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Antimicrobial approach to intra-abdominal infections

in adults
������: Miriam Baron Barshak, MD
������� ������: Stephen B Calderwood, MD
������ ������: Keri K Hall, MD, MS

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Sep 2023.

This topic last updated: Aug 15, 2022.

INTRODUCTION

Infections within the abdominal cavity typically arise because of inflammation or

disruption of the gastrointestinal tract. Less commonly, they can arise from the
gynecologic or urinary tract. Abdominal infections are usually polymicrobial and result in
an intra-abdominal abscess or secondary peritonitis, which may be generalized or
localized (phlegmon).

The approach to antimicrobial selection and administration for intra-abdominal infections

in adults is discussed here. The general and surgical management of these infections are
discussed in detail elsewhere. (See "Management of acute appendicitis in adults" and
"Acute colonic diverticulitis: Medical management" and "Acute colonic diverticulitis:
Surgical management" and "Acute cholangitis: Clinical manifestations, diagnosis, and
management" and "Treatment of acute calculous cholecystitis" and "Acalculous
cholecystitis: Clinical manifestations, diagnosis, and management" and "Overview of
gastrointestinal tract perforation".)

The approach to management of abscesses within specific intra-abdominal organs (such

as the liver or kidney) are also discussed in detail separately. (See "Pyogenic liver abscess"
and "Invasive liver abscess syndrome caused by Klebsiella pneumoniae" and "Renal and
perinephric abscess" and "Management and complications of tubo-ovarian abscess" and
"Posthysterectomy pelvic abscess".)

Spontaneous peritonitis and peritonitis associated with peritoneal dialysis are also
discussed elsewhere. (See "Spontaneous bacterial peritonitis in adults: Treatment and
prophylaxis" and "Microbiology and therapy of peritonitis in peritoneal dialysis".)

MICROBIOLOGY

Intra-abdominal infections usually arise after a breach in the intrinsic mucosal defense
barrier that allows normal bowel flora to inoculate the abdominal cavity. The precise
microbiological spectrum depends on the precise gastrointestinal source (ie, small versus
large bowel).

Colonic flora is especially common in intra-abdominal infections, reflecting the frequency

of associated diseases at this anatomic site, including appendicitis, diverticulitis,
carcinoma of the colon, inflammatory bowel disease, and previous colon surgery. Thus,
the predominant bacteria involved in such infections are coliforms (mainly Escherichia coli,
Klebsiella spp, Proteus spp, and Enterobacter spp) streptococci, enterococci, and anaerobic
bacteria ( picture 1). However, while colonic flora consists of approximately 400 species,
an average of only four to six species are generally recovered from these intra-abdominal
infections. The dominant isolates in most series are Bacteroides fragilis and E. coli
( table 1) [1-6]. The probable factors contributing to this phenomenon include the
limited ability of clinical laboratories to isolate all the different organisms as well as the
ability of specific organisms to cause infection and survive based upon their virulence
factors and capacity to adapt to new environmental conditions. For example, the capacity
of B. fragilis to tolerate small amounts of oxygen contributes to its emergence as a highly
invasive anaerobic pathogen in abdominal infections [7]. Experimental animal studies of
intra-abdominal sepsis suggest that both anaerobes and coliforms contribute to the
pathogenesis although they play different roles, with coliforms contributing to early
sepsis and anaerobes implicated in the late sequelae with abscess formation [8].

Perforation of the proximal bowel, as with perforated peptic ulcer, results in an infection
that is microbiologically distinct, reflecting the flora of the upper gastrointestinal tract. The
predominant microbial species in such cases often include aerobic and anaerobic gram-
positive bacteria or Candida spp. (See "Overview of complications of peptic ulcer disease",
section on 'Perforation'.)

Prior antimicrobial therapy and health care exposures are associated with microbiologic
changes in the bowel flora, and intra-abdominal infections in such settings are thus more
likely to involve nosocomial pathogens, such as Pseudomonas aeruginosa and other drug-
resistant organisms. Enterococci are most likely to be clinically relevant in health care-
associated infections, particularly postoperative infections, in contrast to community-
acquired infections, in which they are frequently isolated but are often not important
pathogens [9,10]. Candida spp are also more common, in both small and large bowel
processes, among patients with hospital-acquired infection, prior antibiotic exposure,
immunocompromising conditions, or with recurrent infection [11]. (See 'Considerations
for specific pathogens' below.)

SOURCE CONTROL AND DRAINAGE

Surgical intervention and/or percutaneous drainage are usually critical to the

management of intra-abdominal infections other than spontaneous peritonitis. Surgical
intervention may be required to close an anatomic breach or debride infected necrotic
tissue, and drainage is usually necessary for clearance of an abscess. When feasible,
percutaneous abscess drainage is preferred [11]. Most clinical treatment failures are due
to failure to achieve such source control.

Surgical or percutaneous intervention also affords the opportunity for collection of

primary specimens for microbiologic analysis (Gram stain, aerobic and anaerobic cultures,
and if appropriate, fungal and mycobacterial studies). This is particularly important for
those patients with intra-abdominal abscesses or otherwise complicated infections, with
prior antibiotic exposure, or with a high risk of infection with resistant organisms. Gram
stain of the specimen can provide early guidance for antibiotic selection and may be the
only source of information if cultures do not grow. Inoculating the specimen directly into
blood culture bottles can increase the microbiologic yield, but this approach has several
drawbacks [11-13]. It forfeits the ability to obtain Gram stain results, unless a separate
specimen is collected for Gram stain, and in polymicrobial infections, competitive growth
in blood culture bottles can hinder identification of all important pathogens, so cultures
with routine media are also important in such cases.

The surgical management of intra-abdominal processes is discussed in detail elsewhere.

(See "Management of acute appendicitis in adults" and "Acute cholangitis: Clinical
manifestations, diagnosis, and management", section on 'Biliary drainage' and "Treatment
of acute calculous cholecystitis" and "Acalculous cholecystitis: Clinical manifestations,
diagnosis, and management", section on 'Management' and "Overview of gastrointestinal
tract perforation", section on 'Indications for abdominal exploration' and "Acute colonic
diverticulitis: Surgical management".)

