Antibiotics in Pediatrics (Vancomycin, Quinolones, Aminoglycosides, Tetracyclines, Chloramphenicol,...

7/24/2019 Antibiotics in Pediatrics (Vancomycin, Quinolones, Aminoglycosides, Tetracyclines, Chloramphenicol, Clindamycin, Macrolides)

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Jillianne Pardo, M.D.

Vancomycin, Quinolones,Tetracyclines, Aminoglycosid

Macrolides, ChloramphenicoClindamycin


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To discuss the mechanism of

indications, dosing, pharmacokineticpharmacodynamicsof the following antim

drug classes!

Vancomycin

Quinolones Tetracycline

Aminoglycosides

Macrolides

Chloramphenicol

"#ecti$es


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Vancomycin%&'C"P(PT)D( A*T)+)"T)C


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VancomycinTricyclic glycopeptide

Produced y Streptococcus orientaandAmycolatopsis orientalis


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Action


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Pharmaco-inetics

Absorption Poorly absorbedfrom the

intestinal tract

Distribution Widelydistributed in the

body CSF levels: 7-30%with meningealirritation

Metabolism Minimalmetabolism

Excre Mostlythe uri


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Pharmaco-ineticsDrug Half-Life (h) Bioavailability

(%)Peak SerumConcentration

(mcg/mL)

Dose (g) PR

E

Vancomycin 5-11 adults

2-4 children

Negligible

oral

bioavailability

15-30 ~1-2 R


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Antiacterial Acti$ityDrug Spectrum of Activity

Vancomycin Bactericidal.

Active against most

gram positive

pathogens

No activity against

gram negatives except

flavobacterium

Staphyloco

(MRSA)

Streptococc

pneumonia

Listeria

Enterococc

Bacillus

Corynebac

Clostridium


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esistance Modi/cation of D0Ala0A0Ala indingsite of peptidoglycan

Altered cell wall metaolism in V

thic-ened cell wall w1 increasednumer of D0Ala0D0Ala residues

Cli i l 2


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Clinical 2ses!Vancomycin

Preparation Neonate

0.5, 0.75, 1, 5, 10 gram IV

preparations

Bacteremia: 10 mkdose

Meningitis: 15 mkdose

Postmenstrual Age Postnatal Age Dosage Interv

14 12

30-36 0-14 12

>14 8

37-44 0-7 12

>7 8

Cli i l 2


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Clinical 2ses!VancomycinAge General DosageCNS Infections,

Endocarditis,

Ostemyelitis, Pneumo

MRSA bacteremia

1mo 12yrs

15mg/kg Q6 20 mg/kg Q6 hr

Adolescent15mg/kg Q6-

Q8

20 mg/kg Q6-8 hr

Adult 15mg/kg Q8- 20 mg/kg Q8-12 hr

Cli i l 2


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Clinical 2ses!VancomycinIndication Pediatric Dose Adult Dos

Endocarditis prophylaxis

for GU or GI procedures

Moderate-risk patients

allergic to ampicillin or

amoxicillin:

20 mg/kg/dose

IV over 1-2 hrs

1 g/dose IV

1-2 hrs

High risk patients allergic

to ampicillin or amoxicillin

Same as above + gentamicin

1.5mkdose for high-risk patien

Cli i l 2


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Clinical 2ses!Vancomycin

Preparation Pseudomembranous colitis

25mg/ml oral

solution

125, 250 mg

capsule

Child: 40-50 mkD q6 PO x 7-10 days

500mg/24h to 2g/24hr)

Adult: 125mg/dose q6 PO x 7-1

Ad erse Drug


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Ad$erse Drugeactions 3e$er, chills, phleitis at )V site 3lushing 4red man syndrome5 and shocdue to histamine release due to rapidinfusion

Dose0related hearing loss

"toto6icity, nephroto6icity when used wdrugs which cause the same reactions


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Drug )nteractions ynergistic with gentamicin streptomycin against (. faecium (. faecalis


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Quinolones

Classi/cation of


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Classi/cation ofQuinolones

Classi/ed y generation ased antimicroial spectrum of acti$ity

1stgeneration47uinolones5! *alidi6ic aci

Fluoroquinolones

2ndgen: *or8o6acin, Cipro8o6acin, "8o6acin 3rd gen: &e$o8o6acin, Mo6i8o6acin, %emi8o6

