Restricted accessResearch articleFirst published online 2010-06
Comparative Efficacy of Besifloxacin and Other Fluoroquinolones in a Prophylaxis Model of Penicillin-Resistant Streptococcus pneumoniae Rabbit Endophthalmitis
To study the efficacy of topical administration of gatifloxacin (0.3%), moxifloxacin (0.5%) ophthalmic solutions, and besifloxacin (0.6%) ophthalmic suspension as prophylaxis and treatment of pneumococcal endophthalmitis.
Methods:
Four groups of New Zealand white rabbits were topically treated with gatifloxacin, moxifloxacin, besifloxacin, and phosphate-buffered saline (PBS) at the following time points: 60, 45, 30, and 15 min before infection, immediately after infection, and then 6, 12, 18, and 24 h postinfection. Penicillin-resistant Streptococcus pneumoniae (PRSP; 106 colony-forming unit [CFU] in 50 μL) was injected into the aqueous humor of each eye. The clinical severity of the eyes was assessed by 2 masked observers 24 h postinfection. Aqueous and vitreous samples were collected, diluted, and plated to determine recovered CFU.
Results:
Fluoroquinolone-treated eyes had significantly lower clinical scores and bacteria recovered from the aqueous humor than the PBS-treated eyes. There was no difference, however, among the fluoroquinolone-treated groups. In contrast, none of the fluoroquinolones reduced the number of bacteria recovered (CFU) from the vitreous humor.
Conclusions:
Besifloxacin is as effective as moxifloxacin and gatifloxacin in a rabbit model for topical prophylaxis and treatment of PRSP-induced endophthalmitis.
JacksonT.L., EykynS.J., GrahamE.M., StanfordM.R.Endogenous bacterial endophthalmitis: a 17-year prospective series and review of 267 reported cases. Surv. Ophthalmol., 48:403–423. 2003.
3.
MillerJ.J., ScottI.U., FlynnH.W.Jr., SmiddyW.E., CoreyR.P., MillerD.Endophthalmitis caused by Streptococcus pneumoniae. Am. J. Ophthalmol., 138:231–236. 2004.
4.
NouriM., TeradaH., AlfonsoE.C., FosterC.S., DurandM.L., DohlmanC.H.Endophthalmitis after keratoprosthesis: incidence, bacterial causes, and risk factors. Arch. Ophthalmol., 119:484–489. 2001.
5.
SorianoF., Perez-TralleroE., PallaresR.et al.Streptococcus pneumoniae endophthalmitis: a study of 36 cases with special reference to antibiotic resistance and treatment options. Clin. Microbiol. Infect., 12:519–526. 2006.
6.
AkovaY.A., BulutS., DabilH., DumanS.Late bleb-related endophthalmitis after trabeculectomy with mitomycin C. Ophthalmic Surg. Lasers, 30:146–151. 1999.
7.
CidM., SabatesN.R.Penicillin-resistant Streptococcus pneumoniae endophthalmitis. Am. J. Ophthalmol., 123:133–135. 1997.
8.
HeavenC.J., MannP.J., BoaseD.L.Endophthalmitis following extracapsular cataract surgery: a review of 32 cases. Br. J. Ophthalmol., 76:419–423. 1992.
MartinE., PestelM., BrasseurG., LemelandJ.F.Penicillin-resistant Streptococcus pneumoniae as a cause of postoperative endophthalmitis. Clin. Infect. Dis., 21:1340–1341. 1995.
11.
McLeodS.D., FlowersC.W., LopezP.F., MarxJ., McDonnellP.J.Endophthalmitis and orbital cellulitis after radial keratotomy. Ophthalmology, 102:1902–1907. 1995.
12.
MulhernM.G., CondonP.I., O'KeefeM.Endophthalmitis after astigmatic myopic laser in situ keratomileusis. J. Cataract Refract. Surg., 23:948–950. 1997.
ToriiH., MiyataH., SugisakaE., IchikawaY., ShinodaK., InoueM.Bilateral endophthalmitis in a patient with bacterial meningitis caused by Streptococcus pneumoniae. Ophthalmologica, 222:357–359. 2008.
20.
Sanchez-TatayD., ArroyoL.A., TarragoD.et al.Antibiotic susceptibility and molecular epidemiology of nasopharyngeal pneumococci from Spanish children. Clin. Microbiol. Infect., 14:797–801. 2008.