EMPIRIC ANTIMICROBIAL THERAPY

Timing — Patients who are critically ill should receive empiric antimicrobial therapy as
soon as possible, ideally once blood and urine samples have been obtained for culture. In
patients who are not critically ill, delaying antibiotic therapy until samples from the site of
abdominal infection have been obtained for culture can be helpful to optimize the
microbiologic yield that guides subsequent antibiotic selection.

Regimens — In general, empiric regimens for intra-abdominal infections include

antimicrobial activity against enteric streptococci, coliforms, and anaerobes ( table 2
and table 3 and table 4). Studies evaluating the relative efficacy of different
antibiotic regimens with these spectra of activity have generally demonstrated equivalent
efficacy (see 'General principles of regimen selection' below). The precise antimicrobial
regimen and indications for broader antimicrobial coverage depend upon several factors
( table 5):

● Whether the infection is community-acquired versus health care-associated.

● Whether there are individual risk factors for infection with resistant bacteria (such as
recent travel to areas of the world that have high rates of antibiotic-resistant
organisms or known colonization with such organisms).

● Whether the patient is considered to be at high risk for adverse outcomes. High-risk
features that are associated with poor outcomes after intra-abdominal infection are
advanced age (>70 years), delay in initial intervention >24 hours, inability to achieve
adequate debridement or control of infection with drainage, other comorbidity (eg,
renal or liver disease, malignancy), immunocompromising condition (eg, poorly
controlled diabetes mellitus, chronic high-dose corticosteroid use, use of other
immunosuppressive agents, neutropenia, advanced HIV infection, B or T lymphocyte
defects), organ dysfunction, severe peritoneal involvement or diffuse peritonitis, low
albumin level, and poor nutritional status [11,14-16].

Patients with community-acquired infections of mild to moderate severity who have none
of these risk factors may not warrant very broad coverage, as the likelihood of resistant
bacteria is low and the consequences of not covering them empirically are less. In
contrast, broad coverage is appropriate in patients who are at risk for infection with
resistant bacteria or who are at risk for adverse outcomes and mortality should empiric
antibiotic therapy not be adequate. Thus, regimen selection is somewhat different for
these different populations. (See 'Low-risk community-acquired infections' below and
'High-risk community-acquired infections' below and 'Health care-associated infections'
below.)

Other factors that influence the choice of regimen include the location or type of infection
(ie, gram-negative anaerobes are generally not critical pathogens in infections arising
from the upper gastrointestinal tract), whether there is a plan for surgical intervention,
the local rates of antibiotic-resistant Enterobacteriaceae, and expected patient tolerance.
Rates of antibiotic resistance in Enterobacteriaceae are high in certain parts of the world,
including east Asia, Africa, and the Middle East, and are especially high in southeast Asia
[17]. Travelers from these areas are at risk for colonization with resistant bacteria; this risk
generally lasts a few weeks but can be prolonged in those with diarrhea or antibiotic
exposure during travel [17-20].

Overarching these considerations are goals for antibiotic stewardship, which generally
favor narrower rather than broader coverage when possible.

The suggested regimens in the following sections are intended to provide general
guidance and may need to be altered to cover emerging resistance patterns that are
specific to the hospital or region; this is more likely to be necessary for the aerobic
component but could also apply to the anaerobic component.

These recommendations are also generally in keeping with the joint Surgical Infection
Society (SIS) and the Infectious Diseases Society of America (IDSA) guidelines on the
management of complicated intra-abdominal infections, which were published in 2010.
The SIS published updated guidelines in 2017, while the IDSA guidelines are in the process
of revision [11,21]. There are some exceptions based on updated in vitro susceptibility
data. As examples, although clindamycin and cefotetan were previously considered
acceptable options for intra-abdominal infections involving anaerobes, these drugs are no
longer recommended due to escalating rates of resistance in the B. fragilis group. As
detailed in those guidelines, ampicillin-sulbactam is also not recommended due to high
rates of resistance among community-acquired E. coli.

Low-risk community-acquired infections — For patients with mild to moderate

community-acquired intra-abdominal infections (eg, perforated appendix or appendiceal
abscess) who have no risk factors for antibiotic resistance or treatment failure ( table 5),
coverage of streptococci, nonresistant Enterobacteriaceae, and (in most cases) anaerobes
is generally sufficient ( table 2). The following initial empiric regimens are appropriate:

● Single-agent regimens – Piperacillin-tazobactam.

● Combination regimens – Cefazolin, cefuroxime, ceftriaxone, cefotaxime,

ciprofloxacin, or levofloxacin, each in combination with metronidazole (although for
most uncomplicated biliary infections of mild to moderate severity, the addition of
metronidazole is not necessary).

When piperacillin-tazobactam or one of the above combination regimens cannot be used,

ertapenem is a reasonable alternative but we try to preserve this agent for more resistant
infections whenever possible.
An oral regimen (for example, a fluoroquinolone plus metronidazole or monotherapy with
amoxicillin-clavulanic acid) is a reasonable choice for empiric therapy for patients with
mild-moderate community-acquired infection who have no risk factors for infection with
antibiotic-resistant organisms and when the prevalence of E. coli susceptibility to the
chosen regimen exceeds 90 percent in the community and hospital. Oral regimens can
still be used if the prevalence of E. coli susceptibility to oral options is less than 90 percent,
but clinicians and patients should be aware of the greater risk of regimen failure in this
case.

For these community-acquired infections, an empiric antimicrobial regimen does not have
to include specific activity against enterococci or Pseudomonas. In several trials, clinical
outcomes for community-acquired intra-abdominal infections have been similar with
empiric regimens that have enterococcal and/or pseudomonal activity and those that do
not [9,22-26].

