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169 Cards in this Set

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Which specific enzymes catalyze cell wall biosynthesis and degradation?
PBP/PSE
Penicillin Binding Proteins/Penicillin Sensitive Enzymes
Which are "essential" PSEs and what does this mean?
PBP1a, PBP 1b, PBP2, PBP 3
These help build up the cell wall and are known as transpetidase (hook AAs together) and transglycolase (hook sugars together) enzymes.

They make up ~10% of PBPs.
Which types of PSE/PBP are "non-essential" PSEs and what does this mean?
PBP4, PBP 5, PBP6
These help tear down the cell all and are known as carboxypetidases (cleaves the terminal alanine of a peptidoglycan unit that is not crosslinked to another unit) and endopeptidase (breaks the AA crosslinked bonds that are formed by by transpeptidase) enzymes.

They make up ~90% of the PBPs.
Why would cell walls need to be broken down?
For reproduction (bacteria reproduce by mitotic fusion so need to breakdown cell wall) and repair (need to chop out the bad part of the cell wall for integrity)
What role does "autolysin" endopeptidase play in bacerial replication?
non-essential
How do penicillins (and other beta-lactams) inhibit bacterial cell wall biosynthesis?
Bind to the active site (PBP) and form an covalent bond between a nucleophile on transpeptidase and the carbonyl bond after hydrolysis of the amide group in the beta lactam ring. This is "irreversible" inhibition similar to AchEIs and MAOIs.

These are competitive inhibitors!
Why is the beta-lactam ring of the penicillins electrophilic and therefore capable of enzyme acylation?
The amide in the beta-lactam ring is reactive due to ring strain and non-coplanar (because no resonance) causing the carbonyl electrophilic and the nitrogen basic which can be protonated.
What general chemical, biochemical, or physiologic conditions may promote opening of the beta-lactam ring?
Acidic, basic, nucleophilic, or enzymatic environments
When is beta-lactam ring opening a "desired" reaction? When is it "undesired"?
It is "desired" on PBP surfaces but "undesired" anywhere other than PBP. If it does open somewhere else, this leads to HYPERSENSITIVITY reactions.
How are all beta-lactam drugs similar in structure? How are they different?
They all have a beta-lactam structure and they are different by the 6-acyl-amino side chain.
How are penicillin drugs sub-classified?
Natural Penicillins: Pen G and Pen V

Antistaphylococcal Penicillins: Methicillin, Nafcillin (Aroyl ASPs)
Oxacillin, Cloxacillin, Dicloxacillin, Flucloxacillin (Isoxazoles)

Amino-penicillins: Ampicillin and Amoxicillin

Carboxypenicillins (ESPs):Carbenicillin and Ticarcillin

Ureido-Penicillins (ESPs): Azlocillin, Mezlocillin, and Piperacillin
What is activity of Penicillins dependent on?
Concentration of drug in periplasmic space, concentration of BLases in periplasmic space, binding affinity of PBPs for drug, bactericidal action on autolysin peptidase, Time (Time>MIC), location of the pathogen (Chlamydia, Rickettsia), amount of bacteria, replicative state (penicillins only active against replicating bacteria), synergism with aminoglycosides vs Enterococci, Pseudomonas, and Listeria, antagonism, HA/CA, and appropriate vs effective drug therapy
What barriers limit penicillin diffusion to the site of action in gram positive bacteria?
cell wall
What barriers are not present in gram positive bacteria?
porin (outer membrane), capsule
Why are Enterococci and Listeria not susceptible to anti-staphylocococcal penicillins?
Because ASPs don't bind to enterococci and Listeria
Are Streptococci, Enterococci, Listeria and gram positive anaerobes (Peptostreptococci, Propionibacterium) likely to produce beta-lactamases that can inactivate penicillin?
No because they don't have an outer membrane and don't produce beta-lactamases.

Know that Enterococci and Listeria are related so if a penicillin is active against Enterococci, it would be active against Listeria.
What is the major mechanism of penicillin resistance for Streptococci, Enterococci, and Listeria?
Modified PBP; they produce PBPs with low or very low affinity for the natural penicillins.

E. faecalis is more susceptible than E. facium.

Ampicillin and Pen G are the most effective when used with an Aminoglycoside to treat E. faecalis and L. monocytogenes infections.
What is the treatment for S. pneumonia (PSSP and PRSP)?
All Penicillins for PSSP

No Penicillins for PRSP
What is the treatment or Enterococcus faecalis/facecium?
All pens but ASP
What is the treatment for L. monocytogenes?
All pens but ASP
What is the treament for Treponema (Syphillis) - atypical, Pasteurella (animal bites), Eikenella (human bites) and N. meningitis (meningitis) - G (-) bugs?
All pens but ASPs
How are staphylococci similar to streptococci and enterococci? How are they different?
They are all gram positive bugs but Staphylococci produce beta-lactamases and have modified PBPs(MRSA/E).
What pens are effective against MSSA/E? What pens are effective against MRSA/E?
ASPs and ESP + BLI
Why, in general, are S. aureus more susceptible to certain penicillins thant S. epidermidis?
Because virtually all S. epidermidis are MRSE!
What is the mechanism of resistance for Staphylococci?
Production of penicillinases that inactivate ALL penicillins except anti-staphylococcal penicillins and those penicillins combined by beta-lactamsese inhibitors (BLIs).

Also resistance by production of modified PBPs with very low (MRSA/MRSE) affinity for ALL penicillins and other beta-lactam drugs.
In general, what do penicillins cover?
MSSA, Streptococci, gram positive anaerobes (Peptostreptococci and Propionibacteria), simple gram negatives that don't produce beta-lactamases (Pasteurella, Eikenella, ad N. meningitis), and Treponema.
What are 3 reasons why many penicillins are generally ineffective or less effective against gram negative pathogens and than gram positive pathogens?
1. Beta-lactamases (all G (-) bugs and Staphylococci)
2. Outer membrane (exclude natural Penicillins except for aminopenicillins - these have increased OM penetration)
3. PBPs
Are aminopenicillins effective against Pseudomonads? Why?
No
The ESPs are effective against more G(-) pathogens than natural penicilins, ASPs, or aminopenicillins. Why?
Because they can penetrate the OM and have increased PBP binding.
List the different mechanisms of resistance and treatment for various strains of E. coli.
1. Non-Beta-lactamase Producer (community/UTI) - penicillins that can penetrate the OM (Aminopenicillins and ESPs)

