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Genetics; Protection II > L1: Introduction to Antimicrobial Therapy > Flashcards

L1: Introduction to Antimicrobial Therapy Flashcards

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1
Q

Inevitable consequence of widespread use:

A
  1. Emergence of antibiotic-resistant pathogens
  2. Increasing need for new drugs
  3. Rising costs of medical care
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2
Q

Agents that inhibit synthesis of bacterial cell walls

A

a. Penicillins, cephalosporins
b. Cycloserine
c. Vancomycin
d. Bacitracin
e. Azole antifungal agents

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3
Q

Agents that act directly on the cell membrane of the microorganism, affecting
permeability leading to leakage of intracellular compounds

A

a. Polymixin

b. Polyene antifungal agents

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4
Q

Agents that affect the function of 30 S or 50 S ribosomal subunits to cause a
reversible inhibition of protein synthesis (bacteriostatic)

A

a. Chloramphenicol
b. Tetracyclines
c. Erythromycin
d. Clindamycin

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5
Q

Agents that bind to the 30 S ribosomal subunit & alter protein synthesis which
eventually leads to cell death (bactericidal)

A

a. Aminoglycosides

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6
Q

Agents that affect bacterial nucleic acid metabolism

A

a. Rifamycins – inhibit RNA polymerase

b. Quinolones – inhibit topoisomerases

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7
Q

Antimetabolites which block essential enzymes of folate metabolism

A

a. Trimethoprim

b. Sulfonamides

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8
Q

For an antibiotic to be effective, it must:

A
  1. Reach its target
  2. Bind to its target
  3. Interfere with its target’s function
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9
Q

0 Outer membrane of gram-negative bacteria is a permeability barrier
that excludes large polar molecules from entering the cell
0 Small polar molecules, including many antibiotics, enter the cell
through channels made up of proteins called porins
0 Absence of, mutation in or loss of the appropriate porin channel can
slow the rate of drug entry into the cell or prevent entry altogether,
reducing the effective drug concentration at the target site
0 For intracellular targets of drugs that require active transport across the
cell membrane, a mutation or environmental condition that shuts down
the transport mechanism confers resistance

A

The drug does not reach its target

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10
Q

0 2nd general MOR
0 Production of inactivating enzymes
b-lactamases
aminoglycoside-modifying enzymes
0 Variation: failure of the bacterial cell to convert an inactive drug to its
active metabolite
Isoniazid resistance among M. tuberculosis

A

The drug is not active

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11
Q

0 May be due to:
Mutation of the natural target – fluoroquinolone resistance
Target modification – ribosomal protein type of resistance to
macrolides & tetracylcines
Substitution with a resistant alternative to the native,
susceptible target – methicillin resistance in staphylococci
v Reduced binding of drug by the critical target substitution
of a new target that does not bind the drug for the native
target

A

The target is altered

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12
Q

§ Molecular basis for resistance to streptomycin (ribosomal mutation),
quinolones (gyrase gene mutation) & rifampin (RNA polymerase gene
mutation)
§ Underlies the drug resistance of M. tuberculosis to anti-tuberculous drugs
§ May occur in the gene encoding:
· The target protein, altering its structure so that it no longer binds the drug
· A protein involved in drug transport
· A protein important fro drug activation
· In a regulatory gene or promoter affecting expression of the target, a transport
protein or an inactivating enzyme

A

Mutations & antibiotic selection

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13
Q

0 Acquisition of bacterial DNA from a bacteriophage (a virus that
propagates on bacteria) that has incorporated DNA from a previous
host bacterium within its outer protein coat
0 Important in the transfer of antibiotic resistance among strains of
Staphylococcus aureus, where some phages can carry plasmids
(autonomously replicating pieces of extrachromosomal DNA) that code
for penicillinase, while other transfer genes encoding resistance for
erythromycin, tetracycline or chloramphenicol

A

Transduction

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14
Q

0 Involves uptake & incorporation of DNA that is free in the environment
into the host genome by homologous recombination
0 Molecular basis of penicillin resistance in pneumococci & Neisseria

