Cell Wall Agents 2 Flashcards
Generally speaking regarding cell wall synthesis inhibitors, are they more likely to inhibit gram positive or negative organisms? What 2 of the following describe their spectrum: narrow, broad and extended?
Gram positive
Narrow and extended
Generally speaking regarding cell wall synthesis inhibitors, are they bacteriocidal or bacteriostatic? How are they cleared from circulation?
Bacteriocidal
Renal clearance
What is the unique component of bacteria cell walls that is targeted by cell wall agents?
Peptidoglycan
What are the 5 examples of peptidoglycan synthesis inhibitors provided?
Vancomycin Fosfomycin Beta-lactams Bacitracin Cycloserine
What is the mechanism of action of fosfomycin? What Kreb cycle component is it analagous to? How is it excreted? How is its spectrum characterized?
Blocks 1-PDG synthesis by mimicking phosphoenol pyruvate (Kreb cycle)
Excreted unchanged in urine
Considered broad spectrum
While fosfomycin doesn’t have a lot of associated toxicities, what are 2 known toxicities? What is it used to treat, and how?
Diarrhea and vaginitis
Single dose treatment of uncomplicated UTI
D-cycloserine work by blocking _. It is an analogue to _. It is considered _ spectrum. It is used for the treatment of _
2 steps of PDG synthesis
D-alanine
Broad spectrum
Tuberculosis (2nd line treatment)
D-cycloserine is administered via _, It is excreted in _ in its [active/inactive] form. It [does / does not] enter the CNS and its major toxicity is _
Orally Urine Active form Does enter CNS CNS side effects (serious)
What is the mechanism of action of bacitracin? How is it administered? How is its spectrum characterized? What is the major associated toxicity?
Depletes lipid carrier necessary for PDG synthesis
Topically
Narrow spectrum
Major nephrotoxicity
What a 2 uses of bacitracin? What is it usually mixed with? What are 2 bugs it is effective against?
Skin and Eye infections
Mixed with polymyxin B
Neisseria and T. Pallidum
What is the mechanism of action of vancomycin? It is rapidly bacteriocidal in _. What is the exception where vancomycin is bacteriostatic?
Binds d-ALA, prevents cross linking of PDG
Dividing bacterial cultures
Bacteriostatic in enterococci cultures
Vancomycin is administered _. Why is it not administered intramuscularly? Orally? How is it excreted? Under what conditions does it get through the CNS?
IV Causes muscle tissue necrosis Poor absorption orally Excreted renally If meminges are inflamed
How is the spectrum of vancomycin characterized? What types of bugs is it active against?
Narrow
Mainly gram +, mainly MRSA
What are 2 mechanisms by which bugs can develop resistance to vancomycin?
vanco resistant enterococci - express vanA, vanB and vanC genes coding for different subunits with reduced binding to vanco
vanco resistant staph aureus - overexpress D-ala which bindings up drug
What are the 3 toxicities associated with vancomycin?
Red man syndrome
Ototoxicity
Nephrotoxicity
What are 2 types of bugs that vancomycin is used to treat? What drug class is it synergistic with?
MRSA, penicillin resistant staph aureus
Aminoglycosides
What are the 4 examples of beta lactam antibiotics provided?
Penicillin
Cephalosporin
Carbapenems
Monobactams
In general, beta lactams act by inhibiting what enzymes? They are structural analogues to what cell wall protein? What is their net effect on PDGs?
Transpeptidases (PBP)
D-alanine
The prevent their crosslinking by binding penicilin binding proteins (PBP)
Beta lactams are bacteriocidal. However, what condition must be met for them to have this property?
The bacteria must be dividing
In general, beta lactam are widely distributed. What is the one area where they are not? How are they excreted and through what route?
Don’t get to CNS
Unmetabolized, via kidneys
In general, most beta lactams are not metabolized. What are the 2 exceptions?
Nafcillin and imipenem
What is the main target of beta lactams? What are 3 other targets of the beta lactams?
Major - gram positive anaerobes
Others - gram negative cocci and rods, spirochetes
What is the most common way by which drugs become resistant to beta lactams? How does MRSA become resistant to beta lactams
Production of beta-lactamases
Expression of altered PBPs
Beyond the Production of beta-lactamases and Expression of altered PBPs, what are 2 other ways to become reisstant to beta lactams?
Alteration of outer mem. proteins (prevent binding to PBP)
Increased expression of efflux pumps
While toxicity associated with beta lactams are minimal, what are 3 acknowledged associated toxicities?
Tissue irritation
Phlebitis with IV admin
Superinfections
Allergy is a major concern with the beta lactams. Cross sensitization can also occur with what types of drugs? What is the difference in time line between acute, accelerated and delayed allergic reaction? Which is most serious? Which is most common?
Cross sensitization with chemically related drugs
Acute - 30 min of adminstration (most serious, anaphylaxis)
Accelerated - 30 min - 48 hrs
Delayed - 2 or more days (most common)
What are the 2 types of penicillin? How do they differ in stability in acid? How do they differ in routes of administration?
Pen G - Acid labile - IM and IV
Pen V - Acid stable - Oral admin
What are the types of bugs that penicillin is effective against? What are they ineffective against?
Effecive - Gram +, Gram - cocci
Ineffective - Gram - rods, and anaerobes
What are the major toxicities associated with both types of penicillin?
