Antibiotics Fluoroquinolones 4th Generation PDF

Pharm II_2024 Antibiotics Fluoroquinolones – 4th Generation > 4 th G eneration: > De sig ne d to c irc um ve nt resistance > 2 m uta tio ns ne c e ssa ry to ind uc e vs o ne m uta tio n in s e c o n d generation > G atifloxacin > M o xiflo xa c in 0.5% > > > (0.3% Zym a r=d /c , 0.5% Zym a xid ) (Vi...

Pharm II_2024 Antibiotics Fluoroquinolones – 4th Generation > 4 th G eneration: > De sig ne d to c irc um ve nt resistance > 2 m uta tio ns ne c e ssa ry to ind uc e vs o ne m uta tio n in s e c o n d generation > G atifloxacin > M o xiflo xa c in 0.5% > > > (0.3% Zym a r=d /c , 0.5% Zym a xid ) (Vig a m o x, M o xe za =d /c ) Be siflo xa c in 0.6% (Be siva nc e ) Diane T.Adamczyk, OD, FAAO Copyright © 2024 185 Need two things to happen for the bacteria to be destroyed You need 2 mutations to induce bacteria to get resistant to this type of drug à topoisomerase and the efflux pumps 189 Pharm II_2024 Antibiotics Drugs Affecting Bacterial DNA Synthesis Fluoroquinolones: 4th Generation 4 th Generation: A d va nta g es vs o ther fluoroq uino lo ne s More effective against gram positives including staph and strep Maintainsactivity against P. aeruginosa Highly soluble With excellent penetration into ocular tissues Active against FQ resistant organisms Diane T.Adamczyk, OD, FAAO Copyright © 2024 186 Provides solution to bacteria that are resistant to the older generation fluroquinolones 190 Pharm II_2024 Antibiotics Drug s A ffec ting Ba c teria l DNA Synthesis Fluoroquinolones: Moxifloxacin > M oxifloxac in 0.5%(Viga mox) > Bacterial Conjunctivitis > G+activity >ciprofloxacin or ofloxacin > No preservative > Antib io tic c o nc e ntra tio n hig h > Near neutral pH (6.8)= Pediatric use:>1 year > Pregnancy Category C (used to be category C but new ones can be used for pregnancy, no human data available, risk of fetal harm minimal b/c no systemic absorption) > Dosage:1 gtt tid x7days Diane T.Adamczyk, OD, FAAO Copyright © 2024 187 Moxi or vigamox is approved for bacterial conjunctivitis - has no preservatives b/c drug company said that it is such a good antibiotic it doesn’t need a preservative to kill bacteria and FDA agreed 191 Pharm II_2024 Antibiotics Drugs Affecting Bacterial DNA Synthesis Fluoroquinolones:Moxifloxacin > M oxifloxac in 0.5%(Viga mox) > C-7:ENHANCESPENETRATION INTO THE CONJUNCTIVA: > Lipophilic properties of the bicyclic ring ma ximize p e ne tra tio n into the conjunctiva > C-8:INCREASESPOTENCY: > M e tho xy sid e g ro up e nsure s a ntimic ro b ia l p o te nc y Diane T.Adamczyk, OD, FAAO Copyright © 2024 188 - The C7 region enhances penetration into the conjunctiva - the C8 helps with the antimicrobial activity - These two aspects of the moxi makes it an effective antibiotic 192 Pharm II_2024 Antibiotics Drugs Affecting Bacterial DNA Synthesis Fluoroquinolones:Gatifloxacin > G a tifloxac in 0.5%(Zyma xid) > Bacterial conjunctivitis > Q2H day 1;BID-QID day 2-7 Diane T.Adamczyk, OD, FAAO Copyright © 2024 189 Gatifloxacin is approved for bacterial conjunctivitis à it has a preservative but it is 4th generation so all of the effectivity is similar 193 Pharm II_2024 Antibiotics Drugs Affecting Bacterial DNA Synthesis Fluoroquinolones:Besifloxacin > Besifloxacin (Besivance) > Tx: Ba c te ria l c o njunc tivitis > Suspension > Dura Site d rug d e live ry syste m > Bro a d sp e c trum > O nly o p htha lmic