Vous êtes sur la page 1sur 11

1035

STATE-OF-THE-ART CLINICAL ARTICLE

Peritonitis: Update on Pathophysiology, Clinical Manifestations, and


Management
Caroline C. Johnson, James Baldessarre, From the Division of Infectious Diseases, Allegheny University of the
and Matthew E. Levison Health Sciences, and Veterans Affairs Medical Center, Philadelphia,
Pennsylvania; and R. W. Johnson Pharmaceutical Research Institute,
Raritan, New Jersey

Downloaded from https://academic.oup.com/cid/article-abstract/24/6/1035/339046 by guest on 24 October 2018


Peritonitis results from any local trigger of inflammation. titis, congestive heart failure, metastatic malignant disease, sys-
Usually infection is the trigger, although infection may not temic lupus erythematosus, and lymphedema and, rarely, in
necessarily be present at the earliest stage. For example, sterile adults with no underlying disease [3]. The presence of ascites
peritonitis may occur in the localized peritoneal space sur- appears to be the common link among these various conditions.
rounding an infected but resectable intraabdominal organ, such The route of infection in primary peritonitis is usually not
as the appendix or gallbladder. In contrast, there may be con- apparent but is thought to be hematogenous, lymphogenous,
tamination of the peritoneum from a defect in the intestinal via transmural migration through an intact gut wall from the
wall, before establishment of infection or onset of an inflam- intestinal lumen, or, in women, from the vagina via the fallo-
matory response, e.g., immediately following penetrating ab- pian tubes. In cirrhotic patients the hematogenous route is most
dominal trauma. Peritonitis has been categorized as primary, likely. Organisms removed from circulation by the liver may
secondary, or (more recently) tertiary. Peritonitis complicating contaminate hepatic lymph and pass through the permeable
peritoneal dialysis can be considered as an additional category. lymphatic walls into the ascitic fluid. In addition, portosystemic
Each of these categories is reviewed herein, with an emphasis shunting greatly diminishes hepatic clearance of bacteremia,
on recent developments in pathogenesis, evaluation, and man- which would tend to perpetuate bacteremia and increase the
agement. opportunity to cause metastatic infection at susceptible sites
such as the ascitic collection.
Primary Peritonitis The infrequency of primary peritonitis in forms of ascites
other than that due to liver disease emphasizes the importance
Pathogenesis. Primary peritonitis is an infection of the peri- of intrahepatic shunting in the pathogenesis of this disease.
toneal cavity not directly related to other intraabdominal abnor- The hepatic reticuloendothelial system is known to be a major
malities. The vast majority of cases are due to bacterial infec- site for removal of bacteria from blood, and animal studies
tion; it is also commonly known as spontaneous bacterial have suggested that destruction of blood-borne bacteria by the
peritonitis. Usually it occurs in the presence of ascites from reticuloendothelial system is impaired in experimental cirrhosis
any of a variety of underlying conditions [1]. In the preanti- and in alcoholic liver disease. The decrease in phagocytic activ-
biotic era, primary peritonitis accounted for Ç10% of all pedi- ity seen in alcoholic cirrhosis is proportional to the severity of
atric abdominal emergencies; it now accounts for õ1 – 2% [2]. the liver disease.
The decline has been attributed to widespread use of antibiotics Enteric bacteria may also gain access to the peritoneal cavity
for minor upper respiratory tract illness. by directly traversing the intact intestinal wall. In an animal
Although primary peritonitis may occur in children without model, Escherichia coli passes from the bowel into the perito-
predisposing disease, it is especially associated with post- neal cavity after the introduction of hypertonic solutions into
necrotic cirrhosis and nephrotic syndrome. In adults, primary the peritoneum. The infrequent occurrence of bacteremia and
peritonitis develops in up to 25% of patients with alcoholic the multiplicity of species in peritoneal fluid when anaerobic
cirrhosis but has also been reported to occur in adults with bacteria are involved suggest that transmural migration of bac-
postnecrotic cirrhosis, chronic active hepatitis, acute viral hepa- teria is the probable route of infection of ascitic fluid in most
of these patients.
In prepubertal girls, the pathogenesis of primary peritonitis
Received 21 January 1997; revised 10 February 1997.
is likely related to an ascending infection of genital origin, as
Reprints or correspondence: Dr. Matthew E. Levison, Division of Infectious suggested by the simultaneous presence of pneumococci in
Diseases, Allegheny University – MCP, 3300 Henry Avenue, Philadelphia, vaginal secretions and peritoneal fluid. Alkaline vaginal secre-
Pennsylvania 19129.
tions that occur in this age group may be less inhibitory to
Clinical Infectious Diseases 1997;24:1035–47
q 1997 by The University of Chicago. All rights reserved.
bacterial growth than the acidic secretions of postpubertal fe-
1058–4838/97/2406–0001$02.00 males.

/ 9c2f$$ju45 05-07-97 17:21:37 cida UC: CID


1036 Johnson, Baldessarre, and Levison CID 1997;24 (June)

Transfallopian spread is also suggested by the development ings of peritoneal irritation. Fever (temperature of ú1007F) is
of primary peritonitis in women with intrauterine devices. The the most common presenting sign, occurring in 50% – 80% of
route of spread in women with gonococcal or chlamydial peri- cases and even in the absence of abdominal signs or symptoms.
hepatitis (Fitz-Hugh – Curtis syndrome) is presumably via the Primary peritonitis should always be considered in the differen-
fallopian tubes and paracolic gutters to the subphrenic space, tial diagnosis of decompensation of previously stable chronic
but it may also be hematogenous. liver disease, especially hepatic encephalopathy.
Although tuberculous peritonitis may result from direct entry Primary tuberculous peritonitis usually is gradual in onset,
into the peritoneal cavity of tubercle bacilli (from the lymph causing fever, weight loss, malaise, night sweats, and abdomi-
nodes, intestine, or genital tract in patients with active disease nal distension. The abdomen may not be rigid and is often
of these organs), it is more likely to be disseminated hematoge- characterized as being ‘‘doughy’’ on palpation. The findings
nously from remote foci of tuberculosis, most commonly in at surgery or laparoscopy consist of multiple nodules scattered

Downloaded from https://academic.oup.com/cid/article-abstract/24/6/1035/339046 by guest on 24 October 2018


the lung. Tuberculous peritonitis may become clinically evident over the peritoneal surface and omentum. Adhesions and a
after the initial focus has completely healed. variable amount of peritoneal fluid are usually present. Simi-
Microbiology. Several decades ago, the organisms reported larly, C. immitis can cause a granulomatous peritonitis with
to cause primary peritonitis in children were Streptococcus variable clinical manifestations.
pneumoniae and group A streptococci. More recently, the num- Although the diagnosis of primary peritonitis can be estab-
ber of nephrotic children with streptococcal peritonitis has de- lished with certainty only after thorough laparotomy to exclude
clined, and the relative frequency of peritonitis due to gram- a primary intraabdominal site of infection, it can usually be
negative enteric bacilli and staphylococci has increased. In surmised from examination of the peritoneal fluid. Fluid ob-
cirrhotic patients, microorganisms of enteric origin account for tained at paracentesis should be analyzed for cell count, differ-
Ç70% of the pathogens. ential count, and protein concentration, and a gram stain and
E. coli is the most frequently recovered pathogen, followed culture should be performed. Specimens for culture should be
by Klebsiella pneumoniae, S. pneumoniae, and other strepto- sent in an airless, capped syringe or injected directly into aero-
coccal species, including enterococci. Staphylococcus aureus bic and anaerobic broth culture media; volumes of §10 mL
is an unusual cause of primary peritonitis, accounting for only will increase the yield of cultures [6].
2% – 4% of cases in most series, but has been noted especially A gram stain of the sediment is diagnostic when positive
in patients with erosion of an umbilical hernia. Anaerobes and but is more commonly negative. Bacteremia occurs in up to
microaerophilic organisms are infrequently reported [4]. Possi- 75% of patients with primary peritonitis due to aerobic bacteria,
ble explanations include the intrinsic bacteriostatic activity of but it is rare in those with peritonitis due to anaerobes. Usually
ascites against Bacteroides species, the relatively high pO2 of the same organisms isolated from the peritoneal fluid are recov-
ascitic fluid, and the lack of optimal anaerobic bacteriologic ered from the blood.
techniques used to study patients in the past. The presence The ascitic fluid protein concentration may be low in primary
of anaerobes correlates strongly with polymicrobial infection. peritonitis (õ3.5 g/L) because of hypoalbuminemia and dilu-
Occasionally, primary peritonitis may also be caused by Neisse- tion of ascitic fluid with transudate from the portal system.
ria gonorrhoeae, Chlamydia trachomatis, Mycobacterium tu- The leukocyte count in peritoneal fluid usually is ú300/mm3
berculosis, or Coccidioides immitis. (ú1,000/mm3 in 85%), with granulocytes predominating in
Patients who have positive cultures of ascitic fluid with few ú80% of cases. However, the total leukocyte count of some
leukocytes and no clinical signs of peritonitis are considered patients with ascites uncomplicated by infection may be simi-
to have bacterascites. This may represent early colonization larly elevated. Indeed, an increase in ascitic leukocyte counts
before a host response. Mortality among patients with a low has been noted during diuresis in patients with chronic liver
leukocyte response is the same as among those with a greater disease.
response. Conversely, several series have identified cases of Other parameters of ascitic fluid that may help in diagnosing
primary peritonitis with negative ascitic fluid cultures, termed primary bacterial peritonitis are pH and lactate concentration
culture-negative neutrocytic ascites [5]. Blood cultures are pos- [7]. An ascitic fluid pH of õ7.35 and a lactate concentration of
itive for one-third of these patients. The frequency of negative ú25 mg/dL are more specific but less sensitive than a leukocyte
results of ascitic fluid cultures may be decreased by inoculating count of ú500/mm3 for diagnostic purposes; using all three
blood culture bottles with ascitic fluid at the bedside. parameters together increases the diagnostic accuracy.
Clinical presentation and evaluation. In children, primary In patients with negative ascitic fluid cultures, endoscopic
peritonitis is an acute febrile illness often confused with acute or laparoscopic peritoneal examination and biopsy may be nec-
appendicitis. Fever, abdominal pain, nausea, vomiting, and di- essary. Peritonitis secondary to other intraabdominal causes
arrhea usually occur, with diffuse abdominal tenderness, re- should be excluded, and specimens appropriate for fungal and
bound tenderness, and hypoactive or absent bowel sounds. In mycobacteriologic cultures should be obtained. In children, if
cirrhotic patients with primary peritonitis, the clinical manifes- gram-negative organisms, a mixed flora, or no organisms are
tations may be atypical. Onset may be insidious, with no find- obtained from peritoneal fluid, full exploratory laparotomy is

