1035
STATE-OF-THE-ART CLINICAL ARTICLE
Peritonitis: Update on Pathophysiology, Clinical Manifestations, and
Management
Caroline C. Johnson, James Baldessarre,
and Matthew E. Levison
Peritonitis results from any local trigger of inflammation.
Usually infection is the trigger, although infection may not
necessarily be present at the earliest stage. For example, sterile
peritonitis may occur in the localized peritoneal space sur-
rounding an infected but resectable intraabdominal organ, such
as the appendix or gallbladder. In contrast, there may be con-
tamination of the peritoneum from a defect in the intestinal
wall, before establishment of infection or onset of an inflam-
matory response, e.g., immediately following penetrating ab-
dominal trauma. Peritonitis has been categorized as primary,
secondary, or (more recently) tertiary. Peritonitis complicating
peritoneal dialysis can be considered as an additional category.
Each of these categories is reviewed herein, with an emphasis
on recent developments in pathogenesis, evaluation, and man-
agement.
Primary Peritonitis
Pathogenesis. Primary peritonitis is an infection of the peri-
toneal cavity not directly related to other intraabdominal abnor-
malities. The vast majority of cases are due to bacterial infec-
tion; it is also commonly known as spontaneous bacterial
peritonitis. Usually it occurs in the presence of ascites from
any of a variety of underlying conditions [1]. In the preanti-
biotic era, primary peritonitis accounted for Ç10% of all pedi-
atric abdominal emergencies; it now accounts for õ1 – 2% [2].
The decline has been attributed to widespread use of antibiotics
for minor upper respiratory tract illness.
Although primary peritonitis may occur in children without
predisposing disease, it is especially associated with post-
necrotic cirrhosis and nephrotic syndrome. In adults, primary
peritonitis develops in up to 25% of patients with alcoholic
cirrhosis but has also been reported to occur in adults with
postnecrotic cirrhosis, chronic active hepatitis, acute viral hepa-
Received 21 January 1997; revised 10 February 1997.
Reprints or correspondence: Dr. Matthew E. Levison, Division of Infectious
Diseases, Allegheny University – MCP, 3300 Henry Avenue, Philadelphia,
Pennsylvania 19129.
Clinical Infectious Diseases 1997;24:1035–47
q 1997 by The University of Chicago. All rights reserved.
1058–4838/97/2406–0001$02.00
/ 9c2f$$ju45 05-07-97 17:21:37
From the Division of Infectious Diseases, Allegheny University of the
Health Sciences, and Veterans Affairs Medical Center, Philadelphia,
Pennsylvania; and R. W. Johnson Pharmaceutical Research Institute,
Raritan, New Jersey
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titis, congestive heart failure, metastatic malignant disease, sys-
temic lupus erythematosus, and lymphedema and, rarely, in
adults with no underlying disease [3]. The presence of ascites
appears to be the common link among these various conditions.
The route of infection in primary peritonitis is usually not
apparent but is thought to be hematogenous, lymphogenous,
via transmural migration through an intact gut wall from the
intestinal lumen, or, in women, from the vagina via the fallo-
pian tubes. In cirrhotic patients the hematogenous route is most
likely. Organisms removed from circulation by the liver may
contaminate hepatic lymph and pass through the permeable
lymphatic walls into the ascitic fluid. In addition, portosystemic
shunting greatly diminishes hepatic clearance of bacteremia,
which would tend to perpetuate bacteremia and increase the
opportunity to cause metastatic infection at susceptible sites
such as the ascitic collection.
The infrequency of primary peritonitis in forms of ascites
other than that due to liver disease emphasizes the importance
of intrahepatic shunting in the pathogenesis of this disease.
The hepatic reticuloendothelial system is known to be a major
site for removal of bacteria from blood, and animal studies
have suggested that destruction of blood-borne bacteria by the
reticuloendothelial system is impaired in experimental cirrhosis
and in alcoholic liver disease. The decrease in phagocytic activ-
ity seen in alcoholic cirrhosis is proportional to the severity of
the liver disease.
Enteric bacteria may also gain access to the peritoneal cavity
by directly traversing the intact intestinal wall. In an animal
model, Escherichia coli passes from the bowel into the perito-
neal cavity after the introduction of hypertonic solutions into
the peritoneum. The infrequent occurrence of bacteremia and
the multiplicity of species in peritoneal fluid when anaerobic
bacteria are involved suggest that transmural migration of bac-
teria is the probable route of infection of ascitic fluid in most
of these patients.
In prepubertal girls, the pathogenesis of primary peritonitis
is likely related to an ascending infection of genital origin, as
suggested by the simultaneous presence of pneumococci in
vaginal secretions and peritoneal fluid. Alkaline vaginal secre-
tions that occur in this age group may be less inhibitory to
bacterial growth than the acidic secretions of postpubertal fe-
males.
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1036 Johnson, Baldessarre, and Levison
Transfallopian spread is also suggested by the development
of primary peritonitis in women with intrauterine devices. The
route of spread in women with gonococcal or chlamydial peri-
hepatitis (Fitz-Hugh – Curtis syndrome) is presumably via the
fallopian tubes and paracolic gutters to the subphrenic space,
but it may also be hematogenous.
Although tuberculous peritonitis may result from direct entry
into the peritoneal cavity of tubercle bacilli (from the lymph
nodes, intestine, or genital tract in patients with active disease
of these organs), it is more likely to be disseminated hematoge-
nously from remote foci of tuberculosis, most commonly in
the lung. Tuberculous peritonitis may become clinically evident
after the initial focus has completely healed.
Microbiology. Several decades ago, the organisms reported
to cause primary peritonitis in children were Streptococcus
pneumoniae and group A streptococci. More recently, the num-
ber of nephrotic children with streptococcal peritonitis has de-
clined, and the relative frequency of peritonitis due to gram-
negative enteric bacilli and staphylococci has increased. In
cirrhotic patients, microorganisms of enteric origin account for
Ç70% of the pathogens.
E. coli is the most frequently recovered pathogen, followed
by Klebsiella pneumoniae, S. pneumoniae, and other strepto-
coccal species, including enterococci. Staphylococcus aureus
is an unusual cause of primary peritonitis, accounting for only
2% – 4% of cases in most series, but has been noted especially
in patients with erosion of an umbilical hernia. Anaerobes and
microaerophilic organisms are infrequently reported [4]. Possi-
ble explanations include the intrinsic bacteriostatic activity of
ascites against Bacteroides species, the relatively high pO2 of
ascitic fluid, and the lack of optimal anaerobic bacteriologic
techniques used to study patients in the past. The presence
of anaerobes correlates strongly with polymicrobial infection.
Occasionally, primary peritonitis may also be caused by Neisse-
ria gonorrhoeae, Chlamydia trachomatis, Mycobacterium tu-
berculosis, or Coccidioides immitis.
Patients who have positive cultures of ascitic fluid with few
leukocytes and no clinical signs of peritonitis are considered
to have bacterascites. This may represent early colonization
before a host response. Mortality among patients with a low
leukocyte response is the same as among those with a greater
response. Conversely, several series have identified cases of
primary peritonitis with negative ascitic fluid cultures, termed
culture-negative neutrocytic ascites [5]. Blood cultures are pos-
itive for one-third of these patients. The frequency of negative
results of ascitic fluid cultures may be decreased by inoculating
blood culture bottles with ascitic fluid at the bedside.
Clinical presentation and evaluation. In children, primary
peritonitis is an acute febrile illness often confused with acute
appendicitis. Fever, abdominal pain, nausea, vomiting, and di-
arrhea usually occur, with diffuse abdominal tenderness, re-
bound tenderness, and hypoactive or absent bowel sounds. In
cirrhotic patients with primary peritonitis, the clinical manifes-
tations may be atypical. Onset may be insidious, with no find-
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CID 1997;24 (June)
ings of peritoneal irritation. Fever (temperature of ú1007F) is
the most common presenting sign, occurring in 50% – 80% of
cases and even in the absence of abdominal signs or symptoms.
Primary peritonitis should always be considered in the differen-
tial diagnosis of decompensation of previously stable chronic
liver disease, especially hepatic encephalopathy.
Primary tuberculous peritonitis usually is gradual in onset,
causing fever, weight loss, malaise, night sweats, and abdomi-
nal distension. The abdomen may not be rigid and is often
characterized as being ‘‘doughy’’ on palpation. The findings
at surgery or laparoscopy consist of multiple nodules scattered
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over the peritoneal surface and omentum. Adhesions and a
variable amount of peritoneal fluid are usually present. Simi-
larly, C. immitis can cause a granulomatous peritonitis with
variable clinical manifestations.
