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Antibiotics > Cell Wall Abx > Flashcards

Cell Wall Abx Flashcards

1
Q

What monitoring must be done when patients are on Daptomycin?

A

Weekly monitoring of creatine phosphokinase to look for myopathy

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2
Q

What is Daptomycin useful for? What body site is it not able to treat?

A

Useful for VRE or VRSA. “When vanc won’t work, try this.”

Never useful for pneumonia as surfactant in lung deactivates drug

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3
Q

What is the first line treatment for syphilis?

A

PCN G

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4
Q

What types of non-IgE hypersensitivity reactions can occur with PCN?

A

IgG or IgM mediated reactions, including serum sickness, autoimmune hemolytic anemia, interstitial nephritis, vasculitis

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5
Q

What is the reaction unique to vancomycin that commonly causes concern for allergy?

A

Red Man syndrome. Due to histamine release from rapid drug infusion, causes redness, itching, sensation of burning up. Patients should only be red from the chest up with this syndrome. Treat by slowing down infusion, premedicating with Tylenol and antihistamine

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6
Q

Third generation cephalosporins

A

Ceftriaxone, cefotaxime, cefdinir, ceftazidime, cefixime

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7
Q

What is the most common cause of bacterial resistance to beta lactam antibiotics?

A

Beta-lactamase hydrolysis of the molecule

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8
Q

How does resistance of the cephalosporins to typical beta-lactamases differ from penicillins?

A

Cephalosporins are more intrinsically resistant to beta-lactamases than penicillins and usually are not paired with a beta-lactamase scavenger. The exception is the 5th generation cephalosporin.

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9
Q

How is penicillin eliminated/metabolized?

A

Renal excretion, with the exception of nafcillin which is excreted in the bile. Requires decreased dose in renal failure, and more time between doses in neonates that have a slower clearance of the drug

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10
Q

What is the definition of neutropenia? Why is it important when considering antibiotic coverage?

A

Neutropenia is defined as <1500neutrophils/mL.

Patients with neutropenia are more susceptible to infection, including infection with gram negative bacteria like pseudomonas that the body would usually be able to prevent setting up infection in sterile sites. If the neutropenic patient is also one that has an in dwelling device or lots of contact with the healthcare system, they have an increased risk of resistant bacterial infection. Thus, neutropenic patients with fever are always hospitalized and antibiotics chosen that include pseudomonal coverage and drug resistant bacteria coverage. Vanc + cefepime or vanc + meropenem are typical choices for neutropenic fever

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11
Q

What is the spectrum of coverage of ceftazidime that sets it apart from the other 3rd gen cephalosporins?

A

Antipseudomonal coverage

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12
Q

Antipseudomonal penicillins

A

Ticarcillin and piperacillin.

Because beta-lactamases are a major defense mech for this bacteria, they are always used in combination with tazobactam. Thus, for a patient with cystic fibrosis and a pseudomonal infection, you will prescribe pip/taz, not piperacillin alone.

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13
Q

What is the actual estimated risk of penicillin type I anaphylaxis in the general population?

A

0.015-0.004%, or approximately 1 in 6500 patients

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14
Q

What is the risk of rash or other reaction to penicillin?

A

1-5% in the general population. Many of these common reactions are not IgE mediated, but will be mistakenly labeled as such

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15
Q

Which cephalosporins break the rule “cephalosporins do not cover enterococci”

A

5th generation cephalosporins: ceftaroline and ceftolazone/tazobactam

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16
Q

What is the clinical use of cefuroxime?

A

Outpatient oral treatment of respiratory infections

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17
Q

4 major bacterial resistance mechs to PCN and its derivatives

A
  1. Beta-lactamase
  2. Failure of abx to penetrate outer membrane of gram neg bacteria
  3. Efflux of drug across outer membrane of gram neg bacteria
  4. Low affinity binding of abx to target PBPs
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18
Q

The natural penicillins are first line drugs for which specific bacterial infections?

A

Neisseria mengiditis, syphilis, and group A streptococcal pharyngitis (PCN G, given IM)

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19
Q

What is the risk when giving cephalosporins to patients that report a PCN allergy?

