/μL; and total bilirubin, 4.4 mg/dL. What organisms are likely to be cultured from
An estimated 70% of cases of SBP are caused by aerobic enteric organisms
considered normal flora of the GI tract.
22 E. coli is the most common pathogen,
3 Other common causes of SBP include Streptococcus
pneumoniae and other Streptococcus species, accounting for 20% of cases.
Enterococcus species are isolated in approximately 5% of cases.
species, anaerobes, and microaerophilic organisms are rarely reported in
community-acquired SBP. SBP is largely a monomicrobial infection.
One of the main mechanisms of pathogenesis associated with the development of
SBP is bacterial translocation, which is the migration of microorganisms through the
GI wall to mesenteric lymph nodes and other structures outside the intestine,
including the bloodstream. Bacteria then infect the ascitic fluid by hematogenous or
23 Certain characteristics of cirrhotic patients facilitate the
pathogenesis of SBP, including bacterial overgrowth, decreased motility, structural
intestinal damage, and decreased host-defense mechanisms that normally function to
eliminate microorganisms. Bacterial overgrowth in the face of decreased motility and
increased gut wall permeability, secondary to structural damage, facilitates
subsequent systemic infection. Reduced opsonic activity and phagocytosis allow the
microorganisms to escape the hosts’ defenses and subsequently infect the ascitic
23 SBP with underlying cirrhosis was previously associated with a greater than
90% mortality rate, but with the advances in antibacterial therapy the rate has been
reduced to approximately 30% to 40%.
22 Gram-negative pathogens are associated
with increased mortality compared with gram-positive pathogens.
and effective antibacterial treatment of SBP are associated with reduced rates of
24 Patient characteristics associated with increased mortality include renal
insufficiency, hypothermia, hyperbilirubinemia, and hypoalbuminemia. To decrease
the rate of renal dysfunction associated with SBP, intravenous albumin at 1.5 g/kg
within 6 hours of diagnosis and 1 g/kg on day 3 may be administered. Albumin acts
as a volume expander to lessen hemodynamic changes, thereby preserving renal
function. Albumin is recommended in patients with a serum creatinine >1 mg/dL,
blood urea nitrogen (BUN) >30 mg/dL, or total bilirubin >4 mg/dL.
Although a positive Gram stain and culture guides antibacterial therapy, nearly
60% of patients with signs and symptoms of SBP have negative cultures.
antibacterial therapy for patients with a diagnosis of SBP is typically empiric and
targeted toward the most likely pathogens as described previously. Ampicillin plus
26 A fluoroquinolone may be considered an alternative in patients
w i t h β-lactam allergies. Levofloxacin and moxifloxacin are preferred over
ciprofloxacin, because of their superior activity against S. pneumoniae, the most
commonly isolated gram-positive bacterial pathogen. Although parenteral therapy is
preferred, oral fluoroquinolones may be as effective in patients with uncomplicated
25 As described earlier, aminoglycosides are not recommended in cirrhotic SBP
therapy because of the risk of nephrotoxicity, and the decision whether or not to use
fluoroquinolones should be based on institutional antibiogram reports.
Antibiotic therapy is recommended until the PMN count from the ascitic fluid falls
below 250 cells/μL, which normally occurs within 5 days.
concluded that a 5-day course of cefotaxime for the treatment of SBP was as effective
M.W. should receive empiric therapy with an antimicrobial agent effective against
E. coli and other common pathogens such as Klebsiella species and S. pneumoniae.
Any of the above-mentioned options would be reasonable empiric choices.
CASE 70-2, QUESTION 3: After treatment is completed, should prophylactic antimicrobial therapy be
Recurrence rates for SBP are high. Cirrhotic patients who survive an episode of
SBP have a 1-year recurrence rate of nearly 70%. Antibiotic prophylaxis should be
administered to the following patients since they are considered high risk for the
development of SBP: patients who have had one or more episodes of SBP; cirrhotic
patients with gastrointestinal bleeding; cirrhotic patients with ascites, who have
impaired renal or liver function; or cirrhotic patients with a low ascitic protein (<1.0
g/dL) or elevated serum bilirubin (>2.5 mg/dL).
Antibiotic prophylaxis in cirrhotic patients is typically initiated to provide
selective decontamination of the GI tract. The goal of this therapy is to reduce the
burden of bacteria and subsequently prevent bacterial translocation and infection.
Prospective, randomized studies in cirrhotic subjects with ascites support the use of
oral antibacterial agents to reduce the rate of recurrence. The agents studied include
29 and trimethoprim–sulfamethoxazole.
a nonabsorbable derivative of rifamycin, has also been shown to significantly reduce
31 Long-term prophylaxis is recommended based on the
significant reduction in rates of recurrence in clinical trials. Long-term prophylaxis in
patients with low ascitic protein, elevated bilirubin, or both may also be beneficial,
but it has not been associated with decreased overall infection or mortality and,
therefore, is not uniformly recommended.
28–30 Clinical trials have provided
evidence to support the use of short-course therapy (7 days) of norfloxacin (no longer
available in the United States) or ceftriaxone in cirrhotic patients presenting with GI
32 Prophylactic therapy prevents bacterial infection and
reduces the risk of rebleeding.
23 Several cost analyses have been performed
demonstrating that prophylactic therapy in high-risk groups of cirrhotic patients is
Because rates of fluoroquinolone-resistant and trimethoprim–sulfamethoxazole–
resistant organisms are more prevalent in patients who receive long-term
prophylactic therapy, its long-term use must be considered when initiating
antibacterial therapy for the treatment of new infections in this patient population.
