithromycin + amoxicillin (or metronidazole) +PPI Quadruple therapy: bismuth subsalicylate + tetracycline + metronidazole + PPI
What antibiotic causes inducible drug resistance in some bacteria, evaluated by a D-test in labs?
Clindamycin
What class of antibiotics is useful at inhibiting bacterial toxin production (e.g. necrotizing fasciitis)?
Protein synthesis inhibitors (clindamycin or linezolid are most effective)
Is linezolid orally bioavailable?
Yes, linezolid has excellent oral bioavailability.
What is lefamulin indicated for?
Community acquired pneumonias (CAP) - broad spectrum for pneumonia pathogens but NOT MRSA
What class of antibiotics can cause achilles tendonitis (and possible tear)?
Fluoroquinolones
What is the drug of choice in treating syphilis (Treponema pallidum)?
Penicillin G (Bicillin L-A) - 3 injections (1 per week)
Brand name for ceftriaxone
Rocephin
Are macrolides effective against Psudomonas?
No.
Are macrolides effective against Clostridium difficile?
Only fidaxomycin (Dificid) - active against C. diff.
Are macrolides effective against Bacteroides fragilis?
No.
Is clindamycin effective against Bacteroides fragilis?
Yes.
What antibiotic is also a monoamine oxidase inhibitor (MAOI)?
Linezolid
Why should the combination of linezolid and meperidine be avoided?
Linezolid is an MAOI + Meperidine is serotonergic = risk of serotonin syndrome
Which fluroquinolone has the broadest Gram NEG coverage?
Ciprofloxacin
Which fluoroquinolone has the broadest Gram POS coverage?
Delafloxacin (including MRSA)
Which two fluoroquinolones are the “respiratory fluoroquinolones”?
Levofloxacin and Moxifloxacin
Why are levofloxacin and moxifloxacin “respiratory fluoroquinolones”?
They cover URI/LRI pathogens: Strep. pneumo. + H. influenzae + Atypicals (Legionella, Francisella, Chlamydophilia, and Mycoplasma pneumoniae)
What antibiotics should be avoided in patients taking Class Ia, Ic or III antiarrhythmics?
Fluoroquinolones (risk of QTc prolongation)
What antibiotic class might cause hypoglycemia in diabetic patients?
Fluoroquinolones
What is the generic name for the 1:5 combination of trimethoprim and sulfamethoxazole (TMP/SMZ)?
Co-trimoxazole
What is the spectrum of activity for nitrofurantoin?
Urinary tract Gram NEG bacilli (but NOT Proteus mirabilis)
What is the spectrum of activity for metronidazole?
Bacteria: anaerobes or anaerobe-like (B. frag., C. diff., H. pylori) Parasites: Entamoeba and Giardia
Which penicillin-beta lactamase inhibitor combination is active against Pseudomonas?
Piperacillin/tazobactam (PIP/TAZ, brand name Zosyn)
Name common pathogens in catheter infections, and drugs of choice to cover them.
Staph - Vancomycin Pseudomonas - PIP/TAZ Lactobacillus - PenG or Amp or Clindamycin
Name desired coverage for dental prophylaxis, and drug of choice.
Strep - amoxicillin note: amoxicillin also covers some enterococci, but is not reliable for Staph or HACEK (oral Gram NEG)
Name empiric pathogens in endocarditis, and drugs of choice to cover them.
Gram POS (Strep, Staph, Enterococci) - Vancomycin (Rifampin can be added for synergy) Gram NEG (HACEK organisms) - Ceftriaxone or Gentamicin
What two drug classes are used in combination for endocarditis caused by Gram NEG rods (Enterobacteriaceae and/or Pseudomonas)?
beta-lactam + aminoglycoside These drug combinations are synergistic. e.g. PIP/TAZ + tobramycin e.g. meropenem + tobramycin e.g. cefepime + tobramycin
Name a drug of choice for endocarditis caused by MSSA.
Antistaphylococcal penicillin (nafcillin or oxacillin)
Name a drug of choice for endocarditis caused by MRSA.
Vancomycin (alone for native valve endocarditis, gentamicin and rifampin added if valve is prosthetic)
Name a drug of choice for the treatment of Strep throat, scarlet fever, or rheumatic fever.
Strep. pyogenes (Group A Strep) - Penicillin (usually Pen VK, but Pen G (Bicillin C-R) or amoxicillin are also ok) or use clindamycin (if allergic to penicillin)
Name a drug of choice for MILD C. diff.-associated diarrhea (CDAD).
Oral Vancomycin - 10 days
Name a drug of choice for MODERATE C. diff.-associated diarrhea (CDAD).
Oral Vancomycin or Fidaxomicin - 10 days
Name a drug of choice for SEVERE C. diff.-associated diarrhea (CDAD).
Vancomycin (via NG tube) + Metronidazole (IV)
Azithromycin is sometimes prescribed for traveller’s diarrhea. Does it cover ETEC?
No, azithromycin covers Campylobacter, Shigella, and Salmonella but not ETEC.
Ciprofloxacin is often prescribed for traveller’s diarrhea. What common diarrhea pathogens does it cover?
- Enterotoxigenic E. coli (ETEC) - emerging FQ resistance - Campylobacter - Salmonella - Shigella
What two actions does bismuth subsalicylate (Pepto Bismol) have?
bismuth metal - GI lumen antimicrobial salicylic acid - antiinflammatory
What are the four drugs used in “bismuth quadruple therapy” for H. pylori?
- bismuth subsalicylate - metronidazole - tetracycline - proton pump inhibitor (PPI)
What are the three drugs used in “non-bismuth quadruple therapy” for H. pylori?
