Antibiotic Therapy for Peritonitis: Treatment Overview, Spontaneous Bacterial Peritonitis, Secondary and Tertiary Peritonitis 09/07/21 19.

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Antibiotic Therapy for

Peritonitis Treatment Overview
Updated: Jul 22, 2019
Author: Vinay Kumar Kapoor, MBBS, MS, FRCS, FAMS; Chief Editor: BS Anand, MD more...

TREATMENT OVERVIEW

Treatment Overview
Peritoneal infections are classified as primary, secondary, or tertiary. Primary peritoneal
infections arise from hematogenous dissemination, usually in the setting of an
immunocompromised state, while secondary infections are related to a pathologic process in an
abdominal organ, such as perforation, ischemia and gangrene, trauma, or a postoperative
problem, such as anastomotic leak. Tertiary peritoneal infection is a persistent or recurrent
infection that exists after an adequate initial therapy for secondary peritonitis.

Antibiotic therapy is used to prevent local and hematogenous spread of an intra-abdominal

infection and to reduce late complications. [1] Several different antibiotic regimens are available
for the treatment of intra-abdominal infections (see Table 1 below). [1]

Single-agent, broad-spectrum therapy and combination therapies have been used against these
infections, although no specific therapy has been found to be superior to another.

Infection of the abdominal cavity requires coverage for gram-negative and gram-positive
bacteria, as well as for anaerobes. Antipseudomonal coverage is recommended for patients who
have had previous treatment with antibiotics or who have had a prolonged hospitalization or any
intervention. [2]

In case of severe infections with features of systemic sepsis, a policy of "hit early and hit hard"
(starting therapy as soon as infection is suspected with broad spectrum antibiotics) reduces the
mortality of infection.

Choice of antibiotics largely depends on whether the infection is community acquired or hospital
acquired (nosocomial), the local spectrum of organisms grown and their sensitivity to antibiotics
(antibiogram) in similar patients in the near past, costs and side effects of the antibiotics, and
comorbidities (especially renal and liver dysfunction) in the patient.

Usually, in patients with intra-abdominal infection who have been treated with proper source
control and prompt surgical intervention, antibacterial therapy is given for 5-7 days, but this
regimen may need to be extended, depending on the clinical situation. [1] Shorter courses also

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Antibiotic Therapy for Peritonitis: Treatment Overview, Spontaneous Bacterial Peritonitis, Secondary and Tertiary Peritonitis 09/07/21 19.53

have been used successfully.

Antibiotics can be discontinued once the clinical signs of infection (eg, fever, tachycardia,
leukocytosis) have resolved. Recurrence is a concern with certain infections, such as those
with Candida and Staphylococcus aureus, and treatment should be continued for 2-3 weeks.

Table 1. Proposed Empirical Antimicrobial Therapy (Open Table in a new window)

Monotherapy Combination Therapy

Beta-lactam/Beta-lactamase inhibitor
Cephalosporin-based
combination

Amoxicillin/clavulanic acid Cefuroxime + metronidazole

Third- or fourth-generation cephalosporin +

Piperacillin/tazobactam
metronidazole

Ticarcillin/clavulanic acid

Cefoperazone/sulbactam

Carbapenems Quinolone-based

Ertapenem Ciprofloxacin + metronidazole

Imipenem/cilastatin

Imipenem/cilastatin/relebactam

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Antibiotic Therapy for Peritonitis: Treatment Overview, Spontaneous Bacterial Peritonitis, Secondary and Tertiary Peritonitis 09/07/21 19.53

Meropenem Aminoglycoside-based

Aminoglycoside + clindamycin

Other Other

Tigecycline Aztreonam + metronidazole

See Peritonitis and Abdominal Sepsis and Surgical Approach to Peritonitis for more complete
information on these topics.

Enterococcal Coverage
In patients with community-acquired peritonitis, coverage for Enterococcus is not recommended.
Enterococcal coverage may be warranted in patients with septic shock who have received
prolonged cephalosporin therapy, in patients who are immunosuppressed and are at risk for
bacteremia, in patients with prosthetic heart valves, and in patients with recurrent intra-
abdominal infections accompanied by severe sepsis. [1]

Candidiasis

Patients with intra-abdominal contamination are at a high risk for candidiasis, and this has led to
the increased use of antifungal prophylaxis. Patients who are immunocompromised or who have
received long-term, broad-spectrum antibiotic therapy (eg, patients with severe acute necrotizing
pancreatitis) or steroid therapy are predisposed to candidal infections.

Other predisposing factors include gastric acid suppressive therapy, central venous
catheterization and intravenous hyperalimentation, malnutrition, and diabetes.

Infection in the Critically Ill

Candida albicans is most commonly isolated from the peritoneum in critically ill patients with
culture-proven intra-abdominal infections and preoperative Acute Physiology and Chronic Health
Evaluation II (APACHE II) scores of greater than or equal to 15.