2. BSBL Producers (2b, TEM-1&2, SHV-1) - rel. resistant to all pens when used alone but susceptible o Aminopenicilins +BLIs and ESPs + BLIs

3. BSBL Hyper producers (TEM-1) with modified porins - resistant to all pens when used alone and rel. resistant to Aminopens + BLIs and ESPs + BLIs ("overwhelm" pens + BLIs)

4. IRBSBAL Producers (rare but 2br and TEM 30-60) - resistant to all pens used alone and Aminopenicillins/ESPs + BLIs

4. ESBL Producers (2be, TEM 3-26 & SHV 2-6) - resistant to all pens when used alone but maybe susceptible to Amiopenicilins/ESP + BLIs - BEST TO NOT USE ANY PENICILLINS
List the mechanisms of resistance for P. aeruginosa.
1. Penicillinase Producers (Type A/community) - resistant to all but ESPs; use ESP + BLIs

2. Group 1 (C/hospital) Chromosomal BLases (Inducible AmpC and Ceph'ases) - resistant to all and induced by ESPs! Only tazobactam (BLI) is effective.
Which penicillin + BLI product combinations are available?
Amoxicillin/Clavulanate

Ampicillin/Sulbactam

Ticarcillin/Clavulanate

Piperacillin/Tazobactam
Which pathogens would be susceptible to a combination of penicillin G and clavulanate? Why is this combination not available?
PenG/Clav could affect the usual natural penicillin-susceptible bugs, as well as: staph, simple G

*no need to make this combo because Amox/Clav already covers all those.

What do BLIs do? What is suicide or mechanism based inhibition?
Their MOA is like MAOIs by binding and forming 2 covalent bonds (1 is revesible and the other is irreversible).

The steps are 1) recognition, 2) acylation - not a permanent covalent bond - can be hydrolyzed, 3) formation of a second electrophilic center (imine), 4) attack by secondary nucleophile on enzyme - permanent inactivation of B-lase
Do BLIs have clinically significantly antibacterial (PBP affinity) when used alone. Why?
No, because they lack the 6-substrate which is required for binding.
What is the efficacy of a particular penicillin/BLI combination dependent upon?
Pharmacokinetic and pharmacodyamic complimentarity, intrinsic activity of the BLI, and intrinsic activity of the penicillin.
What is the treatment for S. aureus (MSSA/E)? (penicillinase producer)
MSSA: ASPs and penicillins + BLI; Cefuroxime (2nd), Ceftaxime (3rd) and Cefepime (4th)

MRSA* (CA/HA): no penicillins or cephs are active against mPBP
What is the treatment for S. epidermidis? (penicillinase producer)
MSSE: ASPs + BLI; Cefuroxime (2nd), Ceftaxime (3rd) and Cefepime (4th)

MRSE: No penicillins or cephs are active against mPBP
What is the treatment for S. pyogenese (group A), S. agalactiae (group B), S. bovis (group D), and S. viridans? (no beta-lactamase productio but may have modified PBPs)
All penicillins and cephs are effective!
Nat, Amino, Ureido penicillins>ASP, Carboxy
What is the treatment for S. pnemoniae? (no beta-lactamase but may have modified PBPs)
PSSP: all penicillins and cephs

ISSP/PRSP: all pencillins less effective or "ineffective" so increase the dose or use another drug
*N-methoxyimino cephs are active: T/FrGCs: Ceftaxime, Ceftriaxone, and Cefapime, SGCs: Cefpodoxime and Cefuroxime
What is the treatment of Entercocci? (lower affinity PBPs and may have BLases but few)
E. faecalis: more penicillin susceptible - ALL penicillns effective except ASPs! (Amino, Ureide Pens > Natural Pens > Carboxy; Ampicillin (AOC) and Pen G combos with Aminoglycosides

*all cephs are ineffective!

E. faecium: less penicillin-susceptable than faecium - ALL penicillns effectie except ASPs! (Amino, Ureide Pens > Natural Pens > Carboxy; Ampicillin and Pen G compos with Aminoglycosides
What is the treatment for L. monocytogenes (gram positive bacilli)? (no BLases but lower affinity PBPs)

These occur in immunocompromised.

All penicillins are effect except ASPs! Amino and Natural penicillins are the most APPROPRIATE in combination with aminoglycosides.

*all cephs are ineffective!
What is the treatment for Peptostreptococci and Propionibacterium? (gram negative anaerobe; no BLases and PBP susceptible)
ALL penicillins and cephs (FGC) effective!
What is the treatment for Clostridia? (gram negative anaerobe; no BLases)
C. difficle (spore former) - ALL PENICILLINS and CEPHS INEFFECTIVE!! Cephs (3rd) may induce CDAD!

non-difficle-C/non-sporeformer (i.e. perfringens) - ALL PENICILLINS AND CEPHS ARE EFFECTIVE EXCEPT ASPs!
What is the treatment for M. catarrhalis (gram negative)?
This is a BSBL producer (75%) so appropriate treament is Penicillin + BLIs - Amoxicillin/Clavulanate (AOC)

*SGC/TGC
What is the treatment for N. gonorrhoeae (gram negative)?
Always assume BLase producer unless it's a college student.

non-BLase: ALL Penicillins (Pen G/Amp AOC)
BSBLs: Pens +BLIs
mPBPs: no Penicillins

*Ceftriaxone (TGC)>SGC
What is the treatment for N. meningitidis (gram negative)?
This is NOT a beta-lactamase producer!!

ALL Penicillins (AOC) or Amp (Alt)

*Ceftriaxone (TGC) or FrGC>SGC
What is the treatment for Acinetobactor sp. (gram negative cocci/bacilli)?
This is a BSBLase-producer and mPBPs

Penicillins alone are ineffective so use ESPs + BLIs (still may not be effective so pick another drug)

*Ceftriaxone (TGC)>SGC
What is the treatment for E. coli (emerging - gram negative bacilli/Enterobacteriaceae)??
This is a BSBL-producer (40%) and possible ESBLs

AOC: Ampicillin/Sulbactam (if not ESBL)

*TGC or SGC (if not ESBL)
What is the treatment for Proteus mirabilis (gram negative bacilli/Enterobacteriaceae)?
This is a BSBL-producer (5%) so only use Ampicillin (AOC)

*TGC or SGC (if not ESBL)
What is the treatment for Salmonella sp. (gram negative bacilli/Enterobacteriaceae)?
This is a BSBL-producer (20%) so only use Ampicillin (AOC).

