Microbial pathogens and strategies for combating them: science, technology and education (A. Mndez-Vilas, Ed.

)
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Negative-pressure wound therapy and the emerging role of incisional

negative pressure wound therapy as prophylaxis against surgical site
infections
Edward W. Kubek MD, Austin Badeau BA, Sara Materazzi MD, Nicholas Berlin BS, Blair A. Wormer
MD, Jamie B. Arton PA-C, and Raffi Gurunluoglu MD, PhD, F.A.C.S.
Denver Health Medical Center, University of Colorado Plastic and Reconstructive Surgery, Denver, Colorado USA
Carolinas Medical Center, Department of General Surgery, Charlotte, North Carolina USA

The goal of this chapter is to review the present understanding of negative pressure wound therapy (NPWT) and current
literature reporting the novel application of incisional negative pressure wound therapy (INPWT) for prevention of
surgical site infection (SSI). A review of NPWT plus a comprehensive review of the literature regarding the prophylactic
use of INPWT and its applications was conducted along with a discussion of future areas of research. Increasing
antimicrobial resistance among surgical patients and the economic implications of INPWT are also explored. Animal
models, anecdotal reports, pilot studies, case series, and more recently, prospective randomized controlled trials, suggest
INPWT will play an increasing role in the prevention of SSI among diverse surgical disciplines. Emerging data supports
INPWT as a prophylactic strategy against the development of SSI. INPWT does not rely on the added use of antibiotics,
but rather, favorably augments the patients own immune function and healing ability at the surgical site. Patients with the
greatest risk for SSI-related morbidity and mortality may benefit significantly from this therapy.

Keywords Negative Pressure Wound Therapy (NPWT); Incisional Negative Pressure; Incisional Negative Pressure
Wound Therapy (INPWT); Surgical Site Infection (SSI); Prophylaxis; vascular endothelial growth factor (VEGF)

1. Introduction
The goal of this chapter is to review NPWT, describe emerging prophylactic applications of NPWT, and discuss the
potential impact on SSI. In this chapter INPWT denotes the prophylactic application of NPWT to a closed incision.
Today, physicians of all disciplines are faced with an aging population and caring for increasing numbers of complex
patients with multiple comorbidities [1-7]. Advances in critical care medicine, trauma critical care, and combat trauma
care allow patients to survive increasingly complex pathologies. Unfortunately, at a similar rate, the resultant infectious
disease pathology and bacterial resistance to antibiotics are becoming similarly more complex [1,6-13]. The incidence
of diabetes and morbid obesity continues to increase in many parts of the world, and is expected to include 40% of the
US population by 2025 [7]. Increasing numbers of patients are at significantly higher risk for Surgical Site Infection
(SSI) and Hospital Acquired Infection (HAI) [2,6]. SSI increases morbidity and mortality, increases healthcare
expenditures, and often requires a prolonged hospital stay [6,12,13]. Long courses of antibiotics are required to treat
many SSIs, especially after a permanent implant such as a mesh or joint prosthesis is placed [6,14]. Prolonged courses
of antibiotics are known to promote antibiotic resistance [14-16]. A growing number of studies suggest that INPWT
may reduce the rate of SSI among high-risk surgical patients [7,17-29]. In the case of existing infection, NPWT
functions synergistically with antibiotic therapy by increasing peri-wound perfusion and antibiotic delivery to the site of
infection [14,30,31]. Prophylactic negative pressure wound therapies have several names in the current literature (Table
1).

Table 1 Commonly used names for NPWT applied to closed surgical incisions
NPWT Negative Pressure Wound Therapy
INPWT Incisional Negative Pressure Wound Therapy
WWT Well Wound Therapy
VAC Vacuum Assisted Closure
IVAC Incisional Vacuum Assisted Closure
CIM Closed Incision Management
TNP Topical Negative Pressure Therapy
PNPWT Prophylactic Negative Pressure Wound Therapy
SWT Subatmospheric Wound Therapy

1.1. History of NPWT

NPWT is recorded in Greek history as early as 400 BC [32]. In those times, a practice known as cupping utilized
negative pressure to extract toxins, venom, and purulent drainage from wounds. Based on modern experience, it is
logical to suspect some cupping techniques succeeded often enough to promote their spread throughout the Roman

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Empire and later Asia and Europe [32]. It wasnt until the 1950s, however, that Redon introduced and published his
evacuated-bottle system of closed suction drainage in the management of surgical patients [33]. As noted by Moues et
al [33], the first five publications making mention of Vacuum Wound Treatment appeared in the Russian surgical
literature in the late 1980s. Fleishman et al applied Redon suction to compressible foam dressings in the early 1990s.
In the mid-1990s Dr. Louis C. Argenta and colleagues developed the first commercially available wound vacuum
assisted closure (VAC) device (KCI Medical, San Antonio, TX USA) [34,35].
NPWT is now practiced worldwide. New research is showing how NPWT exploits ancient and highly conserved
pathways to promote wound healing. Commonly held beliefs regarding the beneficial effects of NPWT, such as the
belief that NPWT lessens the bacterial load of the healing wound [35], have been challenged [36,37]. Modern NPWT
remains a young discipline. Innovative uses and adaptations surface continually [20,22,38-42]. During the literature
search for this study, incisional negative pressure wound therapy (INPWT) had the highest yield as a search term.
Therefore, in this chapter INPWT is used to denote the prophylactic application of NPWT to a closed incision.

2. Negative pressure wound therapy (NPWT)

NPWT applies negative pressure to a wound to promote healing. Most NPWT systems place a reticulated-open-cell-
foam (ROCF) dressing between the wound and negative pressure source. When a vacuum is applied to a ROCF
dressing, the foam collapses in all directions (figure 1) [28]. As the foam compresses and contracts, sub-millimeter
pores in the foam create thousands of suction-cups to the wound surface [43]. Negative pressure and contracting ROCF
act synergistically to amplify their beneficial effects compared to either component used alone [33,43-45].
Innovative work by Argenta and colleagues made negative pressure dressings widely available, allowing surgeons to
develop useful and creative ways to apply them. The ability to modify and tailor negative pressure therapy in countless
combinations has advantages and disadvantages. Applying NPWT to increasingly diverse wound types allowed
clinicians to develop indications and contraindications to its use. In 2011, global expert panels met to develop evidence-
based recommendations for the use of NPWT (table 2) [46, 47].

Table 2 Indications for NPWT [46]

NPWT must be considered to improve the rate of split-thickness skin graft success (A)
Provide temporary wound coverage when primary closure is not possible, or as a bridge to definitive closure (B)
NPWT should be considered in wounds and/or patients with high risk of skin graft loss, using continuous negative
pressure for 3-7 days (B)
Improve healing of fasciotomy incisions (C)
Downscale the complexity of closure procedures (C)
Prevention of burn wound progression in partial-thickness burns (C)
Post-debridement management of flaps with partial necrosis (D)
Management of flap donor sites which cannot be closed primarily (D)

A Must At least one meta-analysis, systematic review, or RCT rated as 1++, and directly applicable to the target population; or a body of
evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results
B Should A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of
results; or extrapolated evidence from studies rated as 1++ or 1+.
C May A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of
results; or extrapolated evidence from studies rated as 2++
D Possible Evidence level 3 or 4; or extrapolated evidence from studies rated as 2+
1++ High quality meta-analyses, systemic reviews of RCTs, or RCTs with very low risk of bias; 1+ Well conducted meta-analyses, systemic
reviews, or RCTs with a low risk of bias; 1- Meta-analyses, systemic reviews, or RCTs with a low risk of bias; 2++ High-quality systematic reviews
of case-control or cohort studies. High-quality case-control or cohort studies with a very low risk of confounding or bias and a high probability that
the relationship is causal; 2+ Well-conducted case-control or cohort studies with a low risk of confounding or bias and a moderate probability that the
relationship is causal; 2- Case-control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal;
3 Non-analytic studies, e.g. case reports, case series, in vivo or in vitro studies; 4 Expert opinion.

