(Detailed) Antibacterials

1. (Detailed) Antibacterials By Sarah E.

2. General Info What is an empirical therapy? • One in which the infecting organism is not known Do you use broad or narrow spectrum drugs for this? • broad spectrum (OR combo) What is a definitive therapy? • One in which the infecting organism is known. Do you use broad or narrow spectrum drugs for this? • narrow spectrum

3. General Info Name all antimicrobials that are contraindicated in pregnant women. • tetracyclines, aminoglycosides, fluorquinolones, sulfonamides, and metronidazole Do you use bactericidal or bacteriostatic drugs in immunocompromised patients? • bactericidal

4. β-lactams Mechanism of action? • bind PBPs and inhibit cell wall synthesis Can be used to treat intracellular organisms? • No. Do not cross membranes Bactericidal or bacteriostatic? • bactericidal for ACTIVELY GROWING BACTERIA Exceptions? • Only static for Enterococcus sp. Predominant mode of excretion? • kidneys Exceptions? • ceftriaxone and anti-Staph penicillins (dicloxacillin- bile)

5. β-lactams Mechanisms of resistance? • β-lactamase production • altered PBPs • altered porins (gram negatives) Name three organisms that have altered PBPs. • pneumococci (ie. Streptococcus pneumoniae), gonococcus, enterococcus • Makes them resistant to most β-lactams! Can these be used to treat Neisseriagonorrhoea? • Only 3rd generation cephalosporins! Can pregnant women take these drugs? • yes!

6. β-lactams Name 5 organisms that encode plasmid β-lactamases. • Haemophilus, E. coli, Neisseria, Salmonella, Klebsiella, Shigella(HEN S(e)KS) Name 2 organisms that have constitutive chromosomal β-lactamases. • Bacteroides, Moraxella Name 3 organisms that have inducible or Extended-Spectrum β-lactamases. • Pseudomonas, Enterobacter, Serratia

7. β-lactams Name the 4 categories of β-lactams. • Penicillins, cephalosporins, carbapenems, monobactams Name 1 non β-lactam cell wall inhibitor • vancomycin

8. Penicillins Name the 4 categories of Penicillins • original, anti-staphylococcal, amino-penicillins, anti-pseudomonal Name 3 places these do NOT distribute. • eye, prostate, CNS (unless meninges are inflamed and leaky!)

9. Penicillins Long or short half-lives? • short What three things can lengthen the half-life? • kidney failure, probenecid*, aspirin (inhibit renal tubular (and CNS!*secretion) Which category of penicillin is NOT affected by those things? • anti-staphylococcals (eliminated via bile, not kidneys) (and also ceftriaxone)

10. Penicillins Name the major adverse effect of penicillins. • allergies!! Anaphylaxis (severe) or rash (mild) Name an adverse effect of oral penicillins. • GI distress/pseudomembranous colitis What can these drugs do to the vagina? • yeast infections! (flora imbalance) What are the toxic effects of these drugs? • seizures (in patients with renal dysfunction or CNS lesions) and hyperkalemia

11. The Original Penicillins Name the “original penicillin” on our list. • Penicillin G When do you use the IV form, these days? • treating endocarditis in combo with an aminoglycoside For which disease is the injectable form the DOC? • PRIMARY SYPHILIS Which form of the original penicillin can be take orally? • penicillin V (acid stable) What do you take penicillin V for? • mild gram (+) cocci infection (eg. GAS “strep throat”)

12. The Original Penicillins Are these useful for most Staphylococcus infections? • No (β-lactamases) Intracellular infections? • No Most gram negatives? • No Streptococcus pneumoniae? • No (altered PBPs) Spirochetes? • YES (syphilis is caused by the spirochete Treponema!)