use > BAK 0.01% > 1 ye a r o ld > Inhibits bacterial DNA gyrase an d topoisomerase IV > Prolongs ocular surface time an d enhances the ra p e utic e ffic a c y Diane T.Adamczyk, OD, FAAO Copyright © 2024 190 - It has no oral counterpart! à it does its job against bacteria and lessens the likelihood of resistance and approved for bacterial conjunctivitis - b/c it is suspension you need to shake it - durasite can be a stand along drug but here it is a vehicle 194 Pharm II_2024 Antibiotics AntibioticsAffecting Bacterial DNA Synthesis Fluoroquinolones:Besifloxacin > Besifloxacin > Bacterial conjunctivitis Equivalent safety and efficacy to Vigamox (moxifloxacin) > Besifloxacin had lowerMIC than gatifloxacin and moxifloxacin for staphylococcal isolates à so you need less of the drug to be as effective as the other drugs à less besi is needed ot go after the bugs as gati or moxi which is a good thing Diane T.Adamczyk, OD, FAAO Copyright © 2024 191 195 Pharm II_2024 Antibiotics AntibioticsAffecting Bacterial DNA Synthesis Fluoroquinolones:Besifloxacin > Besifloxacin > Bacterial conjunctivitis > TID x 7 d a ys > Bacterial corneal ulcer(off label) > Do sa g e (O c ula r The ra p e utic s Ha nd b o o k, 4th e d ): > Loading dose:q15-30 min x 2 hours > Then: q30-60min while awake, and q2h throughout the night for first 2-3 days > Based on presentation and cultures: continue QID remainder of time (usually 2 weeks) Diane T.Adamczyk, OD, FAAO Copyright © 2024 192 Corneal ulcer tx is off label Few fluoroquinolones have been approved to treat off label But the 4th gen are so good practitioners like using it to treat corneal ulcers and this is accepted by the health care community Start off with a loading dose with great frequency à send in troops and bombard the infection and then you can lessen the amount of drops over time 196 Pharm II_2024 Antibiotics Comparison Fluoroquinolones Diane T.Adamczyk, OD, FAAO Copyright © 2024 193 197 Pharm II_2024 Antibiotics Affecting Bacterial DNA Synthesis Fluoroquinolones: C ompa risons Endophthalmitis G+ 4t h generation more potent GAll generations =potent Diane T.Adamczyk, OD, FAAO Copyright © 2024 194 198 Pharm II_2024 Antibiotics C ompa rison of M oxifloxa c in 0.5%to Gatifloxacin 0.3% G re a te r potency of moxifloxacin (G+) > G+:Moxifloxacin >gatifloxacin > G-:Moxifloxacin =gatifloxacin Moxifloxacin does not contain preservatives that may b e toxic to ocular tissues Diane T.Adamczyk, OD, FAAO Copyright © 2024 195 199 Pharm II_2024 Antibiotics Topical Ocular Combination Antibacterial Examples Diane T.Adamczyk, OD, FAAO Copyright © 2024 196 200 Pharm II_2024 Antibiotics Topical Ocular Combination Antibacterial Solutions and Ointments Polymyxin B/Neomycin/Gramicidin Solutions: Polymyxin B/Trimethoprim (Polytrim) Ointments Polymyxin B/Bacitracin (Polysporin) Diane T.Adamczyk, OD, FAAO Copyright © 2024 197 Go after bacteria and the inflammation by doing combination 201 Pharm II_2024 Antibiotics Topical Ocular Antibiotic/Steroid > Solutions/Suspensions/Ointments > Neomycin/Polymyxin B /Dexamethasone (Maxitrol) > Gentamycin/Prednisolone (Pred G) > Tobramycin/Dexamethasone =Tobradex > Sulfacetamide/Prednisolone acetate (Blephamide=d/c) > Tobramycin/Loteprednol=Zylet > Neomycin/Bacitracin/PolymyxinB/Hy drocortisone Diane T.Adamczyk, OD, FAAO Copyright © 2024 198 202 Pharm II_2024 Antibiotics Steroid-Antibiotic Combinations > TobraDex ST > Tobramycin 