%ati8o6acin, pa8o6acin

4thgen:Tro$a8o6acin


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Mechanism of Action

)nhiits acterial D*A replicationy inding to the topoisomerasesof the target pathogen, inhiitingacterial en9yme D*A gyrase


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Pharmaco-inetics

Absorption Good oralbioavailability (80-95%)

Impaired by di- andtrivalent cations(e.g. antacids)

Distribution Widely distributedin body fluids andtissues (including in

CSF and bile) Crosses placenta,and enters breastmilk

Metabolism Converted to activeand inactivemetabolites

Excre Mostlytubula Moxi

partlymetabiliar


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Pharmaco-ineticsDrug Half-Life (h) Oral

Bioavailability

(%)

Peak Serum

Concentration

(mcg/mL)

Oral Dose (mg)P

o

Ciprofloxacin 35 70 2.4 500 R

Gatifloxacin 8 98 3.4 400 R

Gemifloxacin 8 70 1.6 320 R

n

Levofloxacin 57 95 5.7 500 R

Moxifloxacin 910 > 85 3.1 400 N

Norfloxacin 3.55 80 1.5 400 R

Ofloxacin 57 95 2.9 400 R


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Antiacterial Acti$ity

1stgen Spectrum of Activi

Nalidixic acid Gram negative exc

pseudomans

2nd gen

Norfloxacin Least active against b

gram (+) and gram (-

among fluorquinolone


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2ndgen Spectrum of ActiviCiprofloxacin,

Enoxacin,

Ofloxacin

Lomefloxacin,Pefloxacin

Excellent gram (-)

activity

Moderate to good

gram (+) coverageCovers some

atypical

organisms

Enterobacter

Pseudomonas

Neisseria

HaemophilusCamplyobacter

Methicillin-sus

S.aureus

Mycoplasma pn

Chlamydia pne

Ciprofloxacin: Most active against gram negative among fluoroquinolo

Pseudomonas aeruginosa)


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3rdgen Spectrum of Activity

Levofloxacin

Gatifloxacin

Gemifloxacin

Moxifloxacin

Excellent gram (-)

activity

Improved activity

against gram (+)organisms

Coverage of atypical

organixms

Gram nega

organisms

S. Pneumon

Staphylococ

Mycoplasm

chlamydia

Legionella

Mycobacter

Moxifloxacin modest activity against anaerobes; po

against Pseudomonas


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4thgen Spectrum of Activit

Trovafloxacin Excellent gram (-)

activity

Improved activity

against gram (+)organisms

Coverage of atypical

organisms

Broad anaerobic

coverage

Gram negati

organisms

Anaerobes

S. PneumoniStaphylococc

Mycoplasma

chlamydia

Legionellasp


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ummary of Antiacterial Acti$it


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esistance

esistant organisms emerge aout once in :; 2 kg: Q8

> 7 days:

< 1.2 kg: q12hr

1.2-2 kg: q8hr

>2 kg q6hr

PO: 10-30 mkD

(Max: 1.8g/24 hr

IM/IV: 25-40 mk

(Max: 4.8g/24hr)

Bacterial endoca

20mg/kg (Max: 6

1 hr before p

(PO)

Clinical 2ses!Clindamycin


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ClindamycinPreparation Adult

75, 150, 300 mg capsule

75mg/5ml oral solution

150mg/ml injection

PO: 150-450 mg/dose q6-8 hr

1.8g/24h)

IM/IV: 1200-1800 mg/24hr IM/I

(Max: 4.8g/24h)

Bacterial endocarditis: 600 mg

1 hr prior to procedure (P

30 mins prior to procedure

Topical cream, gel Apply to affected area B

Ad$erse Drugeactions


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eac o s Diarrhea, nausea, s-in rashes

)mpaired li$er function andneutropenia

Clostridum difcile

pseudomemranous colitis


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THA*L '"2

Antibiotics in Pediatrics (Vancomycin, Quinolones, Aminoglycosides, Tetracyclines, Chloramphenicol,...

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