13. The Original Penicillins Intracellular Gram negative cocci? • Not really (but some N. meningitidisif you can get the drug there!) What do you have to take care to do if giving with aminoglycosides? • Administer in separate IV lines

14. Anti-staphylococcal penicillins Name the one on our list. • dicloxacillin Are these broad or narrow spectrum? • VERY NARROW What kind of organisms do these treat? • Staphylococcus sp. (duh?) with PLASMID ENCODED β-lactamases How are these excreted? • in the bile!

15. Amino-penicillins Name the one on our list. • Amoxicillin How does the spectrum compare to the original penicillins? • Same for gram-pos, but treats more gram negatives • (Broadest spec penicillins) Which gram negatives? • Moraxella, Haemophilus, Salmonella, Shigella, E. coli Can these be take orally? • yep! (amoxicillin causes minimal GI stress) What do you typically prescribe these for? • otitis media, sinusitis, dental infections, etc…

16. Amino-penicillins Can you use these to treat H. pylori? • yes, in combo with clarithromycin When do you use these prophylactically? • when you’re worried about endocarditis in high risk patients undergoing procedures Are these active against organisms with altered PBPs? • No

17. Amino-penicillins Are these inactivated by β-lactamases? • Yes Name 2 things you can co-administer to prevent this. • clavulanate or tazobactam (β-lactamase inhibitors) Are amino-penicillins effective against Streptococcus pneumoniae? • No (because of altered PBPs) Can these drugs treat Listeria meningitis? • yes, if the meninges are inflamed and leaky

18. Anti-pseudomonalpenicillins Name the one on our list. • piperacillin How does the spectrum of these drugs compare to penicillin and amoxacillin? • Less gram(+), more gram (-) Which gram (-)s? • Pseudomonas, Enterobacter, Serratia Are these inactivated by β-lactamases? • Yes What can you add to prevent this? • clavulanate or tazobactam Are these combinations effective against Pseudomonas species that have inducible chromosomal β-lactamases? • No

19. Penicillins Name the original penicillin. • Penicillin G (Oral=Penicillin V, IM = benzthine penicillin G) Anti-staphylococcals? • Dicloxacillin (also not on the list, nafcillin, oxacillin) Aminopenicillins? • Amoxicillin, (and not on the list ampicillin) Anti-pseudomonals? • Piperacillin β-lactamase inhibitors? • Clavulanate, tazobactam

20. Cephalosporins How many generations are there? • 4 As generation # increases, resistance to β-lactamases… • Increases As generation # increases, activity on gram-positives… • Decreases As generation # increases, activity on gram-negatives… • increases

21. Cephalosporins 1st generation cephalosporins (on our list)? • Cefazolin, cephalexin 2nd generation? • Cefuroxime, cefprozil 3rd generation? • Ceftriaxone, cefixime 4th generation? • cefepime

22. Cephalosporins Are any of these drugs effective against MRSA? • No Enterococcus sp.? • No Listeria monocytogenes? • No Are these drugs more active or less active against gram-negative rods than amoxicillin? • More active

23. Cephalosporins Can you use these drugs in patients with severe penicillin allergies? • No In patients with mild penicillin allergies? • yes In pregnant women? • yes Are these drugs broader or narrower in spectrum than penicillins? • Broader Are oral cephalosporins more or less potent than parenterals? • Less potent

24. Cephalosporins Do oral cephalosporins have a broader spectrum than parenteral cephalosporins? • No Which generation achieves therapeutic concentrations in the CNS? • 3rd generation Does oral administration reach the CNS? • No Name the two drugs in the 3rd generation that are on our list. • ceftriaxone and cefixime

25. 1stGeneration Cephalosporins Name two of these that are on our list. • Cefazolin and cephalexin Are these active (generally) against gram positive cocci? • Yes, including many Staphylcoccus β-lactamases -Name 3 exceptions. • MRSA, Enterococcus, penicillin-resistant pneumococci Are these drugs active against Neisseria? • nope

26. 1stGeneration Cephalosporins Name the gram-negative rods that these drugs can treat. • Proteus mirabiluis, E. coli, Klebsiellapneumoniae (PEcK) Name two indications for cefazolin. • Prophylaxis for surgery, anti-staph in mildly allergic patients Name an indication for cephalexin. • Substitute for oral penicillins (mild infections)