Although the diagnosis of primary peritonitis can be estab-
lished with certainty only after thorough laparotomy to exclude
a primary intraabdominal site of infection, it can usually be
surmised from examination of the peritoneal fluid. Fluid ob-
tained at paracentesis should be analyzed for cell count, differ-
ential count, and protein concentration, and a gram stain and
culture should be performed. Specimens for culture should be
sent in an airless, capped syringe or injected directly into aero-
bic and anaerobic broth culture media; volumes of §10 mL
will increase the yield of cultures [6].
A gram stain of the sediment is diagnostic when positive
but is more commonly negative. Bacteremia occurs in up to
75% of patients with primary peritonitis due to aerobic bacteria,
but it is rare in those with peritonitis due to anaerobes. Usually
the same organisms isolated from the peritoneal fluid are recov-
ered from the blood.
The ascitic fluid protein concentration may be low in primary
peritonitis (õ3.5 g/L) because of hypoalbuminemia and dilu-
tion of ascitic fluid with transudate from the portal system.
The leukocyte count in peritoneal fluid usually is ú300/mm3
(ú1,000/mm3 in 85%), with granulocytes predominating in
ú80% of cases. However, the total leukocyte count of some
patients with ascites uncomplicated by infection may be simi-
larly elevated. Indeed, an increase in ascitic leukocyte counts
has been noted during diuresis in patients with chronic liver
disease.
Other parameters of ascitic fluid that may help in diagnosing
primary bacterial peritonitis are pH and lactate concentration
[7]. An ascitic fluid pH of õ7.35 and a lactate concentration of
ú25 mg/dL are more specific but less sensitive than a leukocyte
count of ú500/mm3 for diagnostic purposes; using all three
parameters together increases the diagnostic accuracy.
In patients with negative ascitic fluid cultures, endoscopic
or laparoscopic peritoneal examination and biopsy may be nec-
essary. Peritonitis secondary to other intraabdominal causes
should be excluded, and specimens appropriate for fungal and
mycobacteriologic cultures should be obtained. In children, if
gram-negative organisms, a mixed flora, or no organisms are
obtained from peritoneal fluid, full exploratory laparotomy is
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CID 1997;24 (June) Peritonitis Update
generally indicated to rule out possible intraabdominal sources
of continuing peritoneal contamination. However, in end-stage
cirrhotic patients, exploratory laparotomy may be life-threaten-
ing, and the likelihood of finding a primary intraabdominal
focus may be small.
Surgery for these patients can be deferred while the response
to antimicrobial therapy is awaited. Patients with primary peri-
tonitis usually respond within 48 hours to appropriate antimi-
crobial therapy. The observation of an exponential rate of de-
cline in the number of ascitic fluid leukocytes after initiation
of antimicrobial therapy for primary peritonitis has been found
to help differentiate primary from secondary bacterial peritoni-
tis [8].
In patients with a subacute or chronic course of primary
peritonitis, other pathogens must be considered, including
M. tuberculosis or C. immitis. The diagnosis of tuberculous
peritonitis can usually be made at operation or laparoscopy and
confirmed by the histologic characteristics of the peritoneal
biopsy specimen and bacteriologic examination of the perito-
neal biopsy specimen and fluid. The diagnosis of C. immitis
peritonitis can be made with a wet mount of ascitic fluid, by
finding the organism in culture, or on histologic examination.
Management and prevention. Because the gram stain is fre-
quently negative in primary bacterial peritonitis, the initial
choice of antimicrobial drug is often empirical, based on the
most likely pathogens. Some of the third-generation cephalo-
sporin antibiotics have been demonstrated to be as efficacious
as the combination of ampicillin plus an aminoglycoside in
primary bacterial peritonitis. They also eliminate the risk of
nephrotoxicity, which is sufficiently frequent in this group of
patients to warrant avoidance of aminoglycosides if an equally
effective alternative antimicrobial regimen can be used.
Other antimicrobial agents such as the broad-spectrum penicil-
lins (e.g., mezlocillin, ticarcillin, and piperacillin), carbapenems
(e.g., imipenem), and b-lactam antibiotic/b-lactamase-inhibitor
combinations (e.g., ticarcillin-clavulanate and ampicillin-sulbac-
tam) are potential alternatives. If peritonitis develops during
hospitalization, the therapeutic regimen, such as administration
of an aminoglycoside antibiotic and an antipseudomonal penicil-
lin or cephalosporin in combination, should also be active against
Pseudomonas aeruginosa.
For those situations in which the gram stain is suggestive of
a Bacteroides species or polymicrobial peritonitis is evident,
antimicrobials with activity against the Bacteroides fragilis
group and other anaerobic organisms should be added (e.g.,
metronidazole, clindamycin). The antimicrobial regimen can
be modified once the results of the culture and susceptibility
tests are available.
In those cases where there is a strong clinical suspicion of
primary bacterial peritonitis but all cultures are sterile, anti-
microbial therapy should be continued. Clinical improvement,
together with a significant decline in the ascitic fluid leukocyte
count, should occur after 24 – 48 hours of antimicrobial therapy
if the diagnosis is correct; failure to respond should prompt an
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1037
examination for additional pathological conditions. Antimicro-
bial therapy is usually continued for 10 – 14 days if improve-
ment is noted, but short-course therapy for 5 days has been
shown to be as efficacious as the longer course in some patients.
Administration of intraperitoneal antimicrobials is not neces-
sary.
Treatment of primary peritonitis is successful in more than
one-half of cirrhotic patients, but because of the underlying
liver condition, the overall mortality has been reported as high
as 95% in some series. Those patients with the poorest progno-
sis were found to have renal insufficiency, hypothermia, hyper-
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bilirubinemia, and hypoalbuminemia [9].
Treatment of peritonitis caused by gram-positive organisms,
as well as of early infections, has been more frequently success-
ful than treatment of gram-negative or late infections. In ne-
phrotic patients with gram-positive infections or in patients
who do not have a preterminal underlying illness, the survival
rate is ú90%.
Given the common occurrence and high mortality of primary
peritonitis in the setting of cirrhosis with ascites, prevention is
a desirable strategy. This is particularly true for patients who
are awaiting liver transplantation. Selective decontamination
of the gut with oral norfloxacin (400 mg daily) has been shown
to reduce the incidence of spontaneous bacterial peritonitis.
Norfloxacin has the disadvantage of selecting for gram-positive
organisms, including S. aureus, and quinolone-resistant gram-
negative organisms. More recently, trimethoprim-sulfamethox-
azole (double-strength, given once daily for 5 days each week)
has been shown to reduce the incidence of peritonitis and be
well tolerated [10]. A survival-rate advantage has not been
demonstrated for any of these preventive regimens.
Secondary and Tertiary Peritonitis
Pathogenesis. Secondary intraabdominal infection usually is
due to spillage of gastrointestinal or genitourinary microorgan-
isms into the peritoneal space as a result of loss of integrity of
the mucosal barrier. Examples include appendicitis, diverticuli-
tis, cholecystitis, penetrating wound of the bowel, and perfora-
tion of a gastric or duodenal ulcer. Secondary infection is rela-
tively common, taking the form of either generalized peritonitis
or localized abscesses. Abscesses may be restricted to the im-
mediate peritoneal space around a diseased intraabdominal or-
gan, such as pericholecystic, periappendiceal, or peridiverticu-
lar abscesses, or to certain peritoneal recesses, such as
interloop, subdiaphragmatic, subhepatic, lesser sac, or pelvic
abscesses.
Peritoneal signs suggestive of appendicitis in immunocom-
promised patients, e.g., patients with AIDS, organ transplant
recipients, and those receiving chemotherapy or corticosteroids
for neoplasms (especially myelosuppressive drugs), may be due
to typhlitis, an inflammation of the cecum [11]. Cecal ulceration
in these patients may progress to perforation and secondary
peritonitis with colonic flora. Perforation complicating penetrat-
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1038 Johnson, Baldessarre, and Levison
ing cytomegalovirus enterocolitis has been described as a com-
mon cause of acute abdomen in patients with AIDS [12].
Tertiary peritonitis has been conceived as a later stage in
the disease, when clinical peritonitis and systemic signs of
sepsis (e.g., fever, tachycardia, tachypnea, hypotension,
elevated cardiac index, low systemic vascular resistance, leuko-
penia or leukocytosis, and multiorgan failure) persist after treat-
ment for secondary peritonitis and either no organisms or low-
virulence pathogens, such as enterococci and fungi, are isolated
from the peritoneal exudate. These organisms may gain access
to the peritoneal cavity by contamination during operative in-
terventions, by selection from the initial polymicrobial perito-
neal inoculum by antibiotic therapy, or by translocation of
bowel flora. Translocation may be promoted by intestinal isch-
emia, endotoxemia, malnutrition, or proliferation of resistant
bowel flora by antibiotic pressure.