A

1) the risk is limited to patients that had an IgE based allergy to PCN
2) the risk in the IgE mediated allergic patients is limited to patients that had response to amoxicillin, ampicillin, and PCN
3) the risk is mediated by the structural similarity of the side chains and only certain cephalosporins carry that risk
4) in general, 3rd and 4th gen cephalosporins do not carry a risk of cross reactivity in PCN allergic patients

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20
Q

What steps do you take when a patient reports a PCN allergy ?

A

1) take a history. Exactly what happened? Anaphylaxis is not subtle. A patient who developed an itchy rash that doesn’t sound like hives may have the rash for other reasons, or may have had an IgG mediated response
2) unless there was clear cut anaphylaxis requiring medical intervention with taking the drug, send the patient for a formal allergy test. Do not label the patient as PCN allergic unless there is good evidence to do so

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21
Q

2nd generation cephalosporins

A

Cefaclor, cefoxitin, cefuroxime, cefotetan

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22
Q

What characteristic of carbapenems makes them Intrinsically resistant to beta lactamases?

A

A conformational change compared to other beta lactam abx that makes them intrinsically resistant to beta lactamases

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23
Q

Major mechs of resistance against the carbapenems

A

Carbapenemases, extended spectrum beta lactamases and altered porin size in gram negative bacteria

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24
Q

Mechanism of action of vancomycin?

A

Binds to D-ala-D-ala (bill y’all) terminus of peptidoglycan, inhibiting both the transpeptidase and transglycosylase enzyme. This inhibits elongation and cross linking of the peptidoglycan chain/wall

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25
Q

What is the mechanism of resistance to fosfomycin?

A

Fosfomycin has to be in the cell to work, and it is transported actively. Thus, resistance is due to inadequate transport into the cell. The unique MOA of the drug and its differing mechanism of resistance make it useful for extended spectrum beta lactamase producing bacterial infections

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26
Q

Bioavailability of vancomycin?

A

Vanc is 0% bio available, and is only given orally if we want to kill bacteria living in the lumen of the gut as a result. It’s oral use is limited to treatment of C. Difficile colitis that has relapsed despite prior courses of treatment.

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27
Q

How does the spectrum of coverage of 3rd gen cephalosporins differ from gens 1 and 2?

A

Lose MSSA coverage (never had MRSA coverage), increased gram neg coverage

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28
Q

What toxicity does vancomycin share with gentamicin?

A

Ototoxicity, can cause enshrine urial deafness. Vanc and gent were used in synergistic combos for years and caused a lot of deafness as a result.

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29
Q

What must patients be warned about when taking cefdinir?

A

The liquid formulation turns stool red and looks like blood

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30
Q

First line coverage for strep throat (GAS pharyngitis)

A

PCN G given IM or amoxicillin PO

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31
Q

What unique characteristic of ceftaroline makes it effective in treating MRSA and VRE?

A

Binds PBP 2a, which is an alto PBP that mediates resistance to methicillin in MRSA and multidrug resistant strep pneumoniae. This is encoded by the MecA gene

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32
Q

How does abx design try to overcome bacterial inactivation of beta lactam abx?

A

1) pair abx w beta lactamase scavenger (clavulanate, tazobactam, sulbactam)
2) molecular changes in the drugs design, namely carbapenems which are stereochemically different and resistant to most beta lactamases

33
Q

What additional monitoring must be done when a patient is on vancomycin?

A

Monitor peak and trough levels in addition to renal toxicity. Peak levels are monitored to ensure they are high enough to kill the infection and not so high that they cause toxicity. Trough levels are monitored to ensure they are not too low and allowing bacteria to replicate. Concentration dependent killing, not time dependent

34
Q

Can PcN and its derivatives be used in brain infections?

A

Yes, PCN can enter the brain when meninges are inflamed. When they are not inflamed, PCN and its derivatives do not enter the brain at high enough levels to be effective

35
Q

Imipinem/cilistatin is a complex of two drugs. What is the purpose of adding the cilistatin?

A

To prevent renal tubular inactivation of the drug, prolonging the half life

36
Q

Name the antistaphylococcal PCNs. What helps determine their spectrum of action?

A

Nafcillin, oxacillin, dicloxacillin. Methicillin isn’t used clinically due to toxicity but is used in the lab. These drugs have a bulky side chain that protects them from many beta lactamases and makes them unable to fit through porins, so they are only good for gram pos infections

37
Q

What is the mechanism of action of daptomycin?

