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216 Cards in this Set

  • Front
  • Back
What is selective toxicity?
the ability of a drug to work on one organism but not another
The spectrum of activity of a antibiotic can be ____ or ____
narrow or broad
Bacteriostatic=
inhibits bacterial cell replication
What is the MIC?
lowest concentration of antimicrobial agent that will inhibit the growth of a microorganism
Bactericidal=
results in bacterial cell death and lysis
What is MBC?
minimum concentration of antimicrobial agent that will result in bacterial death and lysis
The rate and extent of bactericidal activity increases with......

Maximize peak serum concentrations over relatively ______ time frames

This is known as _________
increasing drug concentration;

short;

concentration-dependence
Bactericidal activity does not increase with concentrations that are.....

The bactericidal activity continues as long as....

This is known as ___________
above the MBC;

serum concentrations are above the MBC;

time-dependence
What is a class of antibiotics that are time dependent?
cell wall synthesis inhibitors
What are the two mechanisms of synergy that may be seen with antimicrobial combinations?
blockade of sequential steps in a metabolic sequence (1 drug does 1 step, another does a diff step) or Inhibition of bacterial enzymatic inactivation
Antagonism of two antibacterial drugs is when ....
the effect of combination is less than the added effects of the two individual drugs
What is the basic element of bacterial cell walls?
peptidoglycan
For drugs that inhibit cell wall synthesis, how does selective toxicity occur/
eukaryotes don't have cell walls so it doesn't affect the cells
Which antibacterial drugs inhibit the cell wall synthesis?
beta lactams, vancomycin, bacitracin
Bacitracin is __________ for gram ______ bacteria

It inhibits the ______ step of cell wall synthesis which prevents.....
bactericidal; positive;

dephosphorylation; regeneration of the lipid carrier
Vancomycin acts on the _____stage of cell wall synthesis by....

Attaches to the ____ end of a ____ Residue on the precursor unit and blocks its ........

Activity is concentration- _______ and time-________
second; inhibiting utilization of lipid intermediates in peptidoglycan synthesis;

carboxyl; D-ala; separation from the phospholipid carrier;

independent; dependent
Monobactam, aka ______ is a __________ with an ________ structure instead of the normal __________. It binds to an inactivates ________
Aztreonam; monocyclic beta-lactam; open chain; beta lactam ring;

PBP3
Beta Lactam MOA is by....
inhibiting the transpeptidation reaction which is the final step in peptidoglycan synthesis, irreversibly activating it
Penicillins and Cephalosporins covalently bind to ________on bacterial cell walls.
PCN binding proteins (bacterial cell receptors)
Bactericidal activity of beta lactams (and all other cell wall synthesis inhibitors) is described as concentration-_________ and time-______________.
independent; dependent
What is the more important factor affecting bactericidal activity of beta lactam effectiveness?
The length of time the dose concentration exceeds the MIC/MBC for that organism
The activity of beta lactams against a gram negative bacterium depends on what 3 things?
ability to penetrate the outer membrane, beta lactamase sensitivity, intrinsic ability to bind to PBP
The rate of beta lactam penetration increases as ______ increases.
hydrophillicity
The outer cell membrane of bacteria contains _____. The permeability of these to beta lactams depends on: (3)
porins;

size, hydrophobicity and charge
In the process of the bacterial cell wall synthesis, cross-linking through _____ Reaction is catalyzed by bacterial enzyme _____

Synthesis of ______ occurs which are _________ into larger building blocks and transported outside of the cell membrane. _______ then occurs by forming a _______ bond between two groups catalyzed by ______
transpeptidation; transpepdiase;

cell wall precursors; polymerized; cross-linking; peptide; transpeptidase
Which two antibacterial drugs inhibit cell membrane function?
Polymyxin B and Daptomycin
Polymyxin B is bactericidal for....
gram-negative bacteria
Polymyxin B has relative absence of __________ meaning its nonspecific for cell membranes of ______ and are highly ________
selective toxicity; any kind; toxic
Daptomycin is bactericidal for.....
gram positive aeorbic bacteria
Daptomycin binds to bacterial _____ and causes......