A

Transformation

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15
Q

0 Passage of genes from cell to cell by direct contact through a sex pilus
or bridge
0 Extremely important mechanism fro spread of antibiotic resistance
since DNA that codes fro resistance to multiple drugs may be
transferred
0 First recognized in Japan in 1959 after an outbreak of bacillary
dysentery caused by Shigella flexneri that was resistant to 4 different
classes of antibiotics
0 Transferable genetic material consists of 2 different sets of plasmidencoded
genes:
i. A gene that encodes for the actual resistance
ii.A gene that encodes genes necessary for bacterial conjugation
0 Common among gram-negative bacilli

A

Conjugation

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16
Q

Factors that determine the susceptibility & resistance of microorganisms to
antimicrobial agents:

A
  1. The concentration of antibiotic at the site of infection
    Ø Must be sufficient to inhibit growth of the offending microorganism
    Ø Must remain below the level that is toxic to human cells
  2. Host factors
    Ø Host defenses
    § If intact & active, a minimum inhibitory effect (bacteriostatic agents)
    may be sufficient
    § If impaired, antibiotic-mediated killing (bactericidal effect) may be
    required to eradicate the infection
    Ø Age
    Ø Genetic factors
    Ø Pregnancy
    Ø Drug allergy
    Ø Kidney function
  3. Local factors
    Ø Low pH
    Ø High protein concentration
    Ø Blood flow
  4. Pharmacokinetic factors
    Ø In vitro activity is only a guide as to whether or not an antibiotic is likely to be
    effective in an infection
    Ø Successful therapy also depends upon achieving a drug concentration that is
    sufficient to inhibit or kill the bacteria at the site of the infection without
    harming the host
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17
Q

§ May to a large extent, dictate the route of administration
§ Access to sites of infection depends on multiple factors
· CSF – drug must pass the blood-brain barrier

A

Location of the infection

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18
Q

§ Oral administration is preferable whenever possible

§ Parenteral administration considered in seriously ill patients

A

Route of administration

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19
Q

Antibiotics are used in 3 different ways:

A
  • Empirical therapy
  • Definitive therapy
  • Prophylactic or preventive therapy
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20
Q

§ Requires knowledge of the most likely infecting microorganism
& their susceptibilities to antimicrobial drugs
· Gram’s stain of appropriate specimens
§ Must “cover” all of the likely pathogens since the infecting
organism has not been identified
§ “Broad-spectrum” antibiotics
§ Monotherapy or combination therapy

A

Empirical therapy

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21
Q

§ Culture of appropriate specimens
§ “Narrow-spectrum”, low-toxicity regimen against the identified
pathogen

A

Definitive therapy

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22
Q

§ Highly effective in some clinical settings & in others, is totally
without value & may be deleterious
§ May be used to protect healthy persons from acquisition of or
invasion by specific microorganisms to which they are exposed
§ Used to prevent a variety of infections in patients undergoing
organ transplantation or receiving cancer chemotherapy
§ Recommended for patients with valvular or structural lesions of
the heart predisposing to endocarditis who are undergoing
dental, surgical or other procedures that produce a high
incidence of bacteremia
§ Used to prevent wound infections after various surgical
procedures

A

Prophylactic or preventive therapy

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23
Q

Ø Requires an understanding of the potential for interaction between agents
which may affect either the microorganism or the patient
Ø Antimicrobial agents acting at different targets may enhance or impair overall
antimicrobial activity
Ø May result in:
· Additive effects
· Antagonism
· Synergism
Ø Indications:
· Empirical therapy of severe infections in which a cause is unknown
· Treatment of polymicrobial infections
· Enhancement of antibacterial activity in the treatment of specific infections

A

Therapy with combined antimicrobial agents

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24
Q

Misuses of antibiotics

A
  1. Treatment of untreatable infections
  2. Therapy of fever of unknown origin
  3. Improper dosage
  4. Inappropriate reliance on chemotherapy alone
  5. Lack of adequate bacteriological information
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25
Q

Antibiotics

  • Substances produced by microorganisms that suppress or kill other
    microorganisms. What theory?
A

Germ Theory

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26
Q

Effective for infections due to their selective toxicity to organisms, not the
host.

A

Antimicrobial drugs

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27
Q

Active chemical moiety of the drug which binds to the microbial receptor

A

Pharmacophore

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28
Q

Agents that inhibit synthesis of bacterial cell walls - Bactericidal (kill microorg.)