The cytokine response in peritonitis has been the subject of
a recent excellent review [13]. Undoubtedly, many of the sys-
temic as well as abdominal manifestations of peritonitis are
mediated by cytokines, such as TNF, IL-1, IL-6, IFN-g, and
others. Cytokines appear in the systemic circulation of patients
with peritonitis and to a much greater extent in the peritoneal
exudate [14]. These cytokines are produced by macrophages
and other host cells in response to bacteria or bacterial products,
such as endotoxin [15], or by tissues traumatized during the
operative procedure [16]. Another potential source is direct
translocation of cytokines through the intestinal barrier.
Cytokine responses have been studied in the peritoneal exu-
date in experimental animal models of peritonitis [17 – 20], in
patients with spontaneous bacterial peritonitis [21, 22], in pa-
tients undergoing continuous ambulatory peritoneal dialysis
(CAPD) [23 – 25], and in patients with severe secondary bacte-
rial peritonitis who were undergoing planned relaparotomy
[14]. Antibodies to TNF have been found to fail to protect
against death [26] and failed to reduce serum levels of IL-1
and IL-6 in an experimental model of peritonitis [17, 20, 27].
In contrast, antibodies to endotoxin were found to prevent death
in this model, as well as to reduce bacterial numbers in the
peritoneal exudate [28]. Antibodies to IFN-g also afforded a
protective effect both in this model of experimental peritonitis
and following intravenous injection of endotoxin [29].
Microbiology. With gastrointestinal perforation as the pre-
cipitating event, the number and types of microorganisms iso-
lated from the peritoneal cavity depend on the level of the
perforation. The stomach in the fasting state contains a sparse
microflora of a few relatively more acid-resistant species, e.g.,
lactobacilli or Candida species. Similarly, the duodenum and
proximal small bowel contain a sparse microflora in the fasting
state, whereas the colon contains a high microbial density, i.e.,
about 1012/g, of which ú99.9% are obligate anaerobes, mainly
of the B. fragilis group.
E. coli, the predominant colonic facultative anaerobe, is
found at counts of 106 – 8/g, while enterococci are less numerous
at counts of 104 – 6/g. The characteristic microflora, however,
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CID 1997;24 (June)
can undergo alteration as a result of the primary disease process
or previous antimicrobial therapy. For example, diseases of the
stomach that result in obstruction, the loss of gastric acidity
(e.g., bleeding, gastric ulcer, or carcinoma), or use of acid-
reducing drugs may cause gastric colonization with oral anaer-
obes, such as non-fragilis Bacteroides and Fusobacterium
species and other oropharyngeal organisms, e.g., viridans strep-
tococci, microaerophilic streptococci, Candida species, and
lactobacilli.
Gastric perforation is associated with either sterile chemical
peritonitis or peritonitis due to the above-mentioned pathogens,
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depending on the underlying gastric condition. Similarly, the
normal sparse flora of the small bowel may be altered by gastric
disease or small-bowel ileus.
With perforation of the colon, initially enormous numbers
(a total of Ç1012/mL) of the hundreds of different species
that constitute the normal colonic microflora spill into the
peritoneal cavity. A simplification of the numerous species
then occurs, so that once peritoneal infection is established,
only about five pathogens on average remain, usually three
anaerobic and two aerobic species. In patients with gangre-
nous or perforated appendicitis, the average number of organ-
isms recovered from clinical specimens has been reported to
be as high as 9.8 and 12.7, respectively, with 75% of the flora
consisting of anaerobes [30].
The obligate anaerobes isolated have been found to be more
oxygen-tolerant and have identifiable virulence factors, as com-
pared with the rest of the obligate anaerobic microflora.
B. fragilis is the most frequently isolated anaerobe following
colonic perforation, and E. coli is the most frequently isolated
facultative anaerobe.
In a now-classic series of experiments in rodents, Weinstein
and co-workers clarified the sequence of events that occurs
following contamination of the peritoneum with fecal flora
[31]. In this model, E. coli is responsible for sepsis and mortal-
ity with early peritonitis, and B. fragilis, in concert with
E. coli and possibly other microorganisms such as enterococci,
is responsible for late peritoneal abscess formation. Such syn-
ergy between anaerobes and facultative microorganisms has
long been recognized in mixed infections [32].
Some of the microorganisms isolated apparently owe their sur-
vival largely to the presence of other bacteria in the poly-
microbial infection, such as B. fragilis and E. coli, which if elimi-
nated by specific antimicrobial therapy will result in coincident
disappearance of these other microorganisms. The lower intestinal
flora can be altered in the severely ill, hospitalized patient under
the pressure of antibiotic usage that allows proliferation of multi-
ple-drug-resistant microorganisms, such as P. aeruginosa, Entero-
bacter species, multiple-drug-resistant enterococci, and Candida
species. These microorganisms can then contribute to peritoneal
infection that may follow colonic perforation.
The same microorganisms may also be isolated from patients
with so-called tertiary peritonitis, i.e., persistent peritonitis in
patients with impaired host defenses and multiple organ dys-
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CID 1997;24 (June) Peritonitis Update
function who are unresponsive to initial management [33].
However, monomicrobial infection with microorganisms that
have low pathogenicity, such as Candida species, enterococci,
and coagulase-negative staphylococci, has been noted even in
acute peritonitis in patients with severely impaired defenses
[34]. P. aeruginosa usually is thought of as a nosocomial patho-
gen that emerges under the selective pressure of broad-
spectrum antimicrobial agents. In several studies, however, this
organism has been isolated in up to 24% of patients with acute
community-acquired perforating appendicitis [35, 36].
Although enterococci are found in 20% of intraabdominal
infections, their exact role in polymicrobial infection and the
need for specific antimicrobial therapy remain controversial.
Selective therapy against E. coli and B. fragilis, which has
minimal in vitro activity against enterococci, has been found
to be sufficient to reduce enterococcal counts [37]. Neverthe-
less, in animal models of experimental polymicrobial intra-
abdominal infection, enterococci have been found to be a sig-
nificant component of the inoculum, which enhances abscess
formation, weight loss, bacteremia with B. fragilis and E. coli,
and mortality [37, 38].
Similarly, clinical reports have indicated the emergence of
enterococcal abscesses and bacteremia after treatment of
intraabdominal sepsis with antimicrobial agents that lack sig-
nificant in vitro enterococcal activity [39 – 41]. In addition, a
recent multicenter study of intraabdominal infection has found
that the presence of enterococci in the initial culture, in addition
to APACHE II score, independently predicted treatment failure
with broad-spectrum antimicrobial regimens that lacked spe-
cific enterococcal activity [42]. APACHE II score, age, length
of preinfection hospital stay, and postoperative infections pre-
dicted the presence of enterococci. It is unknown if initial
inclusion of antienterococcal therapy will improve outcome for
these high-risk patients.
Clinical presentation and evaluation. CT has become invalu-
able in evaluating patients suspected of having an intraabdomi-
nal infection. CT- or ultrasonography-guided aspiration of sus-
pected intraabdominal abscesses has also become standard in
evaluating and managing selected patients. Intraabdominal in-
fection encompasses many different pathological and clinical
entities that are associated with widely varying mortality rates
that range from zero to 60%.
The ability to predict outcome and stratify severity of disease
is important for clinical decision-making as well as ensuring
comparability in trials that evaluate different management strat-
egies with surgical protocols or antimicrobial agents [43]. Out-
come has been found to be related mainly to host factors (e.g.,
preoperative nutritional status, organ impairment, the severity
of the patient’s systemic response, and the premorbid physio-
logical reserves, as predicted by the APACHE II scoring sys-
tem) rather than to type and source of the infection [44, 45].
Death from intraabdominal infection, especially when the
tertiary phase is reached, is thought to result from an exagger-
ated uncontrolled cytokine release that is unresponsive to all
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1039
therapeutic attempts [46]. This has led to investigation of endo-
toxin and cytokine levels in circulation to predict outcome.
However, the magnitude of levels of endotoxin, TNF, and
IL-6, in circulation in patients with peritonitis, has not been
invariably related to prognosis [14, 47 – 51]. It has been sug-
gested that cytokine levels in the peritoneal exudate, rather than
the blood, better reflect the severity of the compartmentalized
peritoneal infection and predict outcome [14].
Management and prevention. A skeptical attitude is neces-
sary when reviewing reports on clinical trials of antimicrobial
therapy for intraabdominal sepsis. Surgical therapy alone may
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be sufficient to cure many otherwise healthy, young patients
with intraabdominal infection who have no signs of severe
sepsis; even antimicrobial agents to which the pathogens are
resistant may be associated with a good outcome for these
patients.
To establish a specific role for antimicrobial regimens re-
quires clinical trials with sufficient numbers of high-risk pa-
tients whose severity of illness has been stratified by APACHE
II scoring. Clinical trials are frequently diluted by low-risk
patients, since the sickest patients who would test the efficacy
of the antimicrobial agent are often excluded by strict enroll-
ment requirements.
