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International Wound Journal logoLink to International Wound Journal
. 2008 Jun 28;5(3):399–413. doi: 10.1111/j.1742-481X.2007.00423.x

Negative pressure wound therapy with instillation: a pilot study describing a new method for treating infected wounds

Allen Gabriel 1, Jaimie Shores 2, Cherrie Heinrich 3, Waheed Baqai 4, Sharon Kalina 5, Norman Sogioka 6, Subhas Gupta 7,✉
PMCID: PMC7951189  PMID: 18593390

Abstract

This data review reports the results of 15 patients who were treated with Vacuum‐Assisted Closure® (VAC) negative pressure therapy system in addition to the timed, intermittent delivery of an instilled topical solution for management of their complex, infected wounds. Prospective data for 15 patients treated with negative pressure wound therapy (NPWT)‐instillation was recorded and analysed. Primary endpoints were compared to a retrospective control group of 15 patients treated with our institution‘s standard moist wound‐care therapy. Culture‐specific systemic antibiotics were prescribed as per specific patient need in both groups. All data were checked for normality of distribution and equality of variance and appropriate parametric and non parametric analyses were conducted. Compared with the standard moist wound‐care therapy control group, patients in the NPWT‐instillation group required fewer days of treatment (36·5 ± 13·1 versus 9·9 ± 4·3 days, P < 0·001), cleared of clinical infection earlier (25·9 ± 6·6 versus 6·0 ± 1·5 days, P < 0·001), had wounds close earlier (29·6 ± 6·5 versus 13·2 ± 6·8 days, P < 0·001) and had fewer in‐hospital stay days (39·2 ± 12·1 versus 14·7 ± 9·2 days, P < 0·001). In this pilot study, NPWT instillation showed a significant decrease in the mean time to bioburden reduction, wound closure and hospital discharge compared with traditional wet‐to‐moist wound care. Outcomes from this study analysis suggest that the use of NPWT instillation may reduce cost and decrease inpatient care requirements for these complex, infected wounds.

Keywords: Instillation, Negative pressure wound therapy, Silver nitrate, Vacuum‐assisted closure therapy, Wound‐care infection

Introduction

The detrimental effect of infection on wound healing has long been universally known. Infections complicate the treatment of wounds and impede the healing process by damaging tissue, reducing wound tensile strength and inducing an undesirable inflammatory response 1, 2. It is generally believed that the wound advances from contamination to colonisation when the bacteria on the wound’s surface begin to replicate and increase their metabolic activity. Bacteria and bacterial products, such as endotoxins and metalloproteinases, can disturb all wound‐healing phases.

A heavy bacterial bioburden in a wound increases the metabolic requirements, stimulates a pro‐inflammatory environment and encourages the in‐migration of monocytes, macrophages and leucocytes, all of which can negatively impact wound healing 1, 2, 3, 4. Bacteria can also secrete harmful cytokines that can lead to direct vasoconstriction and decreased blood flow to the wound. Thus, controlling or preventing infections is essential for the normal wound‐healing process to occur. In addition, reduction of infection can also yield significant overall cost savings in health care, as infections lead to thousands of dollars in excess medical charges and lengthened hospital stays every year (5).

Vacuum‐assisted closure (VAC) therapy is a recognised and powerful tool in the wound‐care setting. Chronic and acute wounds of traumatic, surgical or other origin, have had great success with the application of this therapy 6, 7, 8, 9, 10, 11, 12, 13. Despite this, VAC therapy was avoided in infected or heavily colonised wounds and the mainstay of therapy was intravenous, oral and/or topical antimicrobials and frequent standard dressing changes. VAC therapy was introduced by Argenta and Morykwas in 1995, based on the principle of applying topical subatmospheric pressure to acute, subacute and chronic wounds 14, 15. The negative pressure delivers mechanical stress to the underlying cells while removing third space interstitial fluid into a collection canister. Prolonged stretching of the cytoskeleton causes release of intracellular messengers resulting in matrix molecule synthesis and cell proliferation 16, 17.

Scientific studies have reported that VAC therapy enhances blood flow 15, 18, 19 and increases proliferation of reparative granulation tissue 20, 21, 22, 23, 24, 25, 26, 27. Various studies have also shown that this therapy reduces wound size faster than standard moist wound care 28, 29, 30 and that it can be an effective adjunct in bolstering skin grafts 31, 32. As a closed system, negative pressure wound therapy (NPWT) delivered by vacuum‐assisted closure (VAC) provides a moist wound‐healing environment and helps protect wounds from outside bacteria 33, 34.