A
  • Beta-lactams (Penicillins, Cephalosporins, Carbapenems)
  • Beta-lactamase inhibitors
  • Other antibiotics (Vancomycin, Bacitracin, Daptomycin, Teicoplanin,
    Mupirocin, Fosfomycin, Dalbavancin, Telavancin)
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29
Q

Agents that act directly on bacterial cell membranes →impair permeability → leakage
of intercellular contents → cell death.

A
  • Detergents (Polymyxin)
  • Polyene antifungals (Nystatin, Candicidin, Amphotericin B)
    →these bind to cell wall sterols
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30
Q

Agents that affect the function of ribosomal subunits → reversible inhibition of
protein synthesis → Bacteriostatic (will not kill, only stop the growth)

A
  • On 30s = Tetracyclines, Spectinomycin
  • On 50s = Clindamycin, Chloramphenicol, Macrolides (erythromycin,
    clarithromycin, azithromycin)
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31
Q

Agents that bind irreversibly to 30s ribosomal subunit and some sites on 50s → alter
protein synthesis→ rapidly bactericidal

A
  • Aminoglycosides (Gentamicin, Tobramycin, Amikacin, Kanamycin,
    Streptomycin, Neomycin, Sisomycin, Netilmicin)
  • Related agents (Paromomycin, Spectinomycin)
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32
Q

Important Features: Aminoglycosides:

A
  • widely used:
    • combined with beta-lactams for severe infections with gram negative
    bacteria
    • combined with Vancomycin or beta-lactam for gram positive
    endocarditis
    • for the prescription of PTB
  • Route: Parenteral – OD (once daily)
  • (+) conc-dependent killing, post antibiotic effect, synergism w/ combined
    antibiotics
  • ototoxic & nephrotoxic – limits their use
  • ↑ doses = curare-like effect ↔ NMB ( neuromuscular blockers)
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33
Q

Agents that affect bacterial nucleic acid metabolism (Bactericidal)

A
  • Rifamycin - inhibit RNA polymerase

- Quinolones - inhibit topoisomerases

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34
Q

Antimetabolites → block specific metabolism steps essential to microorganism
synthesis of folic acid

A
  • Sulfonamides → bacteriostatic

- Trimethoprim →bactericidal

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35
Q

inhibitory drug concentrations are lower than

bactericidal drug concentration

A

Bacteriostatics

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36
Q

To provide effective antimicrobial action, antibiotic concentration in
body should be greater than

A

minimum inhibitory concentration (>MIC)

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37
Q

cell wall active agents

A

bactericidal

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38
Q

drugs that inhibit

protein synthesis

A

bacteriostatic

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39
Q

o more aggressive Rx – often the drug of choice for
severe infections → ↓colony count down by 99.9%
o priority for severe dse
§ Ex. Endocarditis, meningitis, infxns in
neutropenic pts
o Some bactericidal (Vancomycin, Pen, Ampicillin ) → inhibit
BUT not kill
§ Ex. Against enterococci

A

Bactericidal

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40
Q

o inhibits growth and replication at therapeutic serum levels and
do not kill but allows body immune system to function against
the pathogens.
o Some bacteriostatic agts may act bactericidal on selected
microbes.
§ Ex. Chloramphenicol – bacteriostatic against Gm(-)
rods, BUT, bactericidal against other bacteria, like
Strep pneumoniae.
o Bacteriostatic↔bactericidal in efficacy in immunocompetent
hosts ⇒ may be sufficient Rx for these pts.
Immune system status – if intact, → contributes to
elimination of microorgs

  • If Rx is discontinued before immune system has scavenged the bacteria →
    enough viable microbes may remain & begin a 2nd cycle of infection. (finish
    the course of treatment)
  • Need for bacteridal antibiotics for pts with impaired host defenses.
A

Bacteriostatic

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41
Q

Bactericidal agents

Can be divided into:

A

a. Agents w/ Conc-dependent killing

b. Agents w/ Time-dependent killing

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42
Q

Antimicrobial action increases w/ ↑↑↑ drug conc = pharmacodynamic
factor responsible for efficacy of OD dosing of Aminoglycosides

A

Agents w/ Conc-dependent killing

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43
Q

Bactericidal activity continues as long as serum concs are greater than
the MBC

A

Agents w/ Time-dependent killing

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44
Q

Persistent suppression of microbial growth that occurs after antibiotic
levels have fallen below the MIC → effective OD dose schedule of
Aminoglycosides

A

Postantibiotic effect (PAE)

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45
Q

What should be bacteriostatic or bactericidal without damage to human cells?