*TGC or SGC (if not ESBL)
What is the treatment for Klebsiella pneumoniae (gram negative bacilli/Enterobacteriaceae)??
This is a BSBL-producer (95%) and possible ESBL

AOC: Ureido-penicillins (if no BSBL, ESBL, AmpC, or C'penase)

*T/FrGC (if no ESBL or AmpC - HA)
What is the treatment for Enterobacter sp. (gram negative bacilli/Enterobacteriaceae)?
This is a BSBL-producer (70%) and possible Amp C.

AOC: Ureido-penicillins (if no BSBL)

*T/FrGC (if no ESBL or AmpC - HA)
What is the treatment for Citrobacter freundii (gram negative bacilli/Enterobacteriaceae)?
This is a BSBL-producer (80%) and possible Amp C.

AOC: Ureido-penicillins (if no BSBL)

*T/FrGC (if no ESBL or AmpC - HA)
What is the treatment for Serratia marcescens (gram negative bacilli/Enterobacteriaceae)?
This is a BSBL-producer (90%) and possible Amp C.

AOC: Ureido-penicillins (if no BSBL)

*T/FrGC (if no ESBL or AmpC - HA)
What is the treatment for Pseudomoas aeruginosa (gram negative Pseudomonaceae)?
This is a CPenase-producer (30%) and possible Amp C.

Only ESPs!

AOC: Ureide>Carboxy

*T/FGCs (Cefepime*, Ceftazidime, Cefperazone)
What is the treatment for Burkholdera cepacia (gram negative Pseudomonaceae)?
ALL penicillins are ineffective!

*T/FGCs (Cefepime*, Ceftazidime, Cefperazone)
What is the treatment for Stenotrophomonas maltophilia (gram negative Pseudomonaceae)?
This is a CPenase producer and is intrinsically resistant to all penicillins.

ALL penicillins and cephs are ineffective!
What is the treatment for H. influenzae (simple gram negative bacilli)?
This is a BSBL-producer (35%).

non-BLase: Amino, Ureide, and Carboxy

BLase: Amp + Sulbactam (AOC)

TGCs for menigitis!! S/TGCs for all others
What is the treatment for Pasteurella multocida (simple gram negative bacilli)?
NO BETA-LACTAMASE!

All penicillin except ASP

AOC: Pen G

*all cephs can be used but decrease activity vs pens
What is the treatment for Eikenella corrodens (simple gram negative bacilli)?
NO BETA-LACTAMASE!

AOC: Ampicillin - SHOULD BE AMOXICILLIN BECAUSE COULD LEAD TO CDAD!

*all cephs can be used but decrease activity vs pens
What is the treatment for Bacteriodes fragillis (simple gram negative anaerobes)?
This is a betalactamase producer (75%)

Penicillins alone are ineffective

AOC: Ampicillin + Sulbactam

*Cephamycins (2nd) are most effective
What is the treatment for Legionella (simple gram negative anaerobes)?
NO Penicillins or Cephs!
What is the treatment for Prevotella sp. and Fusobacteria(simple gram negative anaerobes)?
NO BETA-LACTAMASE!

ALL PENs except ASP!

*Cephamycins (2nd) are most effective
Where do penicllins come frome? What is the difference between a true penicllin "antibiotic" and a "semi-synthetic"? Which penicillin products are which?
Penicllin G is a natrual penicillin that is biosynthesized by the fermentation of L-Cysteine with D-Valine to for 6-aminopenicillaic acid (6-APA) and then later Penicillin G.

All others are semi-synthetic because they have a different R-group at the 6-acyl-amino side chain.
What is the significance of the COOH at the 2 position? Which salts can be formed and what are their solubility profiles? How would different salts be used? How are COOH eliminated and distributed?
The 2-position carboxylic acid…always ionized at physiological pH; important for salt formation; acid means tubular secretion (amphoteric pens: GF + TS); distribution effects (acid: ionized, more water soluble, good dissolution—amphoteric: not water soluble, poor dissolution/water solubility)

Na/K --> water soluble (oral, IM, IV)
Ca/Al --> water insoluble (oral, IM—depot!)
Organic base salts --> water insoluble (oral, IM—depot!)
What is the stability of beta-lactams of different penicillins?
The BL ring of pens is not equally reactive; BL ring may be hydrolyzed (inactivated) in stomach acid, on plasma proteins, BLase, or act on PBP.

*Unstable functional groups: carboxy, ureido, BL ring
What is the metabolic profile of penicillins?
Metabolism not major for any penicillin except nafcillin > isoxazoles >> others (liver function?)

*all but nafcillin are cleared renally (TS, maybe + GF) and renal function may dictate half life or ppb. All except nafcillin have half lives = 0.5-1.5 hrs
What is the distribution profile of penicillins?
Plasma protein binding: isoxazoles > nafcillin > nat/carboxy/amino > ureido

*more ppb, less distribution
What is the dosage form and use of Penicillin G?
Crosses BBB!

B lactam hydrolysis limits F (but better than naf/meth)

*free acid (oral): acid catalyzed B lactam ring opening is possible

*Na/K water soluble salts (oral, IM, IV): acidic B lactam ring opening

*organic base water insoluble salts (oral, IM): low gut solubility; better acid stability;
prolonged action if IM
What is the dosage form and use of Penicillin V?
B lactam hydrolysis limited (but better than Pen G/naf/meth)

*Na/K water soluble salts (oral): more B lactam stability than Pen G; better oral bioavailability
What is the dosage form and use of nafcillin?
B lactam hydrolysis limited!!