The goal of wound management is to create an environment that is conducive to wound healing by decreasing the bacterial bioburden and improving perfusion to the wound. NPWT instillation combines NPWT and the timed delivery of topical irrigation solutions (normal saline, distilled water or silver nitrate) to the wound bed. The solutions can be antimicrobials or other fluids used for irrigation in conjunction with the added benefits of NPWT.

To test the benefits of antimicrobial instillation in conjunction with NPWT, a pilot research study was designed to explore the use of VAC therapy plus the intermittent delivery of an instilled antimicrobial topical solution and its effectiveness in treating complex, infected wounds. The number of days of wound treatment, days to wound closure and days to patient discharge were established as endpoints that would best measure the effectiveness of NPWT instillation therapy. It was hypothesised that enhanced reduction in bacterial bioburden would lead to quicker wound closure and patient discharge, resulting in hospital cost savings and reduced patient expense.

Methods

A prospective study of 15 adult patients with the diagnosis of complex, open, infected wounds that were treated with NPWT instillation between January 2005 and April 2006 was conducted. In addition, this group was compared to a retrospective control group of patients treated with our institution’s standard moist wound‐care therapy between January 2004 and December 2005 to determine the effectiveness of NPWT‐instillation therapy. Inclusion criteria for both groups included trunk and extremity wounds with documented qualitative cultures with greater than 105 organisms, age greater than 40 years and documented necrotic tissue. This study was approved by the Institutional Review Board of Loma Linda University Medical Center. All wounds were repeatedly sharply debrided of non viable tissue before NPWT instillation was applied. Swab wound cultures for all patients were taken and submitted on the first day of hospital admission for qualitative culture analysis.

Demographic data and type of infection present on return of initial swab culture were recorded for each patient (Table 1). In the three cases of necrotising fasciitis, the patients were monitored every 8 hours to ensure complete resolution of the necrotic tissue before NPWT‐instillation therapy was applied on hospital day 2. For the remaining 12 patients, NPWT instillation was initiated as a first‐line therapy on hospital day 1, following initial surgical debridement.

Table 1.

Data for NPWT‐instillation therapy group

Patient Age (years) Diagnosis Wound area* (cm2) Initial culture Days of NPWT‐instillation therapy Days to infection clearance Days to wound closure Method of wound closure Days to patient discharge
1 84 Abdominal necrotising fasciitis 300 Staphylococcus enterococcus 14 5 15 Primary closure 17
2 51 Necrotising fasciitis of chest and upper extremity 500 Staphylococcus, Enterococcus 9 5 10 Skin graft 15
3 71 Stage IV sacral pressure ulcer 100 VRE, MRSA 20 10 35 Secondary intention 45
4 65 Open knee joint with exposed hardware 50 Staphylococcus, Enterococcus 5 5 10 Local flap 10
5 51 Open knee joint with exposed hardware 40 Staphylococcus, Enterococcus 10 7 14 Local flap 14
6 45 Surgical wound dehiscence 300 Staphylococcus, Enterococcus 7 7 10 Primary closure 11
7 65 Lower extremity wound 40 VRE, MRSA 10 7 15 Secondary intention 15
8 60 Soft tissue loss of lower extremity 50 Staphylococcus, Enterococcus 5 5 8 Skin graft 11
9 53 Open ankle joint with exposed hardware 40 Staphylococcus, Enterococcus 5 5 5 Local flap 6
10 65 Lower extremity wound with exposed bone 50 VRE, MRSA 15 7 16 Integra/Skin graft 18
11 41 Soft tissue loss of the lower extremity 200 Staphylococcus 10 5 10 Skin graft 15
12 49 Lower extremity wound with exposed bone 30 Staphylococcus 10 7 10 Integra/Skin graft 14
13 62 Abdominal surgical wound dehiscence 100 Enterococcus 7 5 14 Secondary intention 7
14 45 Stage IV pressure ulcer 50 VRE, MRSA 14 5 14 Local Flap 15
15 50 Necrotising fascitis of the upper extremity 60 Streptococcus Enterococcus 7 5 12 Secondary intention 7
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NPWT, negative pressure wound therapy; MRSA, methicillin‐resistant Staphylococcus aureus; VRE; vancomycin‐resistant infections.

*

Post‐debridement.

