Research Article
Culture Results at Pancreatic Necrosectomy: The Microbiology of Infected Pancreatic Necrosis
Charles Coventry1*, Pranavan Palamuthusingam1, Eu Ling Neo1 and Venkat Vanageti2
1Department of Surgery, Royal Adelaide Hospital, Australia
2Senior Research Officer, James Cook University, Australia
*Corresponding author: Charles Coventry, Department of Surgery, Royal Adelaide Hospital, Hepatobiliary Unit, Royal Adelaide Hospital, North Tce., Adelaide SA 5000, Australia
Published: 31 Mar, 2017
Cite this article as: Coventry C, Palamuthusingam P,
Neo EL, Vanageti V. Culture Results
at Pancreatic Necrosectomy: The
Microbiology of Infected Pancreatic
Necrosis. Clin Surg. 2017; 2: 1396.
Abstract
Introduction: Necrotizing pancreatitis occurs in 5-10% of patients with acute pancreatitis. Infected
pancreatic necrosis (IPN) is a feared complication. Historically, causative organisms were Gramnegative
bacteria, but recent international studies now report a predominance of Gram-positive
bacteria. Not all the literature is consistent, and there may be regional variation. There is very limited
Australian data. This study aims to report causative organisms in IPN in the Australian setting.
Materials and Methods: Retrospective medical record review of all patients who underwent
pancreatic necrosectomy at a single centre (tertiary referral center in Adelaide, South Australia)
between January 2005 and December 2015. Intraoperative culture specimens were reviewed and the
Gram-status and antimicrobial sensitivities noted.
Discussion and Results: A total of 1296 patients were admitted for acute pancreatitis in the study
period. 28 patients underwent pancreatic necrosectomy. Mean age 55.71 years (range 30-79),
including twenty males and eight females. All patients had intraoperative cultures taken. 20 cultures
demonstrated growth. There were 12 Gram-negative isolates (34.3%), 20 Gram-positive isolates
(57.1%) and three fungal isolates (8.6%). Two bacterial isolates were antibiotic resistant organisms
(one MRSA and one VRE).
Conclusion: The findings were consistent with the majority of recent international studies
demonstrating a predominance of Gram-positive organisms.
Keywords: Infected pancreatic necrosis; Pancreatic necrosectomy; Necrotizing pancreatitis
Introduction
Necrotizing pancreatitis occurs in approximately 5-10% of patients with acute pancreatitis [1].
It is frequently diagnosed by lack of enhancement of pancreatic parenchyma on contrast computed
tomography (CT) scan of the abdomen. Although the necrosum is often initially sterile, a feared
complication of necrotizing pancreatitis is infected pancreatic necrosis (IPN), which has an
associated mortality rate of around 30% [2]. According to the revised Atlanta criteria, diagnosis of
IPN is suggested radiologically by the presence of gas locules within an acute necrotic collection or
walled-off necrosis on an abdominal CT scan [1]. Alternatively, diagnosis may be made by a positive
culture obtained through aspiration, percutaneous drainage or at operation [1].
Historically, cultures most frequently demonstrated Gram-negative organisms [3,4]. However,
since the early 1990’s, multiple studies have demonstrated a shift towards a predominance of Grampositive
organisms [3,5,6]. This shift coincided with the rise in popularity of prophylactic antibiotics
[3], but appears to have persisted even after prophylactic antibiotics have been dropped from
treatment recommendations in the wake of evidence that their use does not reduce the incidence
of infective complications in necrotizing pancreatitis [7]. A recent increase in the prevalence of antibiotic resistant organisms isolated in patients with IPN has also been reported [8]. Furthermore, there is a growing interest in the prevalence of fungal infection in IPN, which has been linked to
increased mortality [9].
There may be regional differences, however, as not all centers have reported these changes.
Some authors in India [10] and China [11,12] have noted a persistence of Gram-negative organisms
despite the use of prophylactic antibiotics.
To the authors’ knowledge, there have been no large studies that examine causative organisms, resistance patterns and the incidence of fungal infections in
Australasia. The aim of this study is to investigate the organisms
isolated in IPN and their antimicrobial sensitivities in the Australian
setting in order to see if the described trends in bacteriology, antibiotic
resistance and fungal infection described in other regions are present.
Materials and Methods
All patients who underwent pancreatic necrosectomy between
1st January 2005 and 31st December 2015 at a tertiary referral center
in Adelaide, South Australia were identified using theatre records
and the center’s prospective surgical inpatient audit database.