*Na/K salts (oral, IM, IV): more acid unstable than Pen G; methicillin even worse; best if IV, b/c little to no oral bioavailability

*Most potent MSSA drug!!
What is the dosage form and use of Oxacillin?
solubility limited

*Na salt (oral, IM, IV): better acid stability, more oral bioavailability than Pen G but variable among isoxazoles due to different gut solubilities.
What is the dosage form and use of Cloxacillin and Dicloxacillin?
solubility limited

*Na salt (oral)
What is the dosage form and use of Ampicilln?
BBB! Solubility limited

*free amino acid (oral): better B lactam stability but less solubility b/c amphoteric
SO…bioavailability is no greater than Pen G. ORAL—kills bacteria in gut; much eliminated unabsorbed

*Na salt (IM, IV)
What is the dosage form and use of Bacampicillin?
Esterified HCl salt prodrug (oral): better B lactam stability and better
solubility in gut than Pen G. More bioavailability than Pen G or Amp
What is the dosage form and use of Amoxicillin?
Solubility limited (but better than Amp)

*free amino acid (oral): better BL stability than PenG and higher solubility (-OH); better
bioavail than Pen G or Amp
What is the dosage form and use of Ticarcillin?
Bioavailability limited by 6 side chain stability

*di-Na salt (IM, IV): less acid stable than Pen G (decarboxylation); NO oral bioavailabil.--sodium overload?? Platelet dysfunction??
What is the dosage form and use of Piperacillin?
Bioavailability is limited by 6 side chain stability

*Na salt (IM, IV): loss of ureido side chain in stomach acid; less soluble and less acid stable than Pen G; injection only (no oral bioavailability)
Which penicillins are administered orally?
Pen G/V, isoxazoles, bacampicillin, amoxicillin
What type of hypersensitivity reactions are penicillins involved in?
-Type I: anaphylaxis, urticaria, angioedema

-Type II: hemolytic anemia, neutropenia, thrombocytopenia

-Type III: serum sickness, interstitial nephritis

-Type IV: skin rashes (Amp/Amox)
What type of immune reactions are penicillins involved in?
Stevens-Johnsons (penicllin G and ampicillin), toxic epidermal necrolysis, drug fever
What type of other reactions are penicillins involved in?
GI upset, CDAC (Clostridium difficile-associatd colitis), platelet dysfunction, increased serum transaminases, hepatotoxicity, electrolytes (incr Na/decr K), seizures
How do penicillins cause hypersensitivity reactions?
Pens cause hypersensitivity by acylating plasma proteins; they are small, reactive molecules (HAPTENS). Compare to sulfonamides, ASA, PHT

**only Type I absolutely requires therapy cessation
What are some DIs associated with penicillins?
Probenecid/organic acids (TS), aminoglycosides (synergy), aminoglycosides (formulation/admin reactions—do NOT mix in solution because (1)acid/base insoluble complex (2) AG nucleophile reacts with BLactam (3) complex is immunogenic)
How does the cephalosporin and cephamycin ring system differ from that of the penicillins? What is the difference between a cephalosporin and a cephamycin? Why is this important?
In cephlasporins and cephamycins the ring system is a beta-lactam ring fused to a six-membered ring whereas in the penicillins this was a 5 membered ring. The six-membered ring is known as a dihydorthiazine heterocycle. The difference between a cepham and cephlasporin is that the bicyclic ring is fully saturated in the cepham and is unsaturated a c=c in the cephlasporin. A cephamycin is a second-generation cephalosporin that contains a 7-alphamethoxy group that helps to confer B-lactamase resistance.
Compare the reactivity of the beta-lactam of a cephalosporin to the penicillins. Why is there a difference in reactivity?
The beta-lactam ring of a cephalosporin is less reactive than the penicillins since the ring is fused to a six-membered ring instead of a 5-membered ring resulting in less ring strain trying to force the ring apart. With the cephalosporins containing the cephem ring the double bond is an electron withdrawing group that pulls the free pair of electrons on the N closer such that they are less available to attack by a hydrogen. In other words, the N is less basic.
What is the mechanism by which cephalosporins kill bacterial cells? How does this compare to the penicillins with respect to mechanism and PBP affinity?
Inhibition of the PBPs results in compromization of the bacterial cell wall leading to cell death. Cephalosporins preferentially bind to PBP3, which leads to filamentous bacterial cells. Both rx classes acylate the PBP by attacking a nucleophile on the enzyme but the different penicillins have different affinities for the various PBPs. The 7-acylamino group determines affinity and spectrum of affinity for cephalosporins whereas with the penicillins
What does the 2, 3, 7 substituents on the cephalosporin determine?
1) 7-acylamino moiety influences PBP affinity and BLase stability; this is req. for activity and affets spectrum of activity.

2) 3-substituent influences chemical and metabolic stability/instability and ppb. This determines oral bioavailability, half-life, route of admin, ADRs, etc. It also influences spectrum (porin penetration for quat groups vs P. aeruginosa).

3) 2-acidic group is required for PBP binding and directs most cephs toward renal elimination/salt formation (like Pens)

4) Beta-lactam ring is required for acylation and inhibition of PBPs but here, the stability>penicillins and not a factor in oral activity
What determines reactivitivity of cephs?
This is due to the absence of the normal amide resonance and small ring strain (like Pens) but they have LOWER beta-lactam reactivity due to the less ring strain and LOWER nitrogen basicity. The beta-lactam is still reactive enough to inhibit PBPs.
What are the different types of 3 substituents and what do they determine?
1) 3-acetoxy methyl cephalosporin (cephalosporanic acid) - these have an ester attached and is the most reactive goup (> beta-lactam); it is chemically (H+) and metabolically unstable because when it is hydrolyzed, it forms a desacetyl intermediate which reacts with the 2-carboxylic acid and forms a lactone; has a short half-life and if replaced with a carbamate (-NH2 instead of -CH3) it would be more stable and could be used orally; NO ORAL ACTIVITY, SHORT T1/2
2) 3-thioheterocyclic cephalosporins (thiomethyltetrazoles) - these have a tetrazole ring system attached to a sulfur and are chemical (H+) unstable (metabolically stable) because when a nucleophile attacks at the carbon adjacent to the sulfur, it formes a desacetyl intermediate which then becomes a lactone and is eliminated; NO ORAL ACTIVITY, LONGER T1/2
What are the first generation Cephalosporins and what are they used for?
Cefazolin (parental)
Cephalexin (oral)
Cephalothin
Cephapirine
Ceradine
Cefadroxil
Cephradine

Activity:
-As a general rule, FGCs have activity profiles comparable to the ASP and Pen +BLI - Meaning, they are principally used to cover staph and strept. They have the lowest activity of all of the cephalosporins. They are intrinsically ineffective against E. coli producing beta lactamases because they don’t have an AKI group. They may be effective against non-producing beta-lactamase and narrow spectrum beta-lactamase but not BSBL. They are intrinsically ineffective against P. aeruginosa because they don’t get in or survive. They are ineffective against Enterobacteracea because majority of these produce BSBLs.