Table 3 Contraindications to NPWT/Reticulated Open-Cell Foam [47]

Use of foam dressing in direct contact with exposed vital organs (blood vessels, anastamoses, organs, CSF, nerves)
Non-enteric or unexplored fistulas
Inadequately debrided wounds with necrotic tissue or eschar
Untreated osteomyelitis within the wound
Persistence of untreated coagulopathy (foam based systems are not hemostatic)
Malignancy within the wound or near the wound
Sensitivity to dressings which contain silver
Anticipated difficulty with follow-up or patient non-compliance
NPWT should be stopped when an infection develops during therapy (eg, purulent exudate)
NPWT should be used with caution on wounds known to be ischemic

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3. NPWT: Proposed mechanisms of action

NPWT induces macroscopic (macro) and microscopic (micro) changes in healing tissue (table 4). Other potential
mechanisms require further study (table 5). Figure one denotes a typical NPWT dressing applied to an open wound.

Table 4 Beneficial Effects of NPWT occurring on a Macroscopic and Microscopic Level

Macroscopic Effects of NPWT
Creates and maintains a moist wound environment,
shortens time to wound closure [51]
Reduces wound edema [46,52,53]
Helps limit seroma formation [22]
Promotes more robust granulation tissue when compared
to traditional occlusive dressing [43]
Stimulates wound contracture through macro-
deformation [28,46,52,53]
NPWT stabilizes healing tissues through a bolstering
effect [28,46]
Provides appositional forces to both superficial and
deeper healing tissues [28]
Reduces size and complexity of the healing wound [46]
Microscopic Effects of NPWT
Increased expression of VEGF, IL-8 [33,43,44,46,48-
50]. VEGF gradient increases toward the wound [44]
Vigorous angiogenesis in a parallel fashion, oriented
toward the wound compared to fewer tortuous new
vessels observed in controls [44]
Increases blood flow around periphery of the wound;
improves local delivery of antibiotics [31]
Stimulates cell proliferation through micro-deformation
[43,44]
Decreases local blood flow in those tissues in closest
proximity to the ROCF [31,33,43,44,47,48]
Removal of cytokines and other soluble inhibitors of
wound healing (e.g., matrix metalloproteinases) [44,66]
Changes the colonizing flora of the wound, may increase
or have no effect on overall bacterial load [36,37]
Increased neovascularization [50]

Table 5 Proposed actions of NPWT requiring further investigation

Lessens heat loss and promotes normothermia when compared to wet-to-dry dressings, especially for larger wounds
Increases delivery of antibiotics to the healing wound when used to manage SSI
Protects the wound from contamination in the post-operative period
Slows the progression to antibiotic resistance secondary to its prophylactic effects
NPWT may have a beneficial effect on healing bone secondary to up regulation of VEGF [54]

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Fig. 1 Traditional Negative Pressure Wound Dressing.

3.1. NPWT: Macroscopic effects

The macro effects of NPWT are visible at the bedside. Serous fluid removed from the wound is routinely seen in the
collection canister [48]. Reduced edema produces a visible reduction in swelling [52,53]. Visible wound
macrodeformation occurs when a vacuum is applied to ROCF [28]. As air is removed from the system, the foam
contracts; mimicking the forces of intact skin [28,48] and bringing wound edges closer. Clinically, NPWT facilitates
delayed primary closure of fasciotomy wounds without skin grafting [52,53]. NPWT maintains a moist wound
environment confined to the dressing [33]. This keeps bedding dry: wet skin increases heat loss. Compared to wet-to-
dry dressings, this may prevent nearby tissue from becoming macerated, although this has not been tested. NPWT may
also reduce seroma formation. Two studies recently reported statistically significant reductions in seroma formation
with INPWT [22,54]. NPWT also leads to visibly more robust tissue granulation [44,45]. Scherer et al [43] used a
mouse model of NPWT to reproduce visibly more robust granulation tissue consistent with clinical observations in
humans.
There is Grade-A evidence (table 2) supporting the use of NPWT as a mechanical bolster to improve the take of split-
thickness-skin-grafts [33,46,48]. Similarly, a beneficial bolstering effect may exist for patients with large sacral,
thoracic, or abdominal wounds. These patients require frequent turning and position changes by nursing staff to prevent
pressure ulcers, maintain hygiene, and transfer for imaging and other studies. Negative pressure dressings may help
maintain apposition of healing tissue planes during these necessary mechanical stresses [19,28].
Lastly, while post-operative contamination on the wards is not the dominant source of infectious inoculum in SSI [4],
the occlusive nature of NPWT dressings and the relatively infrequent need for dressing changes suggests a potential
benefit, especially in the intensive care unit (ICU) setting where nosocomial infection by cross-contamination is more
likely to occur. Further evidence is needed to substantiate these conclusions.

3.2. NPWT: Microscopic effects

The microscopic changes during NPWT may be more complex and amenable to manipulation (positive or negative)
than current NPWT techniques suggest. Debate exists over whether NPWT has its beneficial effects via increasing or
decreasing blood flow to the wound. Animal models and human data indicate dressings that combine negative pressure
and ROCF alter wound perfusion causing both an increase and decrease in blood flow dependent on the distance from
the wound edge and amount of negative pressure applied. An inner zone of hypoperfusion\hypoxia nearest the ROCF is
surrounded by an outer zone of hyperperfusion (figure 1) [31,33,43,44,47,48]. Optimal negative pressure settings which
induce the most favorable microenvironment likely depend on patient status and wound tissue/location [31,33,47]. Most
studies ignore patient factors such as perfusion pressure or mean arterial pressure when deciding how much negative
pressure to apply to injured tissue. No controlled trials comparing outcomes after varying degrees of negative pressure
exist [47]. In the lungs, ignoring the effect of pressure on local tissue is disastrous [55]. Pressure ulcers are another
example of pressure-related tissue injury.

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3.2.1. The many roles of VEGF

VEGF expression is a highly conserved local adaptation to tissue hypoxia [56,57]. VEGF dependent pathways
responsive to hypoxia exist in Drosophila, even though their phylogeny pre-dates the vascular system [56]. NPWT
exploits these ancient interrelated pathways to the benefit of wound healing. Tissue hypoxia is a very potent stimulus of
VEGF expression [31,56,58]. The inner zone of hypoperfusion/hypoxia induced by NPWT leads to supraphysiologic
increases in local VEGF expression [31,44,50]. The gradient of VEGF hyperexpression progressively increases toward
the zone of hypoxia at the wound-ROCF interface (figure 1) [44].
VEGF is vital in the tissue response to hypoxia during beneficial (healing) and pathologic (tumor growth) processes
[56]. Actions of VEGF include increases in chemotaxis, mitogenesis, hematogenesis, angiogenesis, local vasodilation,
capillary permeability, collagen deposition, and promotion of endothelial survival during serum starvation [44,56].
VEGF is secreted by macrophages, fibroblasts, neutrophils, endothelial cells, and T-cells, among others [56,58] to
promote vascular and lymphatic endothelial proliferation [44]. While NPWT can dramatically increase local VEGF
expression; serum levels appear to remain unchanged [50]. This finding may have safety implications for cancer
patients receiving NPWT as some cancers, such as colorectal cancer, can progress via VEGF related pathways.
Increased VEGF in response to hypoxia occurs within hours [57]. The NPWT phenomenon whereby a zone of tissue
hyperperfusion surrounds an inner zone of hypoperfusion and VEGF hyperexpression arises in humans and is seen in
diabetic rodent models [31,33,43,44]. Diabetics have a decreased ability to form normal vessels during tissue repair
[44]. NPWT models using diabetic mice show NPWT dramatically corrects this deficiency [43]. This may influence the
improved clinical outcomes when NPWT or INPWT is applied to diabetic patients [18,23].

