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(Detailed) Antibacterials. By Sarah E. 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.
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(Detailed) Antibacterials By Sarah E.
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
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
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)
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!
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
β-lactams Name the 4 categories of β-lactams. • Penicillins, cephalosporins, carbapenems, monobactams Name 1 non β-lactam cell wall inhibitor • vancomycin
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!)
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)
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
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”)
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!)
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
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!
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…
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
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
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
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
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
Cephalosporins 1st generation cephalosporins (on our list)? • Cefazolin, cephalexin 2nd generation? • Cefuroxime, cefprozil 3rd generation? • Ceftriaxone, cefixime 4th generation? • cefepime
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
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
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
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
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)
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
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
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
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
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.
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
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)
Cephalosporins (name recap) 1st generation cephalosporins (on our list)? • Cefazolin, cephalexin 2nd generation? • Cefuroxime, cefprozil 3rd generation? • Ceftriaxone, cefixime 4th generation? • cefepime
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
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
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
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!
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)
Carbapenems Name 3 adverse reactions. • Nausea and vomiting • Hypersensitivity • seizures in patients with CNS lesions or renal insufficiency Can pregnant women take these? • Yes.
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
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
Let’s REHASH THE NAMES Because they all sound the same.
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
Cephalosporins 1st generation cephalosporins (on our list)? • Cefazolin, cephalexin 2nd generation? • Cefuroxime, cefprozil 3rd generation? • Ceftriaxone, cefixime 4th generation? • cefepime
Other β-lactams Carbapenems? • Imipenem-cilastatin Monobactams? • aztreonam
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
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
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)
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