**If you have a STAPH infection pick a FGC because they have the narrowest spectrum and are most efficacious
What are the different types of 3 substituents and what do they determine?
3) 3-inert substituents - these have substituents that do not react with the 2-carboxylic acid so they are chemically (H+) and metabolically stable; ORALLY ACTIVE, LOWER PPBs, SHORT T1/2; FOOD MAY DELAY ABSORPTION

4) 3-quaternary ammonium substituents (Ceftazidime, Cefepine) - this adds polarity to the agent and have antipseudomonal activity; NO ORAL ACTIVITY DUE TO POOR GI ABSORPTION

5) Cephalosprin prodrugs - (2-COOR) these have a stable 3 substituent and can be given orally; esterase-mediated hydrolysis is required for activation; FOOD INCREASES ABSORPTION (CEFUROXIME, CEFPODOXIME, CEFDITOREN, CEFAMANDOLE - SGCs)
What are the second generation Cephalosporins and what are they used for?
Cefuroxime (parental)
Cefamandole
Cefonicide
Ceforanide
Cefotetan (parental)
Cefmetazole
Cefoxitin
Cefaclor (oral)
Cefuoxime axetil
Cefpodoxime proxetil
Cefprozil
Loracarbef

1) Small non-ionizable AKI group (H, or CH3) - Effective against S. pneumonia, H. influenza, PRSP, and morexiella (RESPIRATORY PATHOGENS!!!!); Does not block BSBL produced by B. Fragilis (Drug would require cephamycin for activity!)

2) Cephamycin - Makes these drugs less effective against staph and strept because they can’t bind! Prevents inactivation of BSBL of E. coli and B. Fragilis; Always presume B. Fragilis is a gram (-) anaerobe that produces a BSBL

*Side notes*
a) All SGCs can kill non-BSBL producing E. coli
b) Only AKI and Cmycin SGCs kill BSBL E. coli
c) Only AKI SGCs can be used for PRSP
d) Only C’mycin SGC can be used for both gram + and gram – anaerobes
e) None of the FGCs or SGC are effective against Pseudomonads because THEY DON’T GET IN!!!!!
What are third generation Cephalosporins and what are they used for?
Cefotaxime/Ceftriaxone/Ceftazidime (Parental
Ceftizoxime
Moxalactam
Cefoperazone
Cefixime (oral)
Ceftibuten
Cefdinir
Cefditoren pivoxil

***If you’re going to treat meningitis with a cephalosporin then you have to use a third generation because they achieve the best levels of drug in privilege compartments. Never pick a maybe drug!

1) Aminothiazole functional group
*Increases binding to enterobacteracea
*Required for gram – binding

2) Ureido functional group allows for activity against pseudomonas (CEFOPERAZONE - not used anymore due to biliary ADRs)
What are third generation Cephalosporins and what are they used for?
3) AT + AKI (non-ionizable)/ N-Methoxy-imino (CEFDINIR, CEFTIZOXIME, CEFOTAXIME, CEFDITOREN, CEFTRIAXONE)-this gp helps retain activity against more G- and adds protecction agains BLase; the small R gp (H, CH, or OCH3) adds more activity against Strep. *Effective against strept(PSSP/PRSP), but not staph
*These have great activity against respiratory pathogens and bite wound pathogens but you will almost never use these because you have FGC and SGC that are the drug of choice.
*As a general rule, we save these for COMPLEX GRAM – BUGS or PRSP! *They are effective against E. coli, P. mirabilis
What are third generation Cephalosporins and what are they used for?
4) AT + ionizable AKI (CEFIXIME, CEFTIBUTEN)
*No activity against GRAM + bugs (They can’t bind because of the ionizable AKI group)!

5) AT + AKI+ Quat (CEFTAZIDIME, CEFEPIME) - Greatest efficacy against enterbacteracea whether it produces BSBL or not. *Quat - These are very much like piperacillin and ticarcillin in the penicillin family, the difference is if it’s a BSBL producing Pseudomonas or penicillinase producing pseudomonas (These get them, penicillins don’t)*Side note* - The difference between cetazidime and cefepime is that cefepime has activity against PRSP, but cetazidime does not because cetazidime has an ionizable AKI group but cefepime does not because cetazidime has an ionizable AKI group but cefepime does not.
What are bugs that are intrinsically resistant to all Cephalosporins?
-Amp C producing pseudomonas
-MRSA and MRSE
-E. faecalis
-Listeria
-Legionella
-CDAD
-S. maltophilia (stenotrophomonas)
-ESBL, Amp C or C’penamase producing Enterobacteriaceae
How is t1/2 determined for cephs?
1) Biliary excretion (EHR) - 3-methylthiotrizinedione

2) PPB!!!
non-3-methylheterocyclic derivatives < non-acidic 3-methylthiotetrazoles < acidic 3 - methylthiotetrazoles < acidic 3-methylthiotriaxidedione (Ceftriaxone)

3) Metabolism - Cefotaxime is significantly metabolized

**ALL CEPHS UNDERGO GF>TS (except ceftriaxone undergoes biliary)

The nature of the 3-substituent also affects protein binding in that if it contains a 3-NMTT group there is increased plasma protein binding, which increases the half-life of these agents. Ceftriaxone has a 3-methylthiotriazinedione, which yields 95% plasma protein binding (highest of any 3rd generation), is not metabolized, and therefore has the longest half-life.
For a dirty procedure, what type of ceph would you give?
Staph and Strep coverage so FGC or SGC (Cephamycin)
What are the ADRs associated with Cephalosporins?
The most common ADR is a hypersensitivity reaction similar to that of the penicillins with a frequency of less than 2 percent. The maculopapular skin rash is the most common display of a hypersensitivity reaction. Hypersensitivity is again related to the reactive beta lactam ring with the ability to act as a hapten. Cross-reactivity is minimal but an individual who has had a documented history of any anaphylactic reaction to a B-lactam, skin-test reactivity to penicillin metabolites should not be administered a cephalosporin.
What severe GI ADRs are associated with cephalosporins?
Pseudocholelithiasis (Biliary sludging) is due to deposition of ceftriaxone in the biliary tree during enterohepatic recycling. This reaction is more likely to occur with ceftriaxone because hepatic metabolism is an integral part of the elimination of this agent while the rest of the cephalosporins undergo mainly renal elimination. An individual who is receiving TPN or more than 2 grams of this agent daily is more likely to have this reaction occur.
Why is CDAD a significant problem with many cephalosporins/cephamycins?
This generally occurs with TGCs>F/SGCs because they have a broder spectrum and when taken oraly, it can lead to CDAD because kill normal flora
What is chemical mechanism and rationale for the “disulfiram reaction”? Which
cephalosporins/cephamycins are more likely to produce this interaction and why?
It can occur with parenteral agent that has a 3-NMTT side chain however it is the most common with cefoperazone. With this reaction is thought to be a result of cephalosporins inhibiting the complete oxidation of ETOH to acetaldehyde like Disulfiram (inhibits aldehyde dehydrogenase) yielding elevated blood levels acetaldehyde and its symptoms.
Which cephalosporins/cephamycins are more likely to induce hypoprothrombinemia and why?
It is an increase in PT time and is associated with 3-NMTT cephalosporins. In that this side chain allows the inhibition of the vitamin-K dependent clotting factors therefore prolonging the clotting time. The accused cephalosporins include moxalactam, cefamandole, cefotetan, cefmetazole and cefoperazone.
What are some DIs associated with cephalosporins?
1) Decreased absorption: antacids, PPIs, H2-antagonists