- amoxicillin - metronidazole - clarithromycin - proton pump inhibitor (PPI)
Name a first line drug for surgical prophylaxis of commensal skin and enteric aerobic bacteria
Cefazolin (Ancef) - intravenous Covers: Strep, Staph (MSSA and Coag NEG), and E. coli Does NOT cover: Enterococci, Bacteroides
If you wanted to cover for surgical prophylaxis with cefazolin (Ancef), but want anaerobe (Bacteroides) coverage too, what would you add?
metronidazole - covers anaerobes (incl. B. frag.)
What is are two first line drug classes for a ruptured appendix? (likely pathogens include Enterobacteriaceae, Enterococcus faecalis, B. fragilis)
- Extended-spectrum penicillin/beta-lactamase inhibitor combo (e.g. PIP/TAZ) - Carbpenem (e.g. meropenem)
Name two options for prophylaxis for a non-ruptured appendectomy.
- Cephamycin alone (e.g. cefoxitin or cefotetan) - covers Strep, Staph (not MRSA) many enteric Gram NEG, and B. fragilis - Cephalosporin (e.g. cefazolin) + metronidazole (for B. fragilis coverage)
List four antibiotic options for Lyme Disease (Borrelia burgdorferi).
- doxycycline (tetracycline) - aminopenicillin (ampicillin or amoxicillin) - cefuroxime (2nd Gen CP) - ceftriaxone (3rd Gen CP) note: coverage of Borrelia is “spotty” in a particular drug class. Coverage is based on knowing the individual drugs.
List two drugs of choice for covering Neisseria meningitis
- Ceftriaxone (Rocephin) - Meropenem (best CNS access of the carbapenems)
Name a drug of choice for covering Streptococcal meningitis.
Vancomycin
List five drug options for uncomplicated UTI’s
- Bactrim (TMP/SMZ) - Augmentin (AMOX/CLA) - Nitrofurantoin - Ciprofloxacin - Levofloxacin
What cephalosporin covers Neisseria gonorrhea?
Ceftriaxone (Rocephin)
When treating gonorrhea, is it ok to use ceftriaxone alone?
No, add doxycycline (a tetracycline) or azithromycin (a macrolide) to cover Chlamydia trachomatis, which is often concomitant with gonorrhea.
Name a drug of choice for treating bacterial keratitis from contact lens use, common pathogens: Strep, Staph, Pseudomonas, Enterobacteriaceae
Ciprofloxacin (optic solution)
Name a drug of choice for treating bacterial otitis externa (swimmer’s ear), common pathogens: Staph, Pseudomonas
Ciprofloxacin (otic drops) - with steroid
List four drugs of choice for treating pneumonia caused by H. influenzae or Moraxella catarrhalis.
- Augmentin (AMOX/CLA) - Bactrim (TMP/SMZ) - Respiratory FQ (Levo or Moxi) - Ceftriaxone (3rd Gen CP)
List two drugs of choice for treating MRSA pneumonia.
- Vancomycin (could also use telavancin) - Linezolid
List two drugs of choice for treating MSSA pneumonia.
- Antistaphylococcal Pen (nafcillin or oxacillin)- Cefazolin (1st Gen CP)
List three drugs of choice for treating atypical pneumonias (Legionella, Francisella, Chlamydiophila, Mycoplasma)?
- Azithromycin (a macrolide) - Doxycycline (a tetracycline) - Respiratory FQ (Levo or Moxi)
What drug is recommended for dog bites, suspect pathogens: Pasturella, Staph, Bacteroides)?
Augmentin (AMOX/CLA) Could also use Clindamycin + TMP/SMZ if allergic to penicillin
Is Pen G active against Clostridium perfringens (gangrene)?
Yes, but add Clindamycin to block toxin production. note: Pen G NOT active against Clostridium difficile.
What antibiotic inhibits CYP2C9. It can increase warfarin levels and cause bleeding?
sulfamethoxazole-trimethoprim (aka TMP/SMZ, co-trimoxazole, Bactrim)
What IV antibiotic is used for Vancomycin-resistant Gram POS organisms (MRSA and VRE)? It works by forming holes in bacterial membranes, similar to polymyxin B).
Daptomycin
What adverse effect can daptomycin have on muscle?
Rhabdomyalosis (monitor CK levels periodically)
Is sulfamethoxazole-trimethoprim (TMP/SMZ) active against Strep.?
Not reliably. TMP/SMZ is active against Staph. (incl MRSA), Listeria and Nocardia, and has some mixed activity against Gram NEG bacteria.
Why do macrolides stimulate GI motility (and cause diarrhea)?
They activate the motilin receptor.
What fluoroquinolone has activity against MRSA?
Delafloxacin
Aminoglycosides are not active against Gram POS cocci, except for _______.
Gentamicin. It is active against Strep, Staph, Enterococci, but not reliable (resistance is common).
How do beta lactamses confer resistance to beta lactam antibiotics?
They cleave the beta lactam ring, destroying drug activity.
What classes of IV antibiotics of might increase BUN and serum creatinine?
Aminoglycosides and Vancomycin - both are nephrotoxic and often cause an increase in BUN and SCr
How can you prevent Red Man syndrome (flushing) caused by the administration of vancomycin?
- Slow infusion rate - Pretreat with antihistamine
What bacteria grows on Thayer-Martin agar, and what antibiotic would you use to treat the infection?
Neisseria (gonorrheae or meningitidis) - ceftriaxone (Rocephin) However - for gonorrhea, combine with azithromycin or doxycycline to cover Chlamydia (usually concominant infection)
Name the most common pneumonia pathogen in CF patients under 21, and over 21, and list possible treatments.