This results in an inhibition of ____, _____ and ____ synthesis leading to ________

Concentration __________ bactericidal activity
membranes; rapid depolarization of the cell membrane;

protein, RNA, and DNA; cell death;

dependent
Which antibiotic drugs inhibit protein synthesis? (7)
aminoglycosides, tetracyclines, chloramphenicol, macrolides (erythromycin), clindamycin, Quinupristin/dalfopristin, linezolid
Linezolid binds to the _________ and is ___________ (bactericidal vs bacteriostatic)
50S ribosomal subunit; bacteriostatic
Quinupristin/dalfoprisint binds irreversibly to different sites on the ________ which inhibits _________ of mRNA at the _____ step
50S subunit; translocation; elongation
Clindamycin binds to the _____ of bacteria
50S subunit
Chloramphenicol is _______ and binds to the ________ of bacterial. Inhibits __________ which prevents chain elongation by inhibiting .....
bacteriostatic; 50S; peptidyl transferase; peptide bond formation
Tetracyclines are _______ And bind to the _______ of bacteria. Blocks the binding of ______ to mRNA-ribosomal complex at the ___ site. Prevents chain ______
bacteriostatic; 30S ribosomal subunit; aa-tRNA; A; elongation
Aminoglycosides are _______ (concentration-________)

Interacts with the _____ receptor protein of bacteria.

Mechanism: formation of ________ that blocks ribosomal movement along the mRNA. 'Frozen' at _______ stage.
bactericidal; dependent;

30S subunit;

abnormal initiation complex; initiation
Macrolides (erythromycin) are ____________. Bind to the _____ at the ___ site. This interferes with binding of _______ and ______(other drugs) to the 50S site which is a common or overlapping binding site.

Inhibits ____ by preventing proper association of the _____ chain with its binding site after peptide bond formation. Prevents chain ________
bacteriostatic; 50S subunit; P; chloramphenicol; clindamycin;

translocation; peptidyl-tRNA; elongation
Drugs that inhibit protein synthesis have selective toxicity due to........

Bacterial ribosomal subunits are designated as ____ and ____ while mammalians are ____ and ____
differences in ribosomal composition and size;

30, 50;

40, 60
Which antibiotic drugs are antimetabolites that are inhibitors of nucleic acid synthesis/function?
sulfonamides, trimethoprim, combination of the two
Sulfonamides are _____ Drugs that are structural analogs of ______ which is required in the bacterial cell for synthesis of _________
bacteriostatic; PABA; folic acid
Sulfonamies compete with _____ for binding to the enzyme ______ in the folic acid pathway.
PABA; dihydropteroate synthetase
Sulfonamides have selective toxicity because....
mammalians utilize preformed folic acid and have a specialized transport mechanism for its absorption. Bacteria must synthesize folic acid intracellularly
Trimethoprim (TMP) is usually __________. Is a competitive inhibitor of bacterial ___________.

Has a 50,000-fold greater affinity for bacterial _____.
bacteriostatic; dihydrofolate reductase;

DFHR
Combinations of sulfonamide and trimethoprim can be either _____ or ____ and result in sequential blockade of ____ Resulting in synergism.
bactericidal or bacteriostatic; folic acid synthesis
Rifampin is ___________ and is selectively toxic for......
bactericidal; bacterial RNA polymerases only
Rifampin binds to ..........

Inhibits...
DNA-dependent RNA polymerase;

RNA synthesis
Quinolones are ________.

They inhibit bacterial _____ which results in.....

Selective toxicity: What is needed to inhibit eukaryotic DNA synthesis?
bactericidal; DNA gyrase; inhibition of DNA replication;

very high concentrations of the drugs
Nitrofurantoin is __________.

This drug is reduced to toxic intermediates which are highly reactive and cause.......

Activated by bacterial _______ which are much more active than mammalian ones.
bactericidal;

DNA strand breakage by either direct reaction or by generation of oxygen radicals;

nitro reductase enzymes
Metronidazole is _____ for ____ bacteria.

Which group on the drug is reduced by bacterial enzymes to reactive intermediates? what do these intermediates do?

What is the mechanism of selective toxicity of metronidazole?
bactericidal; anaerobic;

nitro-; covalently bind DNA causing cell death;

the chemical reduction requires electron transport proteins adapted for energy production in absence of oxygen that are only present in anaerobes
Inhibition of bactericidal activity by bacteriostatic agents can occur due to what effect?

