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Advanced Pharmacology > Antimicrobial Part I > Flashcards

Antimicrobial Part I Flashcards

1
Q

Bacteriostatic

A 
• Thought to arrest growth and replication of bacteria 
at drug levels achieved
• Most of these agents are 
able to effectively kill 
pathogens, but they are 
unable to meet the 
arbitrary cut-off value in 
the bacterial definition
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2
Q

Bactericidal

A

• Able to effectively kill
>/=99% within 18-24° of
incubation

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3
Q

True or False: It is possible for a drug to be bacteriostatic for one microbe and bactericidal for another

A

TRUE

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4
Q

MBC—Minimum Bactericidal Concentration

A

Lowest concentration of antimicrobial agent that
results in a 99.9% decline in colony count after
overnight broth dilution incubations
MBC is rarely determined in clinical practice

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5
Q

What abx should you not give children?

A

Young children should not receive
Tetracyclines or Quinolones which can
affect teeth, bones and joints

*congenital abnormalities have
been seen after pregnant women have
taken tetracyclines—so should not be
prescribed

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6
Q

When do you use parental route for abx?

A

Parenteral route is used when the med is poorly absorbed from the GI tract and for those with serious infections that need high serum concentrations of the antibiotic

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7
Q

Name to abx poorly absorbed in the gut and do not achieve high enough serum levels via oral ingestion

A

vanc and aminoglycosides

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8
Q

three important properties that greatly

influence the frequency of dosing;

A

Concentration-dependent killing
Time-dependent [concentration-
independent] killing
Postantibiotic effect [PAE]

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9
Q

Concentration Dependent Killing

A

Certain drugs—such as aminoglycosides and Daptomycin show a large increase in the rate of bacterial killing as the concentration of the drug increases from 4 to 64 times the MIC of the drug for the causative pathogen
Giving drugs that exhibit this concentration-killing by a once a day bolus infusion obtains high peak levels—that cause rapid killing of the bug

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10
Q

Postantibiotic Effect [PAE]

A

Persistent suppression of microbial growth that occurs after levels of the drug have fallen below the MIC
Drugs that have a PAE often require one dose per day—especially against gram negative bacteria
[aminoglycosides, fluoroquinolones]

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11
Q

Narrow Spectrum

A 
• Agents acting on a single 
or limited group of 
microbes
• An example—INH is 
active only against 
Mycobacterium 
tuberculosis
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12
Q

Extended Spectrum

A

• Drugs that are modified to be effective against gram + organisms and also against
a number of gram –bacteria
• An example—Ampicillin

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13
Q

Broad Spectrum

A

• Drugs affect a wide variety of microbe
species
• These drugs can alter the nature of the
normal bacterial flora and lead to
superinfection from pathogens such as
C. difficile [the growth of which is normally kept in check by other colonizing bacteria]
• Examples—Tetracyclines,
Fluoroquinolones, Carbapenems

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14
Q

Advantages of combination antimicrobial drugs

A

 Some combinations show synergy [ß-lactams + aminoglycosides]
 Because synergism is pretty rare, we use these combinations in special cases—enterococcal endocarditis
 Combinations often used when infection is of unknown etiology or several organisms with variable sensitivities—such as TB

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15
Q

Disadvantages of Combinations

of Antimicrobial Drugs

A

 Many drugs work only when pathogens are multiplying, so when combinations are given, where one is bactericidal and other is bacteriostatic—the 1st drug may interfere with the action of the 2ndagent
 For example—bacteriostatic tetracyclines interfere with the bactericidal effects of PCN and cephalosporins
 Another concern is development of resistance from giving unneeded combinations

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16
Q

Genetic Alterations Leading to Drug Resistance

A

Acquired antibiotic resistance requires the
temporary or permanent gain or alteration of
bacterial genetic information
Resistance occurs due to the ability of DNA to change/mutate or to move from one organism to another

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17
Q

Red man syndrome

A

Some reactions related to rate of infusion

ex: from rapid infusion of Vancomycin

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18
Q

Patients with history of Stevens-Johnson syndrome or Toxic Epidermal Necrosis from an antibiotic should NEVER_____

A

be rechallenged, not even for antibiotic desensitization

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19
Q

Direct Toxicity

A

High serum drug levels can cause toxicity by directly affecting cellular processes in the patient
Aminoglycosides can cause ototoxicity by interfering with membrane function in the auditory hair cells
Chloramphenicol can be toxic to mitochondria leading to bone marrow suppression
Fluoroquinolones can have effects on cartilage and tendons
Tetracyclines can directly affect bones
Many antibiotics can cause photosensitivity