3.2.2. Changes in microvascular blood flow

Research in this area is primarily based on healthy animal models which poorly represent complex human surgical
patients. The first study to examine local blood flow changes during NPWT was performed by Morykwas et al in 1997
[35]. Using healthy pigs and laser Doppler, they demonstrated a fourfold increase in blood flow near the NPWT
dressing using -125mmHg. Regional changes in wound blood flow during NPWT are likely multifactorial and data are
conflicting [31,33,47]. A subsequent animal study by Wakenfors et al [59] measured microvascular blood flow between
negative pressures of -50mmHg and -200mmHg. They showed increased microvascular blood flow a few centimeters
from the wound edge and a narrow zone of hypoperfusion in the immediate proximity of the wound-ROCF interface.
Higher negative pressures can increase the size of the hypoperfused zone [33]. Malmsjo et al [31] showed similar
results in healthy pigs; with a range of negative pressures between -50mmHg and -175mmHg producing similar
changes in blood flow in various tissues [31] at 0.5cm, 1.0cm, and 2.5cm from the wound edge. At 0.5 cm, blood flow
decreased by 23% 5%, at 1.0 cm, changes varied from wound to wound (animal to animal), and at 2.5cm, blood flow
increased by 19% 7%. Combined with these immediate changes, the neo-angiogenesis during NPWT produces
elongated, parallel, linear capillaries oriented toward the wound compared to tortuous vessels which form during
standard wound care [33,44]. Lastly, VEGF has vasodilating effects via nitric oxide pathways which likely effect
delayed changes hours after the initial application of NPWT [56].

3.2.3. Improved nutrient exchange and cell function

NPWT and INPWT remove edema fluid from the wound and interstitial space and can lessen seroma formation by
similar mechanisms and by providing mechanical stability to healing tissue edges in contact with one another
[22,28,32]. At the capillary bed terminus, cells obtain nutrients and expel waste by diffusion. Increased interstitial
edema thereby compromises resistance to infection and prolongs healing as diffusion distances become larger. This is
particularly problematic in irradiated tissue, where microvascular and lymphatic scarring further compromise these
processes [32]. To clear debris and combat infection, macrophages must traverse interstitial distances after diapedesis as
they leave the circulation and travel to the wound. Vascular permeability promoted by VEGF may facilitate their exit
from the vasculature and mobility toward the wound.

3.2.4. Microdeformation
Optimal wound bed surface-strain and microdeformation up to 0.025mm occur when negative pressure is applied to
ROCF [33,43]. The result is increased endothelial and overall cellular proliferation when compared to occlusive
dressing, suction plus gauze dressing, foam compressed without negative pressure, or suction alone [43]. Deforming
forces applied to the extracellular matrix cause microdeformation of the cytoskeleton. Distortion of the cytoskeleton
stimulates cell proliferation through a complex process known as mechanotransduction [43]. Macroscopically, this same
phenomenon is observed over time when tissue expansion techniques are used in reconstructive surgery.

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3.2.5. Lessening bacterial burden?

Morykwas et al hypothesized early that NPWT would decrease the bacterial load of treated wounds and showed this
using tissue swabs from a pig model for wound infection [35]. This initial investigation, however, had several
limitations. Wound physiology of hospitalized patients is more complex and tissue biopsy is more reliable for
quantifying bacterial load. In contrast, Moues et al [36] later showed that NPWT had no effect on quantitative bacterial
load compared to conventional dressings. Wounds treated with NPWT showed a statistically significant increase in S.
aureus colonization with no increase in invasive infection. At the same time, a significant decrease in non-fermentative
gram-negative bacilli occurred. Weed et al showed that NPWT may even increase the bacterial load of treated wounds
while still having a beneficial effect on healing [37].

3.2.6. Other molecular mechanisms

Nuutila et al [51] performed genome-wide microarrays on wound biopsies taken from human burn patients receiving
NPWT and compared these with controls. NPWT demonstrated dramatic changes in genome-wide expression and
suppression of various genes. Genes most induced were involved in cell-proliferation and inflammation. Those most
suppressed were linked to epidermal differentiation; suggesting prolonged use of INPWT may be counterproductive
where the goal is rapid healing and re-epithelialization [60]. Consistent with these data, Labler et al [50] demonstrated
increased IL-8 expression and neutrophil accumulation, and reduced levels of matrix metalloproteinases in human
subjects treated with NPWT. Animal data support these findings [61].

4. Incisional negative pressure wound therapy (INPWT)

INPWT is a novel prophylactic application of NPWT. Traditionally, NPWT has been used as a salvage technique when
a wound complication or surgical site infection has already occurred [17,21]. INPWT is applied in the operating room
while the field is still sterile (figure 2). The central idea behind INPWT is to induce the beneficial physiologic changes
of NPWT within a non-infected, newly-closed surgical site. Authors investigating INPWT as prophylaxis against SSI
have independently studied patients with a pre-operative risk of SSI approaching 20% or higher (see table 6). This
strategy is being employed with increasing frequency and success in various clinical situations (see table 6a and b).

Fig. 2 Typical Incisional Negative Pressure Wound Therapy.

4.1. Mechanism of action unique to INPWT

INPWT is thought to function like traditional NPWT with some notable differences. Wilkes et al [28] used Finite
Element Analysis (FEA) to show INPWT reduces the lateral stresses on surgical closures by nearly 50% at the level of
the epidermis, dermis, and within the subcutaneous tissue. This stabilizing effect on the closed incision keeps superficial
and deeper tissue layers in contact with one another without shearing. Level-1 evidence supports the use of NPWT as a
stabilizing bolster for skin grafts in a horizontal plane [46]. By keeping incised tissue edges approximated at various
levels of the wound, INPWT bolsters the surgical closure in the horizontal and vertical axis (figure 2) suggesting a
similar benefit in tissues approximated vertically [28]. The macrodeforming forces of NPWT and INPWT mimic the
elastic, compressive effects of intact skin [28]. These effects are visible at the bedside.