0.3%/dexamethasone 0.05% > Increased staying time > Suspension Differs generic tobradex: dexamethasone 0.1%to 0.05% U s e xanthan gum > Decreasessettling of drug in bottle > Increasesviscosity Diane T.Adamczyk, OD, FAAO Copyright © 2024 199 Tobradex ST à The ST is for it being a suspension and it has xanthan gum which increases staying time and b/c of the xanthan gum it has increased viscosity and longer duration on the ocular surface to do its job Dexamethasone is a steroid but it has a higher correlation with increasing IOP à seen in many steroid responders ophthalmically so be careful using this in especially glaucoma pts 203 Pharm II_2024 Antibiotics Antibacterial C onsiderations Diane T.Adamczyk, OD, FAAO Copyright © 2024 200 204 Pharm II_2024 Antibiotics Wills Eye Manual 8th Ed, 2022 Diane T.Adamczyk, OD, FAAO Copyright © 2024 201 - fortified antibiotics is a powder that creates into an antibiotic but needs to be made by a special pharmacy - Made when traditional antibiotics aren’t working 205 Pharm II_2024 Antibiotics Ocular TRUST O c ula r Tra c king Resista nc e in U. S. > Eva lua tes invitro a ntimic robial susc eptibility of: > Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae > To: > Ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim and polymyxin B > Results: methicillin susceptible (MSSA) and methicillin resistant (MRSA): > Fluoroquinolones > MSSA susceptible: approx 80% of fluoroquinolones effective against MSSA > MRSA susceptible: 15.2% of fluoroquinolones effective against MRSA > Trimethoprim: only agent tested with high activity against MRSA AmJOphthal;2008:145;951-58. Diane T.Adamczyk, OD, FAAO Copyright © 2024 202 - Looking at a bunch of fluroquinolones and other drugs and their resistance to the three microbes - fluoroquinolones were found to be resistant against MRSA 206 Antibiotics Diane T.Adamczyk, OD, FAAO Copyright © 2024 Pharm II_2024 203 Trimethoprim is good against MRSA 207 Pharm II_2024 Antibiotics ARM O R – 5 Yea r Results (2015) Antibiotic Resistance Among Ocular Pathogens in the United States Five-Year Results From the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) Surveillance Study (JAMA Ophthalmo.l2015;133(12):1445-1454) Diane T.Adamczyk, OD, FAAO Copyright © 2024 204 Azithromycin is not very effective against MRSA and neither is cipro Chloramphenicol and trimethoprim do well against MRSA 208 Pharm II_2024 Antibiotics > Resistance was observed to ciprofloxacin in 33.5% and to azithromycin in (59.7%) of S a ureus isola tes > although all were susceptible to vancomycin. > resistance greater than 70% for fluoroquinolones (not applicable for besifloxac in) a nd 92.9%for a zithromyc in. > The later-generation fluoroquinolones (besifloxacin, gatifloxacin, and moxifloxa c in) ha d lower M IC 90s overa ll > compared with the earlier ones (ciprofloxacin, levofloxacin, and ofloxacin). Besifloxacin showed the lowest MIC90s, and ciprofloxacin showed the highest (so needed more of the cipro to work so not as good) Diane T.Adamczyk, OD, FAAO Copyright © 2024 205 In 2009 to 2018 - this study does not include besifloxacin 209 Antibiotics Pharm II_2024 -Oxacillin -Azithromycin -Ciprofloxacin -Tobramycin -Tetracycline -Chloramphenicol --Trimethoprim Diane T.Adamczyk, OD, FAAO Copyright © 2024 206 210 Pharm II_2024 Antibiotics ARMOR: isolates from patients with ocular infections Here: isolates specifically collected from the