/ 9c2f$$ju45 05-07-97 17:21:37 cida UC: CID


CID 1997;24 (June) Peritonitis Update 1037

generally indicated to rule out possible intraabdominal sources examination for additional pathological conditions. Antimicro-
of continuing peritoneal contamination. However, in end-stage bial therapy is usually continued for 10 – 14 days if improve-
cirrhotic patients, exploratory laparotomy may be life-threaten- ment is noted, but short-course therapy for 5 days has been
ing, and the likelihood of finding a primary intraabdominal shown to be as efficacious as the longer course in some patients.
focus may be small. Administration of intraperitoneal antimicrobials is not neces-
Surgery for these patients can be deferred while the response sary.
to antimicrobial therapy is awaited. Patients with primary peri- Treatment of primary peritonitis is successful in more than
tonitis usually respond within 48 hours to appropriate antimi- one-half of cirrhotic patients, but because of the underlying
crobial therapy. The observation of an exponential rate of de- liver condition, the overall mortality has been reported as high
cline in the number of ascitic fluid leukocytes after initiation as 95% in some series. Those patients with the poorest progno-
of antimicrobial therapy for primary peritonitis has been found sis were found to have renal insufficiency, hypothermia, hyper-

Downloaded from https://academic.oup.com/cid/article-abstract/24/6/1035/339046 by guest on 24 October 2018


to help differentiate primary from secondary bacterial peritoni- bilirubinemia, and hypoalbuminemia [9].
tis [8]. Treatment of peritonitis caused by gram-positive organisms,
In patients with a subacute or chronic course of primary as well as of early infections, has been more frequently success-
peritonitis, other pathogens must be considered, including ful than treatment of gram-negative or late infections. In ne-
M. tuberculosis or C. immitis. The diagnosis of tuberculous phrotic patients with gram-positive infections or in patients
peritonitis can usually be made at operation or laparoscopy and who do not have a preterminal underlying illness, the survival
confirmed by the histologic characteristics of the peritoneal rate is ú90%.
biopsy specimen and bacteriologic examination of the perito- Given the common occurrence and high mortality of primary
neal biopsy specimen and fluid. The diagnosis of C. immitis peritonitis in the setting of cirrhosis with ascites, prevention is
peritonitis can be made with a wet mount of ascitic fluid, by a desirable strategy. This is particularly true for patients who
finding the organism in culture, or on histologic examination. are awaiting liver transplantation. Selective decontamination
Management and prevention. Because the gram stain is fre- of the gut with oral norfloxacin (400 mg daily) has been shown
quently negative in primary bacterial peritonitis, the initial to reduce the incidence of spontaneous bacterial peritonitis.
choice of antimicrobial drug is often empirical, based on the Norfloxacin has the disadvantage of selecting for gram-positive
most likely pathogens. Some of the third-generation cephalo- organisms, including S. aureus, and quinolone-resistant gram-
sporin antibiotics have been demonstrated to be as efficacious negative organisms. More recently, trimethoprim-sulfamethox-
as the combination of ampicillin plus an aminoglycoside in azole (double-strength, given once daily for 5 days each week)
primary bacterial peritonitis. They also eliminate the risk of has been shown to reduce the incidence of peritonitis and be
nephrotoxicity, which is sufficiently frequent in this group of well tolerated [10]. A survival-rate advantage has not been
patients to warrant avoidance of aminoglycosides if an equally demonstrated for any of these preventive regimens.
effective alternative antimicrobial regimen can be used.
Other antimicrobial agents such as the broad-spectrum penicil-
Secondary and Tertiary Peritonitis
lins (e.g., mezlocillin, ticarcillin, and piperacillin), carbapenems
(e.g., imipenem), and b-lactam antibiotic/b-lactamase-inhibitor Pathogenesis. Secondary intraabdominal infection usually is
combinations (e.g., ticarcillin-clavulanate and ampicillin-sulbac- due to spillage of gastrointestinal or genitourinary microorgan-
tam) are potential alternatives. If peritonitis develops during isms into the peritoneal space as a result of loss of integrity of
hospitalization, the therapeutic regimen, such as administration the mucosal barrier. Examples include appendicitis, diverticuli-
of an aminoglycoside antibiotic and an antipseudomonal penicil- tis, cholecystitis, penetrating wound of the bowel, and perfora-
lin or cephalosporin in combination, should also be active against tion of a gastric or duodenal ulcer. Secondary infection is rela-
Pseudomonas aeruginosa. tively common, taking the form of either generalized peritonitis
For those situations in which the gram stain is suggestive of or localized abscesses. Abscesses may be restricted to the im-
a Bacteroides species or polymicrobial peritonitis is evident, mediate peritoneal space around a diseased intraabdominal or-
antimicrobials with activity against the Bacteroides fragilis gan, such as pericholecystic, periappendiceal, or peridiverticu-
group and other anaerobic organisms should be added (e.g., lar abscesses, or to certain peritoneal recesses, such as
metronidazole, clindamycin). The antimicrobial regimen can interloop, subdiaphragmatic, subhepatic, lesser sac, or pelvic
be modified once the results of the culture and susceptibility abscesses.
tests are available. Peritoneal signs suggestive of appendicitis in immunocom-
In those cases where there is a strong clinical suspicion of promised patients, e.g., patients with AIDS, organ transplant
primary bacterial peritonitis but all cultures are sterile, anti- recipients, and those receiving chemotherapy or corticosteroids
microbial therapy should be continued. Clinical improvement, for neoplasms (especially myelosuppressive drugs), may be due
together with a significant decline in the ascitic fluid leukocyte to typhlitis, an inflammation of the cecum [11]. Cecal ulceration
count, should occur after 24 – 48 hours of antimicrobial therapy in these patients may progress to perforation and secondary
if the diagnosis is correct; failure to respond should prompt an peritonitis with colonic flora. Perforation complicating penetrat-

/ 9c2f$$ju45 05-07-97 17:21:37 cida UC: CID


1038 Johnson, Baldessarre, and Levison CID 1997;24 (June)

ing cytomegalovirus enterocolitis has been described as a com- can undergo alteration as a result of the primary disease process
mon cause of acute abdomen in patients with AIDS [12]. or previous antimicrobial therapy. For example, diseases of the
Tertiary peritonitis has been conceived as a later stage in stomach that result in obstruction, the loss of gastric acidity
the disease, when clinical peritonitis and systemic signs of (e.g., bleeding, gastric ulcer, or carcinoma), or use of acid-
sepsis (e.g., fever, tachycardia, tachypnea, hypotension, reducing drugs may cause gastric colonization with oral anaer-
elevated cardiac index, low systemic vascular resistance, leuko- obes, such as non-fragilis Bacteroides and Fusobacterium
penia or leukocytosis, and multiorgan failure) persist after treat- species and other oropharyngeal organisms, e.g., viridans strep-
ment for secondary peritonitis and either no organisms or low- tococci, microaerophilic streptococci, Candida species, and
virulence pathogens, such as enterococci and fungi, are isolated lactobacilli.
from the peritoneal exudate. These organisms may gain access Gastric perforation is associated with either sterile chemical
to the peritoneal cavity by contamination during operative in- peritonitis or peritonitis due to the above-mentioned pathogens,