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4.2. INPWT: Current studies

Emerging data favor the use of INPWT as prophylaxis against SSI in select patients. A comprehensive literature search
revealed 11 studies investigating INPWT through April, 2013 (table 6a and b). One of the earliest reports of INPWT
was that of Gomoll et al showing zero infections among 35 patients at high-risk for SSI [17]. This was followed by
results from Duke University showing zero infections among 57 obese and diabetic-obese patients requiring open-heart
surgery [18]. Both studies were small, but results suggested a potential benefit of INPWT among high-risk patients
where other modalities had failed [18]. Reddix et al [7,19] followed with two retrospective studies, the second including
235 patients, which supported earlier conclusions regarding the benefits of INPWT. The largest prospective,
randomized controlled trial to date was performed by Stannard et al [21] showing a statistically significant benefit when
INPWT is applied to patients with high energy lower extremity trauma. In their study, those who showed the greatest
risk of infection in the control group (calcaneal fracture) derived the greatest reduction in SSI in the treatment arm [21].
A possible reason for these benefits was posited by Pachowsky et al who demonstrated statistically significant reduction
in seroma formation with INPWT after total hip arthroplasty [22].
Results from studies published in 2012 and 2013 are mixed. In their 2012 RCT, Masden et al [62] showed no benefit
when INPWT was applied to patients undergoing delayed-primary closure of stable chronic wounds of the lower
extremity. While the study was well designed, a confounding factor may be that every patient received INPWT at -
125mmHg. In one pig model, optimal perfusion changes occurred with as little as -50mmHg [31]. Increased negative
pressure can increase the zone of hypoperfusion/hypoxia during INPWT [33]. Patients with chronic lower extremity
wounds have baseline perfusion abnormalities that might respond poorly to -125mmHg; resulting in a larger hypoxic
zone and compromised healing. It is not clear how increasing negative pressure affects blood flow in patients with poor
perfusion. It would be interesting to know if those who failed INPWT had lower baseline perfusion pressures or toe
pressures.
Three retrospective studies from 2013 differ in conclusion. Blackham et al [23] showed a 50% reduction in SSI when
INPWT was applied to laparotomy closures at -125mmHg for 4 days. A retrospective review by Conde-Green et al [54]
showed improved results with INPWT applied to patients after abdominal wall reconstruction. INPWT for 5 days
reduced overall wound complications, dehiscence, seroma formation, and trended toward a reduction in hernia
recurrence at 15 months. SSI; however, was not significantly reduced. Pauli et al [63] also examined the effect of
INPWT after abdominal wall reconstruction and found no reduction in SSI. They applied INPWT for 7 days vs. Conde-
Green et al who used 5 days. Data from human burn patients indicate prolonged negative pressure can inhibit
epithelialization through gene suppression [51], and as such, 48 additional hours of INPWT could inhibit, rather than
promote wound closure. Pauli et al excluded those with simultaneous panniculectomy and/or anterior component
separation as these increase SSI rates. Conde-Green et al included patients with simultaneous panniculectomy and did
not exclude patients requiring component separation. Wilkes et al [28] showed that INPWT stabilizes closed tissues by
reducing lateral strain >50%, and as such, might be well-adapted for panniculectomy incisions. Also, the largest PRCT
to date demonstrated significant benefit with INPWT among those with a higher risk of SSI [21]; Conde-Green et al
included their higher risk patients. Pauli et al may have excluded patients more likely to benefit from INPWT.
Taken together, these 11 studies suggest INPWT can lessen the incidence of SSI and improve wound healing in high
risk surgical patients. Research must focus on where and how best to apply INPWT. The greatest benefit is seen in
reduction of superficial incisional SSI. Early studies (table 6 numbers 1-3) suggest a potential benefit with INPWT
among high risk patients. Studies 4, 6, and 9 reported more than a 50% reduction in SSI among high-risk patients
receiving INPWT. Studies 8 and 11 showed no clear benefit. Perhaps INPWT dressings facilitating deeper tissue
drainage can extend the beneficial effects to deeper tissues and even organ spaces (see CDC criteria section 6.1). The
case of AW below reflects the current literature and illustrates several NPWT techniques, including INPWT.

Table 6a Summary of current reports using INPWT as prophylaxis against SSI and wound related complications. SSD = Standard
Surgical Dressing, INPWT = Incisional Negative Pressure Wound Therapy, ORIF = Open Reduction Internal Fixation
Study Therapy vs Number of
Author, year Study Type Follow-up Wound Type
No. Control Patients
1 Gomoll et al. INPWT vs. Retrospective n = 35 3 months High-risk patients and/or injuries
2006 Historical Control Study meeting high-risk criteria for SSI after
primary closure
2 Zane-Atkins INPWT vs. Retrospective n = 57 30 days Clean-closed Median Sternotomy at
et al. 2009 Historical Control Study high-risk for SSI based on Fowler Score
3 Reddix et al. INPWT vs. Retrospective n = 40 Mean follow-up Closed incisions among morbidly obese
2009 Historical Control Study = 21 months patients (mean BMI = 48.7) undergoing
ORIF for Acetabular Fracture
4 Reddix et al. INPWT vs. Retrospective n = 235 Mean follow-up Closed incision after ORIF for
2010 Historical Control Study = 16.2 months Acetabular Fracture
5 Collie 2011 Pervena System Prospective n = 10 30 days Clean-closed Median Sternotomy at
vs. Historical Cohort Study high-risk for SSI
Control

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6 Stannard et INPWT vs. SSD Multi-center, n = 141 Wounds Surgical site closures after high-energy
al. 2012 in matched Prospective, INPWT vs. followed until derived lower extremity fractures (tibial
controls Randomized n = 122 healed plateau, pilon, and calcaneus)
Controlled Trial SSD
7 Pachowsky et INPWT vs. DD Randomized- n = 10 10 days Closed surgical incisions after total hip
al. 2012 Controlled Pilot (DD) vs. arthroplasty
Study n=9
INPWT
8 Masden et al. INPWT vs. Dry Single-blinded n = 44 Mean follow-up Predominantly chronic, non-healing
2012 Dressing (DD) Randomized INPWT vs. = 113 days lower extremity wounds undergoing
with Silver Controlled Trial n = 47 dry delayed primary closure after
dressing stabilization of the chronic wound bed
9 Blackham et INPWT vs. SSD Retrospective n = 104 30 days Clean and Clean-Contaminated
al. 2013 Study Laparotomy Closures at High-risk for
SSI
10 Conde-Green INPWT vs. Retrospective n = 23 Mean 15 Primarily closed incisions after
et al. 2013 Historical Control Study INPWT vs. months abdominal wall reconstruction among
N = 33 DD morbidly obese patients
11 Pauli et al. INPWT vs. SSD Retrospective n = 49 30 days then up Primarily closed clean-contaminated and
2013 analysis of INPWT vs. to one year contaminated incisions after complex
prospective data n = 70 SSD abdominal wall reconstruction

Table 6b Summary of current reports using INPWT as prophylaxis against SSI and wound related complications. All dressings were
applied under sterile conditions at the conclusion of surgery. OR = Operating Room, POD = Post-operative day, INPWT =
Incisional Negative Pressure Wound Therapy, SSI = Surgical Site Infection, DD = Dry Dressing, GranuFoam Silver Sponge
(Kinetic Concepts Inc, San Antonio, TX USA), Adaptic non-adhesive gauze (Johnson & Johnson, Somerville, NJ USA), VAC =
vacuum assisted closure (Kinetic Concepts Inc), Mepitel (Molnlycke Health Care AB, Goteborg, Sweden), Acticoat (Smith &
Nephew, Hull, UK).
Study
Author and Year Incisional Negative Pressure Dressing Application Results:
No.
1 Gomoll et al. 2006 Closed incision covered with Adaptic (Johnson & Johnson, Zero reported early or late SSI in this high-
New Brunswick, NJ USA) non-adhesive layer. Standard risk cohort of 35 patients.
VAC (KCI, San Antonio, TX USA) sponge 2.5 cm wide to
cover entire length of incision on top of Adaptic layer. Adhesive
drape placed over sponge. Dressing set to -75 mmHg (authors
note skin maceration -125 mmHg). Dressing removed
between POD 3 and 5. Therapy continues until with VAC
changes every 2-3 days until incision is dry.
2 Zane-Atkins, et al. Adaptic non-adhesive gauze placed over closed sternotomy 0% rate of infection in 57 high-risk patients.
2009 incision, GranuFoam Silver (KCI, San Antonio, TX) 1.0 Risk-adjustment predicted 3 SSI for this high-
1.5 cm strip over Adaptic for length of incision. TRAC Pad risk cohort
used to apply negative pressure (setting not given). First
dressing change POD #2 with chest-tube removal. INPWT
applied for 2 more days (total of four days)
3 Reddix et al. 2009 Skin staples spaced more widely than traditional closure. Among these 40 high-risk patients, no wound
Adaptic strip applied over incision. VAC sponge cut 2x2cm for complications or SSI occurred during
length of incision; placed over Adaptic. Sterile, adhesive, hospitalization or at final follow-up
occlusive sheet (drape) applied over sponge. TRAC Pad used
to apply negative pressure at -75mmHg continuous. INPWT left
in place until canister reveals no fluid over 12 hr period (usually
24 to 72 hrs).
4 Reddix et al. 2010 Same technique as No. 3 above Level 1 trauma center infection rate in
matched cohort before and after initiating
INPWT protocol was 6.15% and 1.27%,
respectively (p = 0.0414)
5 Collie 2011 Pervena System (KCI Inc. San Antonio, TX) applied over 0% rate of infection in 10 high risk patients
closed median sternotomy in OR. Dressing remains for 5 days.
Drains, chest tubes, and pain pump tubing brought out away
from wound. Sponge interface is 0.019% ionic silver
impregnated. Constant negative pressure at -125 mmHg
6 Stannard et al. 2012 INPWT applied to high-risk surgical closure in OR. First SSI (INPWT vs. SSD) showed statistically
dressing change performed POD #2, then every 1 to 2 days until significant improvement in overall infection
drainage from wound became minimal. Pressure set at -125 rate (10% vs. 19%, p = 0.049), SSI for closed
mmHg continuous fractures (9% vs. 19%, p < .05), and wound
dehiscence after discharge (8.6% vs. 16.5%, p
= 0.044)
7 Pachowsky et al. Prevena System applied in the OR and left in place for five By POD #10, a statistically significant
2012 days. Ultrasound seroma assessment performed on POD #5 and reduction in seroma formation noted amont
#10. INPWT patients (5.08 5.11 vs. 1.97 3.21
ml, p = 0.021)