2) Distribution: competitive displacement (warfarin)

3) Metabolism: no CYP

4) Excretion: TS competition by probenacid and penicillins but not a problem because mostly elimited by GF
Why is aztreonam classified as a monobactam?
because it has only a single ring
Describe how each component of the aztreoname contribute toward its anti-bacterial spectrum of activity.
1) 2-aminothiazole: affinity for gram negative PBPs
2) Alkoxyamino group: increases BLase stability
3) Acidic N-alkoximino group: gram positive activity
4) Sulfonate: -R group that enhance electrophilicity of the C=O, resulting in BL reactivity for PBP acylaton
5) 2-alpha-methyl group: BLase stability
What is the basis for the chemical reactivity of aztreonam and how is it similar to other beta-lactams in terms of it's basic MOA?
It also has lactam ring opening due to hydrolysis of the amide functionality and acylation of the nucleophile on the PBP3 enzyme.

It's reactivity is not determined by ring strain but by resonance!!!
What facilityates penetration throught the porins of G- bugs for aztreonam?
It's ionic nature incrases penetration through the porins of Enterobacteriaciae and Psuedomonas (but there is some resistance of P. aeruginosa due to mPorins)
What is the spectrum for aztreonam?
Gram negative aerobic and facultative bacteria that do not produce ESBL, AmpC, or C'penases (M. catarrhalis, H. influenzae, Enterobacteriaceae, and P. aeruginosa)

It is resistant to narrow and BSBL!

You can also use it as an alternitive in cases of penicillin allergies

Never use alone as emperic therapy because only get the gram negative and not the gram positive or gram negative anaerobes
What is the dosage form of aztreonam?
IM or IV; can't give oral because very reactive due to H+ catlyzed hydrolysis!
What is the PK of aztreonam?
PPB: 50% ~ pens
Distribution: good including CNS
Metabolism: minimal
t1/2: short, 1.5-2.0 hrs (ESRD 6-8 hrs)
Dializable
Excretion: balanced renal (GF and TS)
How are carbapenems similar ins tructure to the penicilins and cephalosporins?
The "gorillacillins" have a betalactamase ring attached to a pentamer but they are different case thre is no "S" within the pentamer.

This increases ring strain and increases reactivity so you can't give it orally!
How do these structural differences contribute to microbiologic and biodisposition properties?
1) CH2 in place of S - ring strain ?penicillins
2) unsaturation at positions 23 (penem) - facilitates binding to renal DHP-1 (DHP metabolism)
3)6-hydroxyethyl (not "aculamino" like pens) - enhances BLase stability
4) 3-aminoetylthioether (not in pens or cephs)
5) N-formimidoyl group - prevents aminolysis (chemical stability)
What is the MOA of carbapenems?
These bind to PBPs of different bacteria and have acylation of nuchleophile locatd on the protein/enzyme.

It can induce Amp C but it doesn't matter because it is resistant; check after 1-3 days post administration to see if this has occurred so you won't discharge a patient on oral penicillins
What is the spectrum for carbepenems?
G+ bugs (MRSA/E, E. faecium, and Listeria monocytogenses ) and G- (P. aeruginosa and Acinetobacter)

In general, good penetration, BLase stability, hig/broad PBP binding affinity, Time-dependent inhibition, and PK like beta-lactams.

It can treat almost anything but only use for severe infction or "problem" bgs meaning life or limb, ESBL and AmpC producers. Use as infrequently as possible because the more you use --> resistance.

**Don't use imipenam for meningitis because it has the highest seizure rate. And Enterobacter and Psuedomonas are resistant to Imipenam but susceptabal to Mero and Dori. Erta is worst against Pseudomonas!
Rate beta-lactam reactivity of all beta-lactmases by H+ catalyzed hydrolysis by oral admin.
C'pens>Pens>Cephs!

C'pens have to prepared fresh for IV because hydrolysis will occur within the bag.
What are the PK for C'pens?
IV - rarely IM
High doses: for sites of poor drug penetration
Mero and Imi have similar Tmax, Cmax, AUC, and t1/2
Mero, Imi and Dori: have very low ppb (2-15%)but does not effect t1/2