Additional common peritoneal organisms in this patient population are Enterococcus and
Enterobacter species and Staphylococcus epidermidis. These data suggest that the
microbiology of intra-abdominal infections may be inherently different in severely ill patients and
that broader antimicrobial, and possibly antifungal, coverage may be warranted in these cases.

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Spontaneous Bacterial Peritonitis

Spontaneous bacterial peritonitis (SBP) resulting from chronic liver disease or nephritic
syndrome with no obvious source of infection is the most common etiology of primary peritonitis.
Untreated SBP has a mortality rate of up to 50%, but with prompt diagnosis and treatment of the
condition, this figure may be reduced to 20%. Empiric therapy with a third-generation
cephalosporin must be started promptly. [3] SBP usually does not require any surgical
intervention.

The patient with SBP is also likely to require attention to changes in hemodynamic function
related to inflammatory pathways, as well as resultant renal function impairment, although a
discussion of this is beyond the scope of this article.

Specific agents
The infection in SBP is usually monomicrobial and most commonly caused by Escherichia coli.

Initial coverage should include gram-negative enteric bacteria and gram-positive cocci, which
are responsible for 90% of infections. [4] Cefotaxime is effective against 98% of causative
organisms and is considered the treatment drug of choice. Anaerobic, pseudomonal, and
staphylococcal coverage is not needed.

Cefotaxime (2 g IV q8h) has been shown to achieve excellent ascitic fluid levels. The dosing
interval may need to be reduced in patients with renal insufficiency.

Amoxicillin-clavulanic acid has been shown to be as effective as cefotaxime; however, a

parenteral formulation is not available in the United States. [5]

Oral ofloxacin has been reported to be as effective as cefotaxime in the treatment of SBP.
Ofloxacin should not be given to patients who are vomiting, in shock, bleeding, or in renal
failure.

Alternatively, intravenous ciprofloxacin (200 mg q12h for 2 d), followed by oral ciprofloxacin (500
mg q12h for 5 d), has been used successfully. To prevent fluoroquinolone resistance, these
antibiotics should not be used empirically to treat SBP.

When cultures identify a particular pathogen, susceptibility testing allows the clinician to narrow
the spectrum of the antibiotic.

Duration of therapy

The optimal duration of therapy is not known. In patients without shock, ileus, hepatic coma,
and/or renal failure, SBP usually resolves within 2-5 days of starting cefotaxime therapy.
Traditionally, a course of 10 days is recommended, although studies have suggested that 5 days
of therapy (with documentation of a decrease of peritoneal fluid WBC count to < 250 cells/µL)
may be sufficient in most cases. Surgical intervention is not required; in rare cases, laparoscopic
lavage may have to be performed if there is no response after adequate antibiotic therapy.

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Special circumstances

Renal impairment occurs in 33% of patients with SBP. [5] Albumin infusion with cefotaxime has
been shown to improve survival, compared with the use of cefotaxime alone. [6]

Avoid aminoglycosides in patients with liver disease, because these patients are at an increased
risk for nephrotoxicity.

Relapse

The risk of relapse after SBP is high (40-70% in 12 mo); various prophylactic antibiotic regimens
are available. A preliminary study found that long-term norfloxacin (400 mg/d) was effective for
secondary prevention of SBP. [7]

Secondary and Tertiary Peritonitis

In secondary peritonitis, systemic antibiotic therapy is the second mainstay of treatment
following source control (eg, removal of appendix, closure of perforation, resection of
gangrenous bowel, drainage of abscess). [8, 9, 10] Several studies suggest that antibiotic therapy
is not as effective in the later stages of infection and that early (preoperative) systemic antibiotic
therapy can significantly reduce the concentration and growth rates of viable bacteria in the
peritoneal fluid.

Antibiotic therapy begins with empiric coverage (effective against common gram-negative and
anaerobic pathogens), which should be initiated as soon as possible, with a transition made to
narrower-spectrum agents (step down approach) as culture results become available.

Tertiary peritonitis is persistent, residual, or recurrent peritoneal infection after adequate source
control and antibiotic therapy of secondary peritonitis. It manifests as prolonged systemic
inflammatory response syndrome (SIRS), sepsis, and septic shock. Multiple organ dysfunction
syndrome (MODS) associated with tertiary peritonitis responsible for its high mortality. Diagnosis
is established with imaging (ie, computed tomography scanning). Opportunistic, nosocomial and
facultative pathogenic organisms (eg, enterococci and enterobacter) and fungi are usually
involved. Treatment is largely with antibiotics and antifungals; nonsurgical intervention in the
form of image-guided percutaneous catheter drainage may be required if there are any
collections.

Specific conditions and effective agents

Perforations of upper GI tract organs are associated with gram-positive bacteria, whereas distal
small bowel and colon perforations involve polymicrobial aerobic and anaerobic species.