27. 2nd Generation Cephalosporins Name our 2nd generation cephalosporins. • Cefuroxime, cefprozil Do these have more or less activity against gram-positives than generation 1? • Less Name the gram-negatives that these cover. • Haemophilus, Enterbacter, Neisseria, Proteus, E. coli, Klebsiella, Serratia (HEN PEcKS) Which β-lactmases are these NOT resistant to? • Inducible chromosomal lactamases of Pseudomonas, Enterobacter, and Serratia

28. 2nd Generation Cephalosporins Do any of these enter the CNS? • Actually yes. Cefuroxime does, but 3rdGCs are better for menigitis and pneumonia Why are these considered the “lost” generation? • They aren’t often listed of drugs of first choice, and they are more expensive than 1stGCs as substitutes for oral penicillins

29. 3rd Generation Cephalosporins Name our 3rd generation cephalosporins. • Ceftriaxone, cefixime Do these have more or less activity against gram-positives than generation 2? • Less Are these active against bacteria with altered PBPs? • Yes, many of them! (pneumococcus, eg.) Are these active against Streptococcus sp? • Yes! (even though they are generally less potent against gram-positive cocci than 2ndGCs

30. 3rd Generation Cephalosporins Are these more or less active against gram-negatives than 2ndGCs? • More active! Particularly which gram-negatives? • Enterobacteriacieae Which β-lactamases are these NOT resistant to? • Inducible chromosomal lactamases of Enterobacter, Serratia, and Pseudomonas How are these drugs excreted? • Through the urine EXCEPT ceftriaxone

31. 3rd Generation Cephalosporins Name two diseases for which this class is the drug of choice. • Meningitis (initial treatment in kids over 3 months and immuno-competent adults) • Gonorrhea For which kind of bacterial infection (gram+ or gram-) is ceftriaxone a first line drug? • Serious gram-negative infections Is ceftriaxone active against Pseudomonas aeruginosa? • Nope.

32. 3rd Generation Cephalosporins Should you use these drugs to treat otitis media, respiratory tract infections, or UTIs? • No. There are cheaper drugs that work just as well (Note: they ARE recommended for otitis media in regions with resistant infections) Can these drugs treat typhoid fever? • Yes Endocarditis? • Sometimes Community acquired or nosocomial pneumonia • Both when in combination with macrolide or aminoglycoside respectively

33. 4thGeneration Cephalosporins Name our 4th generation cephalosporins (that are on the list) • Cefepime (there’s only one on our list!) Is this generation resistant to inducible chromosomal β-lactamases? • More than the other generations are  What can this treat that 3rd generation cephalosporins can’t? • Pseudomonas, Enterobacter, Serratia, (in other words, nosocomial gram-neg infections)

34. Cephalosporins (name recap) 1st generation cephalosporins (on our list)? • Cefazolin, cephalexin 2nd generation? • Cefuroxime, cefprozil 3rd generation? • Ceftriaxone, cefixime 4th generation? • cefepime

35. All Cephalosporins Name the most common adverse effect for all cephalosporins. • Hypersensitivity reactions (identical to penicillin) Name a side-effect that can occur especially in when these are taken in combination with an aminoglycoside. • Nephrotoxicity

36. All Cephalosporins Do these cause “superinfections” more commonly than amoxicillin or clindamycin? • No, but superinfections can still occur (resistant gram-positives such as C. difficile) Name two side-effects that occur as a result of the method of administration. • Pain with IM, phlebitis with IV

37. Carbapenems Name the ones on our list. • Imipenem-cilastatin Against which species is this class NOT active? • MRSA, most Enterococcus sp. (this is the broadest spectrum β-lactam) Is this class resistant to extended spectrum β-lactamases? • Yes! Most of them! Name three genera of bacteria that have these. • Pseudomonas, Enterobacter, Serratia

38. Carbapenems Can this class be used to treat Pseudomonas aeruginosa? • Yes, but add gentamicin to reduce resistance Can this class be used to treat Aceinetobacter? • Yes When should you use these drugs? • When there are mixed infections and other drugs can’t be used (ie. Try not to use them) Do these drugs get to the CNS? • Yep!