A

Drug serum concentration

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46
Q

What is the aim of the Rx?

A

to maintain equal minimal drug concentration at the infected site to the minimum inhibitory concentration of offending microorganism during dosing interval

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47
Q

If patient has10% or less than N → impaired renal clearance → adverse
effects
- Rx: adjust dosage
o serum creatinine – index of renal function
o # of functioning nephrons decreases with age →
Thus, elderlies are vulnerable to drug accumulation.
Rx: Choose agents who are excreted via biliary routes.

A

Renal dysfunction

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48
Q
  • Rx: antibiotics that are concentrated or eliminated by the liver.
    o Erythromycin, Tetracyclines (to not increase adverse effects)
  • Poor perfusion – ↓ circulation to area supplied by the antibiotic = ↓amount of
    antibiotic to this area
  • Lactation - most drugs go to the breast milk. Antibiotic concentration in milk
    is ↓ but may be harmful to infants.
A

Liver dysfunction

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49
Q

Newborns are vulnerable to toxic effects of what due to immature liver and kidney?

A

Chloramphenicol and

Sulfonamides

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50
Q

What has phagocytes, cellular debris, proteins which bind to drugs or create setting unfavorable to antimicrobial action?

A

Pus

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51
Q

Successful Rx of infected abscesses

A

Drainage

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52
Q

↓pH in abscess cavities or confined infected spaces (pleural space, CSF,
urine) → marked loss of antimicrobial activity of erythromycin,
clindamycin, aminoglycosides.
- Blood (hematoma) – accumulated Hemoglobin → bind Penicillins
and Tetracyclines leading to ↓ efficacy.
- Infected areas lead to ↓ vascular supply resulting to ↓ penetration by
antibiotics
- Anaerobic conditions (Ex. abscess cavities) impair activity of
aminoglycosides
- Chlortetracycline, Nitrofurantoin, and Methenamine are more active in
an acidic environment.
- Foreign bodies in infected site reduces the likelihood of a successful
antimicrobial Rx. (implants)
- Prosthetic materials can be perceived by phagocytes as foreign bodies.
(remove before starting antibiotics)
o EFFECTS: phagocytose or destroy → degranulation
→ depletes intracellular bactericidal substances but
phagocytes are relatively inefficient as bactericidals.

A

Local Factors

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53
Q
  • No human fetal risk or remote possibility of fetal harm

- Drug: none

A

Category A

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54
Q
  • No controlled studies show human risk
  • Animal studies suggest potential toxicity
  • Drugs: Beta lactams, Cephalosporins, Aztreonam, Sulfonamide,
    Erythromycin, Azithromycin, Clindamycin, Metronidazole,
    Nitrofurantoin
  • (safest use)
A

Category B

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55
Q
  • Animal-fetal toxicity demonstrated, human
    risk undefined.
  • Drugs: Chloramphenicol, Vancomycin, Fluoroquinolones, Gentamicin,
    Clarithromycin, Trimethoprim, Sulfamethoxazole
A

Category C

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56
Q
  • Human fetal risk present but benefits outweigh risks

- Drugs: Tetracyclines, Aminoglycosides (except Gentamicin)

A

Category D

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57
Q
  • Contraindicated in pregnancy
A

Category X

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58
Q

likelihood of crossing physical

barriers erected by layers of cells

A

↑ octanol-water partition coefficient

59
Q

concentrate in the bilipid cell

membrane bilayer

A

Hydrophobic agents

60
Q

concentrate in the blood, cytosol, and other aqueous compartments

A

Hydrophilic agents

61
Q

Guarded by the BBB
o Tight junctions that connect endothelial cells of cerebral
microvessels to one another
o Protein transporters
o Antibiotics that are polar at physiologic pH → poor penetration
o ↓ integrity during active bacterial infections → marked ↑ in
penetration