Downloaded from https://academic.oup.com/cid/article-abstract/24/6/1035/339046 by guest on 24 October 2018


terventions, by selection from the initial polymicrobial perito- depending on the underlying gastric condition. Similarly, the
neal inoculum by antibiotic therapy, or by translocation of normal sparse flora of the small bowel may be altered by gastric
bowel flora. Translocation may be promoted by intestinal isch- disease or small-bowel ileus.
emia, endotoxemia, malnutrition, or proliferation of resistant With perforation of the colon, initially enormous numbers
bowel flora by antibiotic pressure. (a total of Ç1012/mL) of the hundreds of different species
The cytokine response in peritonitis has been the subject of that constitute the normal colonic microflora spill into the
a recent excellent review [13]. Undoubtedly, many of the sys- peritoneal cavity. A simplification of the numerous species
temic as well as abdominal manifestations of peritonitis are then occurs, so that once peritoneal infection is established,
mediated by cytokines, such as TNF, IL-1, IL-6, IFN-g, and only about five pathogens on average remain, usually three
others. Cytokines appear in the systemic circulation of patients anaerobic and two aerobic species. In patients with gangre-
with peritonitis and to a much greater extent in the peritoneal nous or perforated appendicitis, the average number of organ-
exudate [14]. These cytokines are produced by macrophages isms recovered from clinical specimens has been reported to
and other host cells in response to bacteria or bacterial products, be as high as 9.8 and 12.7, respectively, with 75% of the flora
such as endotoxin [15], or by tissues traumatized during the consisting of anaerobes [30].
operative procedure [16]. Another potential source is direct The obligate anaerobes isolated have been found to be more
translocation of cytokines through the intestinal barrier. oxygen-tolerant and have identifiable virulence factors, as com-
Cytokine responses have been studied in the peritoneal exu- pared with the rest of the obligate anaerobic microflora.
date in experimental animal models of peritonitis [17 – 20], in B. fragilis is the most frequently isolated anaerobe following
patients with spontaneous bacterial peritonitis [21, 22], in pa- colonic perforation, and E. coli is the most frequently isolated
tients undergoing continuous ambulatory peritoneal dialysis facultative anaerobe.
(CAPD) [23 – 25], and in patients with severe secondary bacte- In a now-classic series of experiments in rodents, Weinstein
rial peritonitis who were undergoing planned relaparotomy and co-workers clarified the sequence of events that occurs
[14]. Antibodies to TNF have been found to fail to protect following contamination of the peritoneum with fecal flora
against death [26] and failed to reduce serum levels of IL-1 [31]. In this model, E. coli is responsible for sepsis and mortal-
and IL-6 in an experimental model of peritonitis [17, 20, 27]. ity with early peritonitis, and B. fragilis, in concert with
In contrast, antibodies to endotoxin were found to prevent death E. coli and possibly other microorganisms such as enterococci,
in this model, as well as to reduce bacterial numbers in the is responsible for late peritoneal abscess formation. Such syn-
peritoneal exudate [28]. Antibodies to IFN-g also afforded a ergy between anaerobes and facultative microorganisms has
protective effect both in this model of experimental peritonitis long been recognized in mixed infections [32].
and following intravenous injection of endotoxin [29]. Some of the microorganisms isolated apparently owe their sur-
Microbiology. With gastrointestinal perforation as the pre- vival largely to the presence of other bacteria in the poly-
cipitating event, the number and types of microorganisms iso- microbial infection, such as B. fragilis and E. coli, which if elimi-
lated from the peritoneal cavity depend on the level of the nated by specific antimicrobial therapy will result in coincident
perforation. The stomach in the fasting state contains a sparse disappearance of these other microorganisms. The lower intestinal
microflora of a few relatively more acid-resistant species, e.g., flora can be altered in the severely ill, hospitalized patient under
lactobacilli or Candida species. Similarly, the duodenum and the pressure of antibiotic usage that allows proliferation of multi-
proximal small bowel contain a sparse microflora in the fasting ple-drug-resistant microorganisms, such as P. aeruginosa, Entero-
state, whereas the colon contains a high microbial density, i.e., bacter species, multiple-drug-resistant enterococci, and Candida
about 1012/g, of which ú99.9% are obligate anaerobes, mainly species. These microorganisms can then contribute to peritoneal
of the B. fragilis group. infection that may follow colonic perforation.
E. coli, the predominant colonic facultative anaerobe, is The same microorganisms may also be isolated from patients
found at counts of 106 – 8/g, while enterococci are less numerous with so-called tertiary peritonitis, i.e., persistent peritonitis in
at counts of 104 – 6/g. The characteristic microflora, however, patients with impaired host defenses and multiple organ dys-

/ 9c2f$$ju45 05-07-97 17:21:37 cida UC: CID


CID 1997;24 (June) Peritonitis Update 1039

function who are unresponsive to initial management [33]. therapeutic attempts [46]. This has led to investigation of endo-
However, monomicrobial infection with microorganisms that toxin and cytokine levels in circulation to predict outcome.
have low pathogenicity, such as Candida species, enterococci, However, the magnitude of levels of endotoxin, TNF, and
and coagulase-negative staphylococci, has been noted even in IL-6, in circulation in patients with peritonitis, has not been
acute peritonitis in patients with severely impaired defenses invariably related to prognosis [14, 47 – 51]. It has been sug-
[34]. P. aeruginosa usually is thought of as a nosocomial patho- gested that cytokine levels in the peritoneal exudate, rather than
gen that emerges under the selective pressure of broad- the blood, better reflect the severity of the compartmentalized
spectrum antimicrobial agents. In several studies, however, this peritoneal infection and predict outcome [14].
organism has been isolated in up to 24% of patients with acute Management and prevention. A skeptical attitude is neces-
community-acquired perforating appendicitis [35, 36]. sary when reviewing reports on clinical trials of antimicrobial
Although enterococci are found in 20% of intraabdominal therapy for intraabdominal sepsis. Surgical therapy alone may

Downloaded from https://academic.oup.com/cid/article-abstract/24/6/1035/339046 by guest on 24 October 2018


infections, their exact role in polymicrobial infection and the be sufficient to cure many otherwise healthy, young patients
need for specific antimicrobial therapy remain controversial. with intraabdominal infection who have no signs of severe
Selective therapy against E. coli and B. fragilis, which has sepsis; even antimicrobial agents to which the pathogens are
minimal in vitro activity against enterococci, has been found resistant may be associated with a good outcome for these
to be sufficient to reduce enterococcal counts [37]. Neverthe- patients.
less, in animal models of experimental polymicrobial intra- To establish a specific role for antimicrobial regimens re-
abdominal infection, enterococci have been found to be a sig- quires clinical trials with sufficient numbers of high-risk pa-
nificant component of the inoculum, which enhances abscess tients whose severity of illness has been stratified by APACHE
formation, weight loss, bacteremia with B. fragilis and E. coli, II scoring. Clinical trials are frequently diluted by low-risk
and mortality [37, 38]. patients, since the sickest patients who would test the efficacy
Similarly, clinical reports have indicated the emergence of of the antimicrobial agent are often excluded by strict enroll-
enterococcal abscesses and bacteremia after treatment of ment requirements.
intraabdominal sepsis with antimicrobial agents that lack sig- Medical management of secondary peritonitis includes use
nificant in vitro enterococcal activity [39 – 41]. In addition, a of antimicrobial therapy and supportive measures to maintain
recent multicenter study of intraabdominal infection has found vital functions, e.g., to improve or maintain circulation, nutri-
that the presence of enterococci in the initial culture, in addition tion, and oxygenation to vital organs. Antimicrobial agents
to APACHE II score, independently predicted treatment failure must penetrate to the site of infection in concentrations that
with broad-spectrum antimicrobial regimens that lacked spe- are sufficient to overcome the effects of high bacterial density,
cific enterococcal activity [42]. APACHE II score, age, length metabolic inactivity and slow growth rate of the bacterial
of preinfection hospital stay, and postoperative infections pre- inoculum, low pH, low redox potential, necrotic tissue, and
dicted the presence of enterococci. It is unknown if initial bacterial products that may lower the drugs’ activity. For
inclusion of antienterococcal therapy will improve outcome for example, aminoglycosides and clindamycin are less active at
these high-risk patients. acid pH values, aminoglycosides are less active at low redox
Clinical presentation and evaluation. CT has become invalu- potentials, and b-lactam drugs are less active against high
able in evaluating patients suspected of having an intraabdomi- bacterial densities.
nal infection. CT- or ultrasonography-guided aspiration of sus- The animal model of intraabdominal sepsis demonstrated the
pected intraabdominal abscesses has also become standard in necessity of treating both the facultative enteric gram-negative
evaluating and managing selected patients. Intraabdominal in- bacilli, namely E. coli, and the anaerobic gram-negative bacilli,
fection encompasses many different pathological and clinical namely B. fragilis. Empirical use of an antimicrobial regimen
entities that are associated with widely varying mortality rates active against these organisms has been well established. In-
that range from zero to 60%. deed, the need for intraoperative cultures to document etiologi-
The ability to predict outcome and stratify severity of disease cal microbes and their antimicrobial susceptibilities has been
is important for clinical decision-making as well as ensuring questioned, because the results are rarely available to influence
comparability in trials that evaluate different management strat- clinical decisions [52].
egies with surgical protocols or antimicrobial agents [43]. Out- Early clinical trials have established the therapeutic regimen
come has been found to be related mainly to host factors (e.g., of clindamycin plus aminoglycoside as the ‘‘gold standard’’
preoperative nutritional status, organ impairment, the severity [53, 54]. Aminoglycosides are frequently underdosed because
of the patient’s systemic response, and the premorbid physio- of fear of nephrotoxicity or because of underestimation of the
logical reserves, as predicted by the APACHE II scoring sys- expanded volume of distribution in critically ill patients with
tem) rather than to type and source of the infection [44, 45]. intraabdominal sepsis. Once-daily aminoglycoside therapy —
Death from intraabdominal infection, especially when the in which the total daily dose is given to patients with normal
tertiary phase is reached, is thought to result from an exagger- renal function as a single dose every 24 hours rather than as
ated uncontrolled cytokine release that is unresponsive to all multiple smaller, divided doses — obviates these dosing prob-