Inhibition of the bacterial growth by the static agent prevents the presence of what required by bactericidal agents?
antagonistic effects;

actively dividing bacteria
What are the two naturally occurring penicillins?
Penicillin G and V
Penicillins have good activity vs gram _____ bacteria but are sensitive to _______ (narrow spectrum penicillinases)

Also active vs non-_____ producing gram ______ bacteria.
positive; beta-lactamase;

beta-lactamase, negative
Which penicillin is resistant to penicillinase?
nifcillin
Nifcillin has a narrow spectrum of activity vs gram _____ bacteria and is inactive vs gram _____ bacteria.
positive; negative
Aminopenicillins have more of an extended spectrum and include _____ and _____.

They are susceptible to __________ and have increased activity vs gram ____ bacteria
ampicillin, amoxicilin;

beta-lactamases; negative
Which types of penicillin are synthetic?
penicillinase-resistant (nifcillin), aminopenicillins (amp, amox), and antipseudomonal (ticarcillin with clavulanate, piperacillin and piperacillin with tazobactam)
Antipseudomonal antibiotics include _______, _______ and _______.

They are sensitive to _______

Have the highest activity vs gram _____ bacteria and are active against __________
ticarcillin with clavulanate, piperacillin, piperacillin with tazobactam;

staph penicillinases;

negative, pseudomonas
Which penicillin do you want to take on an empty stomach?
V
Ampicillin must be taken....
on an empty stomach
Penicillins have increased CNS penetration in active inflammation due to....
increased meningeal permeability
Penicillins are rapidly excreted by the _______ through which structure/mechanism?
kidneys; tubular secretion
What drug blocks tubular secretion of other drugs and prolongs the half life of these drugs?
Probenecid
What bacteria are Penicillin G or V considered DOC for?

These all cause...
S pyogenes (GAS), S agalactinae (GBS), and viridans strep;

pharyngitis
What is the DOC for pneumonia caused by penicillin-sensitive S pneumonia?
Penicillin G or V
What is used to treat syphillis?
PCN G or V
What can ampicillin or amoxicillin be used to treat? (3)
L monocytogenes, meningitis, borrelia burgdorgeri (lymes)
What is the DOC for treating meningococcal meningitis?
ampicillin
Why is amoxicillin preferred over doxy to treat Lymes disease in pregnancy and young kids?
tetracyclines are contraindicated in these populations
What is the cutaneous stage of lymes disease called and what can be used to treat it?
erythema migrans; amoxicillin
Penicilinase resistant penicillins are the DOC for.....
the initial (empiric) tx of pts with suspected penicillinase-producing, methicillin-sensitive staph infections
Penicillinase-resistant penicillins are ineffective against....
gram negative bacteria, enterococci, MRStaph including MRSA and coagulase-negative staph (MRSE)
What is the best treatment for septicemia, pneumonia or intraabdominal sepsis caused by pseudomonas aerunginosa?
antipseudo PCN + beta-lactamase inhibitor+ aminoglycoside
Extended spectrum, antipseudomonal penicillins include _____ and _______ and are the DOC for ______, _______ and ______ caused by pseudomonas aerunginosa
piperacillin, ticarcillin;

septicemia, pneumonia, intra-abdominal sepsis
What is the most useful mono therapy for potential polymicrobial infections?
ampicillin/sulbactam (beta-lactam and beta-lactamase inhibitor)
beta lactams are cross- _______ and cross- _______
sensitizing; reacting
What are the three types of allergic reactions that occur with penicillins?
Immediate (anaphylaxis), accelerated or late reactions
Anaphylactic reactions to penicillins are type _____ hypersensitivity reaction. They are mediated through what mechanism?
1;

IgE Abs on mast cells and basophils
What symptoms occur with accelerated allergic reaction to penicillin? (second type)
urticarial, laryngeal edema or angioedema
What are the two types of late allergic reactions to penicillins?
type III hypersensitivity and Type IV
Type III hypersensitivity reactions occur through ________.

