Antibiotic susceptibility of bacterial pathogens isolated from the

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Antibiotic susceptibility of bacterial pathogens isolated from the aqueous and vitreous humor in the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study Penny A. Asbell, MD, Francis S. Mah, MD, Christine M. Sanfilippo, PhD, Heleen H. DeCory, PhD Bacterial endophthalmitis is a rare but serious complication of ocular surgery, with infection often arising from a patient's own bacterial flora introduced during surgery.1,2 Perioperative local antibacterial prophylaxis is a key strategy to minimize the risk for endophthalmitis3,4 but may be compromised by antibiotic resistance. We examined susceptibility profiles of bacterial pathogens isolated from the aqueous and vitreous humor to antibiotics routinely used in ophthalmic practice. Aqueous and vitreous humor bacterial isolates were obtained from January 1, 2009, through December 31, 2015, as part of the ongoing Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance program. Study methods and 5-year results have been reported.5 Briefly, minimum inhibitory concentrations (MICs) of various antibiotics and the MIC that inhibits the growth of 90% of indicated isolates (MIC90) were determined by broth microdilution, and systemic breakpoints were used to categorize isolates as susceptible, intermediate, or resistant. A total of 182 presumed endophthalmitis isolates (aqueous, n Z 61; vitreous, n Z 121) were obtained from 35 clinical sites including 105 coagulase-

negative staphylococci (CoNS), 32 Staphylococcus aureus, 23 Streptococcus pneumoniae, and 11 each Haemophilus influenzae and Pseudomonas aeruginosa isolates. Staphylococcus epidermidis was the predominant CoNS (85 of 105, 81.0%). Of the CoNS isolates, 50.5% (53/105) were methicillin-resistant (MRCoNS) and 56.2% (59/105) were azithromycin-resistant. Of the S aureus isolates, 34.4% (11/32) were methicillin-resistant (MRSA) and 50% (16/32) were azithromycin-resistant. Figure 1 shows the susceptibility rates among staphylococci by methicillin-resistance phenotype. Approximately one fourth of methicillin-sensitive CoNS (MSCoNS) and the majority of MRCoNS were resistant to fluoroquinolones. Nearly half of MSCoNS and two thirds of MRCoNS were resistant to azithromycin, and almost one third to one half of MRCoNS were resistant to clindamycin or trimethoprim. Nearly all MRSA were resistant to fluoroquinolones and azithromycin, while approximately one third to one half were resistant to tobramycin and clindamycin, respectively. Multidrug resistance (R3 antibiotic classes) was found in 42.9% (45/105) and 28.1% (9/32) of CoNS and S aureus isolates, respectively, and in 15.4% (8/52) and 0% (0/ 21) of MRCoNS and methicillin-sensitive S aureus (MSSA), respectively, compared with 69.8% (37/53) and 81.8% (9/11) in MRCoNS and MRSA, respectively. Consistent with the findings in other studies,6 besifloxacin (Besivance), a chlorofluoroquinolone for which susceptibility breakpoints are not available, had the lowest MIC90 against staphylococcal isolates of the fluoroquinolones (Table 1). Of S pneumoniae isolates, 34.8% (8/23) were azithromycin-resistant and

Figure 1. Resistance among coagulase-negative staphylococci (A) and S aureus (B) isolates by methicillin-resistance phenotype (MRCoNS Z methicillin-resistant coagulase-negative staphylococci; MRSA Z methicillin-resistant S aureus; MSCoNS Z methicillin-sensitive coagulase-negative staphylococci; MSSA Z methicillin-sensitive S aureus). The coagulase-negative staphylococci included in this analysis were 83 S epidermidis, 5 S capitis, 4 S hominis, 4 S lugdunensis, 3 S haemolyticus, and 1 each S pasteuri, S pettenkoferi, S simulans, and S warneri. Two coagulase-negative staphylococci were not speciated. Q 2016 ASCRS and ESCRS Published by Elsevier Inc.

http://dx.doi.org/10.1016/j.jcrs.2016.11.008 0886-3350

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Table 1. Minimum inhibitory concentrations. MIC90 (mg/mL) CoNS Antibiotic Ofloxacin Ciprofloxacin Levofloxacin Gatifloxacin Moxifloxacin Besifloxacin Azithromycin Clindamycin Chloramphenicol Tobramycin Trimethoprim Vancomycin