/ 9c2f$$ju45 05-07-97 17:21:37 cida UC: CID


1040 Johnson, Baldessarre, and Levison CID 1997;24 (June)

lems, because both the bactericidal activity and postantibiotic as the appendix or gallbladder, after resection of the organ.
effect of aminoglycosides are concentration-dependent, while Similarly, contamination of the peritoneum from a defect in
their nephrotoxicity is time-dependent. However, too few se- the intestinal wall, such as immediately following penetrating
verely ill patients with intraabdominal sepsis have been studied abdominal trauma, may also require only operative intervention
to allow recommendation of the general use of single daily to remove the diseased organ and a brief course of antimicrobial
doses of these drugs. therapy [53]. Persistent signs of sepsis suggest formation of
Regimens in which a third-generation cephalosporin is substi- an intraabdominal abscess that requires drainage, continued
tuted for the aminoglycoside or metronidazole is substituted for contamination of the peritoneum from an inadequately con-
clindamycin compare favorably to the ‘‘gold standard.’’ Resis- trolled source, superimposed nosocomial infection with a resis-
tance, however, emerges readily under selective pressure of anti- tant pathogen, or tertiary peritonitis.
microbial therapy with third-generation cephalosporins among Treatment against Enterococcus or Candida species in-

Downloaded from https://academic.oup.com/cid/article-abstract/24/6/1035/339046 by guest on 24 October 2018


certain gram-negative bacilli that produce inducible b-lacta- volved in polymicrobial infections is controversial. Identifi-
mases, such as Enterobacter, Serratia, Citrobacter, Morganella, cation of either microorganism in blood cultures, as the sole
and Acinetobacter species and P. aeruginosa. These organisms organism within residual or recurrent intraabdominal infec-
have a high spontaneous mutation rate for constitutive produc- tion, or as the predominant pathogen on a gram stain of
tion of large amounts of these b-lactamases that confer resistance peritoneal exudate is an indication for specific antimicrobial
to all b-lactam drugs, except the carbapenems (imipenem and therapy plus adequate surgical debridement. Enterococci
meropenem) and cefepime, and are poorly antagonized by sul- have emerged as leading nosocomial pathogens, undoubtedly
bactam, clavulanic acid, and tazobactam. as a result of their inherent resistance to many commonly
Patients likely to be infected with these organisms — e.g., used antimicrobial agents and the recent acquisition of resis-
those having prolonged hospital stays, prior antibiotic treat- tance to previous standard therapy, i.e., with ampicillin,
ment, postoperative peritonitis, or tertiary peritonitis — are best aminoglycosides, and vancomycin. Only clinically unproven
treated with a regimen that includes imipenem, meropenem, agents to which the strains are susceptible in vitro, such
cefepime, a fluoroquinolone, or an aminoglycoside. Resistance as doxycycline, novobiocin, or quinupristin/dalfopristin, are
among isolates of B. fragilis to metronidazole is rare, while available as potential therapeutic agents for infection caused
resistance to clindamycin is now unacceptably high in many by these multiresistant strains of enterococci.
centers. Furthermore, the relative incidence of Clostridium dif- Administration of amphotericin B is standard therapy for
ficile – associated diarrhea and colonization was found to be invasive candidal infection, although amphotericin lipid com-
less following use of metronidazole than that following use of plex is an equally efficacious, less nephrotoxic, but more expen-
clindamycin in a retrospective study [55]. sive alternative. Azoles such as fluconazole and itraconozole
Microaerophilic gram-positive cocci, which are frequent co- are also less toxic, although no comparative trials for candidal
pathogens in polymicrobial anaerobic infection, are resistant peritonitis have been performed. Candida krusei, Candida trop-
to metronidazole, unlike clindamycin, so if metronidazole is icalis, and Torulopsis glabrata are inherently more resistant to
used it should be combined with an agent active against these azoles, and resistance to azoles among previously susceptible
pathogens, such as a b-lactam antibiotic other than aztreonam. Candida species is increasing.
Aztreonam, fluoroquinolones, and aminoglycosides also lack Although a comprehensive discussion of surgical manage-
activity against microaerophilic gram-positive cocci and theo- ment of secondary peritonitis is beyond the scope of this re-
retically may not be optimal agents to combine with metronida- view, certain recent trends will be mentioned [59, 60]. Optimal
zole, although clinical trials of these combinations have been management includes the following: (1) bowel decompression,
found to be efficacious in intraabdominal infection [56]. e.g., by proximal colostomy for perforation, diverticulitis, or
Monotherapy with agents that have activity against both colonic carcinoma; (2) closing of traumatic perforations and
aerobes and anaerobes includes the carbapenems imipenem and resection of a diseased, perforated viscus to stop continued
meropenem and the b-lactam/b-lactamase combinations, such peritoneal contamination; and (3) drainage of any purulent col-
as ampicillin/sulbactam, ticarcillin/clavulanate, and piperacil- lections to reduce the bacterial inoculum and to remove exces-
lin/tazobactam. Unacceptably high B. fragilis resistance to cef- sive levels of proinflammatory cytokines and other adjuvants,
oxitin has been found in many centers; cefotetan, another sec- such as fecal matter, food, blood, bile, bullets, or barium.
ond-generation cephalosporin, is less active than cefoxitin In the absence of perforation, when the disease process, e.g.,
against certain species in the B. fragilis group. acute appendicitis or necrotic bowel, is anticipated to progress,
The duration of antimicrobial therapy after adequate surgery the involved organ is resected. Laparoscopic appendectomy
is usually 5 – 7 days but depends on severity of infection, clini- has been recommended for acute appendicitis, with conversion
cal response, and normalization of the WBC count [53, 57, to open appendectomy for perforated appendix or an inflamma-
58]. Only a short course of antimicrobial therapy (24 hours) is tory mass, as well as laparoscopic cholecystectomy for acute
required for sterile peritonitis that occurs in the peritoneal space cholecystitis (with conversion to an open procedure when tech-
around an infected but resectable intraabdominal organ, such nical difficulties are encountered).