Medical management of secondary peritonitis includes use
of antimicrobial therapy and supportive measures to maintain
vital functions, e.g., to improve or maintain circulation, nutri-
tion, and oxygenation to vital organs. Antimicrobial agents
must penetrate to the site of infection in concentrations that
are sufficient to overcome the effects of high bacterial density,
metabolic inactivity and slow growth rate of the bacterial
inoculum, low pH, low redox potential, necrotic tissue, and
bacterial products that may lower the drugs’ activity. For
example, aminoglycosides and clindamycin are less active at
acid pH values, aminoglycosides are less active at low redox
potentials, and b-lactam drugs are less active against high
bacterial densities.
The animal model of intraabdominal sepsis demonstrated the
necessity of treating both the facultative enteric gram-negative
bacilli, namely E. coli, and the anaerobic gram-negative bacilli,
namely B. fragilis. Empirical use of an antimicrobial regimen
active against these organisms has been well established. In-
deed, the need for intraoperative cultures to document etiologi-
cal microbes and their antimicrobial susceptibilities has been
questioned, because the results are rarely available to influence
clinical decisions [52].
Early clinical trials have established the therapeutic regimen
of clindamycin plus aminoglycoside as the ‘‘gold standard’’
[53, 54]. Aminoglycosides are frequently underdosed because
of fear of nephrotoxicity or because of underestimation of the
expanded volume of distribution in critically ill patients with
intraabdominal sepsis. Once-daily aminoglycoside therapy —
in which the total daily dose is given to patients with normal
renal function as a single dose every 24 hours rather than as
multiple smaller, divided doses — obviates these dosing prob-
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1040 Johnson, Baldessarre, and Levison
lems, because both the bactericidal activity and postantibiotic
effect of aminoglycosides are concentration-dependent, while
their nephrotoxicity is time-dependent. However, too few se-
verely ill patients with intraabdominal sepsis have been studied
to allow recommendation of the general use of single daily
doses of these drugs.
Regimens in which a third-generation cephalosporin is substi-
tuted for the aminoglycoside or metronidazole is substituted for
clindamycin compare favorably to the ‘‘gold standard.’’ Resis-
tance, however, emerges readily under selective pressure of anti-
microbial therapy with third-generation cephalosporins among
certain gram-negative bacilli that produce inducible b-lacta-
mases, such as Enterobacter, Serratia, Citrobacter, Morganella,
and Acinetobacter species and P. aeruginosa. These organisms
have a high spontaneous mutation rate for constitutive produc-
tion of large amounts of these b-lactamases that confer resistance
to all b-lactam drugs, except the carbapenems (imipenem and
meropenem) and cefepime, and are poorly antagonized by sul-
bactam, clavulanic acid, and tazobactam.
Patients likely to be infected with these organisms — e.g.,
those having prolonged hospital stays, prior antibiotic treat-
ment, postoperative peritonitis, or tertiary peritonitis — are best
treated with a regimen that includes imipenem, meropenem,
cefepime, a fluoroquinolone, or an aminoglycoside. Resistance
among isolates of B. fragilis to metronidazole is rare, while
resistance to clindamycin is now unacceptably high in many
centers. Furthermore, the relative incidence of Clostridium dif-
ficile – associated diarrhea and colonization was found to be
less following use of metronidazole than that following use of
clindamycin in a retrospective study [55].
Microaerophilic gram-positive cocci, which are frequent co-
pathogens in polymicrobial anaerobic infection, are resistant
to metronidazole, unlike clindamycin, so if metronidazole is
used it should be combined with an agent active against these
pathogens, such as a b-lactam antibiotic other than aztreonam.
Aztreonam, fluoroquinolones, and aminoglycosides also lack
activity against microaerophilic gram-positive cocci and theo-
retically may not be optimal agents to combine with metronida-
zole, although clinical trials of these combinations have been
found to be efficacious in intraabdominal infection [56].
Monotherapy with agents that have activity against both
aerobes and anaerobes includes the carbapenems imipenem and
meropenem and the b-lactam/b-lactamase combinations, such
as ampicillin/sulbactam, ticarcillin/clavulanate, and piperacil-
lin/tazobactam. Unacceptably high B. fragilis resistance to cef-
oxitin has been found in many centers; cefotetan, another sec-
ond-generation cephalosporin, is less active than cefoxitin
against certain species in the B. fragilis group.
The duration of antimicrobial therapy after adequate surgery
is usually 5 – 7 days but depends on severity of infection, clini-
cal response, and normalization of the WBC count [53, 57,
58]. Only a short course of antimicrobial therapy (24 hours) is
required for sterile peritonitis that occurs in the peritoneal space
around an infected but resectable intraabdominal organ, such
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CID 1997;24 (June)
as the appendix or gallbladder, after resection of the organ.
Similarly, contamination of the peritoneum from a defect in
the intestinal wall, such as immediately following penetrating
abdominal trauma, may also require only operative intervention
to remove the diseased organ and a brief course of antimicrobial
therapy [53]. Persistent signs of sepsis suggest formation of
an intraabdominal abscess that requires drainage, continued
contamination of the peritoneum from an inadequately con-
trolled source, superimposed nosocomial infection with a resis-
tant pathogen, or tertiary peritonitis.
Treatment against Enterococcus or Candida species in-
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volved in polymicrobial infections is controversial. Identifi-
cation of either microorganism in blood cultures, as the sole
organism within residual or recurrent intraabdominal infec-
tion, or as the predominant pathogen on a gram stain of
peritoneal exudate is an indication for specific antimicrobial
therapy plus adequate surgical debridement. Enterococci
have emerged as leading nosocomial pathogens, undoubtedly
as a result of their inherent resistance to many commonly
used antimicrobial agents and the recent acquisition of resis-
tance to previous standard therapy, i.e., with ampicillin,
aminoglycosides, and vancomycin. Only clinically unproven
agents to which the strains are susceptible in vitro, such
as doxycycline, novobiocin, or quinupristin/dalfopristin, are
available as potential therapeutic agents for infection caused
by these multiresistant strains of enterococci.
Administration of amphotericin B is standard therapy for
invasive candidal infection, although amphotericin lipid com-
plex is an equally efficacious, less nephrotoxic, but more expen-
sive alternative. Azoles such as fluconazole and itraconozole
are also less toxic, although no comparative trials for candidal
peritonitis have been performed. Candida krusei, Candida trop-
icalis, and Torulopsis glabrata are inherently more resistant to
azoles, and resistance to azoles among previously susceptible
Candida species is increasing.
Although a comprehensive discussion of surgical manage-
ment of secondary peritonitis is beyond the scope of this re-
view, certain recent trends will be mentioned [59, 60]. Optimal
management includes the following: (1) bowel decompression,
e.g., by proximal colostomy for perforation, diverticulitis, or
colonic carcinoma; (2) closing of traumatic perforations and
resection of a diseased, perforated viscus to stop continued
peritoneal contamination; and (3) drainage of any purulent col-
lections to reduce the bacterial inoculum and to remove exces-
sive levels of proinflammatory cytokines and other adjuvants,
such as fecal matter, food, blood, bile, bullets, or barium.
In the absence of perforation, when the disease process, e.g.,
acute appendicitis or necrotic bowel, is anticipated to progress,
the involved organ is resected. Laparoscopic appendectomy
has been recommended for acute appendicitis, with conversion
to open appendectomy for perforated appendix or an inflamma-
tory mass, as well as laparoscopic cholecystectomy for acute
cholecystitis (with conversion to an open procedure when tech-
nical difficulties are encountered).
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CID 1997;24 (June) Peritonitis Update
Abscesses that present as localized peritonitis may be drained
percutaneously with the aid of ultrasonography or CT, followed
by definitive surgery, if necessary. Percutaneous drainage of
a peridiverticular abscess may permit a subsequent one-stage
procedure of primary resection and immediate anastomosis.
Peritonitis caused by colonic perforation due to diverticuli-
tis or colon cancer has been treated with one of three proce-
dures, depending on the particular clinical situation: (1) a
three-stage procedure, which involves an initial proximal co-
lostomy to decompress the bowel and divert the fecal stream,
followed by resection of the diseased bowel, and finally anas-
tomosis to restore bowel continuity several months later; (2)
a two-stage procedure, which involves initial resection and
temporary proximal colostomy, with either a mucous fistula
or a blind pouch (Hartmann’s procedure), followed by anasto-
mosis; or (3) a one-stage procedure of primary resection and
immediate anastomosis.
The three-stage procedure has traditionally been reserved for
critically ill, high-risk patients; however, the two-stage proce-
dure may be preferred for these patients because it eliminates
the source of peritoneal contamination early [61]. The one-
stage procedure in the patient with colonic perforation has been
questioned because the lumen of the bowel is not cleansed
preoperatively and because of the assumed risk of breakdown
of the anastomosis in the presence of peritonitis. However,
the one-stage primary resection and immediate anastomosis
eliminate need for further hospitalization and shorten disability
due to a colostomy. Indeed, the one-stage procedure has been
shown to be efficacious for the moderate-risk patient with co-
lonic perforation (APACHE II score of £15), even in the
case of emergency when the bowel has not been cleansed or
peritonitis is present [61].