Under 21 - Staph. aurus MSSA: antipseudomonal penicillin or cefazolin MRSA: vancomycin or linezolid Over 21 - Pseudomonas PIP/TAZ, ceftazidime, or cefipime Pseudomonas prophylaxis: inhaled (nebulized) aztreonam (Cayston)
Where on ribosomes do macrolides and clindamycin bind on ribosomes, and what effect does this have?
To the peptide tunnel on the 50S subunit - inhibiting translocation
A pneumatocoele (air-filled cavity) is a radiographic (chest X-ray) finding most often seen with what type of bacterial pneumonia?
Staph. aureus
What is a common mechanism for resistance to macrolides?
Methylation of the 23S rRNA (on the 50S ribosome subinit)
Name an antibiotic that forms holes in Gram NEG bacteria (like a detergent).
Polymyxin B - usually topical drug
What drug is always administered with imipenem (a carbapenem)?
Cilastatin, a DHP-1 inhibitor that prevents renal metabolism of imipenem. This prevents formation of a toxic product, and also prolongs the half-life of imipenem in the body.
Name a first-line drug for methicillin-susceptible Staph. aureus SSTI
Dicloxacillin
Which cephalosporin is effective against MRSA?
Ceftaroline
Name two cell-wall inhibitors that are active against MRSA.
Ceftaroline and Vancomycin
Crepitus (pops and crackles) under skin and joints when palpated is a likely sign of what pathogen?
Clostridium perfringens (gas gangrene) - treat with PenG and Clindamycin (blocks toxin production) - but may result C. diff infection because it is resistant to clindamycin.
Why is bacitracin used topically, but not IV?
It is nephrotoxic.
Is Pseudomonas oxidase-test POS or NEG?
Oxidase Positive
List the four anti-Pseudomonal cephalosporins (and cephalosporin/beta-lactamase inhibitor combinations).
- ceftazidime - ceftazidime/avibactam - cefepime - ceftolozane/tazobactam
What color is Pseudomonas on culture?
Blue-green, because it makes a pigment called pyocyanin
Are aminoglycosides (e.g. gentamicin) active against Pseudomonas?
Yes, they are an alternative (second-line agent). But they are often added on top of first-line choices for enhanced activity in Pseudomonal pneumonia: - PIP/TAZ + AG - Ceftazidime or Cefipime + AG - Carbapenem + AG - FQ (levo- or cipro-) + AG
What antibiotic class is taken into bacteria by an oxygen-dependent process, which makes them ineffective against anaerobes?
Aminoglycosides
What class of antibiotics can cause dizziness or ringing in the ears, because it accumulates in the endolymph?
Aminoglycosides
What antibacterial drugs interfere with folic acid metabolism?
Trimethoprim and Sulfamethoxazole (TMP/SMZ)
What fungal lung infection is sulfamethoxazole-trimethoprim (TMP/SMZ) active against?
Pneumocystis jiroveci penumonia (PCP)
Which class of antibiotics causes tooth discoloration?
Tetracyclines
Which antibiotic causes neophrogenic diabetes insipidus, because it inhibits the actions of ADH (vasopressin) at its receptor?
Demeclocycline - the anti-ADH property of demeclocycline actually makes it useful in the treatment of SIADH
Name an antibiotic drug that is safe to use for an uncomplicated UTI in pregnant women.
- Augmentin (AMOX/CLA) - 1st Gen cephalosporin (e.g. cephalexin) Beta lactams are considered relatively safe in pregnant women, who are not allergic to them.
Which antibiotic classes are best avoided in pregnant women, if safer alternatives are available?
- Tetracyclines - teeth staining - Aminoglycosides - ototoxicity - FQs - may affect cartillege - TMP/SMZ - neural tube and other birth defects
If a patient has a sulfa allergy, should you prescibe TMP/SMZ?
No, sulfamethoxazole has a sulfa moiety.
If a patient is allergic to TMP/SMZ, what types of diuretics can they take safely?
Patients with sulfa allergy can only tolerate potassium-sparing diuretics (e.g. amiloride) or ethacrynic acid (a loop diuretic).
What antibiotic class is used in the prophylaxis of Mycobacterium avium complex (MAC) infections in HIV patients?
Macrolides. Azithromycin is the most common one used in MAC prophylaxis. It is recommended for patients with delayed initiation of ART, or CD4 count <50. Clarithromycin can also be used.
What metabolic enzyme does linezolid inhibit that can lead to serotonin syndrome?
Monamine oxidase (MAO) - Linezolid is an MAOi. Possible serotonin syndrome if linezolid is combined with other MAO inhibitors, serotonin agonists, or drugs that increase serotonin release.
What antibiotics should be avoided in patients taking statins?
Avoid using erythromycin or clarithromycin with statins. These two macrolides are strong inhibitors of CYP3A4. They block the metabolism of many statins (incl. lovastatin and simvastatin), increasing statin levels up to 10-fold. This can cause rhabdomyalosis, as a side-effect of high statin levels. Azithromycin is OK because it does not inhibit CYP3A4.
Is clindamycin a macrolide?
No. Clindamycin is a lincosamide. Macrolides and lincosamides both inhibit the 50S subunit. Avoid confusing clindamycin with clarithromycin.
List drugs that have activity against the Gram NEG anaerobe, Bacteroides fragilis.
- Metronidazole - Beta-lactam/lactamase inhibitor combination (e.g. PIP/TAZ, AMOX/CLA) - Cephamycins (cefotetan, cefoxitin) - Carbepenems (e.g. meropenem)
List drugs that are active against atypical pneumonias.
- Azithromycin - Doxycyxline Respiratory FQs (levofloxacin, moxifloxacin)
Which beta-lactam antibiotic is active against MRSA?
Ceftaroline (advanced-generation cephalosporin)
List the antibiotics that are effective against Pseudomonas aeruginosa.