A

CNS

62
Q

More charged or larger molecule

A

poorer penetration - Central nervous

system

63
Q

o Poor penetration of drug from plasma

o Standard Tx: direct instillation

A

Eye

64
Q

Same dose of drug given to multiple patients → different

pharmacokinetic parameters

A

Between-patient variability

65
Q

Same dose administered to same patient on different occasions
→ different concentration time profile of the drug

A

Inter-occasion or within-patient variability

66
Q

Variability in Drug Response, Different causes:

A

o Genetic variability (different rates of elimination and breakdown)
o Weight, height, age
o Comorbid conditions - renal/liver dysfunction
o Residual variability due to unexplainable factors

67
Q

Prevent wound infection after surgery
o Antimicrobial activity must be present at the wound site at the
time of its closure
§ 1st dose begun within 60 min before surgical
incision and discontinued within 24 hours
o Antibiotic must be active against the most likely contaminating
microorganisms for that type of surgery

A

Chemoprophylaxis

68
Q

• Resistance - MIC >2.0 mg/L
• MRSA - 61% success rate with MIC 0.5 mg/L
∙ 28% for MIC 1.0
∙ 11% for MIC 2.0

A

Vancomycin (higher order antibiotic)

69
Q

dose that achieves IC80 to IC90

exposures at site of infection

A

Optimal dose of antibiotic for a patient

70
Q

Optimal microbial kill by the antibiotic may be best achieved by

A

maximizing

antimicrobial effect

71
Q

Some classes of antimicrobials kill best when concentration

persists above MIC for longer durations of dosing interval

A

• Beta-lactams
• 5-fluorocytosine
• Drug should be dosed more frequently or t ½
prolonged by other drugs

72
Q

Highly effective once daily (OD)

A

Aminoglycosides

73
Q

• Long duration of post-antibiotic effect
• Administer combined doses on an more than
intermittent basis (OD) → maximize effect also toxicity
§ Also ↓ toxicity

A

Rifampin

74
Q

Treating patients who have not been infected yet or have not yet developed
the disease

A

PROPHYLACTIC THERAPY

75
Q

What is the goal of prophylactic therapy?

A

prevent infection

76
Q

Main principle: targeted therapy
o Use narrow-spectrum antibiotics targeted at the most important
agents, not target all possible bacteria
o Limit duration of prophylaxis to be as short as the time in which
max contamination is expected, do not prolong beyond this
time (to prevent resistance)

A

PROPHYLACTIC THERAPY

77
Q

Used in immunocompromised patients
o Therapy based on pathogens that are major causes of morbidity
o AIDS-CD4 count <200 cells per mm3

A

PROPHYLACTIC THERAPY

78
Q

Patients at ↑ risk for infective endocarditis for which prophylaxis
is recommended:

A

o Those with prosthetic material used for heart valve repair/
replacement
o Previous infective endocarditis
o CHD (unrepaired cyanotic heart disease, within 6 mos of repair of
heart disease with prosthetic material, residual defects adjacent to
prosthetic material)
o Postcardiac transplant patients with heart valve defects

79
Q

Prophylaxis recommended for above patients if:

A

o Dental procedures
o Manipulation of gingival tissue or periapical region of teeth
o Perforation of oral mucosa
o Single dose of oral Amoxicillin 30 minutes to 1 hour before
procedure
• IV Ampicillin or Ceftrixone
• Macrolide / Clindamycin – allergic

80
Q

o Meningococcal meningitis prevention after exposure: Rifampin
o Prevention of Gonorrhea/Syphilis
o Macrolides after contact w/ Pertussis
o HIV exposure - 4 weeks therapy with antiretroviral agent

A

Post-exposure prophylaxis

81
Q
  • Delivery of therapy prior to development of symptoms → aborts impending
    disease
  • Short and defined duration of therapy
  • Treatment for CMV after hematopoietic stem cell transplants and
    after solid organ transplantation
A

PRE-EMPTIVE THERAPY

82
Q
  • First determine if drug is indicated
  • Gram staining of infected secretion or body fluid
    o Most valuable and time tested method for ID of bacteria
A

EMPIRICAL TREATMENT IN SYMPTOMATIC PATIENT

83
Q
  • Monotherapy-preferred (Single dose)
  • ↓ Risk of toxicity and selection of antimicrobial-resistant pathogens
  • Combination Treatment
    o Prevent resistance to monotherapy
    o Accelerating rapidity of microbial kill
    o Enhance therapeutic efficacy by use of synergistic interactions or
    enhancing kill
    o Reducing toxicity
A