A

Unique MOA: lipophilic tail inserts into cell membrane, depolarizing it, causing K+ efflux and death

38
Q

First line choice for suspected bacterial meningitis?

A

Cefotaxime, ceftriaxone. The only difference really between these two drugs and their coverage of pathogens/ body sites is that ceftriaxone lasts 24 hours, making it a popular choice in ERs everywhere.

39
Q

Extended spectrum PCNs that do not have anti pseudomonas activity, and their additive

A

Ampicillin and amoxicillin. These can be used alone, or as amp/sulbactam and Amos/clavulanate, which adds a beta lactamases scavenger to ma,e them affective agains class A beta lactamase producing bacteria

40
Q

Use of Cephs to treat enterococcus infections or listeria monocytes ends

A

As a class, they are inactive against both types of bacteria

41
Q

Bacitracin MOA

A

Inhibits cell wall formation by disrupting cycling of the lipid carrier that transfers peptidoglycan subunits to the growing cell wall. These carriers are called bactoprenols, and cycle between and and two phosphate groups. Bacitracin keeps them from being dephosphorylated and thus unable to carry peptidoglycan monomers

42
Q

How does the side chain of the beta lactam molecule determine the spectrum of abx coverage?

A

Beta lactamases with bulky side chains can’t get through some gram neg porins. Porins size can be plasmid mediated or chromosomal. This is one major reason that some beta lactamases cover gram neg bacteria and some don’t.

43
Q

What antibiotic is always included to cover neonatal sepsis due to group B strep and listeria?

A

Ampicillin

44
Q

What mediation can be used to prolong the half life of PCN?

A

Probenecid prevents active tubular transport of the drug and prolongs the half life

45
Q

Name the natural penicillins and their usual spectrum of coverage

A

PCN G and PCN V. These are very susceptible to beta-lactamases

46
Q

What is the mechanism of action of fosfomycin?

A

Chemically novel drug that inhibits cytoplasmic rather than extra cellular reactions. Inhibits enolpyruvate transferase, preventing formation of cell wall component ecetylmuramic acid

47
Q

How many patients reporting a PCN allergy actually have a PCN allergy based on a major review?

A

1 in 10 patients reporting a CN allergic response were actually found to have a PCN allergy on further testing

48
Q

What is the role of Vancomycin in CNS infections

A

Penetrates CNS with inflammation only, similar to penicillins. Used when CSF is abnormal, suggestive of bacterial meningitis, and always used in concert with a third gen cephalosporin. The reason for adding the vanc is to cover multi-drug-resistant S. Pneumoniae. Recall that the mech of resistance for MDR s. Pneumo is alteration of PBP 2a, which would not affect the mechanism of action of vancomycin

49
Q

Cephalosporin dosing has to be decreased in patients with which type of organ failure?

A

Renal failure (just like penicillins)

50
Q

What is the risk of x-reaction between PCN allergy and carbapenem allergy?

A

About 1%, previously estimated much higher

51
Q

Name the carbapenem antibiotics

A

Doripenem, ertapenem, imipinem, meropenem

52
Q

What is aztreonam’s spectrum of activity?

A

Aerobic gram neg rods only

53
Q

What is first line treatment for pseudomonal infections?

A

Pipercillin/tazobactam or Ticercillin/Tazobactam. Another abx w a different mech of activity will usually also be used as Pseudomonas have inductive resistance to so many abx

54
Q

What I the major mechanism of resistance to aztreonam?

A

Beta-lactamases

55
Q

What I the risk of cross-allergy between amoxicillin and first-generation cephalosporins?

A

The risk is actually specific to cephalexin, not to the other first-gen cephalosporin cefazolin, and is 1-10%

56
Q

What is first line tIV treatment for MSSA infections?

A

Nafcillin,Oxacillin, Dicloxacillin

57
Q

Describe the steps in PCN derivatives killing. Bacterial cell

A
  1. Covalent binding to PBP
  2. Can’t cross link wall
  3. Induction of autolytic enzymes
  4. Cell wall ruptures due to high internal osmotic pressure
58
Q

What is the significance of the MecA gene?