The SIS/IDSA 2010 guidelines also list cefoxitin, moxifloxacin, and tigecycline as options,
but we generally avoid using these agents in this setting [11]. This is because of
substantial rates of in vitro resistance to cefoxitin and fluoroquinolones among Bacteroides
spp and coliforms [27,28] and concern for increased mortality associated with tigecycline
compared with other antibiotics for various infections, including intra-abdominal
infections [29,30]. (See "Anaerobic bacterial infections", section on 'Antimicrobial
resistance' and "Treatment of hospital-acquired and ventilator-associated pneumonia in
adults", section on 'Other agents'.)

The SIS 2017 guidelines also list cefoperazone-sulbactam as an alternative, but we

generally avoid using this agent in the interest of antimicrobial stewardship, as it provides
coverage for resistant Pseudomonas spp that is typically not needed for this patient
population [21]. These guidelines also suggest against cefazolin for empiric therapy of
intra-abdominal infections because of the lack of trial data informing its use in such
infections; we continue to use cefazolin as an option for low-risk community-acquired
infections as long as the risk of resistance is not high (eg, local prevalence of cefazolin
resistance in Enterobacteriaceae <10 percent, no recent antibiotic use).

High-risk community-acquired infections — For community-acquired intra-abdominal

infections that are severe or in patients at high risk for adverse outcomes or resistance
( table 5), broader coverage is warranted in an attempt to minimize the risk of
inadequate empiric treatment. We generally include an agent with gram-negative activity
broad enough to cover P. aeruginosa and Enterobacteriaceae that are resistant to
nonpseudomonal cephalosporins in addition to coverage against enteric streptococci and
(in most cases) anaerobes ( table 3). Empiric antifungal therapy is usually not warranted,
but it is reasonable for critically ill patients with an upper gastrointestinal source [21]. For
community-acquired infections that clearly have an abdominal source, coverage for MRSA
is generally not warranted, even in those individuals known to be MRSA-colonized.

The following initial empiric regimens are appropriate in areas where the local rates of
resistance to these antibiotics are <10 percent:

● Single-agent regimens – Piperacillin-tazobactam.

● Combination regimens – Cefepime or ceftazidime, each administered with

metronidazole.

If the patient cannot tolerate beta-lactams or is at risk for infection with an extended-
spectrum beta-lactamase (ESBL)-producing organism (eg, known colonization or prior
infection with an ESBL-producing organism), a carbapenem (imipenem or meropenem)
should be chosen. The SIS 2017 guidelines also recommend adding vancomycin or
ampicillin for regimens other than imipenem or piperacillin-tazobactam to provide
enterococcal coverage, but we do not routinely employ empiric coverage of Enterococcus
spp for community-acquired infections.

For patients who cannot use beta-lactams or carbapenems (eg, because of severe
reactions), vancomycin plus aztreonam plus metronidazole is an alternative regimen.

For critically ill patients who warrant empiric antifungal therapy, an echinocandin (eg,
anidulafungin, caspofungin, micafungin) is appropriate. (See "Management of candidemia
and invasive candidiasis in adults".)

When beta-lactams or carbapenems are chosen for patients who are critically ill or are at
high risk of infection with drug-resistant pathogens, we favor a prolonged infusion dosing
strategy, which is also endorsed by the World Society of Emergency Surgery (WSES) [31].
(See "Prolonged infusions of beta-lactam antibiotics".)

Health care-associated infections — For patients with health care-associated

infections, the likelihood of drug resistance is high. Thus, to achieve empiric coverage of
likely pathogens, in addition to coverage against streptococci and anaerobes, regimens
should at least include agents with expanded spectra of activity against gram-negative
bacilli (including P. aeruginosa and Enterobacteriaceae that are resistant to
nonpseudomonal third-generation cephalosporins and fluoroquinolones). We also usually
use an empiric regimen that has anti-enterococcal activity for patients with health care–
associated intra-abdominal infection, particularly those with postoperative infection, those
who have previously received cephalosporins or other antimicrobial agents selecting for
Enterococcus species, immunocompromised patients, and those with valvular heart
disease or prosthetic intravascular materials ( table 4).
Single-drug regimens that have expanded activity against gram-negative aerobic and
anaerobic bacilli include meropenem, imipenem, and piperacillin-tazobactam.
Combination regimens include ceftazidime or cefepime plus metronidazole. The
combination of vancomycin, aztreonam, and metronidazole is an alternative for those
who cannot use beta-lactams or carbapenems (eg, because of severe reactions).
Cephalosporin-based regimens lack anti-enterococcal activity, so ampicillin or vancomycin
can be added to these regimens for enterococcal coverage until culture results are
available. When beta-lactams or carbapenems are chosen for patients who are critically ill
or are at high risk of infection with drug-resistant pathogens, we favor a prolonged
infusion dosing strategy, if feasible. (See "Prolonged infusions of beta-lactam antibiotics".)

Additions or modifications to the regimen may be indicated if other risk factors are
present:

● For patients with health care-associated intra-abdominal infection who are known to
be colonized with MRSA or who are at risk of having an infection due to this
organism because of prior treatment failure and significant antibiotic exposure,
empiric antimicrobial coverage directed against MRSA, typically with vancomycin,
should be provided. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in
adults: Treatment of bacteremia".)

● For patients at risk for infection with an extended-spectrum beta-lactamase (ESBL)

-producing organism (eg, known colonization or prior infection with an ESBL-
producing organism), a carbapenem (imipenem or meropenem) should be chosen.
(See "Extended-spectrum beta-lactamases", section on 'Preferred agents'.)

● For patients who are known to be colonized with highly resistant gram-negative
bacteria, the addition of an aminoglycoside, polymyxin, or novel beta-lactam
combination (ceftolozane-tazobactam or ceftazidime-avibactam) to an empiric
regimen may be warranted. These agents should be combined with an agent that
has activity against anaerobes (eg, metronidazole). (See "Principles of antimicrobial
therapy of Pseudomonas aeruginosa infections", section on 'Management of
multidrug-resistant organisms' and "Acinetobacter infection: Treatment and
prevention", section on 'Second-line antibiotics' and "Carbapenem-resistant E. coli, K.
pneumoniae, and other Enterobacterales (CRE)", section on 'Approach to treatment'.)