DEFINITIVE TREATMENT WITH KNOWN PATHOGEN

84
Q
  • Infection controlled but not completely eradicated → Tx continued
    at a lower dose
  • Common in AIDS and post-transplant patients
  • Goal: Secondary prophylaxis
A

POST-TREATMENT SUPPRESSIVE TX

85
Q

Resistance due to:

A
  • Reduced entry of antibiotic into the pathogen
  • Enhanced export of antibiotic
  • Release of microbial enzymes that destroy antibiotic
  • Alteration of microbial proteins that transform pro drugs to active
  • Alteration of target proteins
  • Development of alternative pathways to those inhibited by antibiotic
86
Q
  • Proper selection of drug based on microbiological results and
    susceptibility testing
  • Knowledge of drug penetration into infected compartment
  • Knowledge of compartmental pharmacokinetics
A

Success of antimicrobial treatment

87
Q

Thiazolidine ring connected to a __________, attached to a side chain

A

β-lactam ring

88
Q

chief structural requirement for biological

activity

A

PENICILLIN Nucleus

89
Q

determines many antibacterial and

pharmacological characteristic of a particular type of penicillin

A

Side chain

90
Q

greatest antimicrobial activity

o Only natural penicillin used clinically

A

PENICILLIN G

91
Q

What is the MOA of Penicillin?

A

Inhibition of bacterial wall synthesis peptidoglycan synthesis

92
Q

MECHANISM OF BACTERIAL RESISTANCE OF PENICILLIN

A
  • Structural differences in PBPs (PENICILLIN-binding proteins) → targets of
    drug
    o Found in bacterial cell wall
  • Development of HMW PBPs with decreased affinity for PENICILLIN
  • Inability to penetrate site of action
  • Active efflux pumps → remove antibiotic from its site of action before it can
    act
93
Q

Enzymatically (β – lactamases)

4 classes:

A
  • Class A: extended spectrum (ESBLs)
    o Degrade penicillin, some cephalosporins, carbapenems
    o Most worrisome: KPC carbapenemase in Enterobacteriaceae
    → resistant to Carbapanems, penicillin all extended
    spectrum cephalosporins
  • Class B: Zn+ - dependent enzymes
    o Destroy all β-lactams except Aztreonam
  • Class C: active against cephalosporins
  • Class D: Cloxacillin-degrading enzymes
94
Q

What can produce and secrete a large amount of β-lactamase?

A

Gram + bacteria

95
Q

What are factors that influence activity of β – lactams?

A
  • Density of bacterial population

* Age of Infection

96
Q

does not decrease ability of β – lactams to kill bacteria

A

Presence of proteins/other constituents of pus, low pH, low O2 tension

97
Q
  • Readily hydrolyzed by penicillinase
  • Active against sensitive strains of gram + cocci
  • Ineffective against most S. aureus
A

Penicillin G and V

98
Q
  • Nacillin, Oxacillin, Cloxacillin, Dicloxacillin, Flucloxacillin
  • 1st line for penicillinase-producing S. aureus and S. epidermidis
A

Penicillinase-resistant Penicillins

99
Q
  • Extended spectrum including gram – organism: H. influenza, E.coli,
    P. mirabilis
  • Available as coformulations w/a B-lactamase inhibitor (clavulanate,
    sulbactam) (co-Amoxiclav)
A

AminoPCNs – Ampicillin, Amoxicillin

100
Q

Agents w/ Extended antimicrobial activity against Pseudomonas, Enterobacter, and
Proteus

A
  • Azlocillin, Carbenicillin, Mezlocillin, Ticarcillin/Clavulanate, Carbenicillin
    indanyl Na
  • More expensive, used in ICU
101
Q

Achieved readily in tissues and secretion (joint, pleural fluid and bile)

A

THERAPEUTIC CONCENTRATION OF PENICILLIN

102
Q

LOW CONCENTRATION

A

Prostatic secretion, brain tissue, intraocular fluid

103
Q

Many bacteria previously sensitive to PENICILLIN G are now resistant

A 
o Viridans streptococci
o S. pneumonia
o S. auerus
o S. epidermidis
o PENICILLINase-producing gonococci
104
Q