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8 Masden et al. 2012 VAC System placed along the line of closure and set to -125
mmHg continuous. Dressings were removed on POD #3 and
assessed at each post-operative visit. Control dressings were
dry sterile dressings with non-adhesive silicone layer
(Mepitel) and a bacteriostatic single silver layer (Acticoat).
9 Blackham et al. Standard laparotomy closure with surgical skin staples placed 2
2013 cm apart. Single layer Adaptic non-adhesive gauze placed over
closed incision. 2x2cm sterile polyurethane foam along length
of incision. Transparent occlusive dressing, ioban (3M St. Paul,
MN) placed over foam. TRAC Pad used to apply -125 mmHg
continuous. Dressing removed on POD #4.
10 Conde-Green et al. INPWT applied to primary closure after abdominal wall
2013 reconstruction using Adaptic, black ROCF, with overlying
adhesive drape to provide occlusion. Continuous negative
pressure at -125 mmHg for 5 days.
11 Pauli et al. 2013 INPWT applied to clean and clean-contaminated incisions
closed primarily after complex abdominal wall reconstruction.
Adaptic placed over closed incision (subcuticular or staples)
followed by adhesive drape to protect skin and black
GranuFoam Sponge. Dressings placed to -75mmHg and
removed on POD #7
No statistically significant improvement noted
with INPWT vs. DD in rate of SSI (6.8% vs.
13.5%, p = 0.46), wound dehiscence (36.4%
vs. 29.7%, p = 0.54), or rate of reoperation
(21% vs. 22%)
INPWT yielded fewer SSI regardless of
timing (16.0% vs. 35.5%, p = 0.011), fewer
superficial SSI of clean-contaminated cases
(6.0% vs. 27.4%, p = 0.001), fewer wounds
needing to be re-opened (16.0% vs. 35.5%, p
= 0.011), and fewer superficial SSI (6.7% vs.
19.5%, p = 0.015)
INPWT showed decrease in overall wound
complication rate (22% vs. 63.6%, p = 0.020),
wound dehiscence (9% vs. 39%, p = 0.014),
seroma formation (0% vs. 12%, p < 0.05), and
a trend toward statistically significant
reduction in hernia recurrence (4% vs. 9%).
For 30 day rates of SSI, INPWT showed no
benefit over SSD after abdominal wall
reconstruction with primary closure in clean-
contaminated and contaminated operations
(25.8% SSD vs. 20.4% INPWT; p = 0.50)

5. Illustrative case: Patient A.W.

AW presented after being crushed by industrial machinery and went emergently to surgery for small and large bowel
injuries, grade 5 splenic laceration, and pancreatic crush injury. He underwent multiple operations: splenectomy, distal
pancreatectomy, small bowel resections, colon resections, cholecystectomy, end-ileostomy, and transverse colon mucus
fistula. NPWT was used to manage his open abdomen between surgeries. Ultimately he developed a pancreatic leak and
fistula. NPWT was never applied near the pancreas. Thick fluid from the pancreatic leak clogged the black ROCF and
abdominal drains making wound/abdomen care very difficult. Abdominal closure subsequently failed. Absorbable
polyglactin mesh was placed over the omentum and sewn to the fascial edges to contain the peritoneal contents. The
situation necessitated NPWT tailored to the patients needs. A continuously-irrigating NPWT dressing was applied with
four saline ports (each at 10cc/hr) and fenestrated suction tubing between layers of black ROCF. This thinned the thick
abdominal drainage as it entered the black sponge and exited via the fenestrated tubing. Dressing changes were required
only once weekly. Stabilization of the wound and control of the pancreatic and mucus fistula allowed granulation tissue
formation and eventual skin grafting over the intestine. AW transitioned to the rehab unit then home. He was scheduled
for reconstructive surgery one year after his last intra-abdominal operation allowing adhesions and scar tissue to soften
(see figure 3).

Fig. 3 AW before (left) and after (right) abdominal wall reconstruction. INPWT dressing shown at bottom right.

The 16 hour, single stage operation included excision of cicatrix over the intestine, laparotomy, extensive lysis of
adhesions with hydro-dissection, completion right and transverse colectomy, transverse colon mucus fistula takedown,
excision of pancreatico-cutaneous fistula/tract, revision distal pancreatectomy, ileostomy takedown, ileo-colonic
anastomosis, abdominal wall reconstruction with biologic mesh, and component separation with perforator preservation.
Multiple closed suction drains were brought out away from the incision. All incisions were closed in layered fashion
with skin staples spaced 2.5cm to facilitate fluid removal. INPWT was applied to each surgical closure: midline,
ileostomy takedown site, mucus fistula takedown site, and pacratico-cutaneous fistula site (see Figure 3). Sterile

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adhesive drape was applied along, but not over the incisions to protect skin. Black ROCF was placed over the closed
incisions. Continuous INPWT was applied at -75mmHg for 5 days with no interval dressing changes. Six days after
surgery a CT scan of the abdomen was obtained to evaluate an ileus. A small fluid collection was noted incidentally
within the left abdominal wall (figure 3 top right) and drained percutaneously. Gram stain and culture revealed rare
Enterococci. Each incision healed without superficial infection or dehiscence despite high SSI risk and chronic contact
dermatitis from the ileostomy appliance (see Figure 3 bottom right). Nearly two years after surgery AW remains
without delayed infection or hernia recurrence, although he remains at risk for late recurrence. NPWT and INPWT were
essential adjuncts to his care.