The NPWT‐instillation regimen consisted of placing a medical grade, reticulated polyurethane and sterile foam dressing (VAC® GranuFoam®; KCI, San Antonio, TX) in the entire wound cavity and covering with a semi‐occlusive adherent drape to create an airtight seal. A 1–2 cm diameter round hole was cut into the drape, over which a TRAC® pad with tubing was placed. The tubing was then connected to a fluid collection canister contained within the computer‐controlled NPWT‐instillation device (VAC Instill®; KCI, San Antonio, TX). On the opposite side of the foam from this tubing, an additional 1–2 cm diameter round hole was cut in the drape and the second tube was applied. The other end of this tubing was then connected to an intravenous bag containing normal saline, sterile water or silver nitrate solution for instillation.

The NPWT‐instillation device was programmed to cycle through a similar regimen for all solutions: instill the topical solution for 30–45 seconds, follow with a 1‐second hold time to allow the solution to penetrate through the dressing to cover the wound, then deliver 2 hours of negative pressure therapy at 125 mmHg continuously. We believe that the instillation time and the hold time are sufficient to cause the hydro‐debridement effect that we see with this technology. We also believe that activity of silver is instantaneous and there is no need for increased hold times as this may cause for fluid to leak out of the wound and break the existing seal. Approximately 50–75 cm3 of solution was delivered during each instill cycle. VAC Instill® settings are listed in Table 2.

Table 2.

VAC® Instill™ therapy settings

Patient NPWT‐instillation settings NPWT negative pressure setting
Silver nitrate Volume (cc) Instill (seconds) Dwell (seconds) Therapy (hours) mmHg continuous
1 Yes 50–75 30 1 2 −125
2 Yes 50–75 30 1 2 −125
3 Yes 50–75 30 1 2 −125
4 Yes 50–75 30 1 2 −125
5 Yes 50–75 30 1 2 −125
6 Yes 50–75 30 1 2 −125
7 Yes 50–75 30 1 2 −125
8 Yes 50–75 30 1 2 −125
9 Yes 50–75 30 1 2 −125
10 Yes 50–75 30 1 2 −125
11 Yes 50–75 30 1 2 −125
12 Yes 50–75 30 1 2 −125
13 Yes 50–75 30 1 2 −125
14 Yes 50–75 30 1 2 −125
15 Yes 50–75 30 1 2 −125
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NPWT, negative pressure wound therapy; VAC, vacuum‐assisted closure.

Silver nitrate (Teva Pharmaceuticals North America; Wales, PA; NDC 0093‐9614‐13) was the antimicrobial solution of choice used in this study with the goal of decreasing bacterial bioburden 27, 28, 29. Silver nitrate was placed in an empty 1 l Baxter Sterile Water bottle (Baxter: 2F7114) and covered with a special Baxter irrigation cap (Baxter: 2C4010) and subsequently connected to the tubing and covered to protect it from light as seen in Figure 1A–C. As the solution is gravity fed, the instillation bag must be at or slightly above the level of the wound. The delivered volume of solution varies depending on the height of the bag.

Figure 1.

Figure 1

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Vacuum‐Assisted Therapy (VAC® Instill™) therapy set‐up for irrigation of silver nitrate. All tubing and bottles are covered by dark bags or aluminium foil.

The NPWT‐instillation group data were analysed and compared to a retrospective control group of 15 adult patients with complex, infected wounds who received standard wet‐to‐moist dressings and weekly wound consults at Loma Linda University Medical Center during the 2004–2005 calendar years. Control patient records were chosen by random selection and consecutively logged into the control group if they met appropriate inclusion criteria. A retrospective control group was used because of limited patient availability and length of time of follow‐up required for wet‐to‐moist wound treatment. In addition, the management of these wounds in our hands has changed because of the positive outcomes that were seen; therefore the treatment of the infected wounds with the conventional therapy would be considered now to be below the level of standard of care. The same demographic and treatment outcome data were recorded for this retrospective control group as were for the NPWT‐instillation group (Table 3).

Table 3.