● Empiric vancomycin-resistant Enterococcus (VRE) coverage is not generally

recommended, except for patients who are at very high risk for infection due to VRE.
These include liver transplant recipients with an intra-abdominal infection of
hepatobiliary source and patients known to be colonized with VRE. In such cases,
including a VRE-active agent (such as linezolid or daptomycin) in the empiric regimen
 is reasonable. [11]. For those known to be colonized with ampicillin-sensitive VRE,
ampicillin, piperacillin-tazobactam, or imipenem can be used for coverage. (See
"Treatment of enterococcal infections".)

● Empiric antifungal coverage is appropriate for patients at risk for infection with
Candida spp, including those with upper gastrointestinal perforations, recurrent
bowel perforations, surgically treated pancreatitis, heavy colonization with Candida
spp, and/or yeast identified on Gram stain of samples from infected peritoneal fluid
or tissue [21]. Fluconazole can be used for patients who are not severely ill and have
no history of infection with a fluconazole-resistant isolate; otherwise, an
echinocandin can be used. (See "Management of candidemia and invasive
candidiasis in adults".)

TARGETED ANTIMICROBIAL THERAPY

General principles of regimen selection — Targeted antimicrobial therapy is chosen

based on the results of culture and susceptibility testing from appropriate specimens.
Most antibiotic regimens that cover coliforms and anaerobes have comparable efficacy
[32-34].

One meta-analysis evaluated 40 randomized or quasi-randomized controlled trials of

antibiotic regimens in the treatment of secondary peritonitis in adults [32]. All antibiotics
(16 different comparative regimens) showed equivalent clinical success. A subsequent
systematic review identified 16 trials that compared various regimens for complicated
intra-abdominal infections, including ceftriaxone plus metronidazole, piperacillin-
tazobactam, ertapenem, imipenem, meropenem, ceftolozane-tazobactam plus
metronidazole, and ceftazidime-avibactam plus metronidazole [34]. Clinical success
ranged from 75 to 97 percent and comparators were generally of comparable efficacy.

Assessment of culture data — The source and timing of collection of culture material
are critical to the utility of culture results in guiding selection of antibiotics. Specifically,
culture of a specimen that is collected prior to starting antibiotics, from a site that should
be sterile, is the most informative. In the critically ill patient who requires antibiotic
treatment prior to collection of cultures from the site of infection, cultures that are
collected early in the course (eg, within a few hours of antibiotic initiation) are more
meaningful than those that are collected after longer periods of antibiotic exposure.

Culture of a specimen collected days after starting antibiotics, especially if collected from a
chronic drain, is more likely to reflect colonizing bacteria that may have developed
resistance to the treatment regimen but are not necessarily causing infection in the
patient. For this reason, it is advisable to avoid collecting cultures from chronic
drains/fistulae, and results of all such cultures should be assessed carefully for clinical
relevance before decisions are made to target results of these cultures with antibiotic
therapy [11].

Antibiotic stewardship — In the interests of preserving antibiotic efficacy over time for
individual patients and populations, narrowing of antibiotics is advisable once a patient
has improved and/or results of reliable cultures are available. Lower-risk patients with
community-acquired intra-abdominal infection likely do not warrant alteration of therapy
if a satisfactory clinical response to source control and initial therapy occurs, even if
unsuspected and untreated pathogens are later reported [11].

Anaerobic coverage — The anaerobic bacterial component of intra-abdominal infections

is often not determined but assumed and treated empirically. Coverage for anaerobes is
often continued for the duration of the antibiotic course even when anaerobes are not
isolated from cultures, particularly if the cultures were obtained only after initiation of
antibiotics that are active against anaerobes.

Susceptibility of anaerobic pathogens is rarely known at the time that a decision about the
appropriate antibiotic regimen is made since results take a long time, laboratory methods
for isolating anaerobes are not well standardized, and activity is usually predictable based
on in vitro susceptibility testing from reference laboratories [35], clinical trials, and the site
of infection [8,36].

Parenteral versus oral therapy — For patients who are able to eat and tolerate oral
medications and whose relevant organisms are not resistant to oral agents, an
intravenous regimen can be transitioned to an oral regimen once the patient has
demonstrated clinical improvement. Reasonable oral regimens that cover common gut
aerobic and anaerobic bacteria include levofloxacin (750 mg once daily) or ciprofloxacin
(500 mg twice daily), each with metronidazole (500 mg three times daily), or monotherapy
with amoxicillin-clavulanate (875/125 mg two to three times daily), depending on
susceptibility testing.

Considerations for specific pathogens

● Enterococcus spp – These are commonly present in intra-abdominal infections and

often are not covered in the recommended empiric regimens for community-
acquired infections. We agree with the recommendation from the joint Surgical
Infection Society and IDSA guidelines that coverage for Enterococcus is not necessary
unless it is either recovered from the blood or is the only isolate recovered in culture
from the infected site [11].
● Candida spp – Antifungal coverage is warranted if there is growth of Candida spp
from a sterile site. Fluconazole is appropriate for Candida albicans; an echinocandin is
appropriate for fluconazole-resistant Candida spp and as empiric antifungal coverage
in the critically ill patient while awaiting yeast identification and susceptibility testing
results. (See "Management of candidemia and invasive candidiasis in adults".)

● Resistant gram-negative bacilli – Isolation of resistant strains of P. aeruginosa,

Acinetobacter spp, extended spectrum beta-lactamase (ESBL), or carbapenemase-
producing Enterobacteriaceae may warrant specific adjustment of the antibiotic
regimen. The novel cephalosporin-beta-lactamase inhibitor combinations,
ceftazidime-avibactam and ceftolozane-tazobactam, when combined with
metronidazole for anaerobic coverage [37,38], may have niche roles in intra-
abdominal infections caused by mixed flora that include P. aeruginosa resistant to
other antibiotics or ESBL-producing organisms, as long as susceptibility to these
agents is confirmed. Ceftazidime-avibactam has activity against many Klebsiella
pneumoniae carbapenemase (KPC)-producing isolates as well. Management of
infections due to these organisms is discussed elsewhere. (See "Principles of
antimicrobial therapy of Pseudomonas aeruginosa infections" and "Acinetobacter
infection: Treatment and prevention" and "Extended-spectrum beta-lactamases",
section on 'Treatment options' and "Carbapenem-resistant E. coli, K. pneumoniae, and
other Enterobacterales (CRE)", section on 'Approach to treatment'.)