/ 9c2f$$ju45 05-07-97 17:21:37 cida UC: CID


CID 1997;24 (June) Peritonitis Update 1041

Abscesses that present as localized peritonitis may be drained nias, and tertiary peritonitis with organisms such as enterococci
percutaneously with the aid of ultrasonography or CT, followed or Candida species [63 – 65]. Indeed, repeated entry into the
by definitive surgery, if necessary. Percutaneous drainage of inflamed peritoneum may further escalate the cytokine cascade.
a peridiverticular abscess may permit a subsequent one-stage A review concluded that in the absence of randomized con-
procedure of primary resection and immediate anastomosis. trolled prospective trials with appropriate stratification of pa-
Peritonitis caused by colonic perforation due to diverticuli- tients by severity of illness, there is insufficient evidence to
tis or colon cancer has been treated with one of three proce- determine if these procedures improve outcome of severe dif-
dures, depending on the particular clinical situation: (1) a fuse peritonitis [66].
three-stage procedure, which involves an initial proximal co-
lostomy to decompress the bowel and divert the fecal stream,
Peritonitis Complicating Peritoneal Dialysis
followed by resection of the diseased bowel, and finally anas-

Downloaded from https://academic.oup.com/cid/article-abstract/24/6/1035/339046 by guest on 24 October 2018


tomosis to restore bowel continuity several months later; (2) Pathogenesis. Since its development in the late 1970s,
a two-stage procedure, which involves initial resection and CAPD has provided a safe, cost-effective treatment for end-
temporary proximal colostomy, with either a mucous fistula stage renal disease. Unfortunately, the technique is often aban-
or a blind pouch (Hartmann’s procedure), followed by anasto- doned because of its most common complication, peritonitis
mosis; or (3) a one-stage procedure of primary resection and [67]. The incidence of peritonitis complicating CAPD varies
immediate anastomosis. considerably between individual patients and centers. Rates
The three-stage procedure has traditionally been reserved for tend to reflect the experience of the center, the specific technol-
critically ill, high-risk patients; however, the two-stage proce- ogy used, and the users’ susceptibility to infection and ability
dure may be preferred for these patients because it eliminates to comply with procedures [68]. Overall, the average incidence
the source of peritoneal contamination early [61]. The one- of peritonitis is 1.3 – 1.4 episodes per patient per year [69].
stage procedure in the patient with colonic perforation has been More than half of these episodes are experienced by only 25%
questioned because the lumen of the bowel is not cleansed of patients.
preoperatively and because of the assumed risk of breakdown The two most important routes for development of peritonitis
of the anastomosis in the presence of peritonitis. However, in CAPD patients are (1) transluminal, resulting from a break in
the one-stage primary resection and immediate anastomosis sterile technique during dialysate exchange, and (2) contiguous
eliminate need for further hospitalization and shorten disability spread, in which microorganisms access the peritoneum along
due to a colostomy. Indeed, the one-stage procedure has been the tract of the dialysis catheter. Less common portals of entry
shown to be efficacious for the moderate-risk patient with co- are hematogenous spread from a distant site of infection and
lonic perforation (APACHE II score of £15), even in the direct contamination from the gastrointestinal tract. Divertic-
case of emergency when the bowel has not been cleansed or ular disease of the nonsigmoid colon appears to be a risk factor
peritonitis is present [61]. for acquisition of infection of intestinal origin, presumably
Intraoperative peritoneal lavage with saline, following through occult microperforations; however, isolation of multi-
drainage of purulent peritoneal exudates, fecal matter, food, ple enteric pathogens from peritoneal fluid, especially anaero-
and other foreign debris, is standard procedure during laparo- bic bacteria, suggests fecal contamination from gross colonic
tomy for peritonitis. However, radical peritoneal debridement perforations [68].
of all fibrinous deposits on peritoneal surfaces is no longer Microbial factors that may contribute to pathogenesis of
thought to be effective [62]. Continuous peritoneal lavage for peritonitis include ability to grow in dialysis fluids and pro-
48 – 72 hours postoperatively or until the fluid is clear has duction of extracellular slime (biofilm). Once organisms gain
been studied, but at present the evidence is insufficient to access to the peritoneal cavity, further growth may depend on
recommend this procedure. Addition of antibiotics or anti- their survival in the presence of dialysis fluid. Fresh dialysate
septics to intraperitoneal lavage fluid has also been shown to solutions are capable of supporting growth of E. coli but
have no added benefit [53]. not that of staphylococci. However, after instillation into the
Similarly, there has been interest in the role of planned relap- peritoneal cavity, dialysis effluent supports growth of both
arotomies to treat patients with severe peritonitis. Here, the organisms [69].
commitment is made at the first operation to perform laparo- Other studies have shown that the growth of P. aeruginosa
tomies at frequent intervals until the abdomen is macroscopi- and E. coli is enhanced 1,000-fold in dialysis fluids from pa-
cally ‘‘clean,’’ with additional surgical procedures, such as tients with peritonitis, compared with that in such fluids from
resections, performed as necessary [63]. The abdominal fascia uninfected controls [70]. Both staphylococci and Candida albi-
is left open between laparotomies and the defect bridged by cans grow as microcolonies on polymeric surfaces [71]. Sur-
saline-soaked gauze or by a temporary abdominal closure de- rounding biofilm serves to anchor the organisms and protect
vice, such as mesh. them from host defenses and antibiotic activity [72].
These demanding and costly procedures have been compli- The clinical observation that some patients remain free of
cated by multiple fistulas, wound contamination, incisional her- CAPD-related peritonitis for years suggests that host defense

/ 9c2f$$ju45 05-07-97 17:21:37 cida UC: CID


1042 Johnson, Baldessarre, and Levison CID 1997;24 (June)

factors may also be important in the pathogenesis of this infec- Clinical presentation and evaluation. Criteria for the diagno-
tion [73]. Microbial pathogens that reach the dialyzed perito- sis of CAPD-associated peritonitis are (1) signs and symptoms
neal cavity are removed by three major lines of defense. First, of peritoneal irritation, (2) cloudy dialysate effluent with a
despite the dilution of fibrinogen and coagulation proteins, fi- leukocyte count of ú100/mm3, and (3) a positive culture of
brin trapping and sequestration of microorganisms operate ef- dialysate fluid. Any two of these criteria may be adequate to
ficiently in the dialyzed peritoneum. Second, removal of the establish the diagnosis [82]. Clinical manifestations of peritoni-
dialysate serves to eliminate or decrease the inoculum of con- tis vary from mild to severe, depending largely on the virulence
taminating organisms. Finally, a complex interplay of opsoni- of the pathogen and the time course of the infection [67].
zation, phagocytosis, and intracellular killing by peritoneal Generally, turbid dialysate is the first and most common symp-
macrophages, mesothelial cells, and neutrophils serves to com- tom to appear, followed shortly thereafter by abdominal pain
bat bacterial invasion and prevent infection. and tenderness.

Downloaded from https://academic.oup.com/cid/article-abstract/24/6/1035/339046 by guest on 24 October 2018


Unfortunately, the dialyzed peritoneal cavity is not a support- Laboratory evaluation of dialysate effluent is critical to estab-
ive milieu for operation of these cellular and immunologic lishing the diagnosis of CAPD-associated peritonitis. A dialy-
defense mechanisms because of its low pH (5.5 – 6.0), high sate leukocyte count of ú100/mm3 is the traditional diagnostic
osmolarity (300 – 400 mOsmol/kg), and decreased levels of IgG value but is not specific. The differential cell count of dialysate
and complement (1% of their normal levels). A correlation may have a better predictive value. In one study, polymorpho-
between deficiencies in these host defenses and patient risk for nuclear leukocytes comprised ú50% of the total cell count
peritonitis has not been conclusively identified [73]. (mean, 85%) in infected patients, while in uninfected patients
Microbiology. In patients undergoing CAPD, peritonitis is the proportion was õ40% (mean, 12%) [82]. A preponderance
usually caused by a single pathogen that originates from the of eosinophils in the fluid is seen in the self-limited condition
normal flora of the skin or upper respiratory tract. Approxi- ‘‘eosinophilic peritonitis,’’ which often follows placement of
mately 60% – 70% of cases are caused by gram-positive cocci, the Tenckhoff catheter and may represent allergy to the tubing
20% – 30% by gram-negative bacilli, and the remainder by vari- [83, 84].
ous other bacteria, fungi, and mycobacteria [74]. Coagulase- Peritoneal eosinophilia also occurs with fungal peritonitis
negative Staphylococcus is the single most common pathogen, or recent intraperitoneal administration of antibiotics. Gram
followed by S. aureus and species of Streptococcus. Among staining of dialysis fluid detects only 20% – 30% of peritonitis
the gram-negative organisms, most Enterobacteriaceae species episodes. Gram-positive organisms, especially S. aureus, are
have been associated with CAPD peritonitis, but no single more likely to be detected than are gram-negative ones [85].
species predominates in all reported series. Although a rare Cultures offer a greater yield than gram stains but require
pathogen in other types of peritonitis, P. aeruginosa occurs concentration of the dialysate by centrifugation, filtration, or
with relative frequency in CAPD peritonitis (5% – 10% of lysis-centrifugation [86].
cases). It warrants special note because of its association with Even with these specialized methods, 3% – 30% of CAPD-
significant morbidity and late complications [75, 76]. related peritonitis episodes are culture-negative. Presumably,
Fungi have become an important cause of CAPD-related most are due to fastidious, low-virulence organisms or coagu-
peritonitis in recent years because of their increasing frequency lase-negative staphylococci that survive less well in dialysis
and problematic management. Although many different fungi fluid [70]. Cases of culture-negative peritonitis that do not
have been isolated, including Aspergillus, Mucor, Rhizopus, respond to empirical antibiotic treatment should be further in-
Alternaria, Fusarium, Penicillium, and Drechslera species, vestigated by performance of dialysate fluid cultures for myco-
C. albicans accounts for 80% – 90% of cases [74, 76]. Risk bacteria and fungi. Blood cultures are usually negative, regard-
factors for acquisition of fungal peritonitis are bacterial perito- less of the etiologic agent.
nitis within the preceding month, recent hospitalization, pres- Management and prevention. The increased use of intraperito-
ence of extraperitoneal infection, use of immunosuppressive neal antibiotics as therapy for peritonitis has allowed most pa-
agents, and concomitant HIV infection, but diabetes mellitus tients to be treated on an ambulatory basis. Hospitalization is
does not pose a special risk [77, 78]. indicated for those who are severely ill or who are unable to
Mycobacteria have been described as pathogens in fewer than manage administration of intraperitoneal antibiotics at home. A
3% of cases of CAPD-related peritonitis, but they may also variety of antimicrobial agents have been used successfully for
account for a portion of cases labeled as ‘‘culture-negative’’ [79]. treatment, including penicillins, cephalosporins, aztreonam, imi-
Overall, 86% of mycobacterial isolates reported in the literature penem, aminoglycosides, fluoroquinolones, and macrolide and
have been of group IV (rapid growers), such as M. fortuitum and glycopeptide antibiotics. Initial therapy may be guided by results
M. chelonae [80]. One particularly large outbreak involved 17 of the dialysis fluid gram staining, but since these are uncom-
patients who developed infection with M. chelonae following monly positive, empirical treatment with a cephalosporin or van-
treatment with contaminated intermittent peritoneal dialysis ma- comycin plus aminoglycoside is typically initiated.
chines [81]. Other rare causes of peritonitis in patients undergoing In relatively mild episodes of peritonitis, a single agent with
CAPD are viruses, algae, and M. tuberculosis. antistaphylococcal activity may also be suitable. Antibiotic se-