Intraoperative peritoneal lavage with saline, following
drainage of purulent peritoneal exudates, fecal matter, food,
and other foreign debris, is standard procedure during laparo-
tomy for peritonitis. However, radical peritoneal debridement
of all fibrinous deposits on peritoneal surfaces is no longer
thought to be effective [62]. Continuous peritoneal lavage for
48 – 72 hours postoperatively or until the fluid is clear has
been studied, but at present the evidence is insufficient to
recommend this procedure. Addition of antibiotics or anti-
septics to intraperitoneal lavage fluid has also been shown to
have no added benefit [53].
Similarly, there has been interest in the role of planned relap-
arotomies to treat patients with severe peritonitis. Here, the
commitment is made at the first operation to perform laparo-
tomies at frequent intervals until the abdomen is macroscopi-
cally ‘‘clean,’’ with additional surgical procedures, such as
resections, performed as necessary [63]. The abdominal fascia
is left open between laparotomies and the defect bridged by
saline-soaked gauze or by a temporary abdominal closure de-
vice, such as mesh.
These demanding and costly procedures have been compli-
cated by multiple fistulas, wound contamination, incisional her-
/ 9c2f$$ju45 05-07-97 17:21:37
1041
nias, and tertiary peritonitis with organisms such as enterococci
or Candida species [63 – 65]. Indeed, repeated entry into the
inflamed peritoneum may further escalate the cytokine cascade.
A review concluded that in the absence of randomized con-
trolled prospective trials with appropriate stratification of pa-
tients by severity of illness, there is insufficient evidence to
determine if these procedures improve outcome of severe dif-
fuse peritonitis [66].
Peritonitis Complicating Peritoneal Dialysis
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Pathogenesis. Since its development in the late 1970s,
CAPD has provided a safe, cost-effective treatment for end-
stage renal disease. Unfortunately, the technique is often aban-
doned because of its most common complication, peritonitis
[67]. The incidence of peritonitis complicating CAPD varies
considerably between individual patients and centers. Rates
tend to reflect the experience of the center, the specific technol-
ogy used, and the users’ susceptibility to infection and ability
to comply with procedures [68]. Overall, the average incidence
of peritonitis is 1.3 – 1.4 episodes per patient per year [69].
More than half of these episodes are experienced by only 25%
of patients.
The two most important routes for development of peritonitis
in CAPD patients are (1) transluminal, resulting from a break in
sterile technique during dialysate exchange, and (2) contiguous
spread, in which microorganisms access the peritoneum along
the tract of the dialysis catheter. Less common portals of entry
are hematogenous spread from a distant site of infection and
direct contamination from the gastrointestinal tract. Divertic-
ular disease of the nonsigmoid colon appears to be a risk factor
for acquisition of infection of intestinal origin, presumably
through occult microperforations; however, isolation of multi-
ple enteric pathogens from peritoneal fluid, especially anaero-
bic bacteria, suggests fecal contamination from gross colonic
perforations [68].
Microbial factors that may contribute to pathogenesis of
peritonitis include ability to grow in dialysis fluids and pro-
duction of extracellular slime (biofilm). Once organisms gain
access to the peritoneal cavity, further growth may depend on
their survival in the presence of dialysis fluid. Fresh dialysate
solutions are capable of supporting growth of E. coli but
not that of staphylococci. However, after instillation into the
peritoneal cavity, dialysis effluent supports growth of both
organisms [69].
Other studies have shown that the growth of P. aeruginosa
and E. coli is enhanced 1,000-fold in dialysis fluids from pa-
tients with peritonitis, compared with that in such fluids from
uninfected controls [70]. Both staphylococci and Candida albi-
cans grow as microcolonies on polymeric surfaces [71]. Sur-
rounding biofilm serves to anchor the organisms and protect
them from host defenses and antibiotic activity [72].
The clinical observation that some patients remain free of
CAPD-related peritonitis for years suggests that host defense
cida UC: CID
1042 Johnson, Baldessarre, and Levison
factors may also be important in the pathogenesis of this infec-
tion [73]. Microbial pathogens that reach the dialyzed perito-
neal cavity are removed by three major lines of defense. First,
despite the dilution of fibrinogen and coagulation proteins, fi-
brin trapping and sequestration of microorganisms operate ef-
ficiently in the dialyzed peritoneum. Second, removal of the
dialysate serves to eliminate or decrease the inoculum of con-
taminating organisms. Finally, a complex interplay of opsoni-
zation, phagocytosis, and intracellular killing by peritoneal
macrophages, mesothelial cells, and neutrophils serves to com-
bat bacterial invasion and prevent infection.
Unfortunately, the dialyzed peritoneal cavity is not a support-
ive milieu for operation of these cellular and immunologic
defense mechanisms because of its low pH (5.5 – 6.0), high
osmolarity (300 – 400 mOsmol/kg), and decreased levels of IgG
and complement (1% of their normal levels). A correlation
between deficiencies in these host defenses and patient risk for
peritonitis has not been conclusively identified [73].
Microbiology. In patients undergoing CAPD, peritonitis is
usually caused by a single pathogen that originates from the
normal flora of the skin or upper respiratory tract. Approxi-
mately 60% – 70% of cases are caused by gram-positive cocci,
20% – 30% by gram-negative bacilli, and the remainder by vari-
ous other bacteria, fungi, and mycobacteria [74]. Coagulase-
negative Staphylococcus is the single most common pathogen,
followed by S. aureus and species of Streptococcus. Among
the gram-negative organisms, most Enterobacteriaceae species
have been associated with CAPD peritonitis, but no single
species predominates in all reported series. Although a rare
pathogen in other types of peritonitis, P. aeruginosa occurs
with relative frequency in CAPD peritonitis (5% – 10% of
cases). It warrants special note because of its association with
significant morbidity and late complications [75, 76].
Fungi have become an important cause of CAPD-related
peritonitis in recent years because of their increasing frequency
and problematic management. Although many different fungi
have been isolated, including Aspergillus, Mucor, Rhizopus,
Alternaria, Fusarium, Penicillium, and Drechslera species,
C. albicans accounts for 80% – 90% of cases [74, 76]. Risk
factors for acquisition of fungal peritonitis are bacterial perito-
nitis within the preceding month, recent hospitalization, pres-
ence of extraperitoneal infection, use of immunosuppressive
agents, and concomitant HIV infection, but diabetes mellitus
does not pose a special risk [77, 78].
Mycobacteria have been described as pathogens in fewer than
3% of cases of CAPD-related peritonitis, but they may also
account for a portion of cases labeled as ‘‘culture-negative’’ [79].
Overall, 86% of mycobacterial isolates reported in the literature
have been of group IV (rapid growers), such as M. fortuitum and
M. chelonae [80]. One particularly large outbreak involved 17
patients who developed infection with M. chelonae following
treatment with contaminated intermittent peritoneal dialysis ma-
chines [81]. Other rare causes of peritonitis in patients undergoing
CAPD are viruses, algae, and M. tuberculosis.
/ 9c2f$$ju45 05-07-97 17:21:37
CID 1997;24 (June)
Clinical presentation and evaluation. Criteria for the diagno-
sis of CAPD-associated peritonitis are (1) signs and symptoms
of peritoneal irritation, (2) cloudy dialysate effluent with a
leukocyte count of ú100/mm3, and (3) a positive culture of
dialysate fluid. Any two of these criteria may be adequate to
establish the diagnosis [82]. Clinical manifestations of peritoni-
tis vary from mild to severe, depending largely on the virulence
of the pathogen and the time course of the infection [67].
Generally, turbid dialysate is the first and most common symp-
tom to appear, followed shortly thereafter by abdominal pain
and tenderness.
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Laboratory evaluation of dialysate effluent is critical to estab-
lishing the diagnosis of CAPD-associated peritonitis. A dialy-
sate leukocyte count of ú100/mm3 is the traditional diagnostic
value but is not specific. The differential cell count of dialysate
may have a better predictive value. In one study, polymorpho-
nuclear leukocytes comprised ú50% of the total cell count
(mean, 85%) in infected patients, while in uninfected patients
the proportion was õ40% (mean, 12%) [82]. A preponderance
of eosinophils in the fluid is seen in the self-limited condition
‘‘eosinophilic peritonitis,’’ which often follows placement of
the Tenckhoff catheter and may represent allergy to the tubing
[83, 84].
Peritoneal eosinophilia also occurs with fungal peritonitis
or recent intraperitoneal administration of antibiotics. Gram
staining of dialysis fluid detects only 20% – 30% of peritonitis
episodes. Gram-positive organisms, especially S. aureus, are
more likely to be detected than are gram-negative ones [85].