21.
JacobsM.R., GoodC.E., SellnerT., BajaksouzianS., WindauA., AnonJ.B.Nasopharyngeal carriage of respiratory pathogens in children undergoing pressure equalization tube placement in the era of pneumococcal protein conjugate vaccine use. Laryngoscope, 117:295–298. 2007.
22.
HuangS.S., HinrichsenV.L., StevensonA.E.et al.Continued impact of pneumococcal conjugate vaccine on carriage in young children. Pediatrics, 124:e1–e11. 2009.
23.
Centers For Disease Control and Prevention. Emergence of antimicrobial-resistant serotype 19A Streptococcus pneumoniae—Massachusetts, 2001–2006. MMWR. Morb. Mortal. Wkly. Rep., 56:1077–1080. 2007.
24.
MillerD., AlfonsoE.C.Comparative in vitro activity of levofloxacin, ofloxacin, and ciprofloxacin against ocular streptococcal isolates. Cornea, 23:289–293. 2004.
25.
MahF.S.Fourth-generation fluoroquinolones: new topical agents in the war on ocular bacterial infections. Curr. Opin. Ophthalmol., 15:316–320. 2004.
26.
CambauE., MatratS., PanX.S.et al.Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli. J. Antimicrob. Chemother., 63:443–450. 2009.
27.
FukudaH., HiramatsuK.Primary targets of fluoroquinolones in Streptococcus pneumoniae. Antimicrob. Agents Chemother., 43:410–412. 1999.
28.
PestovaE., MillichapJ.J., NoskinG.A., PetersonL.R.Intracellular targets of moxifloxacin: a comparison with other fluoroquinolones. J. Antimicrob. Chemother., 45:583–590. 2000.
29.
SchedletzkyH., WiedemannB., HeisigP.The effect of moxifloxacin on its target topoisomerases from Escherichia coli and Staphylococcus aureus. J. Antimicrob. Chemother., 43,Suppl B:31–37. 1999.
30.
TakeiM., FukudaH., YasueT., HosakaM., OomoriY.Inhibitory activities of gatifloxacin (AM-1155), a newly developed fluoroquinolone, against bacterial and mammalian type II topoisomerases. Antimicrob. Agents Chemother., 42:2678–2681. 1998.
31.
DrlicaK.Mechanism of fluoroquinolone action. Curr. Opin. Microbiol., 2:504–508. 1999.
32.
HaasW., PillarC.M., ZurenkoG.E., LeeJ.C., BrunnerL.S., MorrisT.W.Besifloxacin, a novel fluoroquinolone, has broad-spectrum in vitro activity against aerobic and anaerobic bacteria. Antimicrob. Agents Chemother., 53:3552–3560. 2009.
33.
BertinoJ.S., ZhangJ.Z.Besifloxacin, a new ophthalmic fluoroquinolone for the treatment of bacterial conjunctivitis. Expert Opin. Pharmacother., 10:2545–2554. 2009.
34.
SandersM.E., NorcrossE.W., MooreQ.C.III, ShafieeA., MarquartM.E.Efficacy of besifloxacin in a rabbit model of methicillin-resistant Staphylococcus aureus keratitis. Cornea, 28:1055–1060. 2009.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 18th Informational Supplement: Wayne, PA, 2008.
37.
ZhangJ.Z., CavetM.E., WardK.W.Anti-inflammatory effects of besifloxacin, a novel fluoroquinolone, in primary human corneal epithelial cells. Curr. Eye Res., 33:923–932. 2008.
38.
KowalskiR.P., RomanowskiE.G., MahF.S., YatesK.A., GordonY.J.Topical prophylaxis with moxifloxacin prevents endophthalmitis in a rabbit model. Am. J. Ophthalmol., 138:33–37. 2004.
39.
KowalskiR.P., RomanowskiE.G., MahF.S., SasakiH., FukudaM., GordonY.J.A comparison of moxifloxacin and levofloxacin topical prophylaxis in a fluoroquinolone-resistant Staphylococcus aureus rabbit model. Jpn. J. Ophthalmol., 52:211–216. 2008.
40.
MeierP., WiedemannP.[Endophthalmitis—clinical picture, therapy and prevention]Klin. Monatsbl. Augenheilkd., 210:175–191. 1997.
41.