6. Surgical site infection: incidence

INPWT is a promising prophylactic intervention to reduce the rate of SSI among high-risk surgical patients. Hospital
acquired infection (HAI) ranks among the 10 leading causes of death in the United States [13]. SSI accounts for roughly
20% of HAIs, with reports ranging from 274,000 to 600,000 cases annually in the US. High rates of SSI are reported for
similar operations in the United States and other countries [23]. The 2008-09 National Surgical Quality Improvement
Project (NSQIP) data showed 21% of patients with a BMI >35 who underwent colon resection for cancer developed a
SSI [64]. In Italy, the National Nosocomial Infections Surveillance System (NNIS) reported rates of SSI of up to 37.5%
for open liver and pancreas operations, and 7.3% to 20% for colorectal surgery [23]. The Japanese NNIS reports SSI
rates of 20% to 30% for small bowel and colorectal surgery [23]. This is consistent with reports from Europe and Asia
reporting SSI rates of 12.6% to 35% after colorectal surgery [23]. The risk of SSI after high energy traumatic wounds
ranges from 33-50% [21]. The average rate of SSI for tibial plateau fractures is 27% [21]. In their 2009 pilot study,
Zane Atkins et al estimated the risk of SSI among obese diabetics undergoing coronary artery bypass surgery at 6.1
4%, of these, 33% will die in the first year after surgery; those with a SSI who survive past one year still have
significantly poorer long-term survival [18]. Added to this, rates of diabetes and obesity are predicted to rise in
developed countries [7]. At least 25% of Americans are obese; this figure is expected to reach 40% by 2025 [7]. SSI and
other complications are higher in obese individuals, with increasing complication rates correlating with increasing body
mass index (BMI) [7,64]. Increasing complexity of SSI, especially those involving implanted materials or devices, often
require prolonged courses of antibiotics and additional surgery. Prolonged, frequent, and repetitive antibiotic use
facilitates antibiotic resistance [5,6,9].

6.1. Surgical Site Infection: Morbidity and Mortality

The diagnosis of SSI carries significant morbidity and mortality. Operative and patient-related factors influence the risk
of SSI and severity of the clinical consequences. It is estimated that SSI alone is responsible for up to 30% of deaths
occurring within 30 days of surgery [23]. The Centers for Disease Control (CDC) defines SSI as any infection occurring
within 30 days post-operatively that can be attributed to surgery, and within one year of placing an implant [11]. SSIs
can be categorized as superficial incisional - limited to the skin and subcutaneous tissue adjacent to the incision; deep
incisional - extending to the muscle and fascia surrounding the incision; organ/deep-space - involving an organ or space
that was manipulated intraoperatively [12]. Diagnostic criteria and reporting of SSI are not uniform across the medical
literature. This leads to inter-study variability when reporting rates of SSI [1,6,7]. Discussing the various methods for
delineating rates of SSI is beyond this scope of this chapter.
The consequences of SSIs are many. Patients who develop a SSI after colon cancer resection have a higher risk of
wound dehiscence, pulmonary embolism, and renal failure [64]. SSI significantly increases rates of ICU admission and
readmission [13]. SSI carries a 29% risk of ICU admission for at least one day [13]. Readmission rates approach 41% in
patients with SSI as compared to only 7.4% in non-infected patients. SSI also prolongs hospital stays, with average
increases across specialties of 9.7 days [13]. SSI after cardiovascular surgery increases the length of hospital stay by an
average of 14 days [13,18]. When readmission to the hospital is factored into the total post-operative length of stay,
infected patients spend an overall average of 12 additional days in the hospital [13]. Readmission to the ICU for SSI
exposes the patient to nosocomial pathogens. Prolonged courses of antibiotics, especially for those with infected
implants, increase treatment costs, prolong hospital stays, and promote antibiotic-resistance [3].

6.2. Increasing antibiotic resistance among surgical patients

Complete sterilization of the skin is not possible [1]. Human skin contains 100,000 microbes per 1 cm2 [2]. As much as
20% of skin-associated bacteria exist within hair follicles and sebaceous glands and are not susceptible to topical skin
preps [2]. Source pathogens for SSIs are known to be: (1) present subclinically at the site before surgery, (2) introduced
iatrogenically at the time of surgery, (3) result from hematogenous spread, or an unknown smaller percentage (4), which
contaminate the wound and cause infection in the post-operative period [2,4,12]. SSIs are the most common form of
nosocomial infection in surgical patients [1]. S. aureus is the most common organism isolated in SSI [11]. Hospital and
community acquired strains of S. aureus are resistant to methicillin at an alarming rate, especially in the intensive care
unit [5]. The minimum inhibitory concentration for vancomycin-sensitive S. aureus continues to rise [5]. Reports of

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vancomycin-resistant S. aureus (VRSA) and methicillin resistant S. epidermidis (MRSE) are harbingers of battles that
will surely be fought in the years to come [4,5,9]. These trends, plus the rising incidence of drug-resistant pathogens in
the community, underscore the possibility of introducing increasingly destructive pathogens into the surgical site during
surgery [1,5]. Optimizing non-antibiotic therapies like INPWT, which augment the bodys ability to combat infection
and promote healing, is paramount.
The above has sparked renewed focus on non-antibiotic strategies for preventing and combating surgical site
infection. INPWT is one example. Other non-antibiotic methods for preventing SSI are listed in table 7.

Table 7 Non-antibiotic methods for reducing SSI

Shorten operating room times with preparation, updated surgeon preference cards, and logical organization of intra-operative
surgical supplies near theaters where they are likely to be needed
Minimally invasive techniques with smaller incisions to heal and less tissue handling
Maintenance of normothermia in surgical patients during and after surgery [3,65]
Oxygen therapy administered peri-operatively [65]
Newly developed antiseptic materials and coated implants (silver, lysostaphin, cyanoacrylate-based microbial sealants)
Use of suture materials and implant materials with favorable profile with regards to bacterial adherence (PDS suture [3],
lightweight polypropylene meshes)
Incisional Negative Pressure Wound Therapy in those patients most at risk for SSI
Proper pre-surgical scrubbing
Trimming hair with clippers as opposed to razor [3]
Conservative use of allogenic blood transfusion [2]
Smoking cessation 30 days before surgery and refraining from smoking post-operatively [12].

7. Economic impact of INPWT on SSI

An estimated 234 million surgical operations performed worldwide every year. In a recent study of 2,250 general and
vascular surgery patients, the excess cost associated with SSI was $10,497 per patient [7]. In a much larger study of
723,490 surgical hospitalizations in 2005, the weighted mean difference in length of stay and cost between patients with
and without SSI was 9.7 days and $20,842, respectively [13]. Home health nursing care adds an average of $6,200 per
patient for an average total of $27,029 [23]. It is estimated that SSI contributes to an additional 928,663 hospital-days
and US $1.6 billion in additional treatment costs [13]. A single complicated SSI after sternotomy can cost $80,000
[20]. These figures do not take into account the costs to society in terms of wages lost by patients unable to work after
SSI, nor do they reflect the percentage of patients with SSI who subsequently require long-term disability support.
Lastly, travel and lodging costs, lost wages, and other expenditures by family members who wish to be with their loved
ones in the hospital are not known. It is estimated that total healthcare costs attributable to SSI represent only one tenth
of the total cost burden [1].
Prospective cost analyses of INPWT are currently being conducted [23]. In their 2012 study, Stannard et al [21]
report that INPWT lasted an average of 2.5 days and cost less than $500 US. The cost of therapy was easily offset by
improved outcomes, although they have not yet published formal cost analyses. The 50% reduction in superficial SSI
noted by Blackham et al suggests a cost benefit with INPWT, although this was not specifically examined. Zane-Atkins
et al [18] reported INPWT added, on average, $490 per patient. Although the study was underpowered, validated risk
models predicted three SSIs among their 57 high risk patients. At $490 per patient, the cost of INPWT for all 57
patients would be $27,930. This is near the average cost of $27,029 for one SSI. If INPWT truly prevented 3 SSIs after
sternotomy, then the average savings would be ($27,029 x 3) - $27,930, or, $53,157 US.
Risk indices that accurately predict SSI risk can do more than identify patients to monitor closely in the post-
operative period. Risk models like the National Nosocomial Infection Surveillance (NNIS) system can actually help
prevent SSI by indicating which patients need aggressive prophylactic interventions, such as INPWT, while
highlighting specific risk factors to be eliminated. By correctly matching patients with appropriate therapy, maximal
health and economic benefits can be achieved by patients and healthcare systems alike.