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20
Q

Superinfections

A

Antimicrobials—especially those with broad spectrums or combinations can cause altered normal bacterial flora in respiratory tract, mouth, GI and GU tracts—
thus allowing overgrowth of opportunistic agents, fungi or resistant bacteria
These infections will then require secondary therapy

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21
Q

Antimicrobials are classified by:

A

Chemical structure
Mechanism of action
Activity against particular types
of pathogens

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22
Q

Cell Wall Inhibitors

A

These antibiotics selectively interfere with synthesis of the bacterial cell wall
The cell wall is made of polymer called peptidoglycan that consists of glycan units joined to each other by peptide cross-links
The antibiotics that inhibit cell walls require actively proliferating microorganisms

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23
Q

Families of cell wall inhibitors

A

Penicillins
Cephalosporins
Carbapenems

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24
Q

Penicillins

A

Consist of a core 4 membered ß-lactam ring—which is attached to a thiazolidine ring and an R side chain
Drugs in this family differ from each other in the R substitute attached to the 6-aminopenicillanic acid residue—this side chain affects the drugs spectrum, stability in the stomach acid, cross-sensitivity and susceptibility to bacterial degradation enzymes—better known as ß-lactamases

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25
Q

PCN: MOA

A

Interfere with final stage of cell wall synthesis known as transpeptidation
PCNs compete for & bind to enzymes called penicillin binding proteins [PBPs] which catalyze transpeptidase and facilitate cross-linking of the cell wall
Downstream effect is a weak cell wall and cell death
PCNs are bactericidal and work in a time-dependent mode

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26
Q

PCN: antibacterial spectrum

A

Gram + microbes have a cell wall easily transversed by PCNs—so unless resistance is present, they are susceptible
Gram –microbes have an outer lipopolysaccharide membrane surrounding their cell wall that acts as a barrier to PCNs
However, gram –pathogens do have proteins inserted into this barrier membrane that behave as a water lined channel [porins] that allow some PCNs to enter via this transmembrane canal

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27
Q

Natural Penicillins

A

Penicillin G and Penicillin V are obtained from fermented fungus of PCN
chrysogenum
PCN G [benzyl penicillin] has activity against many gram +, gram –and
spirochetes; it is 5-10 times more potent than PCN V against Neisseria spp. and
anaerobes
Most streptococci are sensitive to PCN G, BUT PCN-resistant viridians
streptococci and Streptococcus pneumoniae isolates are emerging
More than 90% of Staphylococcus aureus are now penicillinase producing and
resistant to PCN G
PCN is DOC for gas gangrene [Clostridium perfringens] and syphilis [Treponema pallidum]
PCN V is only available oral, with a spectrum similar to that of PCN G—not used for severe infections due to limited oral absorption
PCN V more acid stable than PCN G and is oral agent used in less severe infections

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28
Q

Semisynthetic Penicillins

A

Ampicillin and Amoxicillin

Aminopenicillins or extended spectrum penicillins

Created by chemically attaching different R groups to the 6-aminopenicillanic acid nucleus—this extends the gram –coverage to include Haemophilus influenzae, E. coli and Proteus mirabilis

Ampicillin [+/- Gentamicin]—DOC for Listeria
monocytogenes and some enterococcal species

Extended spectrum agents used in URIs

Ampicillin used by dentists to prevent bacterial endocarditis in high risk patients

These drugs are combined with ß-lactamase inhibitors such as clavulanic acid or sulbactam to treat infections from ß-lactamase producing pathogens

Without B-lactamase inhibitor, RSSA is resistant to Ampicillin and Amoxicillin

Resistance from plasmid-mediated penicillinases are a problem—this limits the use of these agents with gram - bugs

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29
Q

Antistaphylococcal Penicillins examples

A

Methicillin [only used in lab testing in US]
Nafcillin
Oxacillin
Dicloxacillin

ß-lactamase [penicillinase]-resistant penicillins
They are used for infections caused by penicillinase-producing staphylococci, including MRSA

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30
Q

Antistaphylococcal Penicillins

A

MRSA—source of serious community acquired and nosocomial infections and is resistant to most commercially available ß-lactam antibiotics
Penicillinase-resistant penicillins have minimal to no activity against gram - infections

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31
Q

Antipseudomonal Penicillins

A

Piperacillin
Active against Pseudomonas aeruginosa
When combined with Tazobactam [Zosyn] extends the antimicrobial spectrum to cover penicillinase-producing organisms [Enterobacteriaceae and Bacteroides spp.]