Data for moist wound‐healing control group

Patient Age (years) Diagnosis Wound area* (cm2) Initial culture Days of wet‐to‐moist treatment Days to infection clearance Days to wound closure Method of wound closure Days to patient discharge
1 56 Stage IV sacral pressure ulcer 150 Staphylococcus, Enterococcus 56 Not cleared Not closed Secondary intention 56
2 62 Stage IV sacral pressure ulcer 250 Staphylococcus, Enterococcus 34 Not cleared Not closed Secondary intention 34
3 48 Necrotising fasciitis of chest and upper extremity 400 Staphylococcus, Enterococcus 28 22 28 Skin graft 30
4 81 Stage IV sacral pressure ulcer 75 VRE, MRSA 45 Not cleared Not closed Secondary intention 45
5 49 Open knee joint with exposed hardware 75 MRSA 35 28 30 Local flap 35
6 51 Open knee joint with exposed hardware 45 Staphylococcus, Enterococcus 20 18 24 Local flap 26
7 49 Abdominal necrotising fasciitis 350 Enterococcus, MRSA 34 30 34 Primary closure/Skin graft 36
8 60 Open tibial wound with exposed hardware 50 MRSA 40 35 40 Local flap 45
9 50 Necrotising fasciitis of chest and upper extremity 250 MRSA 22 18 22 Skin graft 25
10 75 Stage IV sacral pressure ulcer 100 VRE, MRSA 50 Not cleared Not closed Secondary intention 55
11 64 Open tibial wound with exposed hardware 50 MRSA 28 25 28 Local flap 32
12 52 Necrotising fasciitis of chest and upper extremity 350 Enterococcus, MRSA 21 18 21 Primary closure/Skin graft 26
13 59 Open knee joint with exposed hardware 100 Enterococcus 39 35 39 Local flap 43
14 63 Open tibial wound with exposed hardware 100 Staphylococcus, Enterococcus 30 25 30 Local flap/Skin graft 35
15 72 Stage IV sacral pressure ulcer 250 Enterococcus 65 Not cleared Not closed Secondary intention 65
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MRSA, methicillin‐resistant Staphylococcus aureus; VRE; vancomycin‐resistant infections.

*

Post‐debridement.

The primary endpoints of the study were total number of days treated, days to wound closure and days to patient discharge (1, 3). Categorical variables are expressed as percentages and continuous variables are expressed as the mean ± SD. Analysis was performed using the χ2‐test for qualitative data, two‐sample independent t‐test and Wilcoxon rank sum test for quantitative data, and Kaplan–Meier survival analysis for time‐to‐event outcomes to compare the controls to the NPWT‐instillation therapy group. SPSS 12·0 (SPSS Inc., Chicago, IL, USA) was used for data analysis. Statistical significance was defined as P < 0·05 with a two‐tailed test (4, 5, 6).

Table 4.

Treatment outcomes

Control group (n =15) NPWT‐instillation therapy group (n = 15) P‐value
Days treated* 36·47 ± 13·07 9·87 ± 4·31** <0·001
Infection cleared 66·7% 100%** 0·042
Day wound cleared of clinical infection* 25·40 ± 6·57 6·00 ± 1·46** <0·001
Wound closed 66·7% 100% 0·042
Wound closure method (%) 0·606
 Primary 13·3 13·3
 Secondary intention 33·3 26·7
 Skin graft 13·3 33·3
 Local flap 40·3 26·7
Days to wound closure* 29·60 ± 6·54 13·20 ± 6·75** <0·001
Days to patient discharge* 39·20 ± 12·07 14·67 ± 9·18** <0·001
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NPWT, negative pressure wound therapy.

*

Mean ± SD.

**

P < 0·05 compared with control group.

Table 5.

Pre‐treatment status

Control group (n =15) NPWT‐instillation therapy group (n = 15) P‐value
Age (years)* 59·40 ± 10·29 57·13 ± 11·64 0·576
Wound area (cm2)* 173·00 ± 123·73 127·33 ± 137·87 0·098
Albumin* 2·364 ± 0·325 2·350 ± 0·823 0·441
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NPWT, negative pressure wound therapy.

*

Mean ± SD.

Table 6.

Pre‐treatment history

Control group (n =15)(%) NPWT‐instillation therapy group (n = 15)(%) P‐value
Diabetes* 40 53·3 0·715
Smoking history* 20 33·3 0·682
Staphylococcus ** 33·3 60 0·272
Enterococcus ** 60 60 1·000
VRE** 13·3 26·7 0·651
MRSA** 53·3 26·7 0·264
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NPWT, negative pressure wound therapy; MRSA, methicillin‐resistant Staphylococcus aureus; VRE; vancomycin‐resistant infections.

*

Percentage that is diabetic or have smoking history based on medical record.

**

Percentage testing positive from culture test.