Staphylococcus aureus

All

MSCoNS

MRCoNS

All

MSSA

MRSA

O8 64 256 64 32 4 O512 O2 8 8 O128 2

O8 64 128 16 16 1 O512 2 8 8 O128 2

O8 64 256 64 64 4 O512 O2 8 4 O128 2

O8 256 128 32 8 2 O512 O2 8 O256 2 1

0.5 0.5 0.25 0.12 0.06 0.03 512 0.12 8 0.5 2 1

O8 256 256 32 32 2 O512 O2 8 O256 2 1

CoNS Z coagulase-negative staphylococci; MIC90 Z minimum inhibitory concentration that inhibits the growth of 90% of indicated isolates; MRCoNS Z methicillin-resistant CoNS; MRSA Z methicillin-resistant S aureus; MSCoNS Z methicillin-susceptible CoNS; MSSA Z methicillin-susceptible S aureus Chloramphenicol, gatifloxacin, levofloxacin, and trimethoprim were tested against 29 S aureus isolates (n Z 10 MRSA, n Z 19 MSSA) and 97 CoNS isolates (n Z 52 MRCoNS, n Z 45 MSCoNS); all other antibiotics were tested against 32 S aureus isolates (n Z 11 MRSA, n Z 21 MSSA) and 105 CoNS isolates (n Z 53 MRCoNS, n Z 52 MSCoNS)

39.1% (9/23) were resistant to penicillin (oral). All H influenzae isolates were susceptible to all antibiotics tested. Of P aeruginosa isolates, 18.2% (2/11) to 27.3% (3/11) were resistant to fluoroquinolones. As expected, ciprofloxacin had the lowest MIC90 against P aeruginosa (2 mg/mL). Coagulase-negative staphylococci and S aureus are common causes of bacterial endophthalmitis.2,4,7 In this analysis, high levels of resistance were found in staphylococcal isolates to commonly used ophthalmic antibiotics, with the greatest resistance noted among methicillin-resistant strains and a high prevalence of multidrug resistance among these strains. These findings were consistent with those for isolates from other ocular sources obtained in ARMOR and comparable to findings for endophthalmitis isolates in other studies.5,6,8 These data are important when considering antibacterial prophylaxis following surgery. The high MIC90 of moxifloxacin against MRCoNS (64 mg/mL) and MRSA (32 mg/mL) should give pause when considering either dropless cataract surgery using intravitreal delivery of moxifloxacin or intracameral injection of moxifloxacin as prophylaxis. Vancomycin was effective against all staphylococcal isolates but is not available commercially as a topical formulation and is typically reserved for known infections resistant to other antibiotics. With respect to antibiotic prophylaxis on the ocular surface, the antibiotic with the

greatest tear Cmax (maximum concentration) to MIC90 ratio for the majority of ocular bacteria is preferred. Limitations of this analysis include the application of systemic breakpoints to define isolates as susceptible or resistant to ocular treatment. Antibiotic concentrations are likely higher following ocular treatment than with systemic therapy, and the application of systemic breakpoints may therefore overestimate resistance. Information on diagnosis and etiology was not collected, hence the percentage of presumed endophthalmitis isolates from perioperative eyes, as opposed to eyes having intravitreal injections, other procedures, or even open globe injuries, is not known. Finally, these data cannot be used to evaluate species prevalence for bacterial endophthalmitis because the clinical sites participating in ARMOR were requested to submit a defined number of individual bacterial species.

REFERENCES 1. Speaker MG, Menikoff JA. Prophylaxis of endophthalmitis with topical povidone–iodine. Ophthalmology 1991; 98:1769–1775 2. Gower EW, Keay LJ, Stare DE, Arora P, Cassard SD, Behrens A, Tielsch JM, Schein OD. Characteristics of endophthalmitis after cataract surgery in the United States Medicare population. Ophthalmology 2015; 122:1625–1632. Available at: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC4516609/pdf/nihms69 6754.pdf. Accessed November 9, 2016