What is the most common type? What is another example?
immune complexes;

serum sickness; interstitial nephritis
Type IV hypersensitivity reactions are mediated through ______.

Most commonly seen is ______
cells (T cells);

contact dermatitis
Why was PCN d/c as a topical antibacterial?
it had a high rate of PCN-induced contact dermatitis
PCNs can cause neurotoxicity by acting as a ________. What can occur but is rare?
GABA antagonist; myoclonic seizures
What is the most common renal toxicity associated with methicillin but has occurred with PCN G and ampicillin?
interstitial nephritis
PCNs prevent normal platelet ________ and cause prolonged ________.

Seen most often with _____ but the clinically significant bleeding is infrequent
aggregation; bleeding times;

ticarcillin
Which two drugs do you want to take on an empty stomach either 1 hour before meals or 2 hours after?
PCN V and ampicillin
What is the DOC for uncomplicated and complicated bacteremia caused by MRSA? what is second choice?

First line has concentration ________ time _______ bactericidal activity.
vancomycin; daptomycin (both IV)

independent; dependent
What is the DOC for infective endocarditis with a native valve caused by MRSA? what is the second choice?
IV vancomycin, IV daptomycin
What is the DOC for pneumonia caused by MRSA? What is an alternate?
IV vancomycin; linezolid
What is the DOC for osteomyelitis caused by MRSA and how long is it used for?
IV vancomycin; more than 8 weeks
What is the DOC for meningitis caused by MRSA and how long is it used for?
IV vanco; 2 weeks
What is the first line therapy for Acute otitis media caused by pnemumococcal infections?

High risk groups should receive what?
amoxicillin;

amox/clavulanate (augmentin)
To treat acute otitis media in a PCN allergic patient, if urticaria or anaphylaxis did not occur, use ___________
cephalosporin (cefuroxime axetil)
To treat acute otitis media in a PCN allergic patient, anaphylaxis did occur, use ___________
azithromycin
To treat acute otitis media in a PCN allergic patient, if the pt is allergic to beta-alctams and PRSP is certain or presumed, then ____ should be used
clindamycin
Amoxicillin is also effective at treating acute otitis media caused by....
PCN-resistant strep pneumonia (PRSP)
For pts with acute otitis media (pneumo cause) who are non responders (no clinical improvement after 48-72 hours) should give them a high dose ____________ for 10 days

If still no improvement, give ________ via IV or IM for 3 consecutive days.
amox/clavulanate;

ceftriaxone;
What is the minimum duration of therapy for community-acquired pneumonia?
5 days
What can be used to treat pneumoccal meningitis?

For empiric tx, initiate therapy with a _________ AND _______ until the pathogen and susceptibility can be determined.
PCN or ampicillin if susceptible;

cephalosporin (ceftriaxone, cefotaxime); vancomycin
Monobactms (Aztreonam) have no activity vs gram _____ aerobes or anaerobes.

Clinical use includes gram ______ aerobes. Is NOT indicated for _________
positive;

negative; meningitis
Aztreonam is a.....
monobactam
What drugs are included in the carbapenems?
imipenem/cilastatin and meropanem
Meropanem is not degraded by ________ and so does not require cilastatin.

Initially is considered less ______ and has a decreased incidence of ______ compared to imipenem
renal dehydropeptidase;

nephrotoxic; seizures
What is Cilastatin?

What is it used for/to prevent?
competitive inhibitor of renal dihydropeptidase I.

renal metabolism of imipenem by DHPI, blocking the nephrotoxic metabolite and preventing rapid destruction of imipenem
Imipenem/Cilastatn is a _____ spectrum antibacterial agent that is ineffective vs ____ and _____

What is it the DOC for?
MRSA, VRE

neutropenic fever
What are two adverse reactions of imipenem/cilastatin?
seizures and inhibition of GABAergic activity
What are the predisposing factors for seizures when using imipenem/cilastatin?
overdosage, elderly, underlying CNS disorders, renal disease
Imipenem/Cilastatin is a _____ broad-spectrum ______ antibiotic (class)

Is highly resistance to _______ so is effective against organisms that produce this.
bactericidal; beta-lactam;

beta-lactamase
Bacitracin is _______ for gram ______ species but is too nephrotoxic to be used systemically.

