antibiotics in pediatrics (vancomycin, quinolones, aminoglycosides, tetracyclines, chloramphenicol,...
TRANSCRIPT
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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
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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
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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
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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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Antiacterial Acti$ity
2ndgen Spectrum of ActiviCiprofloxacin,
Enoxacin,
Ofloxacin
Lomefloxacin,Pefloxacin
Excellent gram (-)
activity
Moderate to good
gram (+) coverageCovers some
atypical
organisms
Enterobacter
Pseudomonas
Neisseria
HaemophilusCamplyobacter
Methicillin-sus
S.aureus
Mycoplasma pn
Chlamydia pne
Ciprofloxacin: Most active against gram negative among fluoroquinolo
Pseudomonas aeruginosa)
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Antiacterial Acti$ity
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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Antiacterial Acti$ity
4thgen Spectrum of Activit
Trovafloxacin Excellent gram (-)
activity
Improved activity
against gram (+)organisms
Coverage of atypical
organisms
Broad anaerobic
coverage
Gram negati
organisms
Anaerobes
S. PneumoniStaphylococc
Mycoplasma
chlamydia
Legionellasp
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ummary of Antiacterial Acti$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