/ 9c2f$$ju45 05-07-97 17:21:37 cida UC: CID


CID 1997;24 (June) Peritonitis Update 1043

lections are adjusted when the results of cultures and suscepti- 2. Nohr CW, Marshall DG. Primary peritonitis in children. Can J Surg 1984;
27:179 – 81.
bility tests are known. A single specific agent is adequate treat-
3. Conn HO, Fessel JM. Spontaneous bacterial peritonitis in cirrhosis: varia-
ment in the majority of cases of bacterial peritonitis. tions on a theme. Medicine (Baltimore) 1971; 50:161 – 97.
P. aeruginosa, however, has been associated with a high thera- 4. Sheckman P, Onderdonk AB, Bartlett JG. Anaerobes in spontaneous peri-
peutic failure rate and frequent relapses [75, 76]. A synergistic tonitis [letter]. Lancet 1977; 2:1223.
combination of antibiotics, such as an antipseudomonal b-lac- 5. Runyon BA, Hoefs JC. Culture-negative neutrocytic ascites: a variant of
spontaneous bacterial peritonitis. Hepatology 1984; 4:1209 – 11.
tam drug plus an aminoglycoside, has been recommended in
6. Runyon BA, Umland ET, Merlin T. Inoculation of blood culture bottles
addition to removal of the dialysis catheter. with ascitic fluid: improved detection of spontaneous bacterial peritoni-
Intraperitoneal administration of antibiotics is the preferred tis. Arch Intern Med 1987; 147:73 – 5.
method for drug delivery in CAPD-associated peritonitis be- 7. Stassen WN, McCullough AJ, Bacon BR, et al. Immediate diagnostic
cause it achieves high local concentrations and permits self- 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,
treatment by the patient [87 – 89]. Therapy is usually continued
alone and in combination. Gastroenterology 1986; 90:1247 – 54.
for 10 – 14 days but may need to be extended with unusually 8. Runyon BA, Hoefs JC. Ascitic fluid analysis in the differentiation of
severe or slow-to-respond infections. Recommendations for spontaneous bacterial peritonitis from gastrointestinal tract perforation
specific drug doses and routes of administration are the subject into ascitic fluid. Hepatology 1984; 4:447 – 50.
of several reviews [89, 90]. 9. Weinstein MP, Iannini PB, Stratton CW, Eickhoff TC. Spontaneous bacte-
rial peritonitis: a review of 28 cases with emphasis on improved survival
Treatment of fungal peritonitis is controversial because of the
and factors influencing prognosis. Am J Med 1978; 64:592 – 8.
lack of controlled studies and the small numbers of cases seen 10. Singh N, Gayowski T, Yu VL, Wagener MM. Trimethoprim-sulfamethox-
at any single center. Although there are reports of successful azole for the prevention of spontaneous bacterial peritonitis in cirrhosis:
treatment with intraperitoneal and/or systemic antifungal agents a randomized trial. Ann Intern Med 1995; 122:595 – 8.
alone [91, 92], removal of the dialysis catheter is usually prudent 11. Till M, Lee N, Soper WD, Murphy RL. Typhlitis in patients with HIV-1
infection. Ann Intern Med 1992; 116:998 – 1000.
to prevent relapse [68, 93]. A short course of systemic amphoteri-
12. Wilson SE, Robinson G, Williams RA, et al. Acquired immune deficiency
cin B (250–500 mg) is often given following catheter removal. syndrome (AIDS): indications for abdominal surgery, pathology, and
Some evidence has suggested that catheter removal alone may outcome. Ann Surg 1989; 210:428 – 34.
be curative in selected patients. Mycobacterial peritonitis also 13. Schein M, Wittmann DH, Holzheimer R, Condon RE. Hypothesis: com-
requires removal of the dialysis catheter for cure. Most of these partmentalization of cytokines in intraabdominal infection. Surgery
1996; 119:694 – 700.
organisms are resistant to conventional antituberculous agents,
14. Holzheimer RG, Schein M, Wittmann DH. Inflammatory response in peri-
and susceptibilities vary greatly among the species. Antibiotic toneal exudate and plasma of patients undergoing planned relaparotomy
selections should be guided by either in vitro susceptibility test for severe secondary peritonitis. Arch Surg 1995; 130:1314 – 20.
results or published recommendations [79–81]. 15. Giroir BP. Mediators of septic shock: new approaches for interrupting the
Prevention of peritonitis in patients undergoing CAPD requires endogenous inflammatory cascade. Crit Care Med 1993; 21:780 – 9.
intensive education regarding aseptic technique and catheter care. 16. Baigrie RJ, Lamont PM, Kwiatowski D, Dallman MJ, Morris PJ. Systemic
cytokine response after major surgery. Br J Surg 1992; 79:757 – 60.
Efforts to reduce the incidence of peritonitis by using oral or 17. Bagby GJ, Plessala KJ, Wilson LA, Thompson JJ, Nelson S. Divergent
intraperitoneal antibiotics have largely been unsuccessful [94–97]. efficacy of antibody to tumor necrosis factor-a in intravascular and
Although a decrease in the number of random positive dialysate peritonitis models of sepsis. J Infect Dis 1991; 163:83 – 8.
cultures has been observed in clinical studies, occurrence of clini- 18. Astiz ME, Saha DC, Carpati CM, Rackow EC. Induction of endotoxin
cal peritonitis was unaffected by prophylactic antibiotics. In addi- tolerance with monophosphoryl lipid A in peritonitis: importance of
localized therapy. J Lab Clin Med 1994; 123:89 – 93.
tion, topical mupirocin has been used to eliminate nasal coloniza-
19. McMasters KM, Cheadle WG. Regulation of macrophage TNF-a, IL-1 b
tion with S. aureus but has yet to be shown to significantly impact and 1a (1-Aa) mRNA expression during peritonitis is site dependent.
the incidence of CAPD-related peritonitis [98]. J Surg Res 1993; 54:426 – 30.
The most significant advances in the prevention of dialysis- 20. Zannetti G, Heumann D, Gérain J, et al. Cytokine production after intrave-
related peritonitis involve instrumentation changes, including nous or peritoneal gram-negative bacterial challenge in mice: compara-
tive protective efficacy of antibodies to tumor necrosis factor-a and to
(1) devices that facilitate connection of tubing, such as titanium
lipopolysaccharide. J Immunol 1992; 148:1890 – 7.
adapters; (2) devices that help maintain field sterility during 21. Propst T, Propst A, Herold M, et al. Spontaneous bacterial peritonitis is
exchanges, such as ultraviolet light systems and in-line filters; associated with high levels of interleukin-6 and its secondary mediators
and (3) devices that protect intraluminal sterility during in ascitic fluid. Eur J Clin Invest 1993; 23:832 – 6.
exchanges, such as connector systems with disinfectant 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
(Y-connector, O-set). Most such devices have been shown to
spontaneous bacterial peritonitis. Clin Infect Dis 1993; 17:218 – 23.
favorably impact the incidence of peritonitis but add apprecia- 23. Nakahama H, Tanaka Y, Shirai D, et al. Plasma interleukin-6 levels in
bly to the overall cost of CAPD. continuous ambulatory peritoneal dialysis and hemodialysis patients.
Nephron 1992; 61:132 – 4.
References 24. Zemel D, Krediet RT, Koomen GC, Kortekaas WM, Geertzen HG, ten
1. Wilcox CM, Dismukes WE. Spontaneous bacterial peritonitis: a review Berge RJ. Interleukin-8 during peritonitis in patients treated with CAPD:
of pathogenesis, diagnosis, and treatment. Medicine (Baltimore) 1987; an in-vivo model of acute inflammation. Nephrol Dial Transplant 1994;
66:447 – 56. 9:169 – 74.

