1. RESULTS
A total of 90 syringes were prepared by 10 independent analysts
for the 3 conditions
Each syringe preparation required an average of 91 seconds (range
41 – 193 seconds) to complete
No contamination of the syringe needle or drug product was observed
in the speaking,or speaking with a mask,or silent conditions
Positive control plates showed bacterial growth on 5/10 plates in the
speaking condition (range 0 – 17 colonies/plate) and 3/10 plates in the
speaking with mask condition (range 0 – 2 colonies/plate). No growth
was observed on the positive control plates in the silent condition
DISCUSSION
• Results of this study suggest that speaking during syringe preparation
for intravitreal injection does not result in contamination of the syringe
needle or drug product. However, the contaminated plates in both
speaking conditions in the positive control group reveal a notable con-
tamination risk to the syringes under preparation
• In this study,staying silent while preparing syringes achieved a significant
decrease in the proportion of plates contaminated when compared to
Speaking Without Mask condition (p = 0.03) and Speaking With Mask
condition (p = 0.05)
• While the observed risk did not translate to actual contamination on
the syringe needle or drug product, this may have been largely due to
the small sample size (n = 30) in each arm. Given the low incidence
of post-injection endophthalmitis of 0.009 - 0.87%1, the lack of syringe
needle and drug product contamination in this study is consistent with
typical clinical experience
THE EFFECT OF SPEAKING DURING SYRINGE
PREPARATION FOR INTRAVITREAL INJECTION
Wayne Chen, PharmD1, Kevin Kerr, PharmD, MS2, Jane Zhang, PhD2, Melissa Gulmezian, PhD2, Ramakrishnan Srikumar, PhD2, Janet Cheetham, PharmD2,Yehia Hashad, MD2
1University of Southern California School of Pharmacy, Los Angeles, CA, USA. 2Allergan, Inc., Irvine, CA, USA
BACKGROUND
Intravitreal injections are a com-
mon route of administration to treat
retinal diseases such as Age-re-
lated Macular Degeneration, Dia-
betic Macular Edema, and Retinal
Vein Occlusion
Infectious endophthalmitis remains
the most devastating complication
of intravitreal injections which can
lead to severe,irreversible vision loss
despite prompt intervention
Streptococcus viridans, a known
member of normal oral flora, is one
of the most common causative
agents of post-injection endoph-
thalmitis1,2
Streptococcus species have also
been identified as the causative
agent in several large scale en-
dophthalmitis outbreaks involving
the use of compounded bevaciz-
imab for intravitreal injection5,6.Visits
to the implicated pharmacies
yielded questionable compound-
ing procedures6 such as:
spectator allowed in clean room
no face cover or mask
talking during compounding
procedure
no vertical barrier between
pharmacists and drug
Dispersion of oral flora during the
injection procedure has been well
studied3,4, but there have been
no studies exploring the extent of
oral bacterial dispersion during
preparation of a syringe for intravit-
real injection
OBJECTIVE
To assess if speaking during syringe
preparation for intravitreal injection
causes contamination of the sy-
ringe needle and/or drug product.
METHODS
10 recent graduates of ACPE (Accreditation Council for Pharmacy Education) accredited pharmacy schools were recruited to prepare
syringes for this study under 3 different conditions. Each condition was repeated 3 times
Condition 1 Analysts prepared syringes for intravitreal injection while speaking (counting out loud)
Condition 2 Analysts prepared syringes while speaking and wearing a mask
Condition 3 Analysts prepared syringes while staying silent with no mask
Syringe needles were then cut into tubes of Tryptic Soy Broth (TSB) and drug product was spread onto blood agar plates for incubation.
All samples were incubated at 37°C for 72 hours and then assessed for contamination.
CONCLUSIONS
Speaking without a mask during
syringe preparation causes bacterial
dispersion into the drug preparation
field but may not result in contamina-
tion of the syringe needle or drug
product
Physicians should be advised to review
and monitor the conditions in which
syringes for intravitreal injection are
being prepared. If possible, personnel
preparing syringes should be advised to
limit speech during preparation regard-
less of whether or not mask is worn in
order to reduce contamination of the
drug preparation field
Larger studies are needed to deter-
mine if the observed contamination in
the drug preparation field could di-
rectly affect the syringe needle or drug
product, thereby putting patients at
risk for post-injection endophthalmitis
REFERENCES
1. ChenE,LinMY,CoxJ,BrownDM.Endophthalmitisafterin-
travitrealinjection:theimportanceofviridansstreptococci.