8. Conclusion
The enormous human and economic costs of SSI demand continued research on preventing SSI catastrophes. As
healthcare enters an era where outcomes measures and cost are pushed evermore to the forefront, innovative ways to
improve care must be sought. NPWT and INPWT do not rely on increased use of antibiotics, but rather, enhance the
bodys own wound healing ability [43,48]. INPWT can reduce the incidence of SSI, especially when high-risk patients
require high-risk surgery. INPWT may lower healthcare costs, lessen the need for prolonged antibiotic regimens, and
slow the progression of antibiotic resistance. Increasingly sophisticated NPWT and INPWT systems will incorporate
anti-septic adjuncts like silver or continuous irrigation, among others. A systems-wide culture must focus on improving

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surgical outcomes through healthier lifestyles and cost-effective prophylactic therapies applied to properly identified
patients.

References
[1] Dohmen PM. Antibiotic resistance in common pathogens reinforces the need to minimize surgical site infections. Journal of
Hospital Infections 2008; 70(S2): 15-20.
[2] Seibert DJ. Pathophysiology of surgical site infection in total hip arthroplasty. American Journal of Infection Control 1999; 27:
536-42.
[3] Leaper D, McBain AJ, Kramer A, et al. Healthcare associated infection: novel strategies and antimicrobial implants to prevent
surgical site infection. Annals of the Royal College of Surgeons England 2010; 92: 453-458.
[4] Uckay I, Hoffmeyer P, Lew D, Pittet D. Prevention of surgical site infections in orthopaedic surgery and bone trauma: state-of-
the-art update. Journal of Hospital Infection 2013; 1-8.
[5] Fry DE. The Continued Challenge of Staphylococcus aureus in the Surgical Patient. The American Surgeon 2013; 79: 1-10.
[6] Evans HL, Sawyer RG. Preventing Bacterial Resistance in Surgical Patients. Surgical Clinics of North America 2009; 89: 501-
519
[7] Reddix RN, Tyler HK, Kulp B, Webb LX. Incisional Vacuum-Assisted Wound Closure in Morbidly Obese Patients
Undergoing Acetabular Fracture Surgery. The American Journal of Orthopedics 2009; 38(9):446-449
[8] Gaston RG, Kuremsky MA. Postoperative Infections: Prevention and Management. Hand Clinics of North America 2010; 26:
265-280
[9] Falagas ME, Alexiou VG, Pappas G, Makris GC. Do Changes in Antimicrobial Resistance Necessitate Reconsideration of
Surgical Antimicrobial Prophylaxis Strategies? Surgical Infections 2009; 10: 557-562
[10] Edward AM, McAndrews JM, Young VL. Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus: Preventing
Surgical Site Infections Following Plastic Surgery. Aesthetic Surgery Journal 2009; 29: 232-244
[11] Stevens DL. Treatments for skin and soft-tissue and surgical site infections due to MDR Gram-positive bacteria. Journal of
Infection 2009; 59(S1): S32-S39
[12] Kirby JP, Mazuski JE. Prevention of Surgical Site Infection. Surgical Clinics of North America 2009; 89: 365-389
[13] Lissovoy G, Fraeman SM, Hutchins V, et al. Surgical site infection: Incidence and impact on hospital utilization and treatment
costs. American Journal of Infection Control 2009; 37: 387-397
[14] Berrevoet F, Vanlander A, Sainz-Barriga M, Rogiers X, Troisi R. Infected large pore meshes may be salvaged by topical
negative pressure therapy. Hernia 2013; 17:67-73
[15] Horsburgh CR, Shea KM, Phillips P, Lavalley M. Randomized clinical trials to identify optimal antibiotic treatment duration.
Trials 2013
[16] Harbarth S, Samore MH, Lichtenberg D, Carmeli Y. Prolonged antibiotic prophylaxis after cardiovascular surgery and its
effect on surgical site infections and antimicrobial resistance. Circulation 2000; 101(25): 2916-21
[17] Gomoll AH, Lin A, Harris MB. Incisional Vacuum-Assisted Closure Therapy. Journal of Orthopedic Trauma 2006;20:705-
709
[18] Zane-Atkins B, Wooten MK, Kistler J, Hurley K, Hughes GC, Wolfe WG. Does Negative Pressure Wound Therapy Have a
Role in Preventing Poststernotomy Wound Complications? Surgical Innovation 2009;16(2):140-146
[19] Reddix RN, Leng XI, Woodall J, Jackson B, Dedmond B, Webb LX. The Effect of Incisional Negative Pressure Therapy on
Wound Complications After Acetabular Fracture Surgery. Journal of Surgical Orthopaedic Advances 2010;19(2):91-97
[20] Collie A. First experience with a new negative pressure incision management system on surgical incisions after cardiac surgery
in high risk patients. Journal of Cardiothoracic Surgery 2011;6:160
[21] Stannard JP, Volgas DA, McGwin III G, Stewart RL, Obremskey W, Moore T, Anglen JO. Incisional Negative Pressure
Wound Therapy After High-Risk Lower Extremity Fractures. Journal of Orthopaedic Trauma 2012;26:37-42
[22] Pachowsky M, Gusinde J, Klein A, Lehri S, Schulz-Drost S, Schlechtweg P, Pauser J, Gelse K, Brem MH. Negative pressure
wound therapy to prevent seromas and treat surgical incisions after total hip arthroplasty. International Orthopaedics
2012;36:719-722
[23] Blackham AU, Farrah JP, McCoy TP, Schmidt BS, Shen P. Prevention of surgical site infections in high-risk patients with
laparotomy incisions using negative-pressure therapy. The American Journal of Surgery 2013
[24] DeCarbo WT, Hyer CF. Negative-pressure Wound Therapy Applied to High-risk Surgical Incisions. The Journal of Foot &
Ankle Surgery 2010;49:299-300
[25] Dutton M, Curtis K. Well-wound therapy: use of NPWT to prevent laparotomy breakdown. Journal of Wound Care
2012;21(8)386-388
[26] Stannard JP, Zane-Atkins B, OMalley D, Singh H, et al. Use of Negative Pressure Therapy on Closed Surgical Incisions: A
Case Series. Ostomy Wound Management 2009;55(8):58-66
[27] Haghshenasskashani A, Varcoe RL. A new negative pressure dressing (Prevena) to prevent wound complications following
lower limb distal arterial bypass. The British Journal of Diabetes and Vascular Disease 2011;(11):21-24
[28] Wilkes RP, Kilpadi DV, Zhao Y, Kazala R, McNulty A. Closed Incision Management With Negative Pressure Wound Therapy
(CIM): Biomechanics. Surgical Innovation 2012;19(1):67-75
[29] Stannard JP, Gabriel A, Lehner B. Use of negative pressure wound therapy over clean, closed surgical incisions. International
Wound Journal 2012;9(Suppl. 1):32-39
[30] Kercher KW, Sing RF, Matthews BD, Heniford BT. Successful Salvage of infected PTFE mesh after ventral hernia repair.
Ostomy Wound Management 2002;48(40-42):44-45
[31] Malmsjo M, Ingemansson R, Martin R, Huddleston E. Wound Edge Microvascular Blood Flow: Effects of Negtive Pressure
Wound Therapy Using Gauze or Polyurethane Foam. Annals of Plastic Surgery 2009;63:676-681