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32
Q

Antipseudomonal Penicillins: Resistance

A 
Survival in spite of a ß-lactam antibiotic 
can occur by one of three ways—ß-
lactamase production, decreased 
permeability of the drug or altered 
penicillin binding proteins [PBPs]
33
Q

Antipseudomonal Penicillins: ß-Lactamase Production

A 
 This family of enzymes breaks 
down the amide bond of the ß-lactam ring, which causes loss of bactericidal activity—they are the MAJOR cause of resistance to PCNs and are becoming more and more of an issue
 Some ß-lactam antibiotics are poor 
substrates for ß-lactamases and 
resist hydrolysis, thus keeping their 
power over ß-lactamase producing bugs
Gram + organisms secret ß-lactamases 
extracellularly
Gram –organisms inactivate ß-lactam 
drugs in the periplasmic space
34
Q

Antipseudomonal Penicillins: Decreased Permeability of the Drug

A

Reduced penetration of the drug into gram –bugs is more of a problem—they have a complex cell wall that includes aqueous channels [porins]
Pseudomonas aeruginosa lacks high permeability porins
Presence of an efflux pump, actively removes the drug from the site of action can also reduce amount of intracellular drug [Klebsiella pneumoniae]

35
Q

Antipseudomonal Penicillins: Altered Penicillin Binding Proteins [PBPs]

A

Antibiotic exposure can prevent cell wall synthesis and lead to changes or lysis of susceptible bacteria
Modified PBPs have lower affinity for ß-lactam antibiotics—requiring unobtainable levels of the drug to be present to kill the bug—this mechanism explains MRSA resistance to most available ß-lactams

36
Q

Antipseudomonal Penicillins: Pharmacokinetics

A

Administration:
Determined by stability of the drug in gastric acid and severity of infection

Routes:
• Ampicillin + sulbactam [Unasyn]; Piperacillin + tazobactam [Zosyn];
Nafcillin and Oxacillin given IV or IM
• PCN V, Amoxicillin, Dicloxacillin are given PO
• All others are available PO, IV or IM
• Amoxicillin + Clavulanic acid is only oral in the US

Depot Forms:
Procaine PCN G and Benzathine PCN G are given IM as depot
injections—they are slowly absorbed and persist at low levels over long periods

Absorption:
• Acidity of the GI tract interferes 
with absorption of PCNs
• Only 1/3 of PCN V is absorbed 
orally
• Food decreases absorption of 
penicillinase-resistant penicillin 
Dicloxacillin—as gastric emptying 
time increases, the drug is 
destroyed by HCl, so should be 
taken on empty stomach
• Amoxicillin is stable in acid 
environment
37
Q

Antipseudomonal Penicillins: Distribution

A

• ß-lactam antibiotics distribute
throughout body
• All PCNs cross the blood-brain barrier—none are teratogenic
• Penetration into bone and CSF not enough for therapy unless these sites are inflamed—inflamed meninges more
permeable to PCNs—resulting in higher levels in CSF than in serum
• PCN levels in prostate too low to use for treatment

38
Q

Antipseudomonal Penicillins: Metabolism

A

• Host metabolism of the ß-lactam antibiotics usually insignificant; metabolism
of PCN G may occur in those with CKD
• Exceptions—Nafcillin and Oxacillin metabolized by liver

39
Q

Antipseudomonal Penicillins: Excretion

A

• Primary route is organic acid [tubular]
secretory system in the kidney and GFR
• Those with CKD must have dosages reduced
• Nafcillin and oxacillin metabolized in liver
and do not require dose reductions in CKD
• Probenecid [gout prevention drug] inhibits
secretion of PCNs by competing for active
tubular secretion via the organic acid
transporter and can increase blood levels of
PCNs
• PCNs excreted in breast milk

40
Q

Antipseudomonal Penicillins: ADes

A
  • hypersensitivity
  • diarrhea

-nephritis: PCNs—especially
Methicillin [no longer available in US because of this] have the potential to
cause acute interstitial nephritis

-neurotoxicity: Irritating to neuronal tissue and can provoke seizures if injected
intrathecally or if very high dose blood levels are reached—epileptics at risk as PCNs can cause GABAergic inhibition–