Results

There were no statistically significant differences between the control and NPWT‐instillation groups with regard to age, wound area, pre‐albumin levels, diabetes history, smoking history and incidence of infection (5, 6). Patients in the NPWT‐instillation group did differ significantly from the control group with respect to treatment outcome endpoints (Table 4). Compared with controls, patients in the NPWT‐instillation group required significant fewer hospital days of wound treatment (36·5 ± 13·1 versus 9·9 ± 4·3 days, P < 0·001). The NPWT‐instillation‐treated wounds cleared of clinical infection (based on qualitative cultures) earlier (25·4 ± 6·6 versus 6·0 ± 1·5 days, P < 0·001), were closed earlier (29·6 ± 6·5 versus 13·2 ± 6·8 days, P < 0·001) and were discharged earlier (39·2 ± 12·1 versus 14·7 ± 9·2 days, P < 0·001). The Kaplan–Meier survival analysis confirmed highly significant (P < 0·001) shorter duration of treatment for the NPWT‐instillation group compared with the control group for wound clearance of clinical infection, wound closure, treatment and discharge (Figure 2).

Figure 2.

Figure 2

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Kaplan–Meier survival graphs showing proportion of patients over time for days to wound infection clearance (A), days to wound closure (B), days of treatment (C) and days to discharge (D). The negative pressure wound therapy (NPWT) installation therapy group had highly significantly (P < 0·001) less time to endpoint compared with the control therapy group.

A regression analysis comparing the association between wound infection clearance and wound closure is shown in Figure 3. The best‐fit line equation yielded a strong linear relationship between infection clearance and days to wound closure showed by the high R 2‐value of 0·96 for the control group. As the NPWT‐instillation wounds cleared of infection within a relatively short time span (6·0 ± 1·5 days), an association was difficult to find among these patients and the best‐fit line equation yielded a weaker association as indicated by the R 2‐value of 0·60. The equation y = 0·9748x + 4·8409 where y is ‘days to wound closure’ and x is ‘days to wound infection clearance’ may provide a useful guide to predicting length of treatment necessary for infection clearance using standard wet‐to‐moist wound treatment.

Figure 3.

Figure 3

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Regression analysis of ‘days to wound infection clearance’ and ‘days to wound closure’. The regression line is significant (P < 0·001) for predicting rate of wound closure for the control therapy group. NPWT, negative pressure wound therapy.

In the NPWT‐instillation group, all 15 wounds cleared the bacteria bioburden, versus 10 of 15 for the control group. The reason these five control wounds remained colonised throughout care is unknown and the patients have since been lost to follow‐up. Eleven of the 15 NPWT‐instillation‐treated wounds progressed to the point where they could be surgically closed; two of these cases are described in 4, 5. Four wounds were left open to be closed by secondary intention. In the control group, 9 of the 15 wounds progressed to the point of surgical closure and 6 were left to be closed by secondary intention.

Figure 4.

Figure 4

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Case 1. An 84‐year‐old male with abdominal necrotising fasciitis (A). The necrotic tissue was resolved in 24 hours and negative pressure wound therapy instillation was initiated on day 2 with normal saline solution for irrigation. Following confirmation of positive cultures, silver nitrate irrigation was started. On day 5, healthy granulation tissue was present and the wound was noticeably contracted (B). On day 14 (C), the patient was taken to the operating room and the wound was primarily closed. The patient was discharged back to his nursing home facility on day 17 with a closed wound (D).

Figure 5.

Figure 5

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Case 2. A 65‐year‐old male with infected open right knee joint with exposed hardware (A). Infection present for 3 months following an open reduction with internal fixation procedure. Negative pressure wound therapy instillation was initiated (B) with normal saline irrigation, and followed on day 3 with silver nitrate irrigation. By day 5, the wound culture returned negative, and the knee was closed via local flap on day 10. (C) illustrates the granulating knee the day it was closed and (D) shows the knee closed and viable at 6‐month follow‐up.

Discussion

The goal of treating any type of wound is to create an environment that is conducive to normal and timely healing. To achieve this goal, one first has to address and evaluate the underlying issue (disease) to optimise healing. Secondly, most wounds require some form of debridement, if appropriate. Debriding an acute wound enables it to go through the normal wound‐healing phases, assuming that systemic and local factors are functioning normally (35). However, aggressively debriding a chronic wound helps convert it into an acute wound, so that it can progress through the normal phases of wound healing.

The goal of surgical debridement is to excise the wound until only normal, soft and well‐vascularised tissue remains. Frequent debridements regularly remove inhibitors of wound healing (metalloproteases, including the collagenases matrix metalloproteinase 1 and 8 and elastases) and allow growth factors to function more effectively 36, 37, 38. The importance of removing the local inhibitory wound‐healing factors is also one of the factors by which negative pressure wound therapy can successfully convert chronic wounds to healthy healing wounds 14, 15.