/ 9c2f$$ju45 05-07-97 17:21:37 cida UC: CID


1044 Johnson, Baldessarre, and Levison CID 1997;24 (June)

25. Zemel D, Koomen GCM, Hart AA, ten Berge IJM, Struijk DG, Krediet RT. 46. Goris RJA, te Boekhorst TPA, Nuytinck JKS, Gimbrère JSF. Multiple-
Relationship of TNF-a, interleukin-6, and prostaglandins to peritoneal organ failure: generalized autodestructive inflammation? Arch Surg
permeability for macromolecules during longitudinal follow-up of peri- 1985; 120:1109 – 15.
tonitis in continuous ambulatory peritoneal dialysis. J Lab Clin Med 47. Damas P, Ledoux D, Nys M, et al. Cytokine serum level during severe
1993; 122:686 – 96. sepsis in humans: IL-6 as a marker of severity. Ann Surg 1992; 215:
26. Stack AM, Saladino RA, Thompson C, et al. Failure of prophylactic and 356 – 62.
therapeutic use of a murine anti – tumor necrosis factor monoclonal 48. Függer R, Zadrobilek E, Götzinger P, et al. Perioperative TNF-alpha and
antibody in Escherichia coli sepsis in the rabbit. Crit Care Med 1995; IL-6 concentrations correlate with septic state, organ function, and
23:1512 – 8. APACHE II scores in intra-abdominal infection. Eur J Surg 1993; 159:
27. Echtenacher B, Falk W, Männel DN, Krammer PH. Requirement of endog- 525 – 9.
enous tumor necrosis factor/cachectin for recovery from experimental 49. Patel RT, Deen KI, Youngs D, Warwick J, Keighley MRB. Interleukin 6
peritonitis. J Immunol 1990; 145:3762 – 6. is a prognostic indicator of outcome in severe intra-abdominal sepsis.
28. Battafarano RJ, Burd RS, Kurrelmeyer KM, Ratz CA, Dunn DL. Inhibition 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


of splenic macrophage tumor necrosis factor a secretion in vivo by 50. Hamilton G, Hofbauer S, Hamilton B. Endotoxin, TNF-alpha, interleukin-
antilipopolysaccharide monoclonal antibodies. Arch Surg 1994; 129: 6 and parameters of the cellular immune system in patients with intraab-
179 – 86. dominal sepsis. Scand J Infect Dis 1992; 24:361 – 8.
29. Kohler J, Heumann D, Garotta G, et al. IFN-g involvement in the severity 51. Barriere SL, Lowry SF. An overview of mortality risk prediction in sepsis.
of gram-negative infections in mice. J Immunol 1993; 151:916 – 21. Crit Care Med 1995; 23:376 – 93.
30. Bennion RS, Thompson JE, Baron EJ, Finegold SM. Gangrenous and 52. Wittmann DH, Bergstein JM, Frantzides C. Calculated empiric antimicro-
perforated appendicitis with peritonitis — treatment and bacteriology. bial therapy for mixed surgical infections. Infection 1991; 19(suppl 6):
Clin Ther 1990; 12:31 – 44. S345 – 50.
31. Weinstein WN, Onderdonk AB, Bartlett JG, Gorbach SL. Experimental 53. Bohnen JMA, Solomkin JS, Dellinger EP, Bjornson HS, Page CP. Guide-
intra-abdominal abscesses in rats: development of an experimental lines for clinical care: anti-infective agents for intra-abdominal infec-
model. Infect Immun 1974; 10:1250 – 5. tion: a Surgical Infection Society policy statement. Arch Surg 1992;
32. Rotstein OD, Pruett TL, Simmons RL. Mechanisms of microbial synergy 127:83 – 9.
in polymicrobial surgical infections. Rev Infect Dis 1985; 7:151 – 70. 54. Shands JW Jr. Empiric antibiotic therapy of abdominal sepsis and serious
33. Rotstein OD, Pruett TL, Simmons RL. Microbiologic features and treat- perioperative infections. Surg Clin North Am 1993; 73:291 – 306.
ment of persistent peritonitis in patients in the intensive care unit. Can 55. Gerding DN, Olson MM, Johnson S, Peterson LR, Lee JT Jr. Clostridium
J Surg 1986; 29:247 – 50. difficile diarrhea and colonization after treatment with abdominal infec-
34. Sawyer RG, Rosenlof LK, Adams RB, May AK, Spengler MD, Pruett tion regimens containing clindamycin or metronidazole. Am J Surg
TL. Peritonitis in the 1990s: changing pathogens and changing strategies 1990; 159:212 – 7.
in the critically ill. Am Surgeon 1992; 58:82 – 7. 56. Solomkin JS, Reinhart HH, Dellinger EP, et al. Results of a randomized
35. Aronoff SC, Olson MM, Gauderer MWL, Jacobs MR, Blumer JL, Izant trial comparing sequential intravenous/oral treatment with ciprofloxacin
RJ Jr. Pseudomonas aeruginosa as a primary pathogen in children with plus metronidazole to imipenem/cilastatin for intra-abdominal infec-
bacterial peritonitis. J Pediatr Surg 1987; 22:861 – 4. tions. Ann Surg 1996; 223:303 – 15.
36. Yellin AE, Heseltine PNR, Berne TV, et al. The role of Pseudomonas 57. Lennard ES, Derllinger EP, Wertz MJ, Minshew BH. Implications of
species in patients treated with ampicillin and sulbactam for gangrenous leukocytosis and fever at conclusion of antibiotic therapy for intra-
and perforated appendicitis. Surg Obstet Gynecol 1985; 161:303 – 7. abdominal sepsis. Ann Surg 1982; 195:19 – 24.
37. Montravers P, Andremont A, Massias L, Carbon C. Investigation of the 58. Stone HH, Bourneuf AA, Stinson LD. Reliability of criteria for predicting
potential role of Enterococcus faecalis in the pathophysiology of experi- persistent or recurrent sepsis. Arch Surg 1985; 120:17 – 20.
mental peritonitis. J Infect Dis 1994; 169:821 – 30. 59. Wittmann DH, Schein M, Condon RE. Management of secondary peritoni-
38. Matlow AG, Bohnen JMA, Nohr C, Christou N, Meakins J. Pathogenicity tis. Ann Surg 1996; 224:10 – 8.
of enterococci in a rat model of fecal peritonitis. J Infect Dis 1989; 160: 60. Nathens AB, Rotstein OD. Therapeutic options in peritonitis. Surg Clin
142 – 5. North Am 1994; 74:677 – 92.
39. Dougherty SH, Flohr AB, Simmons RL. ‘‘Breakthrough’’ enterococcal 61. Nespoli A, Ravizzini C, Trivella M, Segala M. The choice of surgical
septicemia in surgical patients: 19 cases and a review of the literature. procedure for peritonitis due to colonic perforation. Arch Surg 1993;
Arch Surg 1983; 118:232 – 8. 128:814 – 8.
40. Jones RN. Gram-positive superinfections following beta-lactam chemo- 62. Polk HC Jr, Fry DE. Radical peritoneal debridement for established perito-
therapy: the significance of the enterococcus. Infection 1985; 13(suppl nitis: the result of a prospective randomized clinical trial. Ann Surg
1):S81 – 8. 1980; 192:350 – 5.
41. Barrall DT, Kenney PR, Slotman GJ, Burchard KW. Enterococcal bacter- 63. Wittmann D, Aprahamian C, Bergstein JM. Etappenlavage: advanced dif-
emia in surgical patients. Arch Surg 1985; 120:57 – 63. fuse peritonitis managed by planned multiple laparotomies utilizing
42. Burnett RJ, Haverstock DC, Dellinger EP, et al. Definition of the role zippers, slide fastener, and Velcrow analogue for temporary abdominal
of Enterococcus in intraabdominal infection: analysis of a prospective closure. World J Surg 1990; 14:218 – 26.
randomized trial. Surgery 1995; 118:716 – 23. 64. Teichmann W, Wittmann DH, Andreone PA. Scheduled reoperations
43. Nyström P-O, Bax R, Dellinger EP, et al. Proposed definitions for diagno- (etappenlavage) for diffuse peritonitis. Arch Surg 1986; 121:147 – 52.
sis, severity scoring, stratification, and outcome for trials on intraabdom- 65. Cuesta MA, Doblas M, Castañeda L, Bengoechea E. Sequential abdominal
inal infection. World J Surg 1990; 14:148 – 58. reexploration with the zipper technique. World J Surg 1991; 15:74 – 80.
44. Pacelli F, Doglietto GB, Alfieri S, et al. Prognosis in intra-abdominal 66. Schein M, Hirshberg A, Hashmonai M. Current surgical management of
infections: multivariate analysis on 604 patients. Arch Surg 1996; 131: severe intraabdominal infection. Surgery 1992; 112:489 – 96.
641 – 5. 67. Korbet SM, Vonesh EF, Firanek CA. A retrospective assessment of risk
45. Christou NV, Barie PS, Dellinger EP, Waymack JP, Stone HH. Surgical factors for peritonitis among an urban CAPD population. Perit Dial Int
Infection Society Intra-abdominal Infection Study: prospective evalua- 1993; 13:126 – 31.
tion of management techniques and outcome. Arch Surg 1993; 128: 68. Saklayen MG. CAPD peritonitis: incidence, pathogens, diagnosis, and
193 – 9. management. Med Clin North Am 1990; 74:997 – 1010.