-hematologic effects: Decreased
coagulation can be seen with high doses
of Piperacillin and Nafcillin and perhaps
with PCN G

41
Q

Cephalosporins

A

ß-lactam drugs related structurally and functionally to PCNs
Most Cephalosporins are semisynthetic by attaching side chains to 7-aminocephalosporanic acid
Changes on the acyl side chain at the 7 position effects the antibacterial power; variations at the 3-position change the pharmacokinetic profile
Same MOA as PCNs and affected by same resistance mechanisms
Tend to be more resistant than PCNs to certain ß-lactams

42
Q

Cephalosporins 1st Generation Antibacterial spectrum

A
  • Like PCN G substitute except they cover MSSA; isolates of Strep pneumoniae resistant to PCN G will be resistant to these drugs
  • Modest activity against:
  • Proteus mirabilis
  • E. coli
  • Klebsiella pneumoniae
  • Oral cavity anaerobes, such as Peptostreptococcus
  • Bacteroides fragilis is resistant to these drugs

GRAM POSITIVE COVERAGE

43
Q

Cephalosporins 2nd Generation Antibacterial spectrum

A

• M. catarrhalis
• Gram + coverage is less than 1st generation drugs
• Cefotetan [Cefotan] and Cefoxitin [Mefoxin] covers anaerobes [Bacteroides fragilis]—only cephalosporins with good activity against gram –anaerobes; however neither is 1st line for B. fragilis—currently, a
lot of resistance

GRAM NEGATIVE COVERAGE

44
Q

Cephalosporins 3rd Generation Antibacterial spectrum

A
  • Important players in treating ID
  • Yet, they are less potent against 1st generation drugs when treating MSSA
  • Enhanced coverage of gram –bacilli, including ß-lactamase producing H. influenzae and Neisseria gonorrhea
  • Covers Serratia marcescens and Providencia spp.
  • Ceftriaxone [Rocephin] and Cefotaxime [Claforan] are DOC in meningitis
  • Ceftazidime [Fortaz] covers Pseudomonas aeruginosa [resistance is increasing]
  • Use these drugs cautiously—they can foster bacterial resistance and cause C. difficile infection

GRAM -/+ COVERAGE WITH SOME LOSS OF gram + coverage

45
Q

Cephalosporins 4th Generation Antibacterial spectrum

A

• Cefepime [Maxipime]
• Must be given parenterally
• Wide spectrum with coverage of Staph and
Strep [that are methicillin sensitive]
• Also covers aerobic gram negative bugs—
Enterobacter spp., E. coli, K. pneumoniae, P.
mirabilis and Pseudomonas [refer to local
antibiograms to assess coverage of
Pseudomonas]

EXPANDED COVERAGE

46
Q

Cephalosporins Advanced Generation Antibacterial spectrum

A

• Broad spectrum—only ß-lactam in the US that covers MRSA
• Indicated to treat complicated skin and skin structure infections and CAP
• It binds to PBPs in MRSA and Penicillin resistant Streptococcus pneumoniae
• Covers gram + pathogens and gram –coverage similar to 3rd generation Ceftriaxone
• Does not cover—P. aeruginosa, certain strains of Enterobacteriaceae and Acinetobacter baumannii
• Ceftaroline [Teflaro]
• Twice day dosing limits its use outside
of a hospital setting

47
Q

Pearls for Practice for Cephalosporins.

A

Sanford Guide is your bible to assist in learning what drugs cover what bugs—and it is updated yearly based on resistance patterns and CDC recommendations…
1st generation drugs—gram + bugs*
2nd generation drugs—gram –bugs
3rd generation drugs—covers both but you
lose some gram + coverage*
4th generation—broader coverage and
covers some aerobes and Pseudomonas*

48
Q

Cephalosporins: resistance

A

Develops from:
-Hydrolysis of the beta-lactam ring by
ß-lactamases
-Reduced affinity for PBPs

49
Q

Cephalosporins: administration

A

Many have to be given IV or

IM because of poor oral absorption

50
Q

Cephalosporins: Distribution

A

• Distributes well in body fluids
• Adequate levels in the CSF, regardless of inflammation, are obtained with only a few
of these drugs
• Ceftriaxone [Rocephin] and Cefotaxime [Claforan] used in treating neonatal and childhood meningitis from H. influenzae
• Cefazolin [Ancef; Kefzol] used for surgery prevention due to its coverage of
penicillinase-producing S. aureus getting good tissue and fluid penetration