cornea in the ARMOR study Conclusion: antibiotic resistance among presumed keratitis isolates relatively stable 2009-2019, resistance levels remain high. Optom Vis Sci 2021;98:1113–1121. doi:10.1097/OPX.0000000000001768 Diane T.Adamczyk, OD, FAAO Copyright © 2024 207 The antibiotic resistance amongst ocular microbes remain stable but high 211 Pharm II_2024 Antibiotics Antiba c teria l Review Diane T.Adamczyk, OD, FAAO Copyright © 2024 208 212 Pharm II_2024 Antibiotics Review Antibiotic s for Ocular Conditions > Normal flora/common pathogens > Resistance > C onsidera tion for trea tment > Various Classes of Antibiotics Diane T.Adamczyk, OD, FAAO Copyright © 2024 209 213 Pharm II_2024 Antibiotics Review Antibiotic s for Ocular Conditions > Normal flora/common pathogens > Understanding bacteria > Single cell organism > How differfrom human cells > Princ ip le s o f a ntib io tic a c tio ns > C e ll wa ll in b a c te ria , no t huma ns > C e ll me mb ra ne simila r > Rib o so me s d iffe re nt > Folic acid-bacteria synthesize > DNA g yra se – sup e rc o iling in b a c te ria Diane T.Adamczyk, OD, FAAO Copyright © 2024 210 214 Pharm II_2024 Antibiotics Review Antibiotic s for Ocular Conditions Resistance----mechanisms Bacterial enzymes, Pump mechanism, > Antibiotic permeability, Bacterial genes/ribosome/chromosomal changes, Cross resistance, Inappropriate/misuse Diane T.Adamczyk, OD, FAAO Copyright © 2024 211 215 Pharm II_2024 Antibiotics Review Antibiotic s for Ocular Conditions > Guidelines to effective antimicrobial treatment > Accurate dx, > appropriate drug-use-dosage-route, > augment > Why treatment may fail > Correct Dx? > Correct dosage? > > > > Diane T.Adamczyk, OD, FAAO Copyright © 2024 Resistance, Noncompliance, Inadequate augment, Inadequate immune response 212 216 Pharm II_2024 Antibiotics Bactericidal Antibiotics Inhibit Cell Wall Penicillins Cephalosporins Vancomycin Bacitracin Affect Cytoplasmic Membrane Polymyxin Gramicidin (?some static activity?) Affect Protein Synthesis Aminoglycosides Bacteriostatic Antibiotics Affect Intermediary Metabolism (Folic Acid) Sulfonamides Trimethoprim (may be cidal from synergy when combo drug) Pyrimethamine Affect Protein Synthesis Tetracyclines Macrolides Chloramphenicol (some cidal activity) Affect DNA Synthesis Fluoroquinolones Diane T.Adamczyk, OD, FAAO Copyright © 2024 213 217 Pharm II_2024 Antibiotics Review Antibiotic s C la sses of Drugs > C e ll Wa ll Synthe sis > Penicillin > Use: h o r d e o lu m , p r e s e p ta l cellu litis, d a cry o cy stitis, d a c r y o a d e n it is > A u g m e n t in (A m o x ic illin /C la v u la n a te = B -la c ta m a s e in h ib ito r> p ro te cts p e n ic illin com pon e n t) > > > > C ro ss se n sitiv ity w ith p e n ic illin a lle rg y > 1 to 4 th g e n e ra tio n in c re a se G - > Use: p r e s e p ta l cellu litis, d a cry o cy stitis, d a c r y o a d e n it is , o th e r (fortifie d u se) > C e p h a le xin (Ke fle x); C e fa c lo r (C e c lo r) Bacitracin B > > Diane T.Adamczyk, OD, FAAO Copyright © 2024 D ic lo x a c illin Cephalosporin Ung Vancomycin (for serious infections) > T ox ic > M RSA > E n d o p h th a lm itis 214 218 Pharm II_2024 Antibiotics Review Antibiotic s C la sses of Drugs > Cytoplasmic membrane-osmotic balance > Polymyxin B > G ra m (-) e sp e c ia lly p se ud o mo na s > C o njunc tiva l a nd lid infe c tio ns > Gramicidin > G ra m + > Combinations