Quinolone and Quinolone and Aminoglycoside Aminoglycoside Antibiotics Antibiotics Edgar Rios, Pharm.D., BCPS Edgar Rios, Pharm.D., BCPS MHH Clinical Pharmacist MHH Clinical Pharmacist UTHSCH Clinical Assistant UTHSCH Clinical Assistant Professor Professor
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Quinolone and Aminoglycoside Antibiotics Edgar Rios, Pharm.D., BCPS MHH Clinical Pharmacist UTHSCH Clinical Assistant Professor.
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Quinolone and Quinolone and Aminoglycoside AntibioticsAminoglycoside Antibiotics
Edgar Rios, Pharm.D., BCPSEdgar Rios, Pharm.D., BCPS
MHH Clinical PharmacistMHH Clinical Pharmacist
UTHSCH Clinical Assistant ProfessorUTHSCH Clinical Assistant Professor
OverviewOverview
Chemical StructureChemical StructureClassifications and spectrum of activityClassifications and spectrum of activityMechanism of action and resistanceMechanism of action and resistancePharmacologic properties and Pharmacologic properties and
Mechanisms of resistanceMechanisms of resistance Alterations in target enzymesAlterations in target enzymes
Chromosomally mediatedChromosomally mediated Occur in 1 in 10Occur in 1 in 1066 to 1 in 10 to 1 in 1099 bacteria bacteria Resistance arises in a stepwise fashionResistance arises in a stepwise fashion
Decreased permeationDecreased permeation Changes in porins (OmpF)Changes in porins (OmpF) Efflux pumps (MexAB-OprM)Efflux pumps (MexAB-OprM) Low to intermediate levels of resistanceLow to intermediate levels of resistance Can effect other drugsCan effect other drugs
Plasmid meditated resistancePlasmid meditated resistance qnr geneqnr gene Protects DNA gyrase and topoisomerase IV Protects DNA gyrase and topoisomerase IV Low level resistanceLow level resistance
Respiratory tract infectionRespiratory tract infection XX XX XX
Bone and joint infectionBone and joint infection XX
Skin and skin structure infectionSkin and skin structure infection XX XX XX
aa In combination with metronidazole In combination with metronidazolebb As monotherapy As monotherapy
AminoglycosidesAminoglycosides
AgentAgent SourceSource YearYearStreptomycinStreptomycin Streptomyces griseusStreptomyces griseus 19441944NeomycinNeomycin Streptomyces fradiaeStreptomyces fradiae 19491949KanamycinKanamycin S. kanamyceticusS. kanamyceticus 19571957ParomomycinParomomycin S. fradiaeS. fradiae 19591959SpectinomycinSpectinomycin S. spectabilisS. spectabilis 19621962GentamicinGentamicin Micromonospora purpureaMicromonospora purpurea 19631963
and and M. echinosporaM. echinosporaTobramycin Tobramycin S. tenebrariusS. tenebrarius 19681968Amikacin Amikacin S. kanamyceticusS. kanamyceticus 19711971Netilmicin Netilmicin M. inyoensisM. inyoensis 19751975
Mechanism of ActionMechanism of Action
ResistanceResistanceAlteration in ribosomal binding sitesAlteration in ribosomal binding sites
Mycobacterial resistance to streptomycinMycobacterial resistance to streptomycin
Altered uptakeAltered uptakeStaphStaph spp. and spp. and Pseudomonas aeruginosaPseudomonas aeruginosa
Aminoglycoside modifying enzymesAminoglycoside modifying enzymesPlasmids and transposonsPlasmids and transposonsConfer cross resistanceConfer cross resistanceAmikacin least effectedAmikacin least effected
Bacteria remains “stunned” even without any drugBacteria remains “stunned” even without any drugAllows for a drug free intervalAllows for a drug free interval
Less toxicityLess toxicity
ODA vs Traditional DosingODA vs Traditional Dosing
0
5
10
15
20
25
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Times (Hours)
Con
cent
ratio
n (m
cg/m
l)
ODA Traditional
Once Daily vs Traditional Dosing?Once Daily vs Traditional Dosing?Evidence for once dailyEvidence for once daily
MonitorMonitorLevel 6 – 14 hours after starting the infusionLevel 6 – 14 hours after starting the infusionTrough (Trough (needs to be undetectableneeds to be undetectable), renal function), renal function
Antimicrob Agents Chemother. 1995;39:650-55.
Traditional DosingTraditional DosingHow to dose?How to dose?
Based on volume of distributionBased on volume of distribution (0.25-0.3 L/kg) (0.25-0.3 L/kg)