PENICILLIN G AND V are not effective against

A 
o Amoeba
o Plasmodia
o Rickettsiae
o Fungi
o Viruses
105
Q

o 1/3 of dose absorbed
o pH 2 of gastric juice destroys antibiotic
o Rapid absorption
o Max conc. in blood achieved in 30-60 min.
o Ingestion of food interferes with absorption → administered 30
min. before meals or 2 hours after

A

Oral admin. of PENICILLIN G

106
Q

o More stable in acidic medium

o Better absorbed from GIT

A

Oral admin. of PENICILLIN V

107
Q

o Peak plasma conc. within 15-30 min.
o PENICILLIN G benzathine
• Releases PENICILLIN G slowly from area of injection
• Produces low but persistent conc. in the blood
• Tx for syphilis

A

Parenteral admin. of PENICILLIN G

108
Q

does not readily enter CSF

A

Normal meninges

109
Q

penetrates into CSF easily →

therapeutically effective against susceptible organism

A

Acutely inflamed meninges

110
Q

elevates conc. Of PENICILLIN in CSF by inhibiting
active transport process → no secretion of PENICILLIN from CSF
into bloodstream

A

Preobenecid

111
Q

DOC of sensitive strains of S. pneumonia

A

Pneumococcal infections

112
Q
  • 3rd gen cephalosporin/ 20-24 M units of PCN G daily by continuous IV
    infusion
  • Tx continued for at least 7-10 day, 2-3 days afebrile
A

Pneumococcal pneumonia

113
Q
  • Only if sensitive to PCN
  • Add Vancomycin and 3rd gen cephalosporins
  • Give Dexa prior
A

Pneumococcal meningitis

114
Q
  • Caused by S. pyogenes
  • PCN V 500 mg q 6H x 10D
  • Reduced risk of acute RF
A

Strep pharyngitis

115
Q
  • Viridans group = most common cause of infectious endocarditis
  • Penicillin-sensitive daily doses of 12-20 M units of IV PENICILLIN G for 2
    weeks + Gentamicin 1 mg/kg q 8H
A

Infections caused by other Streptococci

116
Q

Sensitive to PENICILLIN G except B. fragilis

A

Infections with Anaerobes

117
Q

Resistant due to penicillinase

A

Staphylococcal infections

118
Q
  • PENICILLIN G = DOC
  • High doses IV
  • Does not eliminate carrier state→ ineffective for prophylaxis
A

Meningococcal infections

119
Q
  • > Resistant

- Ceftriaxone (3rd gen cephalosporins)

A

Gonococcal infections

120
Q
  • 1°, 2° and latent syphilis of < 1 year duration
    o PENICILLIN G procaine 2.4 M units/day IM
    plus Probenecid 1 g/day orally for 10 days
    o Weekly IM doses of 2.4 M units of PENICILLIN G benzathine
    o Neurosyphilis/CVS syphilis – 18-24M units PCN G x 10-14 days
  • 70-90% of patients with 2° syphilis develop Jarisch-Herxheimer reaction
    o Hours after 1st injection with PENICILLIN
    o Chills, fever, headache, myalgias, arthralgias
    o Syphilitic cutaneous lesions→ become more prominent,
    edematous and brilliant in color
    o Due to release of spirochetal antigens with subsequent host
    reactions to the products
    o Persist for a few hours, rash begins to fade within 48 hours
    o Tx: Aspirin, do not D/C treatment
A

Syphilis

121
Q
  • PENICILLIN G - DOC

- 20 M units IV daily for 6 weeks

A

Actinomycosis

122
Q
  • DOC for gas gangrene

- 12-20 M units/day IV + antitoxin + debridement

A

Clostridial infections

123
Q
  • 200, 000 units PENICILLIN G/V q 12H orally
  • 1.2 M units PENICILLIN G benzathine IM once monthly for 1 yr
  • Or until the Px will become 21 yrs old
A

Recurrences of Rheumatic Fever

124
Q

PENICILLINASE-RESISTANT PENICILLINS

A

Oxacillin, Cloxacillin, Dicloxacillin
o Stable in acidic medium
o Not substitutes for PENICILLIN G, not active against Enterococci
or Listeria
o Potent inhibitors of the growth of most PCNase-producing
Staphylococci