● Actinomyces – Actinomyces are slow-growing filamentous gram-positive anaerobic

bacteria and are part of the normal flora of the mouth and gastrointestinal tract. If
they breach the mucosal surface, these organisms can cause actinomycosis, an
uncommon granulomatous disease that is indolent and sometimes mistaken for
malignancy because of local spread across tissue planes. In the abdomen,
actinomycosis most commonly involves the appendix and ileocecal region. Classic
actinomycosis generally warrants prolonged antibiotic therapy (ie, 6 to 12 months).
(See "Abdominal actinomycosis".)

In patients who present clinically with a syndrome more typical of an abscess caused
by gram-negative organisms and anaerobes (acute presentation, fevers, septic
physiology), the isolation of actinomyces on culture of the infected site is of
uncertain clinical significance. In such cases, we generally include an antibiotic that is
active against actinomyces in the regimen (eg, penicillins) and continue for one to
two months, longer than the duration typically warranted for intra-abdominal
infections. We also monitor closely for symptoms suggestive of classic actinomycosis
with a low threshold for repeat imaging if there is concern for recrudescent infection
following antibiotic discontinuation.
 Infectious disease consultation — Consultation with an expert in infectious diseases
can be especially helpful in the setting of diagnostic uncertainty, for assessment of culture
results to guide narrowing of empiric antibiotics, and in specific complex situations. These
include neutropenic, organ transplant, or otherwise-immunocompromised patients and
patients with antibiotic allergies, potentially infected foreign material (eg, mesh), intra-
abdominal malignancy, inflammatory bowel disease, fistulae, or morbid obesity.

Duration of therapy — The appropriate duration of antimicrobial therapy depends on

whether the presumptive source of the intra-abdominal infection has been controlled.

When adequate source control has been achieved and the contaminated material cleared
from the intra-abdominal space, we generally limit antimicrobial therapy to four to five
days [11]. The efficacy of such a short course of antimicrobial therapy was demonstrated
in the Study To Optimize Peritoneal Infection Therapy (STOP-IT) trial, in which 518 patients
with complicated intra-abdominal infection and adequate source control were randomly
assigned to receive either a fixed course of antibiotics for 4±1 days (experimental group)
or antibiotics until two days after resolution of fever, leukocytosis, and ileus, with a
maximum of 10 days of antimicrobial therapy (control group) [39]. The median duration of
antibiotics was four days in the experimental group versus eight days in the control
group. The composite primary outcome of surgical site infection, recurrent intra-
abdominal infection, or death occurred in a similar percentage of patients in both groups
(21.8 in the experimental group versus 22.3 percent in the control group). No significant
between-group differences were observed in the individual rates of the components of
the primary outcome. Similarly, in a trial of critically ill patients with postoperative intra-
abdominal infections and adequate source control, the 45-day mortality rate was not
different with a short versus longer antibiotic course (8 versus 15 days) [40].

However, there are several situations in which a longer course of antibiotic therapy is
appropriate.

● For patients in whom source control is known to be suboptimal, the optimal duration
of antibiotic treatment is uncertain and decisions on treatment duration must be
made on a case-by-case basis.

● For those patients with uncomplicated appendicitis who do not undergo immediate
surgery, we generally continue antibiotic therapy for approximately 10 days, as in
several trials which suggested the safety of this approach in select patients [41]. (See
'Source control and drainage' above.)

● In some cases, an indwelling catheter is required for ongoing drainage and removal
of infected material. We generally continue antibiotics in such cases until the efficacy
 of catheter drainage is established, for example, until an infected hematoma is
liquefied well enough to drain effectively via catheter. This may require two to three
weeks for a peritoneal abscess. Liver abscess is typically treated for four to six weeks
(see "Pyogenic liver abscess", section on 'Treatment'). If there is chronic active
drainage through the catheter from an ongoing bowel or biliary leak without
accumulation in the peritoneal cavity, discontinuation of antibiotics is usually
reasonable as long as the patient has clinically improved.

Patients with undrained abscesses, uncontrolled ongoing bowel leak, or other unresolved
mechanical problems often develop worsening clinical signs and symptoms of infection
after antibiotics are stopped. We generally refer such patients for repeat surgical or
percutaneous intervention for source control. For patients in whom source control cannot
be achieved, long-term antibiotics are unlikely to be helpful.

In uncertain cases, declining inflammatory markers (such as C-reactive protein [CRP],

erythrocyte sedimentation rate [ESR], and, if available, procalcitonin) can be used
cautiously, in addition to clinical resolution, to support antibiotic discontinuation with
clinical follow-up to assess for signs or symptoms of recurrent infection. Evidence to
support this practice remains indirect.

Several studies have evaluated the utility of inflammatory markers to assist in guiding
antibiotic discontinuation, but most of these have been performed with procalcitonin,
which is not widely available. In one study of patients with secondary peritonitis who
underwent emergency surgery, antibiotic discontinuation based on procalcitonin
thresholds (level <1.0 ng/mL or >80 percent decrease compared with the first
postoperative day), in addition to resolution of clinical signs, was associated with a shorter
duration of antibiotic use and similar adverse events compared with historical controls
[42]. In a separate retrospective study, procalcitonin guidance was associated with a 50
percent reduction in antibiotic duration (5 versus 10 days) among intensive care unit
patients with secondary peritonitis (both with and without septic shock) [43]. However, in
another study of patients with perioperative septic shock in the setting of intra-abdominal
infections, the rate and degree of procalcitonin decrease failed to accurately predict
treatment response [44].