Used in ____ formulations for ____ and ____ infections.
bactericidal agent; positive;

topical; skin; eye
Fosfomycin is the first anti-infective agent to be approved as a single dose treatment for _____.

Concentrations that are bactericidal for E coli are maintained for ______ after a single dose;
UTIs; >3 days
What is currently the most commence cause of skin/soft tissue infections in the ER?
community-acquired MRSA
What is the most common resistance developed to macrocodes? What does it affect?
altered ribosomal target;

50S subunit ribosomal proteins
What is the resistance mechanism that is developed to Rifampin?

What can occur if Rifampin is used alone?
altered DNA-Dependent RNA polymerase;

rapid emergence of resistance
Bacterial resistance can develop to Fluoroquinolones if what occurs?
Mutations in the gene coding for DNA gyrase occur, resulting in decreased quinolone affinity for either the A or B subunit
How do bacteria develop resistance against sulfonamides? (2)
production of increased PABA and an Altered dihydropteroate synthesis with a decreased affinity for sulfonamides
How do bacteria develop resistance to trimethoprim?
altered dihydrofolate reductase which is TMP-insensitive
How do bacteria become resistant to Chloramphinol?
increase production of chloramphenicol acetyltransferase which inactivates the drug and makes it unable to bind to the 50S subunit
What is the basis for selective toxicity for tetracyclines?
selective uptake and accumulation into bacterial cells at inner membrane
How is resistance formed to tetracyclines?
decreased ability of the drug to accumulate due to active efflux
Bacteria become resistant to tetracycline through the presence of _____ genes which code for membrane proteins that.......

This produces a ____ dependent system which functions to....
resistance; mediate energy-dependent efflux;

energy; transport tetracycline out of the cell
What is the most common mechanism of resistance by bacteria to beta lactams?
inactivation of the beta-lactam by beta-lactamases;
MRSA has a decreased affinity of ____ for PCN substrate; betalactams are ______ and _____ has been standard therapy
PBP; ineffective; vanco
Which bacteria become resistant to beta lactams through alteration of the target site?
MRSA and PCN-resistant S pneumonia
What are the three ways that bacteria can become resistant to beta lactams?
inactivation of beta-lactam by beta-lactamases, alteration of target site/alter affinity of PBP, and prevention of access to target site
Which bacteria use the 'prevention of access to the target site' mechanism as a way to become resistant to beta-lactams?

How does this mechanism work?
only gram negative bacteria;

decreases penetration through outer membrane due to mutations in porins
Which beta lactam drug is resistant to beta-lactamases?
Penicillinase-resistant PCNs (nafcillin)
Which drugs inactivate beta-lactamases?
clavulanate potassium, sulbactam sodium
Aztreonam is resistant to most _______ but is ineffective against ______
beta-lactamases; MRSA
Which drug has the broadest spectrum of any currently available beta-lactam?
Imipenem
How do gram positive bacteria become resistant to Imipenem?
through altered PBP1 and PBP2
How do gram negative become resistant to Imipenem?
develop metallo-beta-lactamases
How does P aeruginosa develop resistance to Imipenem?
loses a specific porin that allows the passage of Imipenem
Is Imipenem effective or ineffective against MRSA?
ineffective
What is the major mechanism of resistance to Vancomycin?

_____ genes code for enzymes that produce a ____________ to which vancomycin cannot bind. The terminal D-ala-D-ala in the peptidoglycan is changed to ______________
acquired resistance;

Resistance; modified peptidoglycan side chain; D-ala-D-lactate
What is the most clinically significant mechanism of resistance against amino glycosides?

The degree of efficacy of AGs is directly related to its ability to....
enzymatic inactivation;

resist inactivation by bacterial enzymes
What percentage of all CA-MRSA infections are skin/soft tissue infections?
75
Is CA-MRSA susceptible to a broader range of antibiotics?

What is it typically susceptible to?
yes;

TMP-SMX, clindamycin, long acting tetracyclines (doxy, minocyline)
What are some risk factors for CA-MRSA infections?
lower SES, prison inmates, IV Drug abusers, chronic diseases, military recruits, athletes
Penicillin-resistant Strep Pneumoniae mechanism of resistance appears to be an alteration of _____ in the cell wall and reduced affinity for __________.