Erta has high ppb (>90%) and a longer t1/2 - 4hrs

All have good distribution to CNS except for imi

Renally excreted so adjust dose in renal impairment; removed by hemodialysis
. How does thienamycin compare to penicillin G in terms of chemical reactivity? Is its beta-lactam ring more or less reactive? What other chemical reaction does thienamycin undergo? What is the role of pH in these reactions? How does the “aminolysis” reaction compare to the unique reactivity of ampicillin?
This agent is both chemically and metabolically unstable. With chemical stability, its B-lactam ring is susceptible to dehydropeptidase hydrolysis and aminolysis. In comparison with penicillins, it is more susceptible in acids and bases to hydrolysis. While at neutral pH aminolysis reaction will occur. This reaction occurs when the nucleophilic amino group of the 6-substituent attacks the C=O of the B-lactam ring of another drug molecule. In comparison to ampicillin, which undergoes a similar condensation reaction, the reactivity of the B-lactam is much greater with thienamycin than ampicillin.
How does thienamycin compare to the penicillins in terms of metabolic stability (reactivity)? Which enzymes cleave this drug and why? What is the product and importance of the reaction?
It is also metabolically unstable because it can undergo B-lactam cleavage via an enzymatic reaction. The enzyme involved is mammalian renal dehydropeptidase (DHP-1). This enzyme recognizes a double bond in a peptide substrate and cleaves at a specific peptide bond. In the case of thienamycin this cleavage occurs between the C=O and the N. The product is inactive in that it has no antibacterial activity.
How does the structure of imipenem compare to thienamycin and penicillin G? What role does the additional “formimidoyl” group play in chemical stability? Is the beta-lactam still reactive?
The N-formimidoyl derivative of thienamycin is imipenem where the 3-substituent has had a formimidoyl moiety attached. This increases chemical stability because the sulfur group can longer be attacked by the amino nucleophilic moiety in the 6-side chain therefore preventing the aminolysis reaction. The B-lactam still has the reactivity to exert its antibacterial effect.
How has the metabolic stability of imipenem been improved? What is cilastatin and what does it do (mechanism)?
Because imipenem is still susceptible to metabolism by DHP-1 it is combined with cilastatin which inhibits the activity of DHP-1. This agent is recognized by the enzyme in that it contains the dehydropeptidase double bond but it also contains a bulky cyclopropyl moiety, which prevents catalytic activity of the enzyme. Therefore, this agent ties up DHP-1 so that imipenem can exert is antibacterial effects.
How does the structure of meropenem compare to imipenem and penicillin G? What are the structural differences and what properties do they confer? Why does meropenem not require coadministration of cilastatin to be active?
Meropenem has similar structure to imipenem in terms of B-lactam fused to a carbapenem ring. However, it also contains a B-methyl, which is a CH3 attached to the carbapenem at C4. The 3-substituent is different and this increases activity against p. aeruginosa. The 4-B-methyl group provides stability to DHP-1, therefore, no need to use cilastatin.
How do the carbapenems compare to the penicillins in terms of mechanism of action? List three reasons that account for the relatively broad antimicrobial spectrum of the carbapenems and compare these to penicillins generally.
They bind to pbp’s causing cell death. However depending on the organism their affinity can be very specific. They also have the ability to truly penetrate all bacteria unlike penicillins. This is due to the following:
 small and zwitterionic nature to increase porin penetration
 high affinity for critical pbp’s of the organism
 Highly resistant to hydrolysis by both chromosomal and plasmid B-lactamases because of the nature of the 6-substiuent. However, this substituent also is a strong inducer of chromosomal B-lactamase with minimal affect on the agent.
Describe the key pharmacodynamic properties (PAE, time-dependent bactericidal action) of the carbapenems that contribute to clinical efficacy.
PAE is minor lasting 1-2 hours at the most. These agents are also time-dependent/concentration independent in terms of action. They also have the ability to penetrate and become concentrated in macrophages and to enhance in vitro chemotaxsis, phagocytosis by neutrophils and to stimulate C3b receptor production.
Describe the spectrum of activity of the carbapenems. Which organisms are they effective against and why?
Activity against all clinically important gram positive, gram negative and obligate anaerobes. Meropenem is better with gram negative while imipenem is better with gram positive. They are also able to fight listeria because of ability to penetrate the phagocyte. Moderately active against pneumococci that are penicillins and 3rd generation cephalosporin resistant. Not active against MRSA/E nor S. maltophilia.
What are the primary mechanisms of resistance to the carbapenems? How do these compare with the penicillins? Are the carbapenems resistant to hydrolysis by all beta-lactamases? Which specific organisms may be resistant to the carbapenems and why?
Stable to virtually all B-lactamases including AmpC. However there is a carbapenase produced by S. maltophilia that is starting to cross over to some strains of p. aeruginosa. Also have decreased affinity for MRSA/E, E. faecium, and listeria. Since carbapenems penetrate gram negative through the OmpD porin some p. aeruginosa, e. cloacae, S. maltophilia have lost this porin to decrease penetration by these agents. In addition, p. aeruginosa has an active efflux pump to pump this agent out of the cell.
How is each carbapenem formulated and administered? Why are they not orally bioavailable? Why should reconstituted carbapenem solutions be used promptly?
Neither is absorbed after oral administration due to chemical instability and therefore are formulated for parenteral administration. Imipenem is a powder for reconstitution that needs to be promptly administered after reconstitution due to chemical instability.
Describe the distribution of the carbapenems, including the CSF. How are they cleared? Is metabolism important? What is the route and mechanism of elimination? Why are their half-lives relatively short?
Imipenem
Therapeutic concentration is achieved in many fluids and tissues including the CSF when inflamed. Eliminated renally by GF with t ½ increased by ESRD.

Meropenem
Widely distributed including the CSF. Cleared renally mainly by GF as 75% unchanged drug. Rest is eliminated as an inactive metabolite and ESRD increases t ½.

T ½ is short because main elimination route is rapid through GF as unchanged drug.
What are the principal adverse effects of the carbapenems? How does the adverse reaction and drug interaction profile compare with that of other beta-lactam drugs?
ADR’s similar to other B-lactams including N/V which can increase with an increased infusion rate. CDAD is rare because minimal concentration of agent reaches colon. There have seizures noted due to inhibition of GABA receptors, risk potential increases if had CNS dz, drug dose greater than 2g in elderly and concurrent use of theophylline. There have also been occurrences of pain and inflammation at site of infection. Rash and drug fever occur at rates similar to other B-lactams. More likely to cross react because of a penicillin allergy than cephalosporins.
Why are vancomycin and teicoplanin classified as glycopeptides?
because they both have a sugar and a peptide
How is the peptide portion of vancomycin different fro that of peptides normally found in mammalian systems and why is this important?
It is abnormal/foreign.
What is the importance of the overall polarity and size of the vancomycin molecule in terms of antimicrobial activity?
It is too large and polar to get into gram negative bugs.
What is the importance of the overall polarity and size of th vancomycin molecule interms of biodisposition properties?
Because it is large and polar it is not absorbed in the GI, elimiated renally (polar), not a CYP substrate (protein), and not well distributed (polar)
What does the disaccharide contribute to activity of vancomycin?
Nothing but it does contribute to formulation because it can form HCl salts with the basic nitrogen. This is unlike beta lactams because they are acids or acid salts.
What does the cyclic peptide contribute to activity of vancomycin?
These are amino acids that hav an abnormal structure and stereochemistry (foreign protein) which contributes everything to activity.
What is Teicoplanin?
This is a glycopeptide that is used in the laboratory to define resistance to vancomycin. It is not used clinically because it is not FDA approved!
How are the glycopeptides generally similar in their MOA to beta-lactams? How do they differ?
They are similar by blocking cell wall construction but different because they bind to the substrate (peptidoglycan) insteard of the enzyme. So theyare are uncompetitive inhibitiors. This has utitlity to use in beta-lactam resistance because they do not bind to PBP so no inactivation by beta-lactamases or mPBPs. Very useful in PRSP and MRSE/A.
Where does vancomycin work?
in the periplasmic space between the cell wall and inner membrane (just like pens).
Which structural features are esential for ancomycin to express its MOA?
5-H bonding interactions with the peptidoglycan; once binds to substrate, teh substrate can't bind to PBP so no cell wall synthesis! The lower portion of the peptide is involved in H-bonding.
What are 2 primary MOA by which gram positive bacteria are resistant to beta-lactam drugs? Why is vanco not effected by these mechanisms?
mPBP and BLase (Staph has both); Vanco is not effected because it does not bind to PBP or BLases,
Why is vanco ineffective against gram-negative pathogens?
It can't get into the cell wall because it cant penetrate the outer membrane.
What are the PKs for vancomycin?
Effective only vs GRAM POSITIVIE!!