Whether debridement is with non surgical modalities [maggots (Phaenicia sericata), enzymatic] or surgical, it is defined as removing necrotic tissue, foreign material and bacteria from an acute or chronic wound. This environment impedes the body’s attempt to heal and allows bacteria to proliferate. The development of an infected wound is an ‘exponential progression’ that starts with sterility, followed by contamination, colonisation, critical colonisation and infection. All stages are linked and if attempts are not made to stop the progression at any level, bacteria will continue to replicate and produce a polymeric matrix (glycocalyx), which is adherent to any inert or living surface, and allows bacteria to live in an otherwise hostile environment (39). This biofilm is resistant to topical and systemic antibacterials unless it is violated by debridement modality.

NPWT instillation was introduced to the United States acute care market in 2004 as an evolutionary product to standard NPWT. It combines the mechanisms of action of standard NPWT with timed, intermittent delivery of an instilled topical solution.

From our initial experience with NPWT instillation, we have found the addition of an instilled irrigating fluid to NPWT provides a unique autolytic and mechanical debridement effect that appears to enhance wound healing over our traditional standard of care for these complex, infected wounds. We have found it to be efficacious in treating wounds with high levels of exudate and slough content. At our hospital, NPWT instillation has also played a crucial role in treating wounds that benefit from continuous hydro‐debridement, such as in acute traumatic wounds or acutely debrided wounds because of infected hardware or soft tissue. The hydro‐debridement plays an important role in inhibiting glycocalyx formation and therefore decreasing the biofilm in these open wounds.

NPWT instillation actively removes exudate and microscopic debris to an extent that we have not experienced with other wound‐care modalities. Wolvos determined that the addition of instilled solutions appears to enhance viscosity of the wound fluid, which allows more efficient removal into the canister (40). It should be noted that NPWT instillation is a low‐pressure delivery system for wound irrigation. Wounds with significant debris and bacterial contamination can be irrigated when needed at higher pressures (fluid delivered at 0·6–0·8 kg cm−2 psi such as with a 35‐ml syringe and a 19‐gauge angiocatheter) during dressing changes 41, 42.

Once the wound exudate and slough levels are controlled and minimised, the therapy can be switched to either granufoam or granufoam silver, depending on the need for antimicrobial delivery.

An initial paper describing the combined effect of NPWT and instillation of antiseptics or antibiotics was published by Fleischmann et al. in 1998 (43). Fleischmann is generally credited for pioneering the NPWT‐instillation technique in orthopaedic medicine. Among the 27 patients with acute infections of bone and soft tissues, chronic osteomyelitis or chronic wounds treated with NPWT instillation, the authors found only one instance of recurrence of infection in a patient with chronic osteomyelitis in 3–14 months of follow‐up 43, 44.

Two additional case series describing NPWT instillation and its uses have been previously published. Wolvos describes his experiences with NPWT instillation through a retrospective analysis of five cases (41). Wolvos used NPWT instillation to simultaneously provide pain control and treat grossly contaminated and infected wounds. He reported favourable outcomes in infection and pain control through topical intermittent instillation of a diluted lidocaine solution mixed with antibiotic solutions (41).

Bernstein and Tam published a case series of five diabetic foot wounds that were treated with NPWT instillation (45). The authors compared the use of NPWT instillation to standard NPWT and other historical delivery methods of local antibiotics in post‐surgical wounds and found a reduced length of stay with NPWT instillation. Based on the authors’ initial experience, NPWT instillation was recommended in cases of diffuse or extensively treated osteomyelitis, large areas of post‐debrided exposed bone or joint and where standard NPWT cannot be tolerated because of pain that may be heightened during dressing changes. Bernstein and Tam also recommend NPWT instillation in cases of critical bacterial colonisation levels and as an alternative to antibiotic‐impregnated beads when needed (45).

In the three cases of necrotising fasciitis and systemic infection, intravenous antibiotics were administered to treat the invasive infection. In these situations, literature supports that topical agents alone are not sufficient to reduce infection and culture‐specific systemic antibiotics should be prescribed (46). In each of these three cases, intravenous antibiotics were administered for 1 week and then discontinued for the remainder of therapy. In our experience, systemic antibiotics were not necessary once the local soft tissue was surgically controlled and treated with continuous topical irrigation. In the remaining 12 of 15 NPWT‐instillation patients, we were able to reduce the bacterial bioburden and expedite wound closure through continuous topical irrigation with silver nitrate and without the need for systemic antibiotics.