- PIP/TAZ - Ceftazidime - Cefipime - Cefipime/Avibactam - Ceftolozane/Tazobactam - Carbepenems (except ertapenem) - Ciprofloxacin - Levofloxacin - Aztreonam - Aminoglycosides (usually used in combination w/another drug)
Is it OK to use cephalosporins or carbapenems in patients with known penicillin allergies?
No. There is a potential for cross-reactivity. Aztreonam is OK to use. However, remember that aztreonam has no Gram POS activity.
What antibiotic can interfere with the secretion of creatinine, and give an illusion of renal damage?
TMP/SMZ - can cause up to a 0.5 mg/dL increase in SCr levels. Cimetidine (an H2RA) can also do this, giving an “illusion” of renal insufficiency.
How might aminoglycosides affect serum creatinine levels?
Increase. Aminoglcyosides can cause acute tubular necrosis, increasing SCr levels. Renal failure is usually reversible wen discontinuing the drug. Other potentially nephrotoxic antibiotics: - vancomycin (nephrotoxic at high doses) - ciprofloxacin (crystalizes in alkaline urine) - bacitracin (only for topical use because of this) - polymyxin B (ok to use IV in severe cases)
A patient with a chancre is diagnosed syphilis, but is allergic to Pen G. Name an alternative drug that is not a beta lactam.
Tetracycline or doxycycline.
Protein synthesis inhibitors –> aminoglycosides –> MN: the Tubby cOBRA plans to deport the NEO-nazi GENTs from AMerIKA STat
what are the drugs in this class?
- the Tubby cOBRA = TOBRAmycin
- plans to deport the NEO-nazi = NEOmycin
- GENTs = GENTamicin
- from AMerIKA = AMIKAcin
- STat = STreptomycin
how are we able to create medicatons that selectively interfere with bacerial ribosomes but not eukaryotic ones?
because of the difference in ribosome structure
what is the first ribosomal site to be occupied by bacterial tRNA?
the P site (middle)
tRNA caryhing a formylmethionine AA enters that site
How do aminoglycosides enter bacterial cells?
- For gram positive –> require O2 dependent co-transporter in the cell wall to cross
- For gram negative bacteria –> can cross on their own.
What are the different mechanisms (3) of action of aminoglycosides?
indications for usage of aminoglycosides
treatment of serious infections caused by
aerobic Gram-negative bacteria, including:
Escherichia coli
Enterobacter,
Klebsiella,
Proteus,
Providencia,
Pseudomonas,
Serratia species.
indications for specific usage of tobramycin
what are the possible adverse effects of the Aminoglycosides abx?
- nephrotoxic (neomycin)
- ototoxic
- neurotoxic (they inhibit Acetylcholine release at the neuromuscular junction)
*contraindicated for patients with myasthenia gravis and kidney disease
Abx that has a conentration-dependent MOA
aminoglycosides, ***
As the plasma level is increased above the MIC (minimum inhibitory concentration) aminoglycosides kill an increasing proportion of bacteria and do so at a more rapid rate.
Drugs that have as time-dependent MOA
Many antibiotics, including penicillins and cephalosporins, cause time-dependent killing of microorganisms, wherein their in vivo efficacy is directly related to time above MIC and becomes independent of concentration once the MIC has been reached.
T/F: In most cases, aminoglycosides are used in combination with a beta-lactam antibiotic.
True
Examples include their combined use with penicillins in the treatment of pseudomonal, listerial, and enterococcal infections.
In what two bacterial infections would a combination of penicillin + a protein synthesis inhibitor be used
gram positive staphylococci and streptococci
When you suspect a bacterial infection, you first want to rule out sepsis, what are the signs you would look for?
Sepsis is a whole-body inflammatory response to an infection. Common signs and symptoms include fever, increased heart rate, increased breathing rate, and confusion.
The combination of___ +___ is used to treat Viridans streptococci endocarditis.
penicillin and gentamycin
T/F aminoglycosides are teratogenic
TRUE
At what steps in protein synthesis do aminoglycosides act
- blockage of initiation complex (blocking of P site)
- translocation (because it can’t move if it’s tethered at P)
What antibiotic combination is used to treat staphylococcus aureus endocarditis
For MSSA, use a regular beta-lactam cell wall inhibitor + Gentamycin
For MRSA, use vancomycin (glycopeptide cell wall inhibitor) (mn: it can VANquish the most scary infection) + Gentamycin
what combination is used to treat Viridans streptococci endocarditis.
penicillin + gentamycin
___________are a class of antibiotics that are ineffective against anaerobic bacteria as they require O2 to enter bacterial cells.
Aminoglycosides
mn: AminO2glycosides require O2 to enter bacteria.
Which group of bacteria are Aminoglycosides mainly active against?
Aerobic G- bacteria
How are the tetracyclines categorized
tetracyclines should be taken with or without food?
without
indications for using tetracyclines
at what site of the ribosome do tetracyclines act
A site –> blocks tRNA from binding to A site
what are the side effects of tetracycline
How do Cephalosporin antibiotics influence the nephrotoxicity of Aminoglycosides?
increase
Of the tetracycline family of abx, which medication(s) are effective against MRSA
tigecycline (+glycycycline) and doxycycline
mn: MRSA= mars rover
see attached
what are the most nephrotoxic aminoglycosides?