39. Carbapenems Where is are these eliminated? • In the urine Which part of imipenem-cilastatin is the antibiotic? • Imipenem What the heck is the cilastatin? • Inhibits the renal dihydropeptidase that breaks imipenem into a toxic compound • (note, some other drugs in this class are resistant to breakdown by that enzyme all by themselves)

40. Carbapenems Name 3 adverse reactions. • Nausea and vomiting • Hypersensitivity • seizures in patients with CNS lesions or renal insufficiency Can pregnant women take these? • Yes.

41. Monobactams Name the one on our list. • Aztreonam What is the spectrum of this drug? • Gram negative aerobes!! (very specific) Name 4 genera included in this category. • Pseudomonas, Enterobacter, Serratia, Haemophilus When should you use this drug? • In patients severely allergic to penicillins/cephalosporins who have gram-negative aerobe infection

42. Monobactams Are there adverse effects? • VERY FEW (phlebitis, skin rash, abnormal liver test) How are these excreted? • Urine Do these cross-react with allergy to penicillins? • no

43. Let’s REHASH THE NAMES Because they all sound the same.

44. Penicillins Name the original penicillin. • Penicillin G (Oral=Penicillin V, IM = benzthine penicillin G) Anti-staphylococcals? • Dicloxacillin (also not on the list, nafcillin, oxacillin) Aminopenicillins? • Amoxicillin, (and ampicillin) Anti-pseudomonals? • Piperacillin β-lactamase inhibitors? • Clavulanate, tazobactam

45. Cephalosporins 1st generation cephalosporins (on our list)? • Cefazolin, cephalexin 2nd generation? • Cefuroxime, cefprozil 3rd generation? • Ceftriaxone, cefixime 4th generation? • cefepime

46. Other β-lactams Carbapenems? • Imipenem-cilastatin Monobactams? • aztreonam

47. β-lactams Which are NOT excreted in the urine? • Dicloxacillin (and other anti-staph penicillins), and ceftriaxone Which are effective against Pseudomonas aeruginosa? • Piparcillin-tazobactam(unless there are ESBLs), cefepime (4th GC), carbapenems, monobactams Which used usually against Streptococcussp.? • Penicillin V (mild pharyngitis infections), cephalexin (1st GCs), cefprozil (2nd GCS—but more expensive), ceftriaxone, or cefixime (if resistant because of altered PBPs, as in S. pneumoniae), or cefepime

48. β-lactams Which is the DOC for gonorrhea? • Ceftriaxone or cefixime (3rd GCs) Which is the initial DOC for meningitis? • Ceftriaxone (3rd GC) (immuno-competent and older than 3 months) Tougher question. WHY is this the initial DOC for meningitis? • Most common bacterial cause in adults are Strep. pneumoniae, Neisseria meningitidis, and Haemophilusinfluenzae, and ALL are can be treated with this drug

49. β-lactams Which is the DOC for primary syphilis? • Penicillin G (single IM injection) Which does NOT show allergic cross reaction with penicillins? • Monobactams (aztreonam) Which is used as prophylaxis for surgery (in hospitals WITHOUT high rates of MRSA)? • Cefazolin (1st GC) Which are effective on gram-negatives ONLY? • Aztreonam (monobactams)

50. Glycopeptide cell wall inhibitors Name the one drug in this class. • Vancomycin!!! What is it’s mechanism of action? • Inhibits crosslinking of peptidoglycans by binding D-ala-ala, blocks cell wall synthesis Bactericidal or bacteriostatic? • Bactericidal Gram-positives, gram-negatives, or both? • Gram-positives only Intracellular, extracellular or both? • Extracellular only