125
Q

most active

A

Dicloxacillin

126
Q

Absorption more effective on an empty stomach and

Administered an hour before or 2 hours after meals

A

PENICILLINASE-RESISTANT PENICILLINS

127
Q

o > active than Oxacillin against PENICILLIN-resistant S. aureus
o Most active of the PCNase resistant PCNs, not as potent as PCN G

A

Nafcillin

128
Q

o Meningococci, L. monocytogenes - sensitive
o Salmonella, Shigella (most strains), Pseudomonas, Klebsiella,
Serratia, Acinetobacter, Indole (+) Proteus → resistant

A

Bactericidal for both gram (+) and gram (–) bacteria

129
Q

o Stable in acid
o Well absorbed after oral administration
o Intake of food prior to ingestion diminishes absorption

A

Ampicillin

130
Q

o Absorbed more rapidly and completely GIT than Ampicillin
(major difference)
o More stable in acid
o Lesser incidence of diarrhea
o Similar antimicrobial spectrum to Ampicillin
§ < effective for Shigellosis

A

Amoxicillin

131
Q
  • Active against: S. pyogenes, S. pneumoniae, H. influenza
  • Sinusitis, OM(otitis media), Acute exacerbations of chronic
    bronchitis, epiglottis
  • Most active against both PCN-sensitive and PCN-resistant S. pneumonia
  • Addition of β-lactamase inhibitor – extends spectrum to β-lactamase
    producing H. influenza and Enterobacteriaceae
A

URTI (upper respiratory tract infxn)

132
Q

Ampicillin = effective but with increased resistance

A

UTI

133
Q
  • S. pneumonia or N.meningitidis
  • 20-30% resistant
  • Ampicillin + Vancomycin + 3rd gen Cephalosporin
  • L. monocytogenes = Ampicillin (excellent activity)
A

Meningitis

134
Q
  • Fluoroquinolone/Ceftriacxone = DOC

- High doses Ampicillin (12g/day) for adults

A

Salmonella Infections

135
Q
  • Active against P. aeruginosa and Proteus which are resistant to Ampicillin
  • Ineffective against S. aureus, E. faecalis, Klebsiella, L. monocytogenes
A

ANTIPSEUDOMONAL PENICILLINS

136
Q

o Carbenicillin

o Ticarcillin

A

Carboxypenicillins

137
Q

o Mezlocillin
o Piperacillin
§ Superior activity vs. P. aeruginosa
§ Klebsiella

A

Ureidopenicillins

138
Q

1st PENICILLIN with activity against P. aeruginosa and some

Proteus strains resistant to Ampicillin

A

Carbenicillin

139
Q

o Acid stable, available for oral admin.
o Contains 5 mEq Na+ / gram of drug
§ May produce CHF(congestive heart failure) due to
excess Na+
o Only use is for management of UTI cause by Proteus spp. Other
than P. mirabilis and P. aeruginosa
§ Active component excreted rapidly in urine =
therapeutic conc.

A

Carbenicillin Indanyl Sodium

140
Q

o Extends spectrum of Ampicillin to include P. aeruginosa,
Enterobacteriaceae, Bacteroides spp. And E. faecalis
o (+) β-lactamase inhibitor (Piperacillin- Tazobactam)
§ Broadest antibacterial spectrum of PCNs
o Treatment of patients with serious infections caused by gram –
bacteria
§ Bacteremia, Pneumonias, infections ff. burns, UTI
caused by P. aeruginosa, Proteus, Enterobacter
spp.
o Only available for parenteral administration, expensive (3-5K!)

A

Piperacillin

141
Q

o 2-4x more active vs. P. aeruginosa vs. Carbenicillin

o Less Piperacillin for Pseudomonas

A

Ticarcillin

142
Q

o More active against Klebsiella than Carbenicillin
o More active vs. E. faecalis than Ticarcillin
o Discontinued (D/C) in US

A

Mezlocillin

143
Q

good activity against E.faecalis and B.fragilis - use in

mixed intra-abdominal infections

A

Piperacillin/tazobactam

Genetics; Protection II (11 decks)

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