A

Encodes for an altered PBP 2a, which has a low affinity for many beta lactam drugs. This is the key gene responsible for MRSA and contributes to multi-drug-resistant S. Pneumoniae

59
Q

Why is the spectrum of coverage of the first generation cephalosporins?

A

Gram positives, staphylococci and streptococci. No MRSA, the only gram neg is pan-susceptible e. Coli

60
Q

What is the pseudomonas activity of the carbapenems?

A

All except ertapenem are good antipseudomonals

61
Q

What is the spectrum of activity of Vancomyin?

A

Gram positive only, too big to fit through porins

62
Q

What is the bacteriocidal activity of vancomycin compared to cephalosporins and penicillins?

A

Vanc is reserved for gram positive infections that are resistant to PCNs and cephs because it is actually less bacteriocidal, less able to kill bacteria rapidly, than those other drug classes. People think of it as a big gun, but it isn’t.

63
Q

Comment on the role of altered PBPs in resistance to cephalosporins

A

The altered PBPs are a more prominent mode of resistance to cephalosporins than they are for PCNs. Recall that although multiple modes of resistance to PCN are possible, by far the most common is beta-lactamase, which the cephalosporins are more intrinsically resistant towards. This is why there is only one cephalosporin, a fifth gen, that is packaged with a beta-lactam scavenger

64
Q

What is the spectrum of coverage of the second gen cephalosporins compared to 1st gen?

A

Increased gram neg coverage, particularly for respiratory pathogens

65
Q

What attribute makes penicillin ineffective to treat intracellular infections?

A

Penicillin is polar and can’t enter mammalian cells effectively. It can be used for some infections that have an intracellular component only if large parts of the life cycle for that organism are extracellular. (Rocky mountain spotted fever, gonorrhea - historically, enforce drug resistance became a Robles)

66
Q

Name the first generation cephalosporins

A

Cefazolin and cephalexin

67
Q

What is televancin?

A

Same class of antibiotics as neomycin and same MOA, same spectrum, less toxicity

68
Q

Which cephalosporin is a drug of choice in treatment of neutropenic fever?

A

Cefipime, due to its excellent gram neg coverage which includes antipseudomonal coverage, coverage of multidrug resistant strep Pneumoniae

69
Q

How does spectrum of anti microbial coverage change as the generations of cephalosporins change?

A

With each successive generations, gram negative coverage increases

70
Q

Why is PCN a old choice for treating a breast abscess/infection in a lactating mom?

A

PCN and PCN derivatives get into breast milk and will prevent spread to the baby who is nursing from the affected breast

71
Q

What is the CNS penetrance of first gen cephalosporins?

A

Poor, not used for CNS infections due to no penetrance

72
Q

What are the major side effects/toxicities to watch out for when a patient is taking cofetetan?

A

Disulfuram-like reaction (profuse vomiting, wanting to die) when drink alcohol while on the drug, hypothrombinemia is and bleeding

73
Q

How does active transport of beta-lactam medications cause bacterial resistance to these drugs?

A

Efflux pumps in gram-negative bacteria pump the antibiotic out of the peri plastic space, which is where it has to be to work on the peptidoglycan cell wall. They can be chromosomal or plasmid-mediated.

74
Q

What part of the penicillin derivative molecular structure is inactivate by bacterial enzymes?

A

The beta lactam reign is hydrolysis by bacterial beta-lactamases. They can be plasmid encoded or chromosomally encoded.

75
Q

What is a unique toxicity of daptomycin?

A

Allergic pneumonitis. (Also can’t use in pneumonia because surfactant breaks it down)

76
Q

What characteristic of the carbapenems makes them a good choice for beta-lactamase + bacteria?

A

A conformational change compared to the other beta-lactam antibiotics that makes them intrinsically resistant to beta lactamases

77
Q

What is the usual clinical use of cofetetan and cefoxitin?

A

Think stuff that lives in the GI and Gu tract: contaminated surgical site surgeries, pelvic inflammatory disease, peritonitis

78
Q

What is the only cephalosporin complexed to to a beta-lactamase scavenger?

A

Ceftolazone-tazobactam, a 5th gen cephs that is used with ID physician oversight for serous intra abdominal infections or multidrug resistant UTIs

Antibiotics (3 decks)

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