Most strains resistant to PCN also exhibit resistance to....
PBP; 3 or more PBPs;

other commonly used agents
What are some risk factors for acquiring Vancomycin-Intermediate resistant S-Aureus?
renal failure requiring dialysis, peritoneal catheters or other indwelling devices, MRSA infections treated with repetitive or prolonged courses of vancomycin
How did the Vancomycin-Intermediate Resistant S. Aureus strain develop?
through the selection of naturally occurring mutants during prolonged exposures to vancomycin
What is the mechanism of resistance in the Vancomycin-Intermediate resistant S aureus?

What happens to the vancomycin when used to treat this?
alteration of cell wall to be thicker, more disorganized with decreased cross-linking.

Becomes trapped in periphery and cannot reach its binding site in the growing cell
What are the DOCs for treatment of Vancomycin-Intermediate resistant S Aureus?
linezolid, daptomycin
What is the mechanism of resistance in HA-MRSA?
modified PBP2a leading to decreased affinity for beta-lactams and making it capable to perform peptidoglycan synthetic functions when other PBPs are inhibited
Are ALL beta lactams ineffective vs HA-MRSA?
yes
What is the major mode of transmission of HA-MRSA?
hands of hospital workers after contact with infected patient
Constitutive production of beta-lactamases is when.....

Results in...
the enzyme is always produced;

fairly constant levels of the enzyme
Inducible production of beta-lactamases is when.....
the production of enzyme is linked to drug exposure and disappears when drug is removed
In ICUs, appearance of MDR isolates have been increasing and they are exhibiting resistance towards extended-spectrum _____, ______ and _____
cephalosporins; aminoglycosides; ciprofloxacin
What are some risk factors for MDR enterobacter infections?
nosocomial acquisition, previous use of extended-spectrum cephalosporin (3rd gen)
Enterococci are the second most common bacterial cause of nosocomial _____ and _____ infections and the third leading cause of nosocomial _______.

May be part of the _______in humans.

What are the two major enterococcal pathogens? Which one has much higher resistance rates?
UTIs; surgical wound; bacteremias;

GI normal flora;

enterococcus faecalis and e. faecium; e. faecium
The resistance of the Vancomycin-Reisstant Enterococci is associated with the production of .......

These cause alterations in the normal ________ which results in the loss of normal ..........

The terminal D-ala-D-ala portion of the peptidoglycan side chain is replaced by ________
two distinct membrane-bound bacterial enzymes;

peptidoglycan assembly pathway; vancomycin binding sites;

D-ala-D-lactate
In Vancomycin-Reistant Enterococci, adding a ______ to the treatment will result in a synergistic killing of susceptible enterococci
aminoglycoside
What are some risk factors for the acquisition of VRE?
previous vancomycin use; immunosuppression, use of indwelling catheter or central venous catheters
Which patients do you want to reserve PO vancomycin treatment for?
Abx associated pseudomembranous colitis in pts not responsive to 2 courses of metronidazole or if condition is life threatening.
How can you prevent Vancomycin-Resistant Enterococci from developing (2)
reserve tx using vanco for infections with high suspicion or beta-lactam-ressitant gram positive bacteria; discourage routine use for surgical or nonsurgical prophylaxis
What are the DOCs for non-VRE enterococcal infections?

What is the alternate for PCN allergy or enterococci with high-PCN resistance?
penicillin; ampicillin;

vancomycin
What is the suggested therapy for non-VRE enterococcal bacteremia?
combination of PCN of ampicillin plus an aminoglycoside
What is the standard treatment for non-VRE enteroccal endocarditis?

How long do you treat for in otherwise healthy patients?
What about those who have had sx for >3 mo, prosthetic valves or failure after shorter courses?
combined cell wall agent with an amino glycoside;

4 weeks; 6 weeks
For non-VRE enterococcal endocarditis that has a high level of PCN resistance, treat with...
vancomycin plus aminoglycoside
What are the DOCs for treating bacteria or systemic infections caused by VRE with high-level PCN resistance?
linezolid, daptomycin
Telavancin MOA=

Concentration-________ bacteri______ for gram ____ infections including ______

Has a prolonged PAE (postabx effects) allowing for....
inhibits bacterial cell wall synthesis and disrupts cell membrane barrier function;

dependent; bactericidal; positive; MRSA

once daily dosing
Telavancin is indicated for: (2)

Administered by......
complicated skin/skin structure infections and MRSA;

IV infusion once every 24 hours
What is required as a pre-adminstration test before administering Telavancin?

Avoid telavancin in this population unless....

What are 2 other ADRs?
pregnancy test; the benefits clearly outweigh the risks;

infusion-related reactions, prolongs QT
Daptomycin binds to bacterial membranes and causes........
This leads to:

Is active vs _____, gram _____ bacteria. Retains potency vs resistant strains including isolates that are resistant to _____, ____ and _____

Rapid, concentration -________ bacteri_______ activity.
rapid depolarization of membrane potential; inhibition of protein, RNA and DNA synthesis resulting in cell death;

aerobic; positive; methicillin, vanco, and linezolid;

dependent; bactericidal
Daptomycin is indicated for.....
complicated skin/skin structure infections including MRSA
Daptomycin is the DOC for: (2) strains of bacteria

Is the DOC for _____, ______ and _____ caused by _____ Strains of bacteria;

Is the alternative for _____ and ________
vancomycin-intermediate and vancomycin-resistant S aureus;

bacteremia, systemic infections and endocarditis; VRE

E faecalis and vancomycin-susceptible E faecium
Daptomycin is administered:

How much of this dose is excreted renally? What do you have to adjust to dose for?

Has poor penetration into the _____ so it is not recommended of treatment of ________
by IV infusion in NS over 30 min once daily for 7-14 days;

80%; Clcr<30 mL/min;

lung; pneumonias
Polymyxin B is available in ____ and ____ formulations
topical and parenteral
Polymyxins are _____ that have a surface ______-like action on the outer membranes of gram ____ ______ that disrupts the membrane and causes cell lysis

Due to this unique MOA, the resistance rates are very _____ not selective toxicity is not very ____
peptides; detergent; negative bacilli;

low; high
Polymyxins are effective against gram ___ bacilli (bacteri-____). Have no clinically significant activity against gram ______, ______ and _____
negative; bactericidal; positive; anaerobes, or fungi;
Polymyxins are the drug of last choice for treating.....

Have topical preparations for use for..
life-threatening psudomonas infections or other gram- bacillary resistant strains or where preferred drugs are not tolerated;

skin, eye, and ear infections
Polymyxins have an associated neurotoxicity and produces ___, ____ and ____.

Does this through a noncompetitive ____________ and has an additive effect with.....
paresthesias, dizziness, vertigo;

neuromuscular blockade; aminoglycoside;
Polymyxins have a nephrotoxicity effect and produce _____, _____ and _____.

Who is at high risk of these effects?
azotemia; increased SCr; acute tubular necrosis;

those on other nephrotoxic drugs
Vancomycin is a narrow-spectrum concentration _________, time ______ bacteri______ abx.

Is bacteriostatic vs _______ and has synergistic bactericidal activity when combined with a ______

Is ineffective against gram ____, ______, _______ and ____ organisms.
independent; dependent; bactericidal;

enterococci; aminoglycoside;

negative; mycobacteria; anaerobes; intracellular
CNS penetration of vancomycin is ____ in the absence of inflamed meninges.
poor
How is Vancomycin eliminated from the body?
through glomerular filtration of the unchanged drug
Rapid IV infusion of vancomycin causes.....

Symptoms include:
massive histamine release;

pruritis with rash, flushing
What two toxicities can be induced by vancomycin?
ototoxicity and nephrotoxicity
What is the DOC for septicemia, pneumonia, or wound infections caused by MRSA?
Vancomycin
What is the DOC for septicemia, infected prosthetic devices caused by MRSE?
Vancomycin
What is the DOC for meningitis and ocular infections caused by S pneumonia when used in combination with either cefotaxime or ceftriaxone?
Vancomycin
When combined with an amino glycoside, what is a good alternate to beta-lactams for enterococcal endocarditis?
vancomycin
Cephalosporins are concentration ______ time ________ and have bacteri-_____ activity.
independent; dependent; bactericidal
First generation cephalosporins are similar to extended-spectrum ______ but are more resistant to ________
aminopenicillins; beta-lactamases
First gen cephalosporins are most active against gram ____ bacteria
positive
Second gen cephalosporins have a broader spectrum than first gen and are more resistant to ___________.

Have good activity to gram ____ bacteria, increased activity to gram ____ bacteria.
beta-lactamases;

positive; negative
Cefoxitin has much higher activity vs gram negative ____ and _____ and poor activity vs _______ bacteria.
enterics; anaerobes; gram positive
Cefoxitin is a ___ gen cephalosporin
2nd
Third gen cephalosporins have the highest gram ____ activity and are the most potent agent against _________.

Have the lowest gram ____ Activity.

Have the highest resistance to ____ and the best ____ penetration.
negative; gram negative enterics;

positive;

beta lactamases; CSF
What are the preferred agents for beta-lactamase producing H influenza meningitis?
ceftriaxone, cefotaxime
Ceftazidime, Ceftriaxone and cefotaxime are ____ gen cephalosporins
3rd
Which cephalosporin has antipseudomonal activity?
ceftazidime
CSF penetration for 1st and 2nd gen cephalosporins is.....

It is excellent for _______, ______ and _______
virtually 0 for 1st and 2nd gen agents;

cefuroxime, ceftriaxone, cefotaxime
Cefepime is a ___ gen cephalosporin and is DOC for empiric therapy of.....
4th; neutropenic fever;
What are the 3rd gen cephalosporins?
cefotaxime, ceftriaxone, cefixime, ceftazidine
Ceftaroline is bacteri______, has time______ activity and is active vs ____, ____ and _____.

Approved indications include: (2)
bactericidal; time dependent; MRSA, PRSP, MDR S pneumonia

CA-bacterial pneumonia including S pneumonia; acute bacterial skin and skin structure infections including MRSA
What is the most common adverse reaction to cephalosporins?
allergic reactions
What hematological reaction can occur with cephalosporins?
hypoprothrombinemia
Disulifam (antabuse) reaction occurs when .....
alcohol is ingested within 48-72 hours after dosing with a cephalosporin containing the MTT side chain
Which 3rd gen cep halo has the highest activity vs pseudomonas (most effective of all beta-lactams)?
ceftazidime
Which 3rd gen cephalo is currently the only orally administered 1st line option for uncomplicated gonorrhea now that quinolones are no longer used?
cefixime
Which 3rd gen cephalo is the DOC for gonococcal genital tract infections due to penicillinase-producing N gonorrhea? What do you combine it with to have chlamydia coverage?
Ceftriaxone; doxy or azithromycin
What two 3rd gen cephalos are the DOC for beta-lactamase producing H influenza meningitis?

One of these are combined with Vanco for the empiric treatment of..
cefotaxime, ceftriaxone;;

s pneumonia meningitis
What are the two 1st gen cephalosporins?
cefazolin and cefoxitin
Which 1st gen cephalo has the highest activity against gram-negative bacteria?
cefazolin
1st gen cephalosporins are used as alternative for ____ for staph and strep infections (gram positive cocci).
PCN
Which 1st gen cephalo is used for surgical prophylaxis?
cefazolin
1st gen cephalosporins are ineffective against:
B fragillis, h influenza, listeria, MRSA, PRSP, and enterococci
Cefoxitin has excellent activity vs ____ and _______ (mixed aerobic-anaerobic infections)

Used for ____, _____ and _____ infections. DOC for parenteral therapy of _____ (combined with ____)
anaerobes; facultative gram negative bacilli;

intra-abdominal, pelvic, gyn; PID; doxy
What prodrug was developed for parenteral use of a polymyxin bx? What is it hydrolyzed to invivo?
colistimethat; colistin
Polymyxins cannot cross into the _____ so you need to give it ____ to treat meningitis.
CNS; intrathecally
Polymyxins have very rapid concentration-_______ bacteri____ activity
dependent; bactericidal
Daptomycin has an increased incidence to _______ and a potential DI with _____
myopathy; statins
In the treatment of non-VRE enterococcal endocarditis when there is high resistance to both gentamicin and streptomycin, no combination produces ______
synergy