MasketS.Preventing, diagnosing, and treating endophthalmitis. J. Cataract Refract. Surg., 24:725–726. 1998.
42.
HooperD.C.Fluoroquinolone resistance among Gram-positive cocci. Lancet Infect. Dis., 2:530–538. 2002.
43.
FantinB., DuvalX., MassiasL.et al.Ciprofloxacin dosage and emergence of resistance in human commensal bacteria. J. Infect. Dis., 200:390–398. 2009.
KarlowskyJ.A., ThornsberryC., JonesM.E., EvangelistaA.T., CritchleyI.A., SahmD.F.Factors associated with relative rates of antimicrobial resistance among Streptococcus pneumoniae in the United States: results from the TRUST Surveillance Program (1998–2002)Clin. Infect. Dis., 36:963–970. 2003.
46.
De CaroJ.J., TaC.N., HoH.K.et al.Bacterial contamination of ocular surface and needles in patients undergoing intravitreal injections. Retina, 28:877–883. 2008.
47.
MasonJ.O.III, WhiteM.F., FeistR.M.et al.Incidence of acute onset endophthalmitis following intravitreal bevacizumab (Avastin) injection. Retina, 28:564–567. 2008.
48.
YenerelN.M., DincU.A., GorgunE.A case of sterile endophthalmitis after repeated intravitreal bevacizumab injection. J. Ocul. Pharmacol. Ther., 24:362–363. 2008.
49.
ProkschJ.W., GranvilC.P., Siou-MermetR., ComstockT.L., PaternoM.R., WardK.W.Ocular pharmacokinetics of besifloxacin following topical administration to rabbits, monkeys, and humans. J. Ocul. Pharmacol. Ther., 25:335–344. 2009.
50.
RobertsonS.M., CurtisM.A., SchlechB.A.et al.Ocular pharmacokinetics of moxifloxacin after topical treatment of animals and humans. Surv. Ophthalmol., 50,Suppl 1:S32–S45. 2005.
51.
LevineJ.M., NoeckerR.J., LaneL.C., HerrygersL., NixD., SnyderR.W.Comparative penetration of moxifloxacin and gatifloxacin in rabbit aqueous humor after topical dosing. J. Cataract Refract. Surg., 30:2177–2182. 2004.
52.
CostelloP., BakriS.J., BeerP.M.et al.Vitreous penetration of topical moxifloxacin and gatifloxacin in humans. Retina, 26:191–195. 2006.
53.
ZighelboimS., TomaszA.Penicillin-binding proteins of multiply antibiotic-resistant South African strains of Streptococcus pneumoniae. Antimicrob. Agents Chemother., 17:434–442. 1980.
54.
Contreras-MartelC., Hout-GonzalezC., MartinsA.S., KotnikM., DessenA.PBP active site flexibility as the key mechanism for beta-lactam resistance in pneumococci. J. Mol. Biol., 387:899–909. 2009.
55.
FilipeS.R., TomaszA.Inhibition of the expression of penicillin resistance in Streptococcus pneumoniae by inactivation of cell wall muropeptide branching genes. Proc. Natl. Acad. Sci. U. S. A., 97:4891–4896. 2000.
56.
HooperD.C.Mechanisms of action and resistance of older and newer fluoroquinolones. Clin. Infect. Dis., 31,Suppl 2:S24–S28. 2000.
57.
VanB.F., MichotJ.M., VanE.J., TulkensP.M.Quinolones in 2005: an update. Clin. Microbiol. Infect., 11:256–280. 2005.
58.
AdamH.J., SchurekK.N., NicholK.A.et al.Molecular characterization of increasing fluoroquinolone resistance in Streptococcus pneumoniae isolates in Canada, 1997 to 2005. Antimicrob. Agents Chemother., 51:198–207. 2007.
59.
de la CampaA.G., BalsalobreL., ArdanuyC., FenollA., Perez-TralleroE., LinaresJ.Fluoroquinolone resistance in penicillin-resistant Streptococcus pneumoniae clones, Spain. Emerg. Infect. Dis., 10:1751–1759. 2004.
60.
PletzM.W., McGeeL., JorgensenJ.et al.Levofloxacin-resistant invasive Streptococcus pneumoniae in the United States: evidence for clonal spread and the impact of conjugate pneumococcal vaccine. Antimicrob. Agents Chemother., 48:3491–3497. 2004.