Cultures offer a greater yield than gram stains but require
concentration of the dialysate by centrifugation, filtration, or
lysis-centrifugation [86].
Even with these specialized methods, 3% – 30% of CAPD-
related peritonitis episodes are culture-negative. Presumably,
most are due to fastidious, low-virulence organisms or coagu-
lase-negative staphylococci that survive less well in dialysis
fluid [70]. Cases of culture-negative peritonitis that do not
respond to empirical antibiotic treatment should be further in-
vestigated by performance of dialysate fluid cultures for myco-
bacteria and fungi. Blood cultures are usually negative, regard-
less of the etiologic agent.
Management and prevention. The increased use of intraperito-
neal antibiotics as therapy for peritonitis has allowed most pa-
tients to be treated on an ambulatory basis. Hospitalization is
indicated for those who are severely ill or who are unable to
manage administration of intraperitoneal antibiotics at home. A
variety of antimicrobial agents have been used successfully for
treatment, including penicillins, cephalosporins, aztreonam, imi-
penem, aminoglycosides, fluoroquinolones, and macrolide and
glycopeptide antibiotics. Initial therapy may be guided by results
of the dialysis fluid gram staining, but since these are uncom-
monly positive, empirical treatment with a cephalosporin or van-
comycin plus aminoglycoside is typically initiated.
In relatively mild episodes of peritonitis, a single agent with
antistaphylococcal activity may also be suitable. Antibiotic se-
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CID 1997;24 (June) Peritonitis Update
lections are adjusted when the results of cultures and suscepti-
bility tests are known. A single specific agent is adequate treat-
ment in the majority of cases of bacterial peritonitis.
P. aeruginosa, however, has been associated with a high thera-
peutic failure rate and frequent relapses [75, 76]. A synergistic
combination of antibiotics, such as an antipseudomonal b-lac-
tam drug plus an aminoglycoside, has been recommended in
addition to removal of the dialysis catheter.
Intraperitoneal administration of antibiotics is the preferred
method for drug delivery in CAPD-associated peritonitis be-
cause it achieves high local concentrations and permits self-
treatment by the patient [87 – 89]. Therapy is usually continued
for 10 – 14 days but may need to be extended with unusually
severe or slow-to-respond infections. Recommendations for
specific drug doses and routes of administration are the subject
of several reviews [89, 90].
Treatment of fungal peritonitis is controversial because of the
lack of controlled studies and the small numbers of cases seen
at any single center. Although there are reports of successful
treatment with intraperitoneal and/or systemic antifungal agents
alone [91, 92], removal of the dialysis catheter is usually prudent
to prevent relapse [68, 93]. A short course of systemic amphoteri-
cin B (250–500 mg) is often given following catheter removal.
Some evidence has suggested that catheter removal alone may
be curative in selected patients. Mycobacterial peritonitis also
requires removal of the dialysis catheter for cure. Most of these
organisms are resistant to conventional antituberculous agents,
and susceptibilities vary greatly among the species. Antibiotic
selections should be guided by either in vitro susceptibility test
results or published recommendations [79–81].
Prevention of peritonitis in patients undergoing CAPD requires
intensive education regarding aseptic technique and catheter care.
Efforts to reduce the incidence of peritonitis by using oral or
intraperitoneal antibiotics have largely been unsuccessful [94–97].
Although a decrease in the number of random positive dialysate
cultures has been observed in clinical studies, occurrence of clini-
cal peritonitis was unaffected by prophylactic antibiotics. In addi-
tion, topical mupirocin has been used to eliminate nasal coloniza-
tion with S. aureus but has yet to be shown to significantly impact
the incidence of CAPD-related peritonitis [98].
The most significant advances in the prevention of dialysis-
related peritonitis involve instrumentation changes, including
(1) devices that facilitate connection of tubing, such as titanium
adapters; (2) devices that help maintain field sterility during
exchanges, such as ultraviolet light systems and in-line filters;
and (3) devices that protect intraluminal sterility during
exchanges, such as connector systems with disinfectant
(Y-connector, O-set). Most such devices have been shown to
favorably impact the incidence of peritonitis but add apprecia-
bly to the overall cost of CAPD.
References
1. Wilcox CM, Dismukes WE. Spontaneous bacterial peritonitis: a review
of pathogenesis, diagnosis, and treatment. Medicine (Baltimore) 1987;
66:447 – 56.
/ 9c2f$$ju45 05-07-97 17:21:37
1043
2. Nohr CW, Marshall DG. Primary peritonitis in children. Can J Surg 1984;
27:179 – 81.
3. Conn HO, Fessel JM. Spontaneous bacterial peritonitis in cirrhosis: varia-
tions on a theme. Medicine (Baltimore) 1971; 50:161 – 97.
4. Sheckman P, Onderdonk AB, Bartlett JG. Anaerobes in spontaneous peri-
tonitis [letter]. Lancet 1977; 2:1223.
5. Runyon BA, Hoefs JC. Culture-negative neutrocytic ascites: a variant of
spontaneous bacterial peritonitis. Hepatology 1984; 4:1209 – 11.
6. Runyon BA, Umland ET, Merlin T. Inoculation of blood culture bottles
with ascitic fluid: improved detection of spontaneous bacterial peritoni-
tis. Arch Intern Med 1987; 147:73 – 5.
7. Stassen WN, McCullough AJ, Bacon BR, et al. Immediate diagnostic
criteria for bacterial infection of ascitic fluid: evaluation of ascitic fluid
Downloaded from https://academic.oup.com/cid/article-abstract/24/6/1035/339046 by guest on 24 October 2018
polymorphonuclear leukocyte count, pH, and lactate concentration,
alone and in combination. Gastroenterology 1986; 90:1247 – 54.
8. Runyon BA, Hoefs JC. Ascitic fluid analysis in the differentiation of
spontaneous bacterial peritonitis from gastrointestinal tract perforation
into ascitic fluid. Hepatology 1984; 4:447 – 50.
9. Weinstein MP, Iannini PB, Stratton CW, Eickhoff TC. Spontaneous bacte-
rial peritonitis: a review of 28 cases with emphasis on improved survival
and factors influencing prognosis. Am J Med 1978; 64:592 – 8.
10. Singh N, Gayowski T, Yu VL, Wagener MM. Trimethoprim-sulfamethox-
azole for the prevention of spontaneous bacterial peritonitis in cirrhosis:
a randomized trial. Ann Intern Med 1995; 122:595 – 8.
11. Till M, Lee N, Soper WD, Murphy RL. Typhlitis in patients with HIV-1
infection. Ann Intern Med 1992; 116:998 – 1000.
12. Wilson SE, Robinson G, Williams RA, et al. Acquired immune deficiency
syndrome (AIDS): indications for abdominal surgery, pathology, and
outcome. Ann Surg 1989; 210:428 – 34.
13. Schein M, Wittmann DH, Holzheimer R, Condon RE. Hypothesis: com-
partmentalization of cytokines in intraabdominal infection. Surgery
1996; 119:694 – 700.
14. Holzheimer RG, Schein M, Wittmann DH. Inflammatory response in peri-
toneal exudate and plasma of patients undergoing planned relaparotomy
for severe secondary peritonitis. Arch Surg 1995; 130:1314 – 20.
15. Giroir BP. Mediators of septic shock: new approaches for interrupting the
endogenous inflammatory cascade. Crit Care Med 1993; 21:780 – 9.
16. Baigrie RJ, Lamont PM, Kwiatowski D, Dallman MJ, Morris PJ. Systemic
cytokine response after major surgery. Br J Surg 1992; 79:757 – 60.
17. Bagby GJ, Plessala KJ, Wilson LA, Thompson JJ, Nelson S. Divergent
efficacy of antibody to tumor necrosis factor-a in intravascular and
peritonitis models of sepsis. J Infect Dis 1991; 163:83 – 8.
18. Astiz ME, Saha DC, Carpati CM, Rackow EC. Induction of endotoxin
tolerance with monophosphoryl lipid A in peritonitis: importance of
localized therapy. J Lab Clin Med 1994; 123:89 – 93.
19. McMasters KM, Cheadle WG. Regulation of macrophage TNF-a, IL-1 b
and 1a (1-Aa) mRNA expression during peritonitis is site dependent.
J Surg Res 1993; 54:426 – 30.
20. Zannetti G, Heumann D, Gérain J, et al. Cytokine production after intrave-
nous or peritoneal gram-negative bacterial challenge in mice: compara-
tive protective efficacy of antibodies to tumor necrosis factor-a and to
lipopolysaccharide. J Immunol 1992; 148:1890 – 7.
21. Propst T, Propst A, Herold M, et al. Spontaneous bacterial peritonitis is
associated with high levels of interleukin-6 and its secondary mediators
in ascitic fluid. Eur J Clin Invest 1993; 23:832 – 6.