Retina(Philadelphia,Pa).2011;31(8):1525-33.
2. Mccannel CA. Meta-analysis of endophthalmitis after
intravitreal injection of anti-vascular endothelial growth
factoragents:causativeorganismsandpossibleprevention
strategies.Retina(Philadelphia,Pa).2011;31(4):654-61.
3. WenJC,MccannelCA,MochonAB,GarnerOB.Bacterial
dispersalassociatedwithspeechinthesettingofintravit-
reousinjections.ArchOphthalmol.2011;129(12):1551-4.
4. DoshiRR,LengT,FungAE.Reducingoralfloracontamination
ofintravitrealinjectionswithfacemaskorsilence.Retina
(Philadelphia,Pa).2012;32(3):473-6.
5. Goldberg RA, Flynn HW, Miller D, Gonzalez S, Isom RF.
Streptococcusendophthalmitisoutbreakafterintravitreal
injectionofbevacizumab:one-yearoutcomesandinves-
tigativeresults.Ophthalmology.2013;120(7):1448-53.
6. FrostBA,KainerMA.EyeOpening:AreCompoundingDrugs
Causing Harm? Society for Healthcare Epidemiology of
America2011(PosterPresentation)[August6,2011];
Availableat http://www.ismp.org/docs/paper4263.pdf.
DISCLOSURES
K. Kerr, J. Zhang, M. Gulmezian, R. Srikumar,
J. Cheetham, and Y. Hashad are employees
of Allergan, Inc. and are engaged in clinical
development of pharmaceuticals for oph-
thalmic use
W.Chen received honoraria from Allergan,Inc.
as a post-doctoral fellow in clinical develop-
ment,Retina therapeutic area,at the time this
study was conducted
Materials and equipment were purchased by
Allergan,Inc.
Drug prep
Speaking
without
mask
Speaking
with
mask
Silence
Cut syringe needle with pliers Culture drug contentsCulture syringe needle
37˚C for 24-72hrs 37˚C for 24-72hrs
Culture drug contentsCulture syringe needle
37˚C for 24-72hrs 37˚C for 24-72hrs
Culture drug contentsCulture syringe needle
37˚C for 24-72hrs 37˚C for 24-72hrs
Drug prep Cut syringe needle with pliers
Drug prep Cut syringe needle with pliers
1 2
3
1 2
3
CONDITION1CONDITION2CONDITION3
Speaking
without
mask
Speaking
with
mask
Silence
37˚C for 24-72hrs
1 2
3
1 2
3
CONDITION1CONDITION2CONDITION3
37˚C for 24-72hrs
37˚C for 24-72hrs
Figure 2. POSITIVE CONTROLS
Figure 3 Proportion of Plates Contaminated in Each Condition
in Positive Control Plates
Positive Controls
• Each analyst completed 1 positive control
plate for each aforementioned condition by
holding an exposed blood agar plate at
approximately the same distance required to
prepare the syringes
• Analysts held this position for the same mean
duration of time that was required to prepare
the syringes in each respective condition
Statistical Analysis
Key Analysis Variables:
1. Proportion of contaminated needles
2. Mean Colony Forming Units per plate
Statistical analysis was performed using the
McNemar Asymptotic test to account for data
dependency between syringes prepared by a
single analyst.
© 2015 Allergan, Inc., Irvine, CA 92612.All rights reserved.
Figure 4 Average Number of Bacterial Colony Forming Units (CFUs)
Per Plate in Positive Controls
*Comparison of Speaking Without Mask condition with Silence condition
**Comparison of Speaking With Mask condition with Silence condition
60%
50%
40%
30%
20%
10%
0%
Proportion(%)
Speaking Without Mask Speaking With Mask Silence
0
30%
50%
2.5
2
1.5
1
.5
0
ColonyFormingUnites/Plate
Speaking Without Mask Speaking With Mask Silence
0
0.4
2.3
Range (0 - 17)
Range (0 - 2)
*p = 0.03
*p = 0.05
Figure 1. STUDY DESIGN
76688 ARVO Poster Chen 2015_Layout 1 4/14/15 11:55 AM Page 1