07131022 Maya Fadilla- Antibiotics

7/31/2019 07131022 Maya Fadilla- Antibiotics

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ANTIBIOTICS

MAYA FADILLA

07131022


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INTRODUCTION

for the treatment of severe gram-negativeinfections such as pneumonia or bacteremia,often in combination with a -lactam

antibiotic. used for gram-positive infections such as

infective endocarditis in combination withpenicillins when antibiotic synergy is requiredfor optimal killing

bactericidal


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Example

gentamicin,

tobramycin, netilmicin, and

amikacin


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THERAPEUTIC AND TOXIC

CONCENTRATIONS

The MIC for susceptible bacteria is higher foramikacin than it is for the otheraminoglycosides.

Because the pharmacokinetics is similar for allthese drugs, higher doses of amikacin areneeded to treat infections.

The conventional method of dosingaminoglycoside antibiotics is to administermultiple daily doses (usually every 8 hours)


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Conventional Dosing

For gentamicin, tobramycin, and netilmicin

short-term (1/21 hour) infusions. If a 1-hour

infusion is used, maximum end of infusion peak

concentrations are measured when the infusion is

completed

Therapeutic steadystatepeak concentrations for

gentamicin, tobramycin, and netilmicin aregenerally 510 g/mL for gram-negative

infections


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For gentamicin, tobramycin, and

netilmicin + other antibiotics

gentamicin, tobramycin, or netilmicin are used

synergistically with penicillins or other

antibiotics for the treatment of gram-positiveinfections such as infective endocarditis

steady-state peak concentrations of 35

g/mL are often times adequate.

Therapeutic peak concentrations for amikacin

are 1530 g/mL.


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Concentration/time plot for gentamicin given as a 1/2-hour

infusion


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Extended-Interval Dosing

these studies have shown comparablemicrobiologic and clinical cure rates for manyinfections and about the same rate ofnephrotoxicity (~510%) as with conventional

dosingclinicians have begun using extended-interval

dosing in selected patients.

For Pseudomonas aeruginosa infectionswhere theorganism has an expected MIC 2 g/mL, peakconcentrations between 20 and 30 g/mL andtrough concentrations


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Differential Toxicity Among

Aminoglycosides

Gentamicin accumulates to a greater extent

in kidney tissue when compared to

tobramycin

Because doses of amikacin are larger than for

gentamicin and tobramycin, amikacin in

renal accumulation must be adjusted for

dosage differences

gentamicin is the most widely used

aminoglycoside, followed by tobramycin and

netilmicin


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CLINICAL MONITORING

PARAMETERS

Clinicians should always consult the patients

chart to confirm that antibiotic therapy is

appropriate for current microbiologic cultures

and sensitivities.

Clinicians should be confirmed that the

patient is receiving other appropriate

concurrent antibiotic therapy, such as -lactam or anaerobic agents, when necessary

to treat the infection


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CLINICAL MONITORING

PARAMETERS

Clinicians Measure of serial white blood cell

counts and body temperatures are useful to

determine the efficacy of antibiotic therapy

Clinicians should also be aware thatimmunocompromised patients with a

bacterial infection may not be able to mount

a fever or elevated white blood cell count. Clinicians monitore at the same time intervals

as serum creatinine determination


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BASIC CLINICAL PHARMACOKINETIC

PARAMETERS

aminoglycosides are eliminated almost

completely (90%) unchanged in the urine

primarily by glomerular filtration

aminoglycosides are given intramuscularly

they exhibit very good bioavailability of

~100% and are rapidly absorbed with

maximal concentrations occurring about 1hour after injection. Exceptions to this situation

are patients who are hypotensive or obese


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BASIC CLINICAL PHARMACOKINETIC

PARAMETERS

Oral bioavailability is poor (


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Doses

Manufacture recommended doses for conventional dosingin patients with normal renal function are 35 mg/kg/d

for gentamicin and tobramycin, 46 mg/kg/d for

netilmicin, and 15 mg/kg/d for amikacin.

These amounts are divided into three equal daily doses forgentamicin, tobramycin, or netilmicin, or two or three

equal daily doses for amikacin.

Extended-interval doses obtained from the literature for

patients with normal renal function are 47 mg/kg/d forgentamicin, tobramycin, or netilmicin and 1120 mg/kg/d

for amikacin


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EFFECTS OF DISEASE STATES AND CONDITIONS ON

AMINOGLYCOSIDE PHARMACOKINETICS AND DOSING


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DRUG INTERACTIONS

Aminoglycosides + Vancomycin,14,17,87

amphotericin B, cyclosporin, and

furosemide enhance the nephrotoxicity

potential

Aminoglycosides + penicillins (penicillin

G, ampicillin, nafcillin, carbenicillin,

ticarcillin) can inactivate aminoglycosidesin vivo and in blood specimen tubes intended

for the measurementof aminoglycoside

serum concentrations


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INTRODUCTION

glycopeptide antibiotic used to treat severe gram-positive infections

due to organisms that are resistant to other

antibiotics It is also used to treat infections caused by

other sensitive gram-positive organisms in

patients that are allergic to penicillins. Bactericidal

exhibits time-dependent or concentration-

independen bacterial killing


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THERAPEUTIC AND TOXIC

CONCENTRATIONS

administered as a short-term (1-hour) intravenousinfusion.

Infusion rate related side effects have been notedwhen shorter infusion times (~30 minutes or less)have been used.

Therapeutic range for steady-state peakconcentrations is usually considered to be 2040g/mL.

Because vancomycin does not enter the centralnervous system in appreciable amount when givenintravenously, steady-state peak concentrations of4060 g/mL


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Vancomycin-associated ototoxicity is usually

first noted by the appearance of tinnitus,

dizziness, or high-frequency hearing loss

(>4000 Hz)

vancomycin nephrotoxicity may be

transient serum creatinine increases of 0.5

2.0 mg/dL


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DRUG INTERACTIONS

The most important drug interactions with

vancomycin are pharmacodynamic, not

pharmacokinetic,in nature.

Vancomycin + aminoglycosideenhances the

nephrotoxicity potential


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Thank You

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07131022 Maya Fadilla- Antibiotics