Evidence from randomized trials supporting antibiotic discontinuation based on

procalcitonin levels is mainly from other populations, and these studies have excluded
individuals with intra-abdominal abscesses [45]. Additional studies in patients with intra-
abdominal infections are warranted.
CLINICAL FAILURE

Patients, particularly those with uncertain source control, should be assessed clinically
during antibiotic therapy and after discontinuation for treatment failure, which is
suggested by persistent or recurrent signs and/or symptoms of infection, including fever,
hypotension, nausea, abdominal pain, organ dysfunction, or leukocytosis. In such cases,
the possibility of inadequate source control (eg, an undrained abscess, active bowel leak,
retained infected mesh) should be assessed with repeat imaging. The original
microbiologic data and the antibiotic regimen should also be reviewed to ensure that the
clinically relevant pathogens have been appropriately covered. As noted, most clinical
treatment failures are due to failure to achieve source control; cultures from chronic
drains, surface wounds, or other nonsterile sites cannot be relied upon to identify
organisms requiring targeted antibiotics.

Other considerations in patients with ongoing infectious symptoms or signs include other
nosocomial infections (eg, Clostridioides [formerly Clostridium] difficile colitis, health care-
associated pneumonia or urinary tract infection, or catheter-associated bloodstream
infection). For patients with persistent clinical symptoms and signs but in whom no
evidence of a new or persistent infection is uncovered after a careful investigation,
discontinuation of antimicrobial therapy is warranted [11]. Noninfectious processes such
as thromboembolic disease, drug reaction, and pancreatitis are potential mimickers of
infection.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links: Intra-
abdominal infections in adults".)

SUMMARY AND RECOMMENDATIONS

● Pathogenesis – Intra-abdominal infections usually arise after a breach in the normal

mucosal defense barrier that allows normal bowel flora to inoculate the abdominal
cavity.

● Microbiology – The predominant bacteria involved are coliforms (eg, Escherichia,

Klebsiella spp, Proteus spp, Enterobacter spp), streptococci, and anaerobic bacteria.
Although enterococci are frequently isolated, their clinical relevance is generally
limited to health care-associated infections. (See 'Microbiology' above.)
● Importance of surgical intervention or percutaneous drainage – These
procedures are usually critical to the management of intra-abdominal infections
(other than spontaneous peritonitis) since most clinical treatment failures are due to
failure to achieve source control. Specimens should be obtained during the
procedure for microbiologic stain and culture. (See 'Source control and drainage'
above.)

The surgical management of intra-abdominal processes is discussed in detail

elsewhere. (See "Management of acute appendicitis in adults" and "Acute cholangitis:
Clinical manifestations, diagnosis, and management", section on 'Biliary drainage'
and "Treatment of acute calculous cholecystitis" and "Acalculous cholecystitis: Clinical
manifestations, diagnosis, and management", section on 'Management' and
"Overview of gastrointestinal tract perforation", section on 'Indications for
abdominal exploration' and "Acute colonic diverticulitis: Surgical management".)

● Antibiotic therapy

• Empiric antibiotic selection – Critically ill patients should receive empiric

antimicrobial therapy as soon as possible, ideally once blood and urine cultures
have been obtained. For patients who are not critically ill, antibiotic therapy
should be delayed until after collection of culture samples from the site of
infection.

- Mild to moderate community-acquired infections with no risk factors for

antibiotic resistance or poor outcome ( table 5) – Antibiotics for these
infections should cover enteric streptococci, nonresistant Enterobacteriaceae,
and anaerobes ( table 2). Examples of infections in this category include
perforated appendix or appendiceal abscess. (See 'Low-risk community-
acquired infections' above.)

- Severe community-acquired infections or infections in patients at high

risk for resistance or poor outcome ( table 5) – For these infections, we
generally include antibiotic coverage against Pseudomonas aeruginosa,
Enterobacteriaceae, enteric streptococci, and anaerobes ( table 3). Empiric
antifungal coverage is not typically necessary, but is reasonable for critically
ill patients with an upper gastrointestinal source. (See 'High-risk community-
acquired infections' above.)

- Health care-associated infections – For these infections, we generally

include coverage against P. aeruginosa, resistant Enterobacteriaceae,
streptococci, enterococci, and anaerobes ( table 4). Empiric antifungal
 coverage is reasonable for patients with upper gastrointestinal perforations,
recurrent bowel perforations, surgically treated pancreatitis, heavy
colonization with Candida spp, or microbiologic evidence of yeast on intra-
abdominal specimens. (See 'Health care-associated infections' above.)

• Targeted antibiotic selection – Depending on the results of culture and

susceptibility testing, antibiotic adjustments may be necessary. Regardless of
culture results, coverage for Enterobacteriaceae and anaerobes is often
continued for the full duration of therapy, even if they did not grow in culture.
(See 'Targeted antimicrobial therapy' above.)

Cultures from a chronic indwelling drain more likely reflect colonizing bacteria
rather than clinically relevant pathogens. (See 'General principles of regimen
selection' above.)

• Duration of antibiotic therapy – For patients who have adequate source control,
we suggest limiting antibiotic therapy to four to five days (Grade 2B). Longer
courses are often appropriate if source control is suboptimal or uncertain. (See
'Duration of therapy' above.)

Use of UpToDate is subject to the Terms of Use.

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6. Lucasti C, Jasovich A, Umeh O, et al. Efficacy and tolerability of IV doripenem versus

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7. Baughn AD, Malamy MH. The strict anaerobe Bacteroides fragilis grows in and
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8. Bartlett JG, Onderdonk AB, Louie T, et al. A review. Lessons from an animal model of
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9. Harbarth S, Uckay I. Are there patients with peritonitis who require empiric therapy
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10. Sitges-Serra A, López MJ, Girvent M, et al. Postoperative enterococcal infection after
treatment of complicated intra-abdominal sepsis. Br J Surg 2002; 89:361.

11. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated
intra-abdominal infection in adults and children: guidelines by the Surgical Infection
Society and the Infectious Diseases Society of America. Clin Infect Dis 2010; 50:133.

12. Baron EJ, Miller JM, Weinstein MP, et al. A guide to utilization of the microbiology
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postoperative intraabdominal infections. Infection 2010; 38:255.