Medical records, operative notes, imaging and laboratory results
were accessed. Patient age, gender, date of first admission for acute
pancreatitis and date of operation were recorded. In addition, all
results of microscopy, culture and sensitivity testing taken at the time
of pancreatic necrosectomy were recorded and tabulated. Mortality
was defined as death during the same admission or within three
months of the date that pancreatic necrosectomy was performed.
Antibiotic resistance was defined as the growth of methicillinresistant
Staphylococcus aureus (MRSA), vancomycin-resistant
Enterococci (VRE) or extended-spectrum beta-lactamase (ESBL)
producing Gram-negatives. These organisms have been used as
measures of antibiotic resistance in previous studies looking at
microbiology in IPN [5,8,13].
Table 1
Results
A total of 1296 patients were admitted to our center with acute
pancreatitis during the study period. Of these, 28 patients underwent
operative necrosectomy for necrotizing pancreatitis. The mean age was 55.71 years (range 30-79 years). Of these, 20 were males and eight
were females. The aetiology was varied; five patients had pancreatitis
secondary to alcohol, 17 secondary to cholelithiasis and six were
idiopathic or due to miscellaneous causes. The mean time between
initial presentation with pancreatitis and operative necrosectomy
was 67.46 days (range 10-557 days, median 13.5 days). The technique
of necrosectomy also varied; 24 underwent open procedures via
a midline laparotomy or roof-top incision, two underwent videoassisted
procedures and two underwent laparoscopic procedures that
were later converted to open.
Indications for operative management were varied, and included
pancreatic necrosectomy at the time of emergency laparotomy
for peritonitis and acute clinical deterioration (six, 21.43%) and
abdominal compartment syndrome (one, 3.57%), as well as planned
pancreatic necrosectomy for symptomatic walled-off necrosis that was
not amenable to percutaneous drainage or endoscopic necrosectomy
(21, 75%).
Pre-operatively, 26 of the 28 patients received antimicrobial
agents. One patient received no antimicrobial agents prior to surgery
and one patient had incomplete medical records. The numbers of
antimicrobial agents used per patient are recorded in Table 1 and the
type of agent is recorded in Table 2. Prophylactic antibiotics are not
used in our center for the treatment of necrotizing pancreatitis.
All 28 patients had intraoperative specimens sent for microscopy,
culture and sensitivity. Of these, 20 (71.43%) produced a pathogen
and a total of 25 organisms were isolated from these cultures. These are
recorded in Table 3. Of the positive cultures, 11 were monomicrobial
(39.28%) and nine (32.14%) were polymicrobial.
Altogether, 16 of the 20 cultures (80%) grew one or more colonies
of Gram-positive organisms and nine (45%) demonstrated exclusively
Gram-positive growth. In comparison, ten (50%) of cultures grew
Gram-negative organisms and three (15%) were exclusively Gramnegative.
Seven demonstrated mixed Gram-positive and Gramnegative
growth.
There were two colonies of antibiotic resistant organisms grown
(7.14%). MRSA was isolated in one culture and VRE was isolated
in another. No ESBL-producing organisms were observed. There
were three fungal isolates across the 20 positive cultures and all were
Candida species.
Prior to operative pancreatic necrosectomy, 11 patients underwent
percutaneous drainage under radiological guidance, one underwent
endoscopic retrograde cholangiopancreatography (ERCP) and three
patients underwent endoscopic cystgastrostomy.
Four patients (14.28%) died during the same admission and
seven patients (25%) required subsequent surgical procedures (five
relook laparotomies, one revision of surgical scar and one reversal
of ileostomy). Of the patients who died, two patients had no growth
on intraoperative cultures and two had polymicrobial infections (the
first patient grew Enterococcus, Streptococcus and Candida krusei
and the second patient grew Enterococcus, Proteus mirabilis and
Candia albicans). No antibiotic resistant organisms were observed in
the cultures of the patients who died.
Table 2
Discussion
The most prevalent organisms isolated on culture of intraoperative
specimens were Gram-positive bacteria. The most common individual
organism was Enterococcus spp., followed by Escherichia coli and Staphylococcus aureus. These findings are consistent with most
international studies, which have demonstrated a predominance
of Gram-positive bacteria over the last 20 years [3,5,6,9,14], and in
particular Enterococcus [6,9,14].
Contamination of necrotic pancreatic tissue hypothetically occurs
after bacterial translocation from the gastrointestinal tract [15], most
likely from the small intestine [16]. However, there is currently
debate about whether contamination occurs hematogenously [6] or
via lymphatics [16].