1844 FORMATEX 2013

 Microbial pathogens and strategies for combating them: science, technology and education (A. Mndez-Vilas, Ed.)
____________________________________________________________________________________________

[32] Argenta LC in Weinzweig H. Plastic Surgery Secrets Plus: Second Edition. Mosby Elsevier, Philadelphia, PA 2010;(Chapter
7): 38-44
[33] Moues CM, Heule F, Hovius SER. A review of topical negative pressure therapy in wound healing: sufficient evidence? The
American Journal of Surgery 2011;201:544-556
[34] Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical experience.
Annals of Plastic Surgery 1997;38:563-576
[35] Morykwas MJ, Argenta LC, Shelton-Brown EI, et al. Vacuum-assisted closure: a new method for wound control and
treatment: animal studies and basic foundation. Annals of Plastic Surgery 1997;38:553-562
[36] Moues CM, Vos MC, Van Den Bemd GCM, Stijnen T, Hovius SER. Bacterial load in relation to vacuum-assisted closure
wound therapy: A prospective randomized trial. Wound Repair and Regeneration 2004;12:11-17
[37] Weed T, Ratliff C, Drake DB. Quantifying Bacterial Bioburden During Negative Pressure Wound Therapy. Annals of Plastic
Surgery 2004;52:276-280
[38] Saadi A, Perentes JY, Gonzalez M, Tempia AC, Wang Y, Demartines N, Ris HB, Krueger T. Vacuum-assisted closure device:
a useful tool in the management of severe intrathoracic infections. Annals of Thoracic Surgery 2011;91(5):1582-89
[39] Gabriel A. Integrated negative pressure wound therapy system with volumetric automated fluid instillation in wounds at risk
for compromised healing. International Wound Journal 2012;9 (Suppl. 1): 25-31
[40] Eisenhardt SU, Schmidt Y, Thiele JR, Iblher N, Penna V, Torio-Padron N, Stark GB, Bannasch H. Negative pressure wound
therapy reduces the ischaemia/reperfusion-associated inflammatory response in free muscle flaps. Journal of Plastic,
Reconstructive & Aesthetic Surgery 2012;65:640-649
[41] Steingrimsson S, Gottfredsson M, Gudmundsdottir I, et al. Negative-pressure wound therapy for deep sternal wound infections
reduces the rate of surgical interventions for early re-infections. Interactive CardioVascular and Thoracic Surgery 2012;(15):
406-410
[42] Topaz M. Improved wound management by regulated negative pressure-assisted wound therapy and regulated, oxygen-enriched
negative pressure-assisted wound therapy through basic science research and clinical assessment. Indian Journal of Plastic
Surgery 2012;45(2): 291-301
[43] Scherer SS, Pietramaggiori G, Mathews JC, et al. The Mechanism of Action of the Vacuum-Assisted Closure Device. Plastic
and Reconstructive Surgery 122: 786-798
[44] Erba P, Ogawa R, Ackermann M, et al. Angiogenesis in wounds treated by microdeformational wound therapy. Annals of
Surgery 2011:253(2): 402-409
[45] Borgquist O, Gustafsson L, Ingemansson R, et al. Micro- and macromechanical effects on the wound bed of negative pressure
wound therapy using gauze and foam. Annals of Plastic Surgery 2010;64: 789-793
[46] Krug E, Berg L, Lee C, et al. Evidence-based recommendations for the use of negative pressure wound therapy in traumatic
wounds and reconstructive surgery: steps towards and international consensus. Injury 2011;42: S1-S12
[47] Sorensen HB, Malmsjo M, Rome P, et al. Evidence-based recommendations for negative pressure wound therapy: treatment
variables (pressure levels, wound filler, and contact layer) steps towards an international consensus. Journal of Plastic,
Reconstructive, & Aesthetic Surgery 2011;(64): S1-S16
[48] Orgill DP, Bayer LR. Update on negative pressure wound therapy. Plastic and Reconstructive Surgery 2010;127(Suppl.):
105S-115S
[49] Gupta S. Prologue. International Wound Journal. 2012;(9) (Suppl. 1): iii-vii
[50] Labler L, Rancan M, Mica L, et al. Vacuum-assisted closure therapy increases local interleukin-8 and vascular endothelial
growth factor levels in traumatic wounds. The Journal of Trauma 2009;(66): 749-757
[51] de Laat EHEW, van den Boogaard MHWA, Spauwen PHM, et al. Faster wound healing with topical negative pressure in
difficult-to-heal wounds. Annals of Plastic Surgery 2011;(67): 626-631
[52] Zannis J, Angobaldo J, Marks M, et al. Comparison of fasciotomy wound closures using traditional dressing changes and the
vacuum-assisted closure device. Annals of Plastic Surgery 2009;(62): 407-409
[53] Yang CC, Chang DS, Webb LX. Vacuum-assisted closure for fasciotomy wounds following compartment syndrome of the leg.
Journal of Surgical Orthopaedic Advances 2006;15(1): 19-23
[54] Conde-Green A, Chung TL, Holton LH 3rd, et al. Incisional negative-pressure wound therapy versus conventional dressings
following abdominal wall reconstruction: a comparative study. Annals of Plastic Surgery 2012;(00): 00-00
[55] Slutsky AS, Ranieri VM. Mechanical ventilation: lessons from the ARDSNet trial. Respiratory Research 2000;1(2): 73-77
[56] Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocrine Reviews 2004;(25): 581-611
[57] Marti HH, Risau W. Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its
receptors. Proceedings of the National Academy of Sciences USA 1998;(95): 15809-15814
[58] Kiriakidis S, Andreakos E, Monaco C, et al. VEGF expression in human macrophages in NF-B dependent: studies using
adenoviruses expressing the endogenous NF-B inhibitor IB and a kinase-defective form of the IB kinase 2. Journal of Cell
Science 2003;(116): 665-674
[59] Wackenfors A, Sjogren J, Gustafsson R, et al. Effects of vacuum-assisted closure therapy on inguinal wound edge
microvascular blood flow. Wound Repair and Regeneration 2004;12(6): 600-606
[60] Nuutila K, Siltanen A, Peura M, et al. Gene expression profiling of negative-pressure-treated skin graft donor site wounds.
Burns 2013;(39): 687-693
[61] Derrick KL, Norbury K, Kieswetter K, et al. Comparative analysis of global gene expression profiles between diabetic rat
wounds treated with vacuum-assisted closure therapy, moist wound healing, or gauze under suction. International Wound
Journal 2008;(5): 615-624
[62] Masden D, Goldstein J, Endara M, et al. Negative pressure wound therapy for at-risk surgical closures in patients with multiple
comorbidities. Annals of Surgery 2012;(255): 1043-1047
[63] Pauli EM, Krpata DM, Novitsky YW, et al. Negative pressure therapy for high-risk abdominal wall reconstruction incisions.
Surgical Infections 2013;(14): 1-5

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[64] Byrnside V, Glasgow M, Gurunluoglu R. The vacuum-assisted closure device in treating craniofacial wounds. Journal of Oral
and Maxillofacial Surgery 2010;68(4): 935-942
[65] Quinn A, Hill ADK, Humphreys H. Evolving issues in the prevention of surgical site infections. Surgeon 2009;(7): 170-2
[66] Moues CM, van Toorenenbergen AW, Heule F, et al. The role of topical negative pressure in wound repair: expression of
biochemical markers in wound fluid during wound healing. Wound Repair and Regeneration 2008;(16): 488-494.

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