Neomycin and Gentamicin
mn: the Neo nazi gentleman is incredibly toxic because he is racist
what are the two pathways that arachidnoic acid can take
what type of pain medication disrupts this balance
selective COX 2 inhibitors
what type of pain medication can cause kindey injury (therefore is contraindicated) in patients who already have strain on their kidney
non-acetylated NSAIDS (non selective)
when kidney function is compromised (old age or heart disease), NSAIDS can cause renal injury because of the lack of regululation of the renal arteriole
MOA of metronidazole
Fluoroquinalones and their MOA
they are:
Ciprofloxacin (1st gen)
Levofolxacin; Moxifloxacin (2nd gen)
what are the 30S inhibiting antibiotics versus the 50S inhibiting antibiotics
____ and ____ are aminoglycosides used to treat TB.
Streptomycin and amikacin
The most commonly used aminoglycoside
gentamicin
what is the mechanism of bacterial resistance to aminoglycosides
inactivation by acetylation, adenylation, or phosphorylation
of the aminoglycosides, which one is most ototoxic
amikacin
(mn: both start with vowels)
what is the first line of defense for lyme disease?
docycyline
unlike the other tetracyclines, ______________ is effective against Lhyme disease, malaria, and MRSA
doxycycline
Fanconi syndrome is a side effect of which family of abx
tetracyclines
Fanconi syndrome is a rare disorder of kidney tubule function that results in excess amounts of glucose, bicarbonate, phosphates (phosphorus salts), uric acid, potassium, and certain amino acids being excreted in the urine.
Mycobacterium Leprae - LEPROSY
Dapsone
Rifampin
Clofazamine
——————————————————————————-
- agranulocytosis
- hemolytic anemia in G6PD deficiency
- bite cells and Heinz bodies seen in RBC’s
- leonine facies seen in lepromatous leprosy
natural Penicillins
Penicillin G
penicillin V (oral)
(blue)
——————————————————————————–MOA (green)
-Beta Lactam Ring interferes with transpeptidation reaction of bacterial cell wall synthesis
-pBP forms peptidoglycan cross links, penicillin’s will halt peptidoglycan synthesis in the cell walls: bactericidal
Delivery
- penicillin V is acid stable and only used in minor infections due to poor bioavailability (oral)
- administered IV (pen G)
Used to Treat
-against gram (+) organisms (Staph and Strep)
-Oral Penicillin V treats streptococcal pharyngitis
(“Red bandanna”)
- Penicillin G or V treats rheumatic fever
- Strep Viridians endocarditis
-GBS prophylaxis
- Actinomyces Israeli
- Clostridium Perfringens causing gangrene
- pastuerella pen g
- benzathine pen g treats syphilis (spirochete)
- penicillin G - treats Neisseria meningitides
Resistance
Beta Lactamases are immune to penicillin
(“Beta Trooper shooting down a ship”)
-beta lactamases expressed by plasmid genes (“Circular shape”)
Adverse Reactions
Type 1 IgE mediated hypersensitivity reaction
(“Astronaut shutting eyes w/ IgE missiles on ship”)
-drug-induced autoimmune hemolytic anemia
(+ direct coombs test) (“Exploding asteroids w/ IgG”)
-drug induced interstitial nephritis
(“Kidney shaped nebula”)
anti staph penicillin
Nafcillin
Oxacillin
Dicloxacillin
- bulky R-groups prevent beta-lactamase binding
- Narrow spectrum, only activity against staphylococci
- empiric treatment for skin and soft tissue infections (folliculitis, abscesses)
Tricuspid pyramids: treatment for staph endocarditis
Fish bones: treatment for Staph osteomyelitis
broad spectrum penicillins
+beta lactamase inhibitors
- *Amoxicillin**
- amoxicillin – oral bioavailability
amoxicillin and ampicillin to treat strep throat
- amoxicillin treats otitis media and sinusitis caused by strep pneumoniae, Haemophilus influenza, moraxella catarrhalis
- amoxicillin and ampicillin treat pneumonia caused by strep pneumoniae, H. influenza
H Wing ship: activity against Haemiphilus influenza
-amoxicillin is part of the triple therapy (with clarithromycin and a PPI) for helicobacter pylori infection
- amoxicillin treats Lyme Disease caused by Borrelia burgdorferi
- amoxicillin prophylaxis against encapsulated bacteria (s. pneumo, H. Flu) in asplenic patients
- Amoxicillin prophylaxis before dental procedures in patients at high risk for endocarditis
Ampicillin
–IV administration
- ampicillin treats anaerobic infections (enterococcus)
- Gram Positive enterococcus
- ampicillin resistant strains of Enterococcus due to beta-lactamase production
- ampicillin treats meningitis caused by Listeria monocytogenes
- activity against gastrointestinal and urinary tract gram (-) rods
-sensitive to beta-lactamases
(typically used with clavulanate)
Piperacillin/Ticarcillin
- Paired with beta lactamase inhibitors to prevent cleavage of beta lactamases
- piperacillin and ticarcillin treat anaerobic infections,
- active against pseudomonas
**Beta lactamase inhibitors
Sulbactam
Tazobactam
Calvulanate**
1st generation cephalosporins
(“LEX”)
Cephalexin
- *Cefazolin
- ——————————————————————————-**
- activity against gram( +)organisms (staph and strep)
- treats cellulitis, abscesses caused by staph and strep
- treats S. pyogenes
- activity against gram (-) UTI bugs (Proteus, E Coli, Klebsiella) 1st gen
- cefezolin for surgical prophylaxis
2nd generation cephalosporins
