116 / 150
Discussion and/or Conclusion(s):
This study characterises a heter-
ogenous cluster of renal transplant patients developing PCP. Notable
clinical features included a universal lymphopenia, low eGFR, CMV
viraemia and several patients being a considerable time out from
transplant. A number of the cases overlapped in time and place
such that cross-transmission is suspected and further characterisation
of this is being undertaken. This cluster illustrates the persistent risk
of opportunistic infection, many years from transplantation, and
represents a precedent in Scotland, and an emerging challenge
worldwide.
Topic: Pathogenesis
ID: 4710
Characterization of macrophage mediated immune responses to
mycobacterial infections
Gunjan Kak
1
, Brijendra K. Tiwari
2
, Cecil Antony F
2
, Yogendra Singh
3
,
Krishnamurthy Natarajan
2
.
1
Dr. Ambedkar Center for Biomedical
Research,
2
Dr. B.R Ambedkar Centre for Biomedical Research,
3
CSIR Institute of Genomics and Integrative Biology
Background:
Interferon-gamma (IFN-
γ
) is a key cytokine in immunity
towards tuberculosis. IFN-
γ
−
/
−
or IFN-
γ
receptor IFN-
γ
R
−
/
−
knockout
mice rapidly succumb to tuberculosis. The pathogen has evolved many
ways to mitigate the effects of IFN-
γ
. The down regulation of IFN-
γ
R on
the surface of macrophages is one such strategy.
Aim(s)/Objective(s):
The objective of the study is to characterize
IFN-
γ
mediated macrophage responses to mycobacterial infections,
key host factors regulating IFN-
γ
R expression on macrophages in
response to M. tb infection and to explore the dichotomy in the profile
and susceptibility patterns of this very immunologically relevant
cytokine.
Method(s):
Human THP-1 cell line, murine bone marrow derived
macrophages (BMDMs) and human peripheral blood mononuclear
cells (PBMCs) were used for study. Flow cytometry, confocal imaging
and western blots were employed for investigations.
Results:
Data shows that both M. tb and M. bovis BCG are potent down
regulators of IFN-
γ
R on macrophages. Many host factors and signalling
pathways are employed by M. tb to exhibit this phenomenon. TLR
pathway specifically, adaptor molecule TRAF6, calcium homeostasis,
PKC and MAPK ERK are involved in aiding M. tb mediated receptor
down modulation. Also, genes of calcium cysteine protease pathway
which were previously identified by our lab and linked to mediating
negative immunity against M. tb also regulate IFN-
γ
R on macrophages
in response to M. tb infections.
Discussion and/or Conclusion(s):
Thus M. tb employs various host
factors to elicit its immune suppressive effects to downregulate surface
receptor expression of IFN-
γ
R. By down regulating the receptor
levels the pathogen is successfully able to avert the protective effects
of IFN-
γ
.
ID: 5028
Pro-infectious agents can augment
Staphylococcus aureus
virulence
Emma Boldock
1
, Daria Shamarina
2
, Tomasz Prajsnar
2
, Bas Surewaard
3
,
Stephen Renshaw
2
, Simon Foster
2
.
1
Sheffield Teaching Hospitals NHS
Trust,
2
University of Sheffield,
3
University of Calgary
Background:
Staphylococcus aureus is an invasive human pathogen
associated with significant mortality. Host-pathogen dynamics during
infection are poorly understood but recent work demonstrates that
with high dose inocula, an immunological bottleneck allows clonal
expansion of few bacteria, which go on to cause abscesses. Models of
S. aureus infection are characterized by the requirement for a large
bacterial inoculum and the impact of surrounding microflora on
S. aureus pathogenicity is under-explored.
Aim(s)/Objective(s):
To interrogate the clonal expansion phenom-
enon further and to investigate the need for a large bacterial
inoculum to establish S. aureus infection, mixed strain inocula were
tested in both the zebrafish embryo and murine models of systemic
infection.
Results:
In both infection models, purified, particulate bacterial cell
wall peptidoglycan was able to augment infection by low dose
S. aureus but inert particulate beads or solubilised peptidoglycan did
not. Commensal bacteria e.g. Micrococcus luteus were also able to
augment pathogenesis of low dose S. aureus.
In the murine model, the infective dose could be lowered from 10
7
to
10
4
CFU in the presence of these potentiators and the liver appears to
be the focal point of loss of immune control. Innate immune
dysfunction and chemokine dysregulation have been shown to
underpin this augmentation phenomenon.
Discussion and/or Conclusion(s):
These results have important
ramifications regarding human S. aureus disease as it may begin to
explain how initiation of infection occurs, as S. aureus primarily enters
via a wound or invasive procedure. These data demonstrate that other
bacteria (and even their components) enable S. aureus to initiate
infection.
Topic: Surgical site infections
ID: 4465
Can local champions help to drive forward initiatives to reduce
cardiac surgical site infections?
Lilian Chiwera, Willian Newsholme, Neil Wigglesworth,
Christopher Blauth.
Guy
’
s & St Thomas
’
NHS Foundation Trust
Background:
Surgical site infections are a big challenge and have
devastating consequences for patients. Adult cardiac Surgical Site
Infection Surveillance (SSIS) at Guy
’
s and St Thomas
’
NHS Foundation
Trust commenced in 2009 as a patient safety initiative amid reported
increased incidence of Surgical Site Infections (SSIs). Before this
time, infection incidence was unclear because data collection was not
standardised.
Aim(s)/Objective(s):
We aimed to establish baseline SSI rates in adult
cardiac surgery and employ targeted interventions as per Department
of Health and National Institute for Health and Care Excellence (NICE)
best evidence guidelines. This gave us an opportunity to standardise
practice and improve patient outcomes, quality, safety and efficiency in
line with organisational targets. We also aimed to embed the SSI
detailed investigation protocol mirroring the NICE SSI quality standard
(2013).
Method(s):
We developed and established use of local data collection
protocols in line with Public Health England recommendations and
identified local champions. This strong SSIS leadership helped us to
develop a multidisciplinary collaborative approach that eased the
burden of data collection and optimised open communication. This
enabled us to address potential practice concerns more effectively
through a series of initiatives.
Results:
SSI rates fell from 5.4% in 2009 to 1.1% in 2015 and CABG rates
from 6.5% in 2009 to 1.2% in 2015; considerably below the national
average (4.7%). We saved an estimated £706,000 over a 7 year period.
Discussion and/or Conclusion(s):
The use of local champions and a
multidisciplinary collaborative approach enabled us to successfully
implement evidence based practice and demonstrate significant
reductions in SSI incidence.
ID: 4562
Surgical site infection (SSI) after caesarean delivery
–
comparison
of skin closure using staples and subcuticular suture
Gerard McIlvenny, Mark McConaghy, Eileen Morelli,
Lourda Geoghegan.
Public Health Agency
Background:
The most common methods for caesarean section skin
closure are metal staples or absorbable sutures. Both oppose skin
edges to facilitate wound healing. Staples are regarded as quicker and
easier than sutures to use. To date no large study has conclusively
Abstracts of FIS/HIS 2016
–
Poster Presentations / Journal of Hospital Infection 94S1 (2016) S24
–
S134
S111