51
Q

Cephalosporins: Elimination

A 
• Through tubular secretion and/or GFR
• Dose reduction in renal disease
• Ceftriaxone is excreted through the 
bile into the feces, no dose reduction on 
those with CKD
52
Q

Cephalosporins: ADEs

A

• Generally well-tolerated
• Those who have had anaphylaxis, Stevens-
Johnson Syndrome or Toxic Epidermal Necrolysis
to PCNs should not be prescribed a Cephalosporin
• Use with caution in those with PCN allergy
• Cross-reactivity between Cephalosporins and
PCNs is 5-10%
• Highest chance of cross-sensitivity between PCN
is with 1st generation Cephalosporins

53
Q

Carbapenems

A 
Synthetic ß-lactam antibiotics that 
differ from PCNs in that sulfur atom 
of the thiazolidine ring has be 
externalized and replaced by a 
carbon atom
Imipenem [Primaxin] is prototype drug
Meropenem [Merrem]
Doripenem [Doribax]
Ertapenem [Invanz]
54
Q

Imipenem [Primaxin] is prototype drug

A

• Resists breakdown by ß-lactamases, but
not metallo-ß-lactamases
• Can be used empirically as it is active against gram + and gram –ß-lactamase producing pathogens, anaerobes and
Pseudomonas

55
Q

Meropenem [Merrem]

A

• Bacterial coverage similar to Imipenem

56
Q

Doripenem [Doribax]

A

• Bacterial coverage similar to Imipenem
• May be active against resistant strains of
Pseudomonas

57
Q

Ertapenem [Invanz]

A

• Does not cover Pseudomonas, Enterococcus spp. or Acinetobacter spp.

58
Q

Carbapenems : Pharmacokinetics

A

• Imipenem, Meropenem and Doripenem penetrate well into tissues, fluids and CSF [when meninges are inflamed]
• Meropenem reaches therapeutic levels in the meninges even without inflammation
• Excreted by glomerular filtration
• Because Imipenem is cleaved by a dehydropeptidase in the brush border of the proximal tubule, it is combined with cilastin to protect the drug from this cleavage
• Other Carbapenems do not require co-
administration
• Ertapenem is given once per day [IV]
• All of these agents must be dose reduced
in CKD

59
Q

Carbapenems : ADE

A

• Nausea, Vomiting and Diarrhea can be seen with Imipenem
• Eosinophilia and neutropenia are less than with other ß-lactams
• High levels of Imipenem can cause seizures [less chance with other
carbapenems]
• Because carbapenems and PCNs share a common bicyclic core cross
sensitivity may occur
• Use carbapenems cautiously in those with PCN allergy [cross sensitivity
rate is <1%]

60
Q

Monobactams

A

Disrupt bacterial cell wall synthesis—
unique because ß-lactam ring is not fused
to another ring
Aztreonam [Azactam] is the prototype
drug
Aztreonam mainly covers gram –bugs—Enterobacteriaceae and Pseudomonas
Does not cover gram + or anaerobic bacteria
Given IV or IM
Can accumulate in those with CKD
Relatively non-toxic, but can cause phlebitis, rash and elevated LFTs [rare]
Shows little cross-sensitivity with other ß-lactams—so can be used in those allergic to PCN, Cephalosporins or Carbapenems

61
Q

ß-Lactamase Inhibitors

A

Hydrolysis of the ß-lactam ring—either by cleavage with a ß-lactamase or by acid, destroys the antimicrobial effect
ß-lactamase inhibitors, such as Clavulanic acid, Sulbactam and Tazobactam contain a ß-lactam ring, but alone have not antimicrobial effects or cause any S
Avibactam and Vaborbactam are also ß-lactamase inhibitors, but they lack the core ß-lactam ring
ß-lactamase inhibitors function by inactivating ß-lactamases, and protecting the antibiotics that are normal substrates for these enzymes
ß-lactamase inhibitors are combined with ß-lactamase-sensitive antibiotics, such as Amoxicillin, Ampicillin and Piperacillin

62
Q

Cephalosporin + ß-lactamase Inhibitor Combinations

Ceftolozane + Tazobactam [Zerbaxa]