**Cefoxitin
Cefuroxime
Cefotetan
——————————————————————————–**
-same coverage as 1st gen with extended gram (-) coverage (2nd Gen)
-activity against H. flu, Neisseria, Serratia (HENS)
3rd generation cephalosporins
Ceftriaxone
Cefotaxime
Ceftazidime
——————————————————————————-
-extended gram negative coverage beyond 2nd gen
- ceftriaxone and cefotaxime empiric treatment for meningitis
- activity against H Flu
- treats community and hospital acquired pneumonia
- ceftazidime treats pseudomonas infections
- ceftriaxone treats endocarditis caused by Strep Viridians and HACEK organisms
- activity against gram (-) G.I. bugs
- single dose of IM ceftriaxone is first line txt for gonorrhea
- ceftriaxone treats Lyme disease caused by Borrelia burgorferi
4th generation cephalosporins
(“prime”)
- *Cefepime
- ——————————————————————————-** -broad spectrum
- *- Pseudomonas** coverage
- *-G+ / G- broad spectrum
- cefepime treatsbacterial meningitis**
5th generation cephalosporins
Ceftaroline
-broad spectrum
- Beta-lactamases ineffective against cephalos
cephalo’s have same adverse effects as penicillin
nephritis
hemolytic anemia
hypersensitivity reaction
cross reactivity with penicillin allergies
cephalosporin’s Resistance is gained by altered PBP’s and extended spectrum beta lactamases
Monobactam
(“AZ-3M”)
- *Aztreonam**
- has activity against aerobic gram negative rods
-monobactams and carbapenems treat Pseudomonas infections
-monobactam treats serious systemic infection with gram negative pathogens
(meningitis, pneumonia, sepsis)
- monobactams can be used in patients with a H/O penicillin allergy
- monobactams are resistant to beta-lactamases, ring shape on gun to remind us that beta lactamases are encoded by plasmid genes. they cleave beta lactams
Carbapenems
(“hover car”)
Doripenem
Imipenem
Meropenem
Ertapenem
monobactams and Carbapenems treat pseudomonas infections
-broad spectrum carbapenems
-carbapenems treat anaerobic infections
(aspiration pneumonia, intra-abdominal infections)
“when others fail we get the job done”:
use of carbapenems with bugs resistant to other available treatments
-monobactam treats serious systemic infection with gram negative pathogens
(meningitis, pneumonia, sepsis)
- imipenem inactivated by dehydropeptidase in renal tubules
- cilastin inhibits dehydropeptidase in the renal tubules preventing degradation of imipenem
-GI side effects of carbapenems
- carbapenem may cause skin rash
- imipenem lowers the seizure threshold
- monobactams are resistant to extended spectrum beta-lactamases
Chloramphenicol
- binds reversibly to 50s ribosome, inhibiting peptide bond formation and halting translation
- bacteriostatic
- empiric treatment for meningitis in developing countries (S. Pneumo, H Flu, N Meningitidis)
- alternative agent in serious rickettsial infections (rocky mountain spotted fever) useful in pregnant women
- anemia due to dose related reversible suppression of RBC production
- aplastic anemia
-accumulation of the drug in newborns-grey baby syndrome
(due to ineffective glucuronic acid conjugation system)
-causes flaccidity, hypothermia, shock (floatation device looks like a liver)
Antifolate drugs
Sulfamethoxazole (SMX)
Trimethoprim (TMP)
- usually used together = Bactrim = SMX/TMP
- Broad spectrum
PABA → Dihydrofolate →tetrahydrofolate → purines → DNA
-SMX is a PABA analog that blocks dihydropterate synthetase
- TMP /Pyrimethamine blocks **dihydrofolate reductase
- ——————————————————————————-**-
1st line treatment for UTI and travellers dhiarrea
-activity against MRSA as 2nd line
activity against nocardia
activity against gram positives (incl. chlamydia and nocardia)
-treats pneumocystis jirovecii pneumonia (PJP)
- PJP prophylaxis for cd4<200
- toxoplasmosis prophylaxis with TMP/SMX for CD4 <100
-Pyramethamine/sulfadizine treat toxoplasmosis caused by toxoplasma gondii
Antifolate drugs
side effects
- pancytopenia
- megaloblastic fireworks
- teratogen in the 1st trimester anti-folate effects cause neural tube defects
- sulfa allergy – fever, urticarial, rash
- Hemolytic anemia in G6PD deficiency
- Bite cells and Heinz bodies seen in RBC’s
- stevens-johnson syndrome
type IV renal tubular acidosis →hyperkalemia
-interstitial nephritis
-photosensitivity
-kernicterus in the neonate
(sulfonamides when used in the lath month of pregnancy displace bilirubin in the neonate)
- sulfonamides displace warfarin from albumin causing over anticoagulation and bleeding
- inhibition of cytochrome 450
- causes drug induced lupus
Tetracyclines
**Tetracycline
Oxytetracycline
Doxycycline
Minocycline
——————————————————————————–**
- bind irreversibly to 30s ribosomal subunit
- broad spectrum
- activity against MRSA
-activity against tick borne bacteria
(Rickettsia, Erlichia, Francisella, Borrelia)
- activity against Brucella
- treats culture negative endocarditis caused by coxiella
- activity against yersenia
- treats chlamydial cervicitis and urethritis
- treats chlamydial pelvic inflammatory disease
- treats chlamydial bronchitis and atypical pneumonia
- treats atypical “walking” pneumonia by Mycoplasma
- treat acne
- Causes tooth discoloration in young children
- deposits in fetal teeth and **bone