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3. American Academy of Ophthalmology. Cataract in the Adult Eye; Preferred Practice PatternÒ. San Francisco, CA, American Academy of Ophthalmology, 2016; Available at: http://www.aao.org/ Assets/e14f2979-177b-4169-8e0c-33bdf267b137/6361230495 25130000/cataract-in-the-adult-eye-ppp-in-press-pdf. Accessed November 9, 2016 4. Packer M, Chang DF, Dewey SH, Little BC, Mamalis N, Oetting TA, Talley-Rostov A, Yoo SH; for the ASCRS Cataract Clinical Committee. Prevention, diagnosis, and management of acute postoperative bacterial endophthalmitis. J Cataract Refract Surg 2011; 37:1699–1714. Available at: http://ascrs.org/ sites/default/files/resources/endophthalmitis.pdf. Accessed November 9, 2016 5. Asbell PA, Sanfilippo CM, Pillar CM, DeCory HH, Sahm DF, Morris TW. Antibiotic resistance among ocular pathogens in the United States: five-year results from the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) Surveillance study. JAMA Ophthalmol 2015; 133:1445–1454. Available at: http://www.grueye.org/files/jcarticles/Aburime% 20Jan%202016_2.pdf. Accessed November 9, 2016 6. Miller D, Chang JS, Flynn HW, Alfonso EC. Comparative in vitro susceptibility of besifloxacin and seven comparators against ciprofloxacinand methicillin-susceptible/ nonsusceptible staphylococci. J Ocul Pharmacol Ther 2013; 29:339–344 7. Gentile RC, Shukla S, Shah M, Ritterband DC, Engelbert M, Davis A, Hu D-N. Microbiological spectrum and antibiotic sensitivity in endophthalmitis; a 25-year review. Ophthalmology 2014; 121:1634–1642 8. Schimel AM, Miller D, Flynn HW Jr. Endophthalmitis isolates and antibiotic susceptibilities: a 10-year review of cultureproven cases. Am J Ophthalmol 2013; 156:50–52

Transconjunctival intrascleral intraocular lens fixation with double-needle and flanged-haptic technique: Ultrathin line between success and failure Andrew M.J. Turnbull, BM, PGCertMedEd, FRCOphth, Stephen C. Lash, BM, MCOptom, MBA, FRCOphth We are now using Dr. Shin Yamane's method of transconjunctival intrascleral intraocular lens (IOL) fixation with the double-needle technique and flanged haptics in cases with inadequate capsule support. In the video,A,B Yamane describes the elegant use of a 30-gauge needle to externalize the haptics of a 3-piece IOL before using heat to create a flanged haptic tip that permits intrascleral fixation without slippage. We would like to highlight a crucial aspect of the surgery that is not apparent in the video and can be the difference between success and failure. After carefully studying the video, we performed the technique for the first time in 2 consecutive patients with varying results. Both patients were aphakic following prior complicated cataract surgery, with insufficient capsule support for standard sulcus fixation. After pars plana vitrectomy was performed and residual lens matter cleared, the

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Yamane method was used with two 30-gauge needles (BD Microlance, Becton, Dickinson and Co.) and our standard 3-piece IOL (Tecnis ZA9003, Abbott Medical Optics, Inc.). In patient 1, the IOL haptics were implanted in the lumen of the needles with moderate difficulty, causing slight distortion of the temporal haptic. Despite this, both haptics were readily externalized. Using fine-tip high-temperature cautery (Accu-Temp, Beaver-Visitec International, Inc.) held close to but not touching the haptics, the haptic tips were flanged and repositioned through the conjunctiva and buried in the sclera. The IOL was well-centered, and the technique was much quicker and easier than other scleral fixation techniques we have used. In patient 2, it was again difficult to implant the haptics, with the needle lumen appearing too narrow to accommodate the haptic. Despite our best efforts, the haptics became distorted and eventually broke, necessitating IOL explantation. Another IOL was implanted and this time, 27-gauge needles were used to externalize the haptics per Yamane et al.’s earlier technique.1 Although this was much easier, the tract created by the larger bore needle was too wide to prevent slippage of the flanged haptic. Reflecting on these problems, we presumed that a different IOL with thinner haptics was required. However, the opposite is true. The 30-gauge needle required is of the “ultrathin wall” variety, with a larger internal diameter but the same external dimensions as a regular needle.C This facilitates insertion of the haptic and leaves a sufficiently narrow tract to enable secure fixation of the flanged haptic. This key detail is not included in the video, but in our experience, the needle specification was the ultrathin line between success and failure. Using a regular 30-gauge needle is possible but unpredictable and dependent on an element of good fortune and has a high risk for haptic damage. The ultrathin-wall 30-gauge needle used in the Yamane video can be obtained in Europe from TSK Laboratory Europe B.V. and in the United States from Dermatologic Lab & Supply, Inc.

REFERENCES 1. Yamane S, Inoue M, Arakawa A, Kadonosono K. Sutureless 27gauge needle–guided intrascleral intraocular lens implantation with lamellar scleral dissection. Ophthalmology 2014; 121:61–66. Available at: http://www.aaojournal.org/article/S0161-6420(13)00803-8/ pdf. Accessed October 16, 2016

OTHER CITED MATERIAL A. Yamane S, “Flanged IOL Fixation with Double-Needle Technique,” film presented at the XXXIV Congress of the European Society of Cataract and Refractive Surgeons, Copenhagen, Denmark, September 2016

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