Historical control patients were used in this study to ensure sufficient medical record data with all patients receiving standard moist wound‐care therapy. Prior to conducting this study, it was determined that at least 15 patients needed to be enrolled into each study group to ensure reasonable statistical power and representation of both groups. This was based on power and sample size calculations using pilot study results of treatment outcomes with α= 0·05 and β= 0·80. Standard moist wound‐care therapy was the treatment for the control group per historical patient treatment at our facility. As the positive outcomes with the antimicrobial installation and VAC therapy, we did not feel that it was appropriate to enrol patients in the conventional wet‐to‐moist dressing changes group, as it is considered for us to be inferior to the current standard of care at our facility.

The resurgence of interest in silver products for wound care stems from the increase in the level of bacterial resistance to traditional antibiotics. For example, rates of methicillin‐resistant Staphylococcus aureus (MRSA) increased steadily over the past decade from about 30% in 1989 to approximately 40% in 1997 among intensive care units (ICU) patients (47). Unlike traditional antibiotics, ionic silver has multiple mechanisms of action, such as inhibiting cellular respiration, denaturing nucleic acids and altering cellular membrane permeability 48, 49. An adequate concentration of silver coupled with its various mechanisms of action make it difficult for micro‐organisms to develop resistance because they would have to undergo several mutations to develop defence mechanisms against silver‘s multi‐pronged attack (46).

Silver nitrate has long been a choice as a topical antimicrobial based on clinical studies that substantiate its merits in treating wounds 50, 51, 52, 53. Silver is a broad‐spectrum antimicrobial with claims for efficacy in the elimination of Gram‐positive and Gram‐negative bacteria, yeasts/fungi, MRSA and vancomycin‐resistant infections (VRE) (46). In this NPWT‐instillation patient study, silver nitrate was effective in clearing all cases of MRSA (n = 4) and VRE (n = 4) within 10 days.

The silver nitrate irrigation fluid used in this study was purchased in a 0·5% ready‐made solution (1·25 g per 250 cm3 of water). On purchasing the solution, it was transferred to a dry evacuation container for storage. Because of silver nitrate’s sensitivity to light, all the tubing, including the tubing that connects directly into the foam dressing, and bottles were covered by dark bags or aluminium foil, with bags being the quickest and easiest method of coverage (Figure 1C). The irrigating bag of silver nitrate was changed every other day with each dressing change to minimise any effects of light exposure.

Silver nitrate is contraindicated for those with a silver allergy or hypersensitivity to silver. Leucopenia, bone marrow toxicity and renal or hepatic damage through silver deposition are other complications reported from the use of silver nitrate, but they are rare and probably of marginal significance (54). As silver nitrate can stain bedding and devices, the NPWT‐instillation device should be at least 5 minutes into the negative pressure cycle so as to remove all free‐floating silver nitrate fluid from the tubing before removing dressing. Once the silver nitrate is pulled through the dressing tubing and the clamp is closed, leaking is minimised.

Application of topical antibiotics and antiseptics to wounds continues to be a controversial subject in wound care. The strongest argument against the topical use of antimicrobial agents, such as nanocrystalline silver and silver nitrate on wounds is that they have been found, by primarily using in vitro models, to be cytotoxic to cells essential to the wound‐healing process, such as fibroblasts, keratinocytes and leucocytes 55, 56. As in vitro results are not always predictive of what may happen in vivo, numerous studies have been conducted on animal and human models. Drosou et al. (2) performed a literature review of relevant animal studies and clinical trials examining the effects of commonly used topical antibiotics and found despite cytotoxicity data, in most of clinical trials 50, 57, 58 topical antibiotics appeared to be safe and were not found to negatively influence wound healing.

Wright et al. noted a higher frequency of apoptosis and reduced levels of matrix metalloproteinase in a porcine model of contaminated wounds treated with silver (59). The results suggest that silver may help to alter or compress the inflammatory events in wounds, thus facilitating the early phases of wound healing (59). Differing effects of silver seen in the lab versus clinical practice may best be explained by the organic and inorganic materials in wound fluid that bind ionic silver and render it inactive. This level of reactivity cannot be duplicated in vitro, which typically results in a higher concentration of silver that can be cytotoxic to viable cells in vitro (54).

In our practice, we have historically observed favourable results in wound healing with the use of silver nitrate. For this study, we did not quantitatively measure cytotoxity levels of silver nitrate for any of these wounds. However, we observed anecdotally that the net effect of the silver nitrate had a positive effect on wound healing. In each of the 15 NPWT‐instillation cases, we continued with the silver nitrate instillation past the point of bacterial bioburden clearance because of consistently observed progression towards closure with each dressing change.