- ——————————————————————————-**
- multivalent cations (calcium, iron, magnesium) decrease absorption
- GI side effects (nausea, vomiting, diarrhea)
- Photosensitivity
- Fanconi syndrome (type 2 RTA) associated with use of expired tetracycline’s
- resistance via efflux pumps, and alteration of ribosome
- eliminated fecally, safe in renal failure patients
Fluoroquinolones
- *Cipro (old)**
- *Levo**
- *Moxi**
- mainly indicated for gram negatives (Cipro best)- esp UTI and GI infections
- treat gram negative UTI’s (E. coli and proteus)
Complicated UTI’s, levofloxacin and ciprofloxacin treat UTI caused by Pseudomonas
-treat gram negative causes of gastroenteritis (shigella, E. Cola, Salmonella)
- treat salmonella gastroenteritis
- treat anthrax caused by B. Anthracis
- treat gram negative salmonella osteomyelitis
- respiratory quinolones= the 2nd gen quinones: Levo and moxi. –> treat community acquired pneumonia (s. Pneumonia) - typical
- Cipro best to treat atypical “walking “ pneumonia caused by mycoplasma pneumonia and Legionella
-indicated for STIs: chlamydia (levo) and mycoplasma (moxi)
-2nd gen are indicated for some gram positive: anaerobes (but not Cipro)
- *-not recommended for children under 10 years of age
- ——————————————————————————**
-sickle cell patients are at increased risk of Salmonella osteomyelitis
-divalent and trivalent cations
(calcium, iron, magnesium, decrease absorption
- risk of prolonged QT interval
- GI Side effects N/V
- risk of tendon and cartilage damage in the elderly
- risk of tendon rupture in steroid users
- teratogenic – damage to growing cartilage
Aminoglycosides
Neomycin
Paromycin
Streptomycin
Gentamicin
Tobramycin
Amikacin
——————————————————————————–
-binding to the 30s ribosomal subunit
-activity against aerobic gram negatives, actively transported cell membrane
-coupled with cell wall active drugs
(beta-lactams, vancomycin) to allow entry into the cell
-transported into bacteria via an oxygen dependent process (aerobic bacteria)
- *-ivy administration**
-Neomycin remains active in the GI tract until secreted with feces
- neomycin used in bowel prep before colorectal surgery
- Paromycin, luminal agent active against parasital infections
- ——————————————————————————–streptomycin treats tularemia caused by Francisella tularensis
- streptomycin treats the plague caused by Yersinia pestis
- gentamycin treats resistant gram negative infections (Enterobacter, serratia, Klebsiella)
-systemic gram negative infections
(septicemia, nosocomial RTI, complicated UTI, intra-abdominal infection)
- activity against pseudomonas (aerobic gram negative)
- tobramycin -activity similar to gentamycin
- activity against enterococcus when coupled with a cell wall active agent (penicillin, vancomycin)
-inactivated by an acetylation enzyme
(E. faecium against tobramycin)
- Amikacin Activity against E. faecium w/ acetylation enzymes
-Activity against pseudomonas
(gentamycin, tobramycin, amikacin)
———————————————————————————
-myasthenia gravis is an absolute contraindication to aminoglycoside use, due to post NMJ Blockade
-Teratogenic – deafness in newborn
ototoxicity (vestibular or cochlear damage)
- nephrotoxicity (due to acute tubular necrosis)
- acute tubular necrosis (brown casts)
Peaks and troughs in undulating terrain: monitoring of serum drug levels
Macrolides
“FACES”
Fidaxomycin
Azithromycin
Clarithromycin
Erythromycin
Spiramycin
———————————————————————————acts on bacterial 50s ribosomal subunit, Irreversible inhibition of translocation
- bacteriostatic
- treats Bordetella pertussis
- prophylaxis for Bordetella pertussis for family members
- Azithromycin treats atypical pneumonia caused by M. Pneumoniae
- treats walking pneumonia caused by legionella
- Azithromycin treats atypical chlamydia pneumoniae, and urethritis and cervicitis caused by Chlamydia
- Azithromycin treats infections with Bartonella
- Azithromycin and clarithromycin have activity against mycobacterium avium
- Azithromycin prophylaxis for patients **CD4<50
- ——————————————————————————--oral Erythromycin treatsneonatal conjunctivitiscan pneumonia caused bychlamydia trachomatis**
- Erythromycin drops treat neonatal conjunctivitis caused by N. Gonorrhea
- Erythromycin treats **diphtheria
- ——————————————————————————-**
- Azithromycin and clarithromycin treat community acquired pneumonia caused by Strep pneumoniae
-Clindamycin + atovaquone treats babesiosis
- *-**Clarithromycin, amoxicillin, and PPI are triple therapy for **H. Pylori
- ——————————————————————————-**
- increased GI motility
- Acute cholestatic jaundice
- prolonged QT interval
- CYP450 inhibit
Clindamycin
bacterial 50s ribosomal subunit, inhibiting translocation
Bacteristatic
- Activity against staph and strep
- treats S.Pyogenes (GAS) and soft tissue infections (cellulitis)
Activity against MRSA
-Anaerobe activity
Lung stains with holes: excellent penetration into abscesses
treats oral infections and aspiration pneumonia caused by Bacteroides fragilis
activity against clostridium perfringens
topical clindamycin treats moderate to severe inflammatory acne
Uterus Machine: clindamycin plus gentamicin (gently cleaning the uterus) treats polymicrobial female genital tract infection.