/ 9c2f$$ju45 05-07-97 17:21:37 cida UC: CID


CID 1997;24 (June) Peritonitis Update 1045

69. Linblad AS, Novak JW, Nolph KD, Stablein DM, Cutler SJ. The 1987 86. Bailie GR, Eisele G. Continuous ambulatory peritoneal dialysis: a review
USA National CAPD Registry report. Trans Am Soc Artif Intern Organs of its mechanics, advantages, complications, and areas of controversy.
1988; 34:150 – 6. Ann Pharmacother 1992; 26:1409 – 20.
70. Sheth NK, Bartell CA, Roth DA. In vitro study of bacterial growth in 87. Morse GD, Farolino DF, Apicella MA, Walshe JJ. Comparative study of
continuous ambulatory peritoneal dialysis fluids. J Clin Microbiol 1986; intraperitoneal and intravenous vancomycin pharmacokinetics during
23:1096 – 8. continuous ambulatory peritoneal dialysis. Antimicrob Agents Chemo-
71. Marrie TJ, Noble MA, Costerton JW. Examination of the morphology ther 1987; 31:173 – 7.
of bacteria adhering to peritoneal dialysis catheters by scanning and 88. Bennet-Jones D, Wass V, Mawson P, et al. A comparison of intraperitoneal
transmission electron microscopy. J Clin Microbiol 1983; 18:1388 – 98. and intravenous/oral antibiotics in CAPD peritonitis. Peritoneal Dialysis
72. Holmes CJ, Evands R. Biofilm and foreign body infection — the signifi- Bulletin 1987; 7:31 – 3.
cance to CAPD associated peritonitis. Peritoneal Dialysis Bulletin 1986; 89. Keane WF, Everett ED, Fine RN, et al. CAPD-related peritonitis manage-
6:168 – 77. ment and antibiotic therapy recommendations: Travenol Peritonitis
73. Holmes CJ. Peritoneal host defense mechanisms in peritoneal dialysis. 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


Kidney Int 1994; 46(suppl 48):S58 – 70. 7:55 – 62.
74. von Graevenitz A, Amsterdam D. Microbiological aspects of peritonitis 90. Keller E, Reetze P, Schollmeyer P. Drug therapy in patients undergoing
associated with continuous ambulatory peritoneal dialysis. Clin Micro- continuous ambulatory peritoneal dialysis: clinical pharmacokinetic
biol Rev 1992; 5:36 – 48. considerations. Clin Pharmacokinet 1990; 18:104 – 17.
91. Rubin J, Kirchner K, Walsh D, Green M, Bower J. Fungal peritonitis
75. Krothapalli R, Duffy WB, Lacke C, et al. Pseudomonas peritonitis and
during continuous ambulatory peritoneal dialysis: a report of 17 cases.
continuous ambulatory peritoneal dialysis. Arch Intern Med 1982; 142:
Am J Kidney Dis 1987; 10:361 – 8.
1862 – 3.
92. Venning MC, Ford M, Gould GK. Successful treatment of fungal peritoni-
76. Kaczmarski EB, Tooth JA, Anastassiades E, Manos J, Gokal R. Pseudomo-
tis in CAPD using oral fluconazole [letter]. Nephrol Dial Transplant
nas peritonitis with continuous ambulatory peritoneal dialysis: six year
1990; 5:555.
study. Am J Kidney Dis 1988; 14:413 – 7.
93. Nagappan R, Collins JF, Lee WT. Fungal peritonitis in continuous ambula-
77. Eisenberg ES, Leviton I, Soeiro R. Fungal peritonitis in patients receiving
tory peritoneal dialysis — the Auckland experience. Am J Kidney Dis
peritoneal dialysis: experience with eleven patients and review of the
1992; 20:492 – 6.
literature. Rev Infect Dis 1986; 8:309 – 21.
94. Sharma BK, Smith EC, Rodriquez H, Pillay VKG, Gandhi VC, Dunea G.
78. Dressler R, Peters AT, Lynn RI. Pseudomonal and candidal peritonitis as
Trial of oral neomycin during peritoneal dialysis. Am J Med Sci 1971;
a complication of continuous ambulatory peritoneal dialysis in human 262:175 – 8.
immunodeficiency virus – infected patients. Am J Med 1989; 86: 95. Axelrod J, Meyers BR, Hirschman SZ, Stein R. Prophylaxis with cephalo-
787 – 90. thin in peritoneal dialysis. Arch Intern Med 1973; 132:368 – 71.
79. Dunmire RB 3d, Breyer JA. Nontuberculous mycobacterial peritonitis 96. Low DE, Vas SI, Oreopoulos DG, et al. Prophylactic cephalexin ineffective
during continuous ambulatory peritoneal dialysis: case report and review in chronic ambulatory peritoneal dialysis [letter]. Lancet 1980; 2:
of diagnostic and therapeutic strategies. Am J Kidney Dis 1991; 18: 753 – 4.
126 – 30. 97. Churchill DN, Taylor DW, Vas SI, et al. Peritonitis in continuous ambula-
80. Hakim A, Hisam N, Reuman PD. Environmental mycobacterial peritonitis tory peritoneal dialysis patients: a randomized clinical trial of co-trimox-
complicating peritoneal dialysis: three cases and review. Clin Infect Dis azole prophylaxis. Peritoneal Dialysis Bulletin 1988; 8:125 – 8.
1993; 16:426 – 31. 98. Pérez-Fontán M, Rosales M, Rodrı́guez-Carmona A, et al. Treatment of
81. Band JD, Ward JI, Fraser DW, et al. Peritonitis due to a Mycobacterium Staphylococcus aureus nasal carriers in CAPD with mupirocin. Adv
chelonei – like organism associated with intermittent chronic peritoneal Peritoneal Dial 1992; 8:242 – 5.
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 The ‘‘Conflict-of-Interest Policy’’ of the Office of Con-
peritoneal dialysis effluent. J Clin Microbiol 1987; 25:2367 – 71.
tinuing Medical Education, UCLA School of Medicine,
83. Digenis GE, Khanna K, Panatlony D. Eosinophilia after implantation of
the peritoneal catheter. Peritoneal Dialysis Bulletin 1982; 2:98 – 9.
requires that faculty participating in a CME activity dis-
84. Gokal R, Ramos JM, Ward MK, Kerr DNS. ‘‘Eosinophilic’’ peritonitis close to the audience any relationship with a pharmaceu-
in continuous ambulatory peritoneal dialysis (CAPD). Clin Nephrol tical or equipment company which might pose a poten-
1981; 15:328 – 30. tial, apparent, or real conflict of interest with regard to
85. Ludlam HA, Price TNC, Berry AJ, Phillips I. Laboratory diagnosis of their contribution to the program. The author reports no
peritonitis in patients on continuous ambulatory peritoneal dialysis. J
conflict of interest.
Clin Microbiol 1988; 26:1757 – 62.

/ 9c2f$$ju45 05-07-97 17:21:37 cida UC: CID