M.W. has cirrhosis, a previous episode of SBP, and a high total bilirubin; thus, he
is at high risk for recurrence. Prophylactic antimicrobial therapy should be
considered and may be a cost-effective measure. M.W. would benefit from
ciprofloxacin 500 mg PO daily. The use of trimethoprim–sulfamethoxazole would
depend on local resistance patterns.
Continuous Ambulatory Peritoneal Dialysis–Associated
PATHOGENESIS AND CLINICAL PRESENTATION
QUESTION 1: H.M., a 33-year-old woman with HIV and end-stage renal disease, has undergone continuous
antimicrobial agents be administered?
Following SBP, peritoneal dialysis is another cause of primary peritonitis. An
estimated 45% of patients undergoing CAPD will experience at least one episode of
peritonitis in the first 6 months of dialysis. Approximately 60% to 70% of patients
exhibit peritonitis during the first year of dialysis, and recurrent infection occurs in
3 CAPD-associated peritonitis is theorized to originate from
contamination of the catheter by organisms of the normal skin flora, contamination of
the peritoneum from an exit-site or subcutaneous-tunnel infection, contamination of
the dialysate fluid, or bacterial translocation.
3 Alterations in host defenses of the
peritoneum may also have a role in the development of CAPD-associated
Clinical manifestations of CAPD-associated peritonitis include abdominal pain
and tenderness, which is observed in 60% to 80% of patients. Nausea and vomiting
occur in approximately 30% of patients, whereas 10% will have diarrhea and 10%
to 20% will present with fever. The diagnosis of peritonitis is made on the basis of
clinical signs and symptoms along with examination of the dialysate fluid for cell
counts, Gram stain, and culture. Characteristically, the dialysate fluid will be cloudy
and have a WBC count greater than 100 cells/μL with a neutrophilic predominance
35 The Gram stain may be negative in 5% to 10% of cases, and blood
cultures are typically negative.
In most cases, peritonitis is commonly caused by a
The most common causative organisms are gram-positive bacteria, accounting for
60% to 80% of isolates. Coagulase-negative Staphylococcus species (S.
epidermidis) are the most common causative organisms, followed by S. aureus and
Streptococcus species. Gram-negative bacilli are isolated in approximately 15% to
30% of cases, with E. coli being the most common. Other common gram-negative
organisms include Klebsiella species, Enterobacter species, Proteus species, and P.
aeruginosa. Anaerobes, fungi, and mycobacteria constitute the less commonly
In general, empiric antibiotic therapy should be directed against the most common
causative organisms, both gram-positive and gram-negative, until cultures of
peritoneal fluid are available. Intraperitoneal (IP) delivery of antibacterial agents is
the preferred route of administration for the treatment of CAPD-associated
peritonitis. The IP route provides very high local concentrations of antibacterial
available, antibacterial therapy should be adjusted as necessary. With appropriate
therapy, a clinical response should be expected within the first 48 hours.
Treatment guidelines for CAPD-associated peritonitis provide a systematic
approach for antimicrobial selection, dosing guidelines, and duration of therapy.
Initial IP therapy recommendations include vancomycin or a first-generation
cephalosporin for gram-positive coverage plus an antibacterial agent with
35 Because of the increasing rates of MRSA and
methicillin-resistant S. epidermidis, vancomycin may be the most appropriate initial
therapy for gram-positive organisms, although cefazolin remains effective in certain
36–38 Gram-negative therapy options include ceftazidime,
cefepime, piperacillin–tazobactam, or a carbapenem.
intolerant of β-lactams, aztreonam may be considered as an alternative agent for
however, oral therapy should not be used in severe cases of peritonitis. The
increasing prevalence of fluoroquinolone-resistant gram-negative E. coli, however,
is decreasing the utility of these agents.
Refractory peritonitis, presence of cloudy effluent after 5 days of IP therapy, may
require removal of the catheter, suggesting an exit-site or tunnel infection. Oral
antibiotic therapy, or intravenous therapy if severe, may be required for cases
involving S. aureus or P. aeruginosa. When S. aureus is isolated, the infection usually
necessitates the removal of the dialysis catheter. Vancomycin is recommended for
MRSA (with or without rifampin) for 1 week, although monotherapy with
vancomycin is adequate, particularly if the infected catheter is removed. Conversely,
cefazolin alone is adequate for MSSA. Coagulase-negative Staphylococcus species
do not require prompt catheter removal as they typically respond well to
antimicrobial therapy. Methicillin resistance is common for S. epidermidis; thus,
vancomycin is normally used. Enterococcus species or Streptococcus species should
dalfopristin, or daptomycin. In the case of culture-negative peritonitis and clinical
When a single gram-negative organism is cultured (e.g., E. coli, Klebsiella
species, or Proteus species), therapy can be narrowed based on susceptibility.
Isolation of P. aeruginosa most often indicates a severe infection, which may also
involve the dialysis catheter. Therapy options include an antipseudomonal β-lactam
such as ceftazidime, cefepime, or piperacillin–tazobactam with or without a
fluoroquinolone or an aminoglycoside. In general, the β-lactam antimicrobials
achieve peritoneal fluid concentrations exceeding typical minimum inhibitory
concentrations for most commonly encountered facultative gram-negative and
Aztreonam can be used in the case of severe immunoglobulin E (IgE)-mediated
penicillin allergy. Polymicrobial peritonitis is uncommon and may indicate a more
process. Table 70-3 lists antimicrobial dosing guidelines for the treatment of
peritonitis associated with CAPD.
Intraperitoneal Antibiotic Dosing