Antibiotic therapy appears to be less effective in tertiary peritonitis than in other forms of
peritonitis. Resistant and unusual organisms (eg, Enterococcus, Candida, Staphylococcus,
Enterobacter, Pseudomonas species) are found in a significant proportion of cases.

Culture results may be especially important in tertiary peritonitis, which is more likely to involve

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Antibiotic Therapy for Peritonitis: Treatment Overview, Spontaneous Bacterial Peritonitis, Secondary and Tertiary Peritonitis 09/07/21 19.53

gram-positive bacteria (enterococci); antibiotic-resistant, gram-negative bacteria; and yeast. In

community-acquired infections, a second- or third-generation cephalosporin or a quinolone with
or without metronidazole provides adequate coverage, as do broad-spectrum penicillins with
anaerobic activity (ie, ampicillin/sulbactam) and newer quinolones (ie, trovafloxacin,
clinafloxacin).

Most studies suggest that single-drug therapy is as effective as dual- or triple-combination

therapy in mild to moderate abdominal infections.

For peritoneal dialysis–associated infections, a Cochrane review of all published randomized

controlled trials did not find any significant differences between antimicrobial agents or
combinations, with similar response and relapse rates for glycopeptide regimens and first-
generation cephalosporins. [11] Intraperitoneal antibiotics had a lower failure rate than
intravenous regimens. Risk for early peritonitis is reduced with perioperative intravenous
antibiotics; other prophylactic approaches are not yet proven.

In severe and hospital-acquired intra-abdominal infections, imipenem, piperacillin/tazobactam,

and a combination of aminoglycosides and metronidazole are often effective.

A study of nearly 400 patients documented that ertapenem, a novel carbapenem with a half-life
that allows once-a-day dosing, was more effective (86.7% success rate) than
piperacillin/tazobactam (81.2% success rate) in the treatment of complicated intra-abdominal
infection and was well tolerated. Additional clinical antimicrobial studies are underway to
investigate the efficacy of new quinolones in the treatment of intra-abdominal infection.

Peritonitis can be caused by perforation of a tubercular ulcer (usually in the small intestine),
rupture of a caseous lymph node or as primary tuberculous peritonitis due to involvement of the
peritoneum. Diagnosis of tuberculosis is established by histologic examination of the resected
bowel, lymph node or peritoneal biopsy. Treatment of tuberculous peritonitis includes anti-
tubercular therapy.

Considerations for spectrum testing

With persistence of the infection (ie, tertiary peritonitis) and prolonged critical illness, obtaining
peritoneal fluid and/or abscess cultures with sensitivities at operation or drainage is important to
properly treat unusual (eg, gram-positive organisms, fungi) and resistant organisms (eg,
Enterococcus, Staphylococcus, Pseudomonas, resistant Bacteroides, Candida species).

Certain preexisting conditions, immunocompromised state, gastric acid suppression therapy,

and recent antibiotic use may also influence the spectrum of microorganisms. Consultation with
infectious disease specialists is warranted in these cases.

Duration of therapy
The optimal duration of antibiotic therapy must be individualized and depends on the underlying
pathology, severity of infection, speed and effectiveness of source control, and patient response
to therapy. In uncomplicated peritonitis in which there is early, adequate source control, a course
of 5-7 days of antibiotic therapy is adequate in most cases. Mild cases (eg, early appendicitis,
cholecystitis) may not need more than 24-72 hours of postoperative therapy.

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Inadequate initial therapy has been linked to worse outcomes, and these outcomes could not be
significantly changed by later specific or prolonged therapy. Antimicrobial therapy should
continue until signs of infection (eg, fever, tachycardia, leukocytosis) have resolved; if signs of
infection continue, persistent infection or the presence of a nosocomial infection should be
investigated.

Complicated persistent infections and infections in immunocompromised patients may warrant a

prolonged course of antibiotic therapy. In these cases, continuously seeking and aggressively
treating all new extraperitoneal and new or persistent intra-abdominal sources is important. The
length of the individual course of treatment is variable and is often linked to the signs of
resolution of the inflammatory process (eg, lack of fever for >24-48 h, return of the white blood
cell [WBC] count to the reference range levels).

Dangers of prolonged therapy

Some patients demonstrate persistent signs of inflammation without a defined infectious focus.
In these patients, continued broad-spectrum antibiotic therapy may be more harmful than
beneficial (eg, may promote emergence of resistant organisms or Clostridium difficile colitis),
and a trial of antibiotic therapy cessation under close surveillance may be warranted.

Intra-abdominal abscess

Antibiotics alone are seldom sufficient to treat intra-abdominal abscesses, and adequate
drainage (image-guided percutaneous catheter drainage or surgical drainage) of the abscess is
of paramount importance. For most of the commonly used antibiotics, drug levels achieved in
the abscess fluid are generally below the minimum inhibitory concentration–90 (MIC90) for
Bacteroides fragilis and Escherichia coli, and repeated dosing or high-dose therapy does not
improve penetration significantly.

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