The silver nitrate appeared to provide an effective barrier against further bacterial penetration (60). There were no incidences of recurrent infection or odour during dressing changes for any of the patients throughout the length of therapy. Additionally, we noted an even distribution of silver effect to the entire wound surface at each dressing change, which, we suspect, is because of the dressing’s conformance to the contours of the wound. There was noticeable odour reduction as well as decreased pain with dressing changes. Clearly other antiseptics can also be used; however, our clinical experience with silver with its polymicrobial coverage has been successful. In addition, this is also a solution that is cleared by the Food and Drug Administration for topical instillation.

Because of the significantly shorter wound closure rates observed for the NPWT‐instillation group, we hypothesised that the combined effect of silver nitrate and NPWT in reducing bacterial bioburden had a correlated effect on the rate of wound closure. To test this probable correlation, we conducted a regression analysis. An equation was fit to the number of ‘days to wound infection clearance’ and the ‘days to wound closure’ summarised by the model y = 0·9748x + 4·8409 where y is the ‘days to wound closure’ and x is ‘days to wound infection clearance’.

The results showed a statistically significant association between decrease of bacterial bioburden and wound closure for the control group. The association was very strong (R 2= 0·96 and P < 0·001) and suggests that approximately 96% of the variation in the time to wound closure can be explained by the time it takes for wound infection to clear. The P‐value indicates that the day infection was cleared is a highly significant predictor of days to wound closure. As the NPWT‐instillation therapy wounds decreased of bacterial bioburden within a relatively short time span (6·0 ± 1·5 days), an association was difficult to evaluate within the NPWT‐instillation group and the equation yielded a weaker association as indicated by the R 2‐value of 0·60. The results of both relationships are shown in Figure 5.

The high costs of treating infections are primarily driven by antibiotic treatment costs, patient care and prolonged hospital stays, including time spent in ICUs. It has been reported that patients with a surgical site infection have a 2·2‐fold increased risk of dying, a 60% increased risk of being admitted to an ICU and a twofold increased hospital length of stay compared with uninfected patients (61).

In this pilot study, the mean number of days of wound treatment for the control group was 36·5 days versus 9·9 days for the NPWT‐instillation group, yielding a total difference in wound treatment time of 26·6 days between the two groups. Most wound‐care patients of both groups were treated in the medical surgical ward. The high correlation between the decrease in bioburden and wound closure and the significant difference in treatment endpoints may indicate overall cost reduction for the NPWT‐instillation group versus the control group.

Conclusion

The use of VAC therapy with silver instillation has changed the management of complicated infected or colonised wounds and has become the standard of care at our facility. It has enabled surgeons to perform less complex reconstructive procedures for major soft tissue defects and it saves donor site morbidity and decreases anaesthesia time. Patzakis et al. and Patzakis and Zalavras have shown that only 18% of infections after open fractures are caused by an organism initially cultured from the traumatic wound, suggesting that many of the infections after open fractures are nosocomial acquired, making the broad‐spectrum treatment of these wounds in even more crucial 62, 63. Although early coverage is important, at times this is not possible because of the severe oedema, an unstable patient or indistinct zone of injury of the extremity. Therefore temporising wounds with VAC therapy and supplying the broad‐spectrum antimicrobial instillation (silver nitrate) is an optimal bridge to final closure.

In this pilot study, NPWT instillation showed a significant decrease in the mean time to bioburden reduction and wound closure, compared with traditional wet‐to‐moist wound care. Outcomes from this study analysis suggest that the use of NPWT instillation may result in overall cost savings and decreased in‐patient care requirements for these complex, infected wounds. We believe patient tolerance and compliance with the therapy is enhanced with the decreased time to closure and sooner hospital discharge. The improved outcomes also affect indirect costs such as loss of work days, recovery time and mortality. However, this study has all the limitations of a retrospective study and caution should be used in the interpretation of the data. Additional studies with larger patient samples are needed to further substantiate the results of this novel wound treatment therapy.

Acknowledgements

The authors wish to thank Karen Beach, BS, for her editorial assistance (funded by KCI). Financial disclosures: Subhas Gupta, MD, PhD, FRCSC, FACS no financial interests or commercial associations; Allen Gabriel, MD is a member of the speakers bureau and clinical advisory panel of Kinetic Concepts, Inc.; the remaining authors have no financial interests or commercial associations.

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