The observed change in microbiology of IPN noted over the last
two decades has occurred with the rise in popularity of prophylactic
antibiotic use [3]. Recently, given evidence demonstrating the
ineffectiveness of prophylactic antibiotics in preventing infective
complications of necrotizing pancreatitis [7,17,18], many centers
(including our own) no longer use prophylactic antibiotics, opting
instead for a targeted antibiotic approach where antibiotics are
initiated upon evidence of infection [19].
It is likely that the previous practice of prophylactic antibiotics
and the current practice of targeted use of antibiotics in necrotizing
pancreatitis are at least partially responsible for the increase
in Gram-positives [3]. Furthermore, in the wake of literature
suggesting improved outcome with early enteral feeding [20], the
practice of keeping patients fasting for prolonged periods has also
been abandoned. It has been suggested the early enteral feeding
improves gut barrier function and limits bacterial translocation [21].
It is possible, therefore, that this change in practice is also partially
responsible for the change in flora noted over the last 15 years,
although data regarding early feeding was not specifically collected
in our study.
The proportion of antibiotic resistant organisms was lower than
that reported by other authors [5,8,13], with only two isolates from
two separate patients demonstrating significant antibiotic resistance
in the intraoperative specimens taken. It is difficult to say why this
has been observed, but local infection control practices and use of antibiotics in the community may play a role.
The number of fungal isolates was consistent with international
literature, with three intraoperative specimens positive for fungal
growth (8.6%). This is within the 7-14% described in other studies
[22]. Two of the three patients who grew fungal isolates on their
intraoperative cultures died during the same admission. Although
data on fungal infection in IPN and mortality is conflicting [23],
Schmidt “et al.” [9], when looking at culture results in patients who
underwent endoscopic transmural drainage and necrosectomy for
IPN, found an association between the presence of fungal isolates on
index culture and mortality.
Polymicrobial infections have associated with higher mortality
in IPN in some studies [19]. In this study, nine of the 20 positive
cultures (45%) were polymicrobial and two of these nine patients died
(compared to none of the 11 patients with monomicrobial growth on
intraoperative cultures).
There is very limited data on bacterial isolates from IPN in
Australasia at present. A study by Jacob “et al.” [22], concerning
operative management of abdominal compartment syndrome and
IPN in eleven patients with "acute pancreatitis in Alice Springs,
Northern Territory reported a total of three positive intraoperative
cultures from a total of six. Two grew both Enterococcus spp. and E.
coli and one grew E. coli alone.
Various authors have recommended the use of carbapenem or
quinolone antibiotics in IPN as these classes have been shown to
have good penetrance of pancreatic tissue [24] and are active against
both Gram-negative and Gram-positive organisms [17,19]. These
recommendations would appear to be suitable for the Australian
setting given our findings.
The major limitations of our study were that is retrospective and
that (due to the rarity of the condition), the sample size was small.
The audit database used also did not accurately record patients who
underwent percutaneous drainage or endoscopic necrosectomy
for necrotizing pancreatitis alone, without the need for operative management. Inclusion of this group of patients would potentially
have added further power. The majority of patients were administered
antimicrobial agents pre-operatively, and the type of agents used
varied widely as this study included antimicrobials initiated for
all indications (such as respiratory and urinary tract infections)
occurring anytime from admission to operative management. This
has the potential to alter the flora grown on intra-operative culture.
Furthermore, pre-operative insertion of percutaneous drains could
hypothetically also alter the organisms subsequently isolated from
intra-operative cultures.
Our study also demonstrated a high rate of open procedures. This
is partially explained by the inclusion of emergency laparotomies
for peritonitic deteriorating patients with IPN and a laparotomy for
abdominal compartment syndrome.
Our findings indicate that the shift in the type organisms isolated
in patients with IPN in Australia is consistent with the changes
observed internationally in the last two decades. This is the first
study of its kind regarding patients in Australasia that the authors are
aware of and helps to demonstrate that recommendations regarding
the treatment of patients with IPN (in particular recommendations
regarding antimicrobial usage) are likely to be applicable to the
Australasian setting also. Confirmation of these findings across other
centers in the region would be useful.
Table 3
Conclusion
There has been an internationally-observed change in the type of pathogens isolated from cultures in IPN over the last two decades from Gram-negative to Gram-positive organisms. Data concerning the Australian populace has been lacking, but these findings indicate that this change is consistent in Australia also. This has implications for antibiotic choice for clinicians treating patients with IPN.
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