Although tetracyclines are cross-reactive, ____________ is resistant to this because it is in the tetracyclin derivative category known as ____________.
*Tigecycline - Glycylcylins
What classes of microbials can tetracyclines be used against? (list some of the major targets) What 2 general conditions are they commonly used to treat?
- Gram-pos aerobes (*MSSA) - Gram-neg aerobes - Anaerobes - bacteroides spp. - Misc. bacteria. - legionella, chlamydophila, chlamydia, mycoplasma, ureaplasma, rickettsia (sketchy) - Often used for STI infections and dz's caused by tick bites!
Does tigecyclin have a more or less broad spectrum of activity vs. tetracyclins? Which organism is tigecyline notably not active against?
- Broader * Pseudomonas
Besides being inactive vs. pseudomonas, what 2 other conditions does tigecycline NOT treat?
*UTIs and *bacteremia
*What type of meds are tetracyclines and glycylcyclines contraindicated with?
Di and tri-valent cations (they should even avoid dairy due to Ca2+) - Must separate administration by a few hours
What are the major serious side effects a/w tetracyclines/tigecycline?
- Severe N/V - Photosensitivity (should avoid sun)
What can occur if expired tetracyclines are prescribed?
Fanconi-like syndrome a/w renal failure
What drug acts synergistically w/sulfas?
Trimethoprim (also inhibits folate/purine synth pw but at a different enzyme--dihydrofolate reductase)
What is the precursor of purine synthesis? - How is it affected by purine synthesis pw inhibitors?
PABA - Builds up
What drugs are in the combination Bactrim?
Explain the target organisms (only) of the broad-spectrum antibiotic TMP-SMX (Bactrim).
gram-pos: *staph aureus (MRSA, CA-MRSA) Gram-neg: - Stenotrophomonas maltophilia. Other: - Pneumocystis carinii. Plus many more (broad spectrum)
When giving Bactrim, what lab level should be monitored and why?
CrCl (kidney function; eliminated partially by kidney)
*What are the (3) major clinical uses of TMP-SMX?
1. Acute, chronic, or recurrent UTIs 2. Acute or chronic bacterial prostatitis 3. Skin infections due to CA-MRSA
What are the major adverse effects a/w TMP-SMX/Bactrim?
- Leukopenia - Thrombocytopenia - Rash/hypersensitvity - Renal impairment (crystaluria)
Are dose adjustments required in renal failure when giving chloramphenicol?
No, metabolized by liver
*What 2 major adverse effects are the reason that chloramphenicol isn't available in the U.S.?
- Gray Baby Syndrome (resp failure, death) - Aplastic anemia (no RBC production)
What are the 2 urinary tract agents that we need to know?
- Nitrofurantoin - Methenamine
What is nitrofurantoin used for? What is methenamine used for?
- Nitrofurantoin: used solely for UTIs - Methenamine: used solely as prophylaxis for UTIs if they’ve had recurrent UTIs
Which of the enterobacteriacea are lactose fermenters and which are non-lactose fermenters? (All ferment glucose, oxidase negative, reduce nitrate, and use MacConkey)
- Lactose fermenters: E. coli, klebsiella, Enterobacter, Citrobacter, Serratia - Non-lactose fermenters: Salmonella, Shigella, Proteus, Yersinia
Distinguish the characteristics of the 5 types of E. coli.
o Enterotoxigenic E. coli (ETEC): Profuse watery diarrhea (Traveler’s diarrhea) o Enteropathogenic E. coli (EPEC): infants; diarrhea w/mucus but no gross blood o Enteroinvasive E. coli (EIEC): blood, mucus, and many leukocytes in stool o Enterohemorrhagic E. coli (EHEC): Bloody diarrhea w/o pyuria. May progress to HUS. ♣ Shiga-toxin producing E. coli (STEC) via E. coli O157:H7 o Enteroaggressive E. coli (EAggEC): Watery diarrhea w/blood and mucus
MoA for tetracyclines/glycylcyclines? - Static or cidal?
Reversibly bind 30S ribosomal subunit to inhibit ptn synth. - Bacteriostatic.
Mech of resistance for tetracyclines/glycylcyclines? (Which drug is more resistant to these mechs?)
- Efflux pumps - Ribosomal protection proteins - Enzymatic inactivation (Tigecycline more resistant to these mechs)
Where's an important body areas that Tetracyclines/Glycylcyclines, distribute to? - What about Bactrim?
Prostate - Same for bactrim
What 2 tetracyclines/glycylcyclines are excreted, unchanged, in the urine?
Do tetra/glycylcyclines have to be modified w/renal disease?
No - Doxycycline, minocycline (metab) and tigecycline (biliary) - excreted mainly by non-renal routes
What is tigecycline often used to treat?
Which demo is tetra/tigecycline contraindicated in?
Pregnant (category D) - Affects their children (e.g. teet
What's the MoA of sulfonamides? - Static or cidal?
Inhibits dihydropterate reductase (folate/purine synthesis) - Bacteriostatic.
What's the MoA of trimethoprim? - Static or cidal, when combined w/sulfas?
Inhibits dihydrofolate reductase - Becomes cidal w/bacteriostatic sulfas
What is another name for Trimethoprim-Sulfamethoxazole (TMP-SMX)? - How is the spectrum of activity/resistance affected when the drugs are combined?
Bactrim - Broader spectrum, decreased resistance
What organism group does bactrim not have activity against?
What organisms are targeted by chloramphenicol?
- Gram-pos - Gram-neg - Anaerobes (+ and -), etc. (3rd world use only)
What is chloramphenicol's MoA? (cidal or static)
Binds 50S ribosomal subunit (bacteriostatic)
(MoA). In acidic pH, methenamine is converted to ammonia and ____________.
What is the MoA for nitrofurantoin?
Not well understood
Besides tetracyclines, what other drug class are di-tri-valent cations contraindicated in?
Fluoroquinolones (cipro, levo, moxi, gemi)