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17. Woerther PL, Burdet C, Chachaty E, Andremont A. Trends in human fecal carriage of
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M. Clin Microbiol Rev 2013; 26:744.

18. Peirano G, Laupland KB, Gregson DB, Pitout JD. Colonization of returning travelers
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21. Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society Revised Guidelines
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25. Malangoni MA, Song J, Herrington J, et al. Randomized controlled trial of moxifloxacin
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 34. Golan Y. Empiric therapy for hospital-acquired, Gram-negative complicated intra-
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35. Snydman DR, Jacobus NV, McDermott LA, et al. Update on resistance of Bacteroides
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36. Tally FP, Gorbach SL. Therapy of mixed anaerobic-aerobic infections. Lessons from
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37. Lagacé-Wiens P, Walkty A, Karlowsky JA. Ceftazidime-avibactam: an evidence-based

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38. Snydman DR, McDermott LA, Jacobus NV. Activity of ceftolozane-tazobactam against a
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39. Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy
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40. Montravers P, Tubach F, Lescot T, et al. Short-course antibiotic therapy for critically ill
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41. Livingston E, Vons C. Treating Appendicitis Without Surgery. JAMA 2015; 313:2327.

42. Huang TS, Huang SS, Shyu YC, et al. A procalcitonin-based algorithm to guide
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43. Maseda E, Suarez-de-la-Rica A, Anillo V, et al. Procalcitonin-guided therapy may

reduce length of antibiotic treatment in intensive care unit patients with secondary
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44. Jung B, Molinari N, Nasri M, et al. Procalcitonin biomarker kinetics fails to predict
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Topic 101694 Version 27.0
GRAPHICS

Mixed flora in peritoneal fluid from a ruptured

viscus

Gram stain of peritoneal fluid (x1000) shows several different

organisms, including gram-positive cocci in chains, gram-positive
rods, plump enteric gram-negative bacilli, and thinner gram-
negative rods. Mixed fecal flora grew from this specimen.

Courtesy of Harriet Provine.

Graphic 77736 Version 3.0

Bacteriology of intraabdominal sepsis

Cases studied 759

Bacteriology

Aerobes only 132 (17)*

Anaerobes only 7 (1)*

Anaerobes plus aerobes 620 (82)*

Bacterial isolates Number of isolates ¶

Aerobes 1256

Escherichia coli 306

Pseudomonas aeruginosa 121

Klebsiella 119

Other gram-negative bacilli 270

Enterococcus 277

Staphylococcus aureus 111

Other gram-positive cocci 62

Anaerobes 1187

Bacteroides species 443

Bacteroides fragilis 133

Clostridium species 306

Peptostreptococcus 220

Fusobacterium 35

Miscellaneous 116

* Number of isolates (percent).

¶ Numbers of isolates are greater than numbers of cases since the majority of cases had more
than one microorganism isolated.

Data from Stone HH et al. Arch Surg 1983.

Graphic 79147 Version 5.0

Empiric antibiotic regimens for low-risk community-acquired intra-
abdominal infections in adults

Dose

Single-agent regimen

Piperacillin-tazobactam* 3.375 g IV every 6 hours

Combination regimen with metronidazole*

One of the following:

Cefazolin 1 to 2 g IV every 8 hours

or

Cefuroxime 1.5 g IV every 8 hours

or

Ceftriaxone 2 g IV once daily

or

Cefotaxime 2 g IV every 8 hours

or

Ciprofloxacin 400 mg IV every 12 hours or

500 mg PO every 12 hours

or

Levofloxacin 750 mg IV or PO once daily

Plus:

Metronidazole¶ 500 mg IV or PO every 8 hours

For empiric therapy of low-risk community-acquired intra-abdominal infections, we cover

streptococci, Enterobacteriaceae, and anaerobes. Low-risk community-acquired intra-
abdominal infections are those that are of mild to moderate severity (including perforated
appendix or appendiceal abscess) in the absence of risk factors for antibiotic resistance or
treatment failure. Such risk factors include recent travel to areas of the world with high rates
of antibiotics-resistant organisms, known colonization with such organisms, advanced age,
immunocompromising conditions, or other major medical comorbidities. Refer to other
UpToDate content on the antimicrobial treatment of intra-abdominal infections for further
discussion of these risk factors.

The antibiotic doses listed are for adult patients with normal renal function. The duration of
antibiotic therapy depends on the specific infection and whether the presumptive source of
infection has been controlled; refer to other UpToDate content for details.

IV: intravenously; PO: orally.

* When piperacillin-tazobactam or one of the combination regimens in the table cannot be

used, ertapenem (1 g IV once daily) is a reasonable alternative.

¶ For most uncomplicated biliary infections of mild to moderate severity, the addition of
metronidazole is not necessary.

Graphic 106948 Version 13.0

Empiric antibiotic regimens for high-risk community-acquired intra-
abdominal infections in adults

Dose

Single-agent regimen

Imipenem-cilastatin 500 mg IV every 6 hours

Meropenem 1 g IV every 8 hours

Doripenem 500 mg IV every 8 hours

Piperacillin-tazobactam 4.5 g IV every 6 hours

Combination regimen with metronidazole

ONE of the following:

Cefepime 2 g IV every 8 hours

OR

Ceftazidime 2 g IV every 8 hours

PLUS:

Metronidazole 500 mg IV or orally every 8 hours

High-risk community-acquired intra-abdominal infections are those that are severe or in

patients at high risk for adverse outcomes or antimicrobial resistance. These include patients
with recent travel to areas of the world with high rates of antibiotics-resistant organisms,
known colonization with such organisms, advanced age, immunocompromising conditions, or
other major medical comorbidities. Refer to the UpToDate topic on the antimicrobial
treatment of intra-abdominal infections for further discussion of these risk factors.

For empiric therapy of high-risk community-acquired intra-abdominal infections, we cover

streptococci, Enterobacteriaceae resistant to third-generation cephalosporins, Pseudomonas
aeruginosa, and anaerobes. Empiric antifungal therapy is usually not warranted but is
reasonable for critically ill patients with an upper gastrointestinal source.