22. Zeni F, Tardy B, Vindimian M, et al. High levels of tumor necrosis
factor-a and interleukin-6 in the ascitic fluid of cirrhotic patients with
spontaneous bacterial peritonitis. Clin Infect Dis 1993; 17:218 – 23.
23. Nakahama H, Tanaka Y, Shirai D, et al. Plasma interleukin-6 levels in
continuous ambulatory peritoneal dialysis and hemodialysis patients.
Nephron 1992; 61:132 – 4.
24. Zemel D, Krediet RT, Koomen GC, Kortekaas WM, Geertzen HG, ten
Berge RJ. Interleukin-8 during peritonitis in patients treated with CAPD:
an in-vivo model of acute inflammation. Nephrol Dial Transplant 1994;
9:169 – 74.
cida UC: CID
1044 Johnson, Baldessarre, and Levison
25. Zemel D, Koomen GCM, Hart AA, ten Berge IJM, Struijk DG, Krediet RT.
Relationship of TNF-a, interleukin-6, and prostaglandins to peritoneal
permeability for macromolecules during longitudinal follow-up of peri-
tonitis in continuous ambulatory peritoneal dialysis. J Lab Clin Med
1993; 122:686 – 96.
26. Stack AM, Saladino RA, Thompson C, et al. Failure of prophylactic and
therapeutic use of a murine anti – tumor necrosis factor monoclonal
antibody in Escherichia coli sepsis in the rabbit. Crit Care Med 1995;
23:1512 – 8.
27. Echtenacher B, Falk W, Männel DN, Krammer PH. Requirement of endog-
enous tumor necrosis factor/cachectin for recovery from experimental
peritonitis. J Immunol 1990; 145:3762 – 6.
28. Battafarano RJ, Burd RS, Kurrelmeyer KM, Ratz CA, Dunn DL. Inhibition
of splenic macrophage tumor necrosis factor a secretion in vivo by
antilipopolysaccharide monoclonal antibodies. Arch Surg 1994; 129:
179 – 86.
29. Kohler J, Heumann D, Garotta G, et al. IFN-g involvement in the severity
of gram-negative infections in mice. J Immunol 1993; 151:916 – 21.
30. Bennion RS, Thompson JE, Baron EJ, Finegold SM. Gangrenous and
perforated appendicitis with peritonitis — treatment and bacteriology.
Clin Ther 1990; 12:31 – 44.
31. Weinstein WN, Onderdonk AB, Bartlett JG, Gorbach SL. Experimental
intra-abdominal abscesses in rats: development of an experimental
model. Infect Immun 1974; 10:1250 – 5.
32. Rotstein OD, Pruett TL, Simmons RL. Mechanisms of microbial synergy
in polymicrobial surgical infections. Rev Infect Dis 1985; 7:151 – 70.
33. Rotstein OD, Pruett TL, Simmons RL. Microbiologic features and treat-
ment of persistent peritonitis in patients in the intensive care unit. Can
J Surg 1986; 29:247 – 50.
34. Sawyer RG, Rosenlof LK, Adams RB, May AK, Spengler MD, Pruett
TL. Peritonitis in the 1990s: changing pathogens and changing strategies
in the critically ill. Am Surgeon 1992; 58:82 – 7.
35. Aronoff SC, Olson MM, Gauderer MWL, Jacobs MR, Blumer JL, Izant
RJ Jr. Pseudomonas aeruginosa as a primary pathogen in children with
bacterial peritonitis. J Pediatr Surg 1987; 22:861 – 4.
36. Yellin AE, Heseltine PNR, Berne TV, et al. The role of Pseudomonas
species in patients treated with ampicillin and sulbactam for gangrenous
and perforated appendicitis. Surg Obstet Gynecol 1985; 161:303 – 7.
37. Montravers P, Andremont A, Massias L, Carbon C. Investigation of the
potential role of Enterococcus faecalis in the pathophysiology of experi-
mental peritonitis. J Infect Dis 1994; 169:821 – 30.
38. Matlow AG, Bohnen JMA, Nohr C, Christou N, Meakins J. Pathogenicity
of enterococci in a rat model of fecal peritonitis. J Infect Dis 1989; 160:
142 – 5.
39. Dougherty SH, Flohr AB, Simmons RL. ‘‘Breakthrough’’ enterococcal
septicemia in surgical patients: 19 cases and a review of the literature.
Arch Surg 1983; 118:232 – 8.
40. Jones RN. Gram-positive superinfections following beta-lactam chemo-
therapy: the significance of the enterococcus. Infection 1985; 13(suppl
1):S81 – 8.
41. Barrall DT, Kenney PR, Slotman GJ, Burchard KW. Enterococcal bacter-
emia in surgical patients. Arch Surg 1985; 120:57 – 63.
42. Burnett RJ, Haverstock DC, Dellinger EP, et al. Definition of the role
of Enterococcus in intraabdominal infection: analysis of a prospective
randomized trial. Surgery 1995; 118:716 – 23.
43. Nyström P-O, Bax R, Dellinger EP, et al. Proposed definitions for diagno-
sis, severity scoring, stratification, and outcome for trials on intraabdom-
inal infection. World J Surg 1990; 14:148 – 58.
44. Pacelli F, Doglietto GB, Alfieri S, et al. Prognosis in intra-abdominal
infections: multivariate analysis on 604 patients. Arch Surg 1996; 131:
641 – 5.
45. Christou NV, Barie PS, Dellinger EP, Waymack JP, Stone HH. Surgical
Infection Society Intra-abdominal Infection Study: prospective evalua-
tion of management techniques and outcome. Arch Surg 1993; 128:
193 – 9.
/ 9c2f$$ju45 05-07-97 17:21:37
CID 1997;24 (June)
46. Goris RJA, te Boekhorst TPA, Nuytinck JKS, Gimbrère JSF. Multiple-
organ failure: generalized autodestructive inflammation? Arch Surg
1985; 120:1109 – 15.
47. Damas P, Ledoux D, Nys M, et al. Cytokine serum level during severe
sepsis in humans: IL-6 as a marker of severity. Ann Surg 1992; 215:
356 – 62.
48. Függer R, Zadrobilek E, Götzinger P, et al. Perioperative TNF-alpha and
IL-6 concentrations correlate with septic state, organ function, and
APACHE II scores in intra-abdominal infection. Eur J Surg 1993; 159:
525 – 9.
49. Patel RT, Deen KI, Youngs D, Warwick J, Keighley MRB. Interleukin 6
is a prognostic indicator of outcome in severe intra-abdominal sepsis.
Br J Surg 1994; 81:1306 – 8.
Downloaded from https://academic.oup.com/cid/article-abstract/24/6/1035/339046 by guest on 24 October 2018
50. Hamilton G, Hofbauer S, Hamilton B. Endotoxin, TNF-alpha, interleukin-
6 and parameters of the cellular immune system in patients with intraab-
dominal sepsis. Scand J Infect Dis 1992; 24:361 – 8.
51. Barriere SL, Lowry SF. An overview of mortality risk prediction in sepsis.
Crit Care Med 1995; 23:376 – 93.
52. Wittmann DH, Bergstein JM, Frantzides C. Calculated empiric antimicro-
bial therapy for mixed surgical infections. Infection 1991; 19(suppl 6):
S345 – 50.
53. Bohnen JMA, Solomkin JS, Dellinger EP, Bjornson HS, Page CP. Guide-
lines for clinical care: anti-infective agents for intra-abdominal infec-
tion: a Surgical Infection Society policy statement. Arch Surg 1992;
127:83 – 9.
54. Shands JW Jr. Empiric antibiotic therapy of abdominal sepsis and serious
perioperative infections. Surg Clin North Am 1993; 73:291 – 306.
55. Gerding DN, Olson MM, Johnson S, Peterson LR, Lee JT Jr. Clostridium
difficile diarrhea and colonization after treatment with abdominal infec-
tion regimens containing clindamycin or metronidazole. Am J Surg
1990; 159:212 – 7.
56. Solomkin JS, Reinhart HH, Dellinger EP, et al. Results of a randomized
trial comparing sequential intravenous/oral treatment with ciprofloxacin
plus metronidazole to imipenem/cilastatin for intra-abdominal infec-
tions. Ann Surg 1996; 223:303 – 15.
57. Lennard ES, Derllinger EP, Wertz MJ, Minshew BH. Implications of
leukocytosis and fever at conclusion of antibiotic therapy for intra-
abdominal sepsis. Ann Surg 1982; 195:19 – 24.
58. Stone HH, Bourneuf AA, Stinson LD. Reliability of criteria for predicting
persistent or recurrent sepsis. Arch Surg 1985; 120:17 – 20.
59. Wittmann DH, Schein M, Condon RE. Management of secondary peritoni-
tis. Ann Surg 1996; 224:10 – 8.
60. Nathens AB, Rotstein OD. Therapeutic options in peritonitis. Surg Clin
North Am 1994; 74:677 – 92.