Diane T.Adamczyk, OD, FAAO Copyright © 2024 215 219 Pharm II_2024 Antibiotics Review Antibiotic s C la sses of Drugs > Protein synthesis > Aminoglycoside B ind to 30S ribosomal subunit, distorts structure Neomycin-contact dermatitis Gentamicin-anterior segment infections Tobramycin-similar gentamicin; > good for gentamicin resistant pseudomonas strains, > more potent against P. aeruginosa Diane T.Adamczyk, OD, FAAO Copyright © 2024 216 220 Pharm II_2024 Antibiotics Review Antibiotic s C la sses of Drugs > Protein synthesis > Tetracycline Binds to 30S ribosomal subunit, preventing binding of aminoacyl-tRNA to ribosome Use: chlamydia, acne rosacea, meibomianitis (affect free fatty acids) Prior Pregna nc y C ategory D=do not use pregna nc y ADR: photosensitivity/toxic rx; depress bone growth; tooth development; pseudotumor cerebri; potentiate coumadin (do not use under age of 8) Tetra c yc line, doxyc yc line Diane T.Adamczyk, OD, FAAO Copyright © 2024 217 221 Pharm II_2024 Antibiotics Review Antibiotic s C la sses of Drugs > Protein synthesis > Macrolides B in d to 50S ribosomal subunit >inhibit bacterial protein synthesis Lo w toxic ity Use : c hla myd ia , se b a c e o us g la nd d ysfunc tio n Erythromycin (ointment a nd oral) Safe in Pregnancy (prior category B) à erythromycin is not a concern if used opthalmically for pregnancy Azithromycin (Zithromax, Azasite ophthalmic) M ay use in Pre g na nc y (Prio r C a te g o ry B); C hla myd ia -1000mg sing le d o se ( 1 g a n d 1 d o s e to tre a t c h la m y d ia ) Clarithromycin – chlamydia, Avoid pregnancy (Prior Category C) Diane T.Adamczyk, OD, FAAO Copyright © 2024 218 222 Pharm II_2024 Antibiotics Review Antibiotic s C la sses of Drugs > Protein synthesis > Chloramphenicol –aplastic anemia > Clindamycin Diane T.Adamczyk, OD, FAAO Copyright © 2024 219 223 Pharm II_2024 Antibiotics Review Antibiotic s C la sses of Drugs > Intermediary Metabolism/Folic Ac id > Sulfonamides Use: > Chlamydia, > Toxoplasmosis (Sulfadiazine/pyrimethamine or sulfamethoxazole/trimethoprim (Bactrim) Resistance Contraindication: PABA drugs a nd purulent exudates > Pyrimethamine Use: toxoplasmosis > Trimethoprim Use : surfa c e o c ula r infe c tio n C o mb o with p o lymyxin B=Po lytrim (infa nts) Diane T.Adamczyk, OD, FAAO Copyright © 2024 220 So sulfa + anesthetic wil neattvie the use of the drug b/c anestehtic has PABA 224 Pharm II_2024 Antibiotics Review Antibiotic s C la sses of Drugs Drugs Affecting DNA Synthesis Fluoroquinolones Inhibit bacterial DNA gyrase (topoisomerase IIand IV) Ophthalmic Use: conjunctivitis, keratitis, corneal ulcer, pre/post operative Diane T.Adamczyk, OD, FAAO Copyright © 2024 221 225 Pharm II_2024 Antibiotics Review Antibiotic s C la sses of Drugs Drugs Affecting DNA Synthesis: Fluoroquinolones > All ophtha lmic used for ba c teria l c onjunc tivitis > 2n d Generation > Ofloxacin (Ocuflox)-corneal ulcer > Ciprofloxacin (Ciloxan) –corneal ulcer, corneal precipitates > No rflo xa c in (C hib ro xin)-d /c > 3rd Generation > Levofloxacin (Quixin 0.5%) (Iquix 1.5%-corneal ulcer)- superior to c ip ro flo xa c in, o flo xa c in > 4th Generation > Moxifloxacin (Moxeza=d/c)(Vigamox) (no preservative) - better G + tha n g a tiflo xa c in > Gatifloxacin (0.3%=Zymar=DC; 0.5%=Zymaxid) > Besifloxacin (Besivance) Suspension - DuraSite vehicle; only o p htha lmic use Diane T.Adamczyk, OD, FAAO Copyright © 2024 222 226