Local rates of resistance should inform antibiotic selection (ie, agents for which there is >10%
resistance among Enterobacteriaceae should be avoided). If the patient is at risk for infection
with an extended-spectrum beta-lactamase (ESBL)-producing organism (eg, known
colonization or prior infection with an ESBL-producing organism), a carbapenem should be
chosen. When beta-lactams or carbapenems are chosen for patients who are critically ill or are
at high risk of infection with drug-resistant pathogens, we favor a prolonged infusion dosing
strategy. Refer to other UpToDate content on prolonged infusions of beta-lactam antibiotics.

The combination of vancomycin, aztreonam, and metronidazole is an alternative for those

who cannot use other beta-lactams or carbapenems (eg, because of severe reactions).

The antibiotic doses listed are for adult patients with normal renal function. The duration of
antibiotic therapy depends on the specific infection and whether the presumptive source of
infection has been controlled; refer to other UpToDate content for details.
IV: intravenous.

Graphic 106949 Version 12.0

Empiric antibiotic regimens for health care-associated intra-abdominal
infections in adults

Dose

Single-agent regimen

Imipenem-cilastatin 500 mg IV every 6 hours

Meropenem 1 g IV every 8 hours

Doripenem 500 mg IV every 8 hours

Piperacillin-tazobactam 4.5 g IV every 6 hours

Combination regimen

ONE of the following:

Cefepime 2 g IV every 8 hours

OR

Ceftazidime 2 g IV every 8 hours

PLUS:

Metronidazole 500 mg IV or orally every 8 hours

PLUS ONE of the following (in some cases*):

Ampicillin 2 g IV every 4 hours

OR

Vancomycin 15 to 20 mg/kg IV every 8 to 12 hours

For empiric therapy of health care-associated intra-abdominal infections, we cover

streptococci, enterococci, Enterobacteriaceae that are resistant to third-generation
cephalosporins and fluoroquinolones, Pseudomonas aeruginosa, and anaerobes. We include
coverage against methicillin-resistant Staphylococcus aureus (MRSA) with vancomycin in those
who are known to be colonized, those with prior treatment failure, and those with significant
prior antibiotic exposure. Empiric antifungal coverage is appropriate for patients at risk for
infection with Candida spp, including those with upper gastrointestinal perforations, recurrent
bowel perforations, surgically treated pancreatitis, heavy colonization with Candida spp,
and/or yeast identified on Gram stain of samples from infected peritoneal fluid or tissue. Refer
to other UpToDate content on treatment of invasive candidiasis.

If the patient is at risk for infection with an extended-spectrum beta-lactamase (ESBL)-

producing organism (eg, known colonization or prior infection with an ESBL-producing
organism), a carbapenem should be chosen. For patients who are known to be colonized with
highly resistant gram-negative bacteria, the addition of an aminoglycoside, polymyxin, or
novel beta-lactam combination (ceftolozane-tazobactam or ceftazidime-avibactam) to an
empiric regimen may be warranted. In such cases, consultation with an expert in infectious
diseases is advised.

When beta-lactams or carbapenems are chosen for patients who are critically ill or are at high
risk of infection with drug-resistant pathogens, we favor a prolonged infusion dosing strategy.
Refer to other UpToDate content on prolonged infusions of beta-lactam antibiotics.

The combination of vancomycin, aztreonam, and metronidazole is an alternative for those

who cannot use other beta-lactams or carbapenems (eg, because of severe reactions).

The antibiotic doses listed are for adult patients with normal kidney function. The duration of
antibiotic therapy depends on the specific infection and whether the presumptive source of
infection has been controlled; refer to other UpToDate content for details.

IV: intravenous.

* We add ampicillin or vancomycin to a cephalosporin-based regimen to provide enterococcal

coverage, particularly in those with postoperative infection, prior use of antibiotics that select
for Enterococcus, immunocompromising condition, valvular heart disease, or prosthetic
intravascular materials. Coverage against vancomycin-resistant enterococci (VRE) is generally
not recommended, although it is reasonable in patients who have a history of VRE
colonization or in liver transplant recipients who have an infection of hepatobiliary source.

Graphic 106950 Version 12.0

Risk factors that warrant broad empiric antimicrobial coverage for
intra-abdominal infections

Factors associated with mortality

Age >70 years

Medical comorbidity (eg, renal or liver disease, presence of malignancy, chronic

malnutrition)

Immunocompromising condition (eg, poorly controlled diabetes mellitus, chronic high-dose

corticosteroid use, use of other immunosuppressive agents, neutropenia, advanced HIV
infection, B or T leukocyte deficiency)

High severity of illness (ie, sepsis)

Extensive peritoneal involvement or diffuse peritonitis

Delay in initial intervention (source control) >24 hours

Inability to achieve adequate debridement or drainage control

Factors associated with infection with antibiotic-resistant bacteria

Health care-acquired infection

Travel to areas with higher rates of antibiotic-resistant organisms* within the few weeks
prior to infection onset or if antibiotics were received during travel

Known colonization with antibiotic-resistant organisms

* High rates of antibiotic resistance have been reported from southeast Asia, east Asia, the
Middle East, and Africa.

References:
1. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal
infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases
Society of America. Clin Infect Dis 2010; 50:133.
2. Woerther PL, Burdet C, Chachaty E, Andremont A. Trends in human fecal carriage of extended-spectrum
β-lactamases in the community: toward the globalization of CTX-M. Clin Microbiol Rev 2013; 26:744.

Graphic 105865 Version 3.0

Contributor Disclosures
Miriam Baron Barshak, MD Equity Ownership/Stock Options: Boston Scientific, Inc [Medical
devices]. All of the relevant financial relationships listed have been mitigated. Stephen B
Calderwood, MD Consultant/Advisory Boards: Day Zero Diagnostics [Whole genome sequencing for
microbial identification and determination of antimicrobial susceptibility]. All of the relevant
financial relationships listed have been mitigated. Keri K Hall, MD, MS No relevant financial
relationship(s) with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found,
these are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.

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