Allergies
Stevens - Johnson syndrome
What is the major toxicity associated with pen G and not pen V?
Dose dependent neurotoxicity and seizures
What types of microbes should penicilin not be used against? What microbe has many penicilin resistant strains?
Don't use against penicillinase producing microbes Streptococcus pneumoniae (many are resistant)
Beyond strept. pneumoniae, what are 4 other microbes against which penicillin can be used?
Staphylococcal sp.
Neisseria meningitidis
Clostridium sp.
Treponema pallidum
What are the 4 examples of penicillinase resistant penicillins?
Oxacillin
Cloxacillin
Nafcillin
Methicillin
What 2 microbes are the penicillinase resistant penicillins used to treat clinically?
Penicillinase-producing Staphylococci and
Streptococci
What is an adverse effect associated with methicillin? What about oxacillin?
Methicillin: interstitial nephritis
Oxacillin: hepatitis at high doses
What are the 3 classes of extended spectrum penicillins? What enzyme expressed by bacteria is able to destroy these drugs?
Aminopenicillins, carboxypenicillins and
ureidopenicillins
- Beta lactamase
What are the 2 examples of aminopenicillins provided? Are the stable or labile in acid? How are they administered? Which is not affected by food?
Ampicillin and amoxicillin
Acid stable
Oral admin
Amoxicillin not affected by food
What microbes are the aminopenicillins effective against? What are 4 examples provided?
Non-lactamase gram- bacilli
E. coli, H. influenza, Salmonella, Shigella
What type of penicillin can be used as a prophylactic against bacterial endocarditis?
Amoxicillin
What are the 2 examples of carboxypenicillins provided? How are they administered? What are they used against?
Carbenicillin and ticarcillin
Parenteral admin
Anti-pseudomonas
What are the 2 examples of piperacillin provided? How are they administered? What are they used against?
Piperacillin and mezlocillin
Parenteral administration
Anti- pseudomonas
Ureidopenicillins are reserved for use against _, (2) and are used in combination with _ to prevent resistance
Serious systemic klebsiella or pseudomonas infections
Used in combo with aminoglycosides
What are the 3 examples of beta-lactamase inhibitors? What is their mechanism? How are they used?
Clavulanic acid
Sulbactam
Tazobactam
They are beta-lactamase suicide inhibitors
Used in combination with extended spectrum penicillins
What is the mechanism of action of the cephalosporins? What is they main adverse effect associated with them?
Inhibit cell wall synthesis
Allergy
What is the clearance route of the cephalosporins? How are they metabolized?
Cleared by kidneys
Minimal metabolism
What are the mechanisms of bacterial resistance of the cephalosporins? (2)
Induce Amp C (Cephalosporinase)
Low affinity penicillin binding proteins
They cephalosporins are likely to be cross allergenic with _
Penicillins
What are the 4 examples of cephalosporins provided? What generations do they belong to?
1st - Cefazolin
2nd - Cefuroxime
3rd - Cefotaxime
4th - Cefepime
Which of the cephalosporins has the broadest spectrum against gram+ cocci (surgical
prophylaxis); effective against gram- bacilli?
Cefazolin
Which of the cephalosporins the the only group with significant activity against anaerobes?
Cefuroxime
Which of the cephalosporins is most widely used treatment in children / infants with
moderate to severe infections?
Cefotaxime
Which of the cephalosporins is antipseudomonal and has high resistance to beta-lactamases?
Cefepime
Which of the cephalosporins is antipseudomonal and antipneumococcal and has activity against serious gram - infections such as meningitis, pneumonia, gonorrhea?
Cefotaxime
What are the 3 examples of carbapenems provided? What major bacterial resistance product are they largely resistant to?
Imipenem, meropenem and ertapenem
Beta-lactamase
Among the carbepenems, penicillins and cephalosporins, which has the broadest activity? Why shouldn’t the carbapenems be co-administered with penicillins or cephalosporins?
Cerbepenems
Induces beta-lactamases that inactivate penillins and cephalosporins, antagonizing their bacteriocidal effects
While the carbepenems are resistant to beta lactamase, what is the major mechanism by which resistance occurs?
Alteration of penicillin binding proteins
Which of the carbepenems is inactivated by the kidneys? How can this be reduced?
Imipenem
Co-admin with cilastatin, a dehydropeptidase inhibitor
The carbapenems are cross allergenic with _
Penicillins
What is the clinical use of the carbapenems?
2nd line therapy for serious nosocomial infections
What is the example of a monobactam provided? What is its mechanism? What is its interaction with beta lactamases? Like the carbepenems, is it cross reactive with penicillin?
Aztreonam
Binds the penicillin binding proteins
Resistant to beta lactamases
It is not cross reactive with penicillins
How is aztreonam administered? How is it kept out of the CNS? What are its 3 uses?
IM or IV
It enters an inflammed CNS
Gram - UTI, lower resp. tract infection, systemic infection
What is the spectrum of aztreonam, i.e. what bugs is it effective against?
Gram - aerobes and pseudomonas
What is the example of the cell membrane agent provided? What is its mechanism? How is it administered and how is it eliminated?
Daptomycin
It causes membrane depolarization
Administered IV
Renal excretion
The spectrum of daptomycin is very similar to that of what drug? What are 2 types of drug resistant bacteria that daptomycin treats? What is the major associated adverse effect?
Vancomycin
VREF and MRSA
Myopathy