61. Nespoli A, Ravizzini C, Trivella M, Segala M. The choice of surgical
procedure for peritonitis due to colonic perforation. Arch Surg 1993;
128:814 – 8.
62. Polk HC Jr, Fry DE. Radical peritoneal debridement for established perito-
nitis: the result of a prospective randomized clinical trial. Ann Surg
1980; 192:350 – 5.
63. Wittmann D, Aprahamian C, Bergstein JM. Etappenlavage: advanced dif-
fuse peritonitis managed by planned multiple laparotomies utilizing
zippers, slide fastener, and Velcrow analogue for temporary abdominal
closure. World J Surg 1990; 14:218 – 26.
64. Teichmann W, Wittmann DH, Andreone PA. Scheduled reoperations
(etappenlavage) for diffuse peritonitis. Arch Surg 1986; 121:147 – 52.
65. Cuesta MA, Doblas M, Castañeda L, Bengoechea E. Sequential abdominal
reexploration with the zipper technique. World J Surg 1991; 15:74 – 80.
66. Schein M, Hirshberg A, Hashmonai M. Current surgical management of
severe intraabdominal infection. Surgery 1992; 112:489 – 96.
67. Korbet SM, Vonesh EF, Firanek CA. A retrospective assessment of risk
factors for peritonitis among an urban CAPD population. Perit Dial Int
1993; 13:126 – 31.
68. Saklayen MG. CAPD peritonitis: incidence, pathogens, diagnosis, and
management. Med Clin North Am 1990; 74:997 – 1010.
cida UC: CID
CID 1997;24 (June) Peritonitis Update
69. Linblad AS, Novak JW, Nolph KD, Stablein DM, Cutler SJ. The 1987
USA National CAPD Registry report. Trans Am Soc Artif Intern Organs
1988; 34:150 – 6.
70. Sheth NK, Bartell CA, Roth DA. In vitro study of bacterial growth in
continuous ambulatory peritoneal dialysis fluids. J Clin Microbiol 1986;
23:1096 – 8.
71. Marrie TJ, Noble MA, Costerton JW. Examination of the morphology
of bacteria adhering to peritoneal dialysis catheters by scanning and
transmission electron microscopy. J Clin Microbiol 1983; 18:1388 – 98.
72. Holmes CJ, Evands R. Biofilm and foreign body infection — the signifi-
cance to CAPD associated peritonitis. Peritoneal Dialysis Bulletin 1986;
6:168 – 77.
73. Holmes CJ. Peritoneal host defense mechanisms in peritoneal dialysis.
Kidney Int 1994; 46(suppl 48):S58 – 70.
74. von Graevenitz A, Amsterdam D. Microbiological aspects of peritonitis
associated with continuous ambulatory peritoneal dialysis. Clin Micro-
biol Rev 1992; 5:36 – 48.
75. Krothapalli R, Duffy WB, Lacke C, et al. Pseudomonas peritonitis and
continuous ambulatory peritoneal dialysis. Arch Intern Med 1982; 142:
1862 – 3.
76. Kaczmarski EB, Tooth JA, Anastassiades E, Manos J, Gokal R. Pseudomo-
nas peritonitis with continuous ambulatory peritoneal dialysis: six year
study. Am J Kidney Dis 1988; 14:413 – 7.
77. Eisenberg ES, Leviton I, Soeiro R. Fungal peritonitis in patients receiving
peritoneal dialysis: experience with eleven patients and review of the
literature. Rev Infect Dis 1986; 8:309 – 21.
78. Dressler R, Peters AT, Lynn RI. Pseudomonal and candidal peritonitis as
a complication of continuous ambulatory peritoneal dialysis in human
immunodeficiency virus – infected patients. Am J Med 1989; 86:
787 – 90.
79. Dunmire RB 3d, Breyer JA. Nontuberculous mycobacterial peritonitis
during continuous ambulatory peritoneal dialysis: case report and review
of diagnostic and therapeutic strategies. Am J Kidney Dis 1991; 18:
126 – 30.
80. Hakim A, Hisam N, Reuman PD. Environmental mycobacterial peritonitis
complicating peritoneal dialysis: three cases and review. Clin Infect Dis
1993; 16:426 – 31.
81. Band JD, Ward JI, Fraser DW, et al. Peritonitis due to a Mycobacterium
chelonei – like organism associated with intermittent chronic peritoneal
dialysis. J Infect Dis 1982; 145:9 – 17.
82. Males BM, Walshe JJ, Amsterdam D. Laboratory indices of clinical perito-
nitis: total leukocyte count, microscopy, and microbiologic culture of
peritoneal dialysis effluent. J Clin Microbiol 1987; 25:2367 – 71.
83. Digenis GE, Khanna K, Panatlony D. Eosinophilia after implantation of
the peritoneal catheter. Peritoneal Dialysis Bulletin 1982; 2:98 – 9.
84. Gokal R, Ramos JM, Ward MK, Kerr DNS. ‘‘Eosinophilic’’ peritonitis
in continuous ambulatory peritoneal dialysis (CAPD). Clin Nephrol
1981; 15:328 – 30.
85. Ludlam HA, Price TNC, Berry AJ, Phillips I. Laboratory diagnosis of
peritonitis in patients on continuous ambulatory peritoneal dialysis. J
Clin Microbiol 1988; 26:1757 – 62.
/ 9c2f$$ju45 05-07-97 17:21:37
1045
86. Bailie GR, Eisele G. Continuous ambulatory peritoneal dialysis: a review
of its mechanics, advantages, complications, and areas of controversy.
Ann Pharmacother 1992; 26:1409 – 20.
87. Morse GD, Farolino DF, Apicella MA, Walshe JJ. Comparative study of
intraperitoneal and intravenous vancomycin pharmacokinetics during
continuous ambulatory peritoneal dialysis. Antimicrob Agents Chemo-
ther 1987; 31:173 – 7.
88. Bennet-Jones D, Wass V, Mawson P, et al. A comparison of intraperitoneal
and intravenous/oral antibiotics in CAPD peritonitis. Peritoneal Dialysis
Bulletin 1987; 7:31 – 3.
89. Keane WF, Everett ED, Fine RN, et al. CAPD-related peritonitis manage-
ment and antibiotic therapy recommendations: Travenol Peritonitis
Management Advisory Committee. Peritoneal Dialysis Bulletin 1987;
Downloaded from https://academic.oup.com/cid/article-abstract/24/6/1035/339046 by guest on 24 October 2018
7:55 – 62.
90. Keller E, Reetze P, Schollmeyer P. Drug therapy in patients undergoing
continuous ambulatory peritoneal dialysis: clinical pharmacokinetic
considerations. Clin Pharmacokinet 1990; 18:104 – 17.
91. Rubin J, Kirchner K, Walsh D, Green M, Bower J. Fungal peritonitis
during continuous ambulatory peritoneal dialysis: a report of 17 cases.
Am J Kidney Dis 1987; 10:361 – 8.
92. Venning MC, Ford M, Gould GK. Successful treatment of fungal peritoni-
tis in CAPD using oral fluconazole [letter]. Nephrol Dial Transplant
1990; 5:555.
93. Nagappan R, Collins JF, Lee WT. Fungal peritonitis in continuous ambula-
tory peritoneal dialysis — the Auckland experience. Am J Kidney Dis
1992; 20:492 – 6.
94. Sharma BK, Smith EC, Rodriquez H, Pillay VKG, Gandhi VC, Dunea G.
Trial of oral neomycin during peritoneal dialysis. Am J Med Sci 1971;
262:175 – 8.
95. Axelrod J, Meyers BR, Hirschman SZ, Stein R. Prophylaxis with cephalo-
thin in peritoneal dialysis. Arch Intern Med 1973; 132:368 – 71.
96. Low DE, Vas SI, Oreopoulos DG, et al. Prophylactic cephalexin ineffective
in chronic ambulatory peritoneal dialysis [letter]. Lancet 1980; 2:
753 – 4.
97. Churchill DN, Taylor DW, Vas SI, et al. Peritonitis in continuous ambula-
tory peritoneal dialysis patients: a randomized clinical trial of co-trimox-
azole prophylaxis. Peritoneal Dialysis Bulletin 1988; 8:125 – 8.
98. Pérez-Fontán M, Rosales M, Rodrı́guez-Carmona A, et al. Treatment of
Staphylococcus aureus nasal carriers in CAPD with mupirocin. Adv
Peritoneal Dial 1992; 8:242 – 5.
The ‘‘Conflict-of-Interest Policy’’ of the Office of Con-
tinuing Medical Education, UCLA School of Medicine,
requires that faculty participating in a CME activity dis-
close to the audience any relationship with a pharmaceu-
tical or equipment company which might pose a poten-
tial, apparent, or real conflict of interest with regard to
their contribution to the program. The author reports no
conflict of interest.
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