Judo practitioner with Sai: gentamicin paired with clindamycin for broad coverage
-treats bacterial vaginosis from gardenella vaginallis
causes pseudomembranous colitis caused by C.Diff
Oxazolidinones
Linezolid
- binds reversibly to 50s ribosome, inhibiting peptide bond formation and halting translation
- activity against gram positive bacteria (staph, strep, enterococcus)
- MRSA activity
- treats nosocomial MRSA infections (hospital acquired pneumonia)
- activity against vancomycin resistant bacterial strains
- activity against **vancomycin enterococcus
- ———————————————————————————**
Broken plates: thrombocytopenia
Cut security camera wire: optic neuropathy ( and peripheral neuropathy)
-stocking-glove peripheral neuropathy
Happy face: serotonin syndrome
(weak inhibitor of MAOI, so can cause serotonin syndrome)
Glycopeptides
Vancomycin
-inhibition of cell wall synthesis by directly binding
D-ALA-D-ALA oligopeptides
- activity against gram (+) bacteria
- activity against methicillin resistant Staph aureus (MRSA)
- CNS penetration – activity against penicillin-resistant strep pneumo /meningitis
- Bone penetration–treats MRSA osteomyelitis
- activity against nosocomial MRSA infections (hospital acquired pneumonia, lung stains on her uniform)
- activity against S. epidermidis
- empiric treatment of endocarditis
- activity against Enterococcus
- oral vancomycin treats Clostridium difficile colitis
- IV administration
- altered PBP’s ineffective against vancomycin
- beta-lactamases ineffective against vancomycin
- altered peptidoglycan structure (D-ALA-D-LAC) confers resistance to vancomycin
——————————————————————————-
Vancomycin
Side effects
- red man syndrome due to histamine release
- thrombophlebitis at injection site
- ototoxicity
- nephrotoxicity
- Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome
Mupirocin
Protein synthesis inhibitor - Inhibits isoleucyl tRNA synthesis
-Gram (+)positive bacteria (resistant staphylococci)
-Topical
-Dermatology (impetigo)
Metronidazole
-free radical metabolites disrupt bacterial DNA
(form free radicals) Bactericidal
- Coverage of polymicrobial anaerobic infections (intra-abdominal infections)
- activity against Entamoeba histolytica (liver abcess)
- activity against giardia
- treats vaginitis and cervicitis caused by protozoal infection(treat both patient and partner)
- treats bacterial vaginosis caused by gardenella
- substitute for amoxicillin in the triple therapy for helicobacter pylori infection in penicillin allergic patients
- activity against anaerobic bacteria
(bacteroides, prevotta, fusobacterium, clostridium) - treats pseudomembranous colitis caused by clostridium
- Clindamycin above the diaphragm, metronidazole below
B-Lactamase inhibitors
Tazobactam
Sulbactam
Calvulanic acid
Polymyxins
bind LPS in the outer membrane of Gram-negative and disrupt both the outer and inner membranes.
causing membrane damage, suggesting a detergent-like mode of action. bactericidal
Polymyxin B- IV, otic, ophthalmic, topical
- G (-)
- *Pseudomonas **
Polymyxin E (colistin) -IV, aerosol
- Pseudomonas (Cystic fibrosis) → given aerosol
- do not enter CNS
- Neuro/nephro toxicity
Glycyl-cyclines
Tigecycline - Minocycline derivative
- Protein synthesis inhibitor S 30 subunit - reversible inhibition
- Bacteriostatic
- MRSA, VRE, tetracycline resistant
- IV
- large Vd, low plasma concentration
- Bile (long elimination half-life)
- similar to tetracyclines →Pancreatitis (may be fatal)
Fluoroquinolones
Nor floxacin
Cipro floaxcin
Levo floxacin
Moxi floxacin
——————————————————————————–
- mainly indicated for gram negatives
- Unwinding braid: inhibit bacterial DNA gyrase (Topoisomerase)
- treat gram negative UTI’s (E. coli and proteus)
- elevating (levo) and sipping (cipro) from Bladder cup: Complicated UTI’s, levofloxacin and ciprofloxacin treat UTI caused by Pseudomonas
- empiric treatment for pyelonephritis
- treat acute prostatitis
- treat gram negative causes of gastroenteritis (shigella, E. Cola, Salmonella)
- treat salmonella gastroenteritis
- treat anthrax caused by B. Anthracis
- treat gram negative salmonella osteomyelitis
- respiratory quinolones treat community acquired pneumonia (s. Pneumonia)
- respiratory quinolones treat atypical “walking “ pneumonia caused by mycoplasma pneumonia (levofloxacin and moxifloxacin)
- respiratory quinolones treat atypical pneumonia caused by Legionella
- not recommended for children under 10 years of age
-sickle cell patients are at increased risk of Salmonella osteomyelitis
-divalent and trivalent cations
(calcium, iron, magnesium, decrease absorption
- risk of prolonged QT interval
- GI Side effects N/V
- risk of tendon and cartilage damage in the elderly
- risk of tendon rupture in steroid users
- teratogenic – damage to growing cartilage
Ketolides
- *Telithromycin**
- Bactericidal
- as macrolides + macrolide resistant bacteria
- Hepatotoxicity
- QT prolongation
- visual disturbances,
- CYP3A4 inhibitor
Streptogramins
Streptogramins A + B
(A= Dalfopristin | B= Quinupristin)
Protein synthesis inhibitor - bind to different sites on the S50 ribosome
By themselves, streptogramins A and B are bacteriostatic.
Together bactericidal.
Given in mixture of 70:30 (A:B)
- A - disrupts elongation
- B - Releases incomplete peptide chains Long PAE
-G+ive cocci (also MDR strains)
-intracellular bacteria,
E.faecium and VRE
- IV
- Inhibits CYP3A4
-Infusion related phlebitis,
hyperbilirubinemia,
Arthralgia-myalgia.
Bacitracin
- *-Cell wall synthesis inhibitor
- interferes with dephosphorylation**
- gram (+) positive bacteria
- topical (good for skin infection), sometimes in combination with neomycin or polymyxin
- nephrotoxic
Fidaxomicin
Protein synthesis inhibitor
- Inhibits RNA polymerase - disruption of transcription
- Bactericidal
- narrow , (G+) (c.difficile)
- Oral
- ——————————————————————————–GI (nausea, vomiting)
- hypersensitivity
Urinary antiseptics
Methenamine
Decomposes to formaldehyde in acidic pH
(toxic for bacteria)
- oral
- Chronic suppressive therapy for UTI
- GI distresses
- ——————————————————————————-Nitrofurantoin
Damages bacterial DNA- reduced to highly active intermediates
-uncomplicated lower UTI
(in pregnancy, in children, in case of resistance)
———————————————————————————GI symptoms
-hypersensitivity pulmonary reaction