Bacterialcidal (like BLs) vs all but Enterococci

Post-antibiotic effect (like BLs)

Time dependent killer (like BLs)
Which bugs are innately resistant to vancomycin? Which are susceptable?
Gram negatives - innately resistant

Gram positive - susceptible
Which bacteria have acquired resistance to vancomycin and by what mechanism?
Enterococci by altered target binding.
What is Van A resitance?
This resistance occurs in 90% of bugs. This is a high level vancomycin resistance (HLVR) and this is resistant to vanco and teico. It has a MIC of >256 mcg/ml so very resistant because needs to be <10. Van B-E are only vancomycin resistant. You could gie more vanco but you'll never have enough to kill the bug so you just have to us a diffeent drug.
What is the MOA for Van A resistance?
It involves the production of a ligase to make a modified peptidoglycan in which vancomycin can only make 4 H-bonds rendering it ineffective. In this case VAREF stains which have low affinity for beta-lactams (vancomycin and ampicillin resistant), you would have to use Linezolid and Quinupristin/dalfopristin (AOC) to treat the patient.
What has been replaced in the peptidoglycan structure to make it Van A?
The "NH" was replaced by an "O" which can't donate a H-bond. This is the difference between alanine and lactate. Regardless of the substitution, the lactate can still bind to PBP in order to make a cell wall.
Why must vancomycin be administered IV to treat non-GI infections? Why is it administered IV and not IM or by some other route?
Vancomycin is too poar to be absorbed in the gut so needs to be given IV.

It is the primary treatment for CDAD and used orally behind metronidazole (due to cheap).

It is too caustic to be dumped into muscle --> irritation; so only give IV!
What should be done to insure safety when vancomycin is admistered IV?
Pretreat for all histamine released
What chemical properties contibute to vancomycin's oral efficacy in the treatment of CDAD?
It's polarity and size (too large to go through pores of GI)
Does vancomycin distribute equally well to all body compartments? Does it distribute adeuately to the CNS?
No!
How is vancomycin cleared?
Renally --> GF
Do vancomycin doses need to be adjusted in severe renal impairment? Hepatic impairment?
Renal - yes

Hepatic - no
What is GISA/VISA?
This stands for Glycopeptide/Vancomycin resistant S. aureus. It is also methicillin-resistant. This type doesn't involve Van A, possibly cell wall binding up the vancomycin so it can't get through.
What is "tolerant" Staphylococci (S. epidermidis in prosthetic devices, heart valves, joints)?
These are tolerant to the bactericidal actions of vancomycin and are difficult to identify in labs. You would need to increase the dose of vancomycin and give with gentamycin (AG) and/or rifampin.
Can you use a combination of Vancomycin + Gentamycin (AG) and/or rifampin to treat MRSA?
No, it is less effective than just treating with Vancomycin alone!
What is the spectrum for Vancomycin?
Corynebacterium jekium (opportunistic)
CDAD
Staphylococcal enterocolitis
MRSA/E (AOC)
MSSA/E (beta-lactam allergy)
Entrococcus (AOC in serious infections)
PRSP (AOC)
PSSP (beta-lactam allergy)
Strep. viridans
Bacillus
Listeria
Clostridium difficle
What are the PKs of vancomycin?
IV (not IM); Intrathecal for CSF because poor distribution to CNS

Cleared renally by GF

ADRs - Red neck/man syndrome (anaphylactoid) due to histamine release (pretreat by slowing the infusion rate, increasing solvent volume, and giving antihistamine); Ototoxicity is reversible so stop drug; also neprhtoxicity is rare but stop drug

Low nephrotoxicity but increased with renal impairment
What are the DIs with vancomycin?
DI - coadmin. with basic drugs...don't give with penicillin because it will chemically react with eachother and inactivate both --> placebo!

Other DIs- AGs: caution with nephrotoxicity and ototoxicity (monitor!); IB soln incompatibility with acid salts (vanco is an HCL salt); oral vanco and bile acid sequestrants immediately eliminates vanco so need to stop the bile acid sequestrants!
What is the MOA of Daptomycin?
It binds to and rapidly depolarizes the bacterial INNER membrane by disrupting DNA/RNA, protein biochemistry and respiration.
Are there any mechanisms of resistance for daptomycin?
No!
What is the spectrum for daptomycin?
Effective only against Gram positives!

Can use with Strept, MSSA/E, MRSA/E, and Enterococcus/VRE

Basically it can treat ANY GRAM POSITIVE BUG!!!
What is ADME of Daptomycin?
IV: large, polar, unstable peptide

Highly ppb (>90%) but dependent on renal stats clearance

Metabolism: Yes; but NO CYPs!

Renal Elimination: reduce dose in ESRD or increase the interval

DIs: Statins!!! Stop Statin when in use because increased myopathy!!
What are the PKs for daptomycin?
Bactericidal (like BLs)
Post-antibiotic (like BLs)
Concentration dependent (unlike BLs)
Synergy with beta-lactams and AGs
What lab values are common for bacterial meningitis?
PMNs > 300 mm
murky CSP
high protein counts
low glucose
What are the infecting agents of bacterial meningitis?
Strep, E. coli, Listeria, H. influenzae, N. meningitis
What is the AOC for the treatment of meningitis by age group?
Neonates: Strep, E. coli, Listeria, H. influezae --> Ampicillin and Ceftriaxone

Young adults: N. meningitis, S. pneumoniae -->Ceftriaxone or Cefotaxime + Vancomycin

Elderly: S. pneumoniae, N. meningitis --> Ceftriaxone or Ceftaxime + Vancomycin

Immunicompromised: Listeria --> Ampicillin