A

Ceftolozane + Tazobactam [Zerbaxa]
3rd generation cephalosporin + ß-lactamase inhibitor
IV medication used to treat resistant Enterobacteriaceae and multi-drug resistant Pseudomonas aeruginosa
It has some activity against some ß-lactamase-producing bacteria [select strains of extended spectrum ß-lactamases; ESBLs]
This agent has narrow gram + and limited anaerobic activity

63
Q

Cephalosporin + ß-lactamase Inhibitor Combinations

Ceftazidime + Avibactam [Avycaz]

A

Ceftazidime + Avibactam [Avycaz]
3rd generation cephalosporin + ß-lactamase inhibitor
IV medication with broad gram –activity including Enterobacteriaceae and Pseudomonas aeruginosa
Adding Avibactam allows the drug to resist hydrolysis against broad spectrum ß-lactamases
Little activity against Acinetobacter, anaerobes and gram + bugs

64
Q

Cephalosporin + ß-lactamase Inhibitor Combinations

A 
Both of these drugs are used to treat 
intra-abdominal infections [with 
Metronidazole] and for management 
of complicated UTIs
These agents are reserved for the 
treatment of infections due to 
multiple-drug resistant pathogens
65
Q

Carbapenem + ß-lactamase Inhibitor Combinations

A

Meropenem + Vaborbactam [VaBomere]
Carbapenem + ß-lactamase Inhibitor
Approved for the treatment of complicated UTIs including pyelonephritis
Drug has activity against Enterobacteriaceae producing a broad spectrum of ß-lactamases, except mettallo- ß-lactamases

66
Q

Vancomycin

A

Tricyclic glycopeptide active against aerobic and anaerobic gram + pathogens—MRSA, MRSE, Enterococcus spp., Clostridium difficile
The drug is bactericidal
Used in skin and soft tissue infections,
infective endocarditis, nosocomial
pneumonia
Dosing frequency depends on GFR—
monitoring creatinine clearance is needed
to optimize exposure while minimizing
toxicity
Best cure rates occur when trough is 10-20 mcg/mL
For activity against Staph aureus—AUC/MIC ratio is used—this ratio should be >/= 400
Initial trough levels are drawn before the 4th or 5th dose to ensure proper dosing

67
Q

Vancomyocin ADEs

A

nephrotoxicity, infusion related reactions [“Red-Man” Syndrome and phlebitis], ototoxicity

68
Q

Oral vancomycin is limited to the management of ____

A

c diff

69
Q

Lipoglycopeptides

A 
Telavancin [Vibativ]
Oritavancin [Orbactiv]
Dalbavancin [Dalvance]
Bactericidal concentration-dependent 
semi-synthetic lipoglycopeptide drugs 
active against gram + pathogens
Spectrum is similar to Vancomycin—
staphylococcus, streptococcus and 
enterococcus
Agents are MORE potent than 
Vancomycin and may cover VR isolates
70
Q

Lipoglycopeptides

A

 These drugs inhibit bacterial cell wall synthesis; lipid tail is essential to anchor the drug to the cell walls to improve target site binding Telavancin is an alternative to Vancomycin for acute bacterial skin and skin structure infections [ABSSSIs], hospital acquired pneumonia from resistant gram + organisms, including MRSA

 Use of Telavancin may be limited by ADEs—nephrotoxicity, risk of fetal harm, interactions with drugs that prolong the QTc interval [Quinolones, Macrolides]—renal function and pregnancy test must the evaluated before prescribing this drug

Oritavancin and Dalbavancin have long ½ lives [245° and 187° respectively]—can be used as single doses for managing ABSSSs as outpatients

As with other glycopeptides—infusion reactions may occur; Oritavancin and Telavancin are known to interfere with phospholipid reagents used in managing coagulation—so other agents should be prescribed if patient is on heparin or other anti-coagulants that must have blood monitoring

71
Q

Examples of Lipoglycopeptides

A

Telavancin and Oritavancin

72
Q

Daptomycin

A

Bactericidal concentration-dependent cyclic lipopeptide antibiotic that is an alternative to other agents, such as Vancomycin or Linezolid, to treat infections caused by resistant gram + organisms, such as MRSA and VRE
Used to treat complicated SSSIs and bacteremia from S. aureus, including those with right sided infective endocarditis [not used for left sided BE]
This drug is inactivated by pulmonary surfactants—so it cannot be used to treat pneumonia
Given IV once a day

73
Q

Fosfomycin

A

-Bactericidal synthetic derivative of phosphonic acid—blocks cell
wall synthesis by inhibiting a key step in peptidoglycan synthesis

-Used for UTIs from E. coli or E. faecalis—and is considered 1st line
for acute cystitis

-Cross resistance is not likely because of its unique MOA

-Rapidly absorbed after oral ingestion—distributes well into kidneys,
bladder and prostate

-Excreted in active form in urine and maintains high levels for days—
allowing for one time dosing

-ADEs—diarrhea, vaginitis, nausea and headache

74
Q

Polymyxins

A 
Polymyxin B—prototype drug
🔽
Colistin[Coly-Mycin M]
🔽
Cation polypeptides that bind to 
phospholipids on bacterial cell membrane of 
gram –pathogens
🔽
Detergent like effects that disrupt cell 
membrane and cause cell death
🔽
Concentration dependent bactericidal 
agents
75
Q

Polymyxins

A

Active against Pseudomonas aeruginosa, E.
coli, K. pneumoniae, Acinetobacter spp.,
Enterobacter spp.

Proteus and Serratia are resistant

Polymyxin B is available parenteral, ophthalmic, otic and topical

Colistin is available as a prodrug, colistimethate sodium, given IV or nebulized

Use of these drugs is limited due to renal and neurotoxicity [when used systemically]

However, with increasing gram –resistance, these agents are now used as salvage therapy for multi-drug resistant infections

76
Q

Vancomyocin

A

MOA: inhibits bacterial cell wall synthesis

Pharmacodynamics: combination of time and concentration time dependent. Bactericidal

Common antibacterial spectrum: Activity limited to gram positive organisms. Staph aureus (including MRSA) Strep Pyogenes, S. agalactiae, pencillin-resistant S. pnejmooniae, corynebacterium jeikeium, vancomyocin susceptible enterococcus

Unique antibacterial Spectrum: c diff (oral only)

Route: IV/PO

Adim. Time: 60-90 min IV infusion

Pharmacokinetics: renal elimination. half life 6-10 hrs. Dose is adjusted based on renal function and serum trough levels

Unique AE: Infusion-related reactions due to histamine release: fever, chills, phlebitis, flushing (red man); dose related to ototoxicity, and nephrotoxicity

Key Learning Points: Drug of choice for severe MRSA infections; oral form only used for C. diff infection; monitor serum trough concentrations for safety and efficacy

77
Q

Daptoymycin

A

MOA: causes rapid depolarization of the cell membrane, inhibits intracellular synthesis of DNA,RNA,and protein

Pharmacodynamics: concentration dependent

Common antibacterial spectrum: Activity limited to gram positive organisms. Staph aureus (including MRSA) Strep Pyogenes, S. agalactiae, pencillin-resistant S. pnejmooniae, corynebacterium jeikeium, vancomyocin susceptible enterococcus

Unique antibacterial Spectrum: vancomyocin-resistant E. faecalis and E. faecium (VRE)

Route: IV

Adim. Time: 2 min IVP or 30 min IV infusion

Pharmacokinetics: renal elimination. Half life 7-8 hrs. Dose is adjusted based on renal function

Unique AE: Elevated hepatic transaminases and creatine phosphokinase (check weekly), myalgias, and rhabdomyolysis (consider holding HMG-CoA reductase inhibitors (statins) while receiving therapy

Key Learning Points: Daptomyocin is inactivated by pulmonary surfactants and should never be used in the treatment of pneumonia

78
Q

Telavancin

A

MOA: inhibits bacterial cell wall synthesis; disrupts cell membrnae

Pharmacodynamics: concentration dependent; Bactericidal

Common antibacterial spectrum: Activity limited to gram positive organisms. Staph aureus (including MRSA) Strep Pyogenes, S. agalactiae, pencillin-resistant S. pnejmooniae, corynebacterium jeikeium, vancomyocin susceptible enterococcus

Route: IV

Unique antibacterial Spectrum: some isolated vancomyocin resistant enterococci

Adim. Time: 60 min IV infusion

Pharmacokinetics:

Unique AE: taste disturbances, foamy urine, QTc prolongation, interferes with coagulation labs (PT/INR, aPTT, ACT), not recommended in pregnancy (box warning recommends pregnancy test prior to initiation)

Key Learning Points: Use with caution in patients with baseline renal dysfunction (CrCl<50 mL/min) due to higher rates of treatment failure and mortality in clinical studies; any necessary coagulation labs should be drawn just prior to the telavancin dose to avoid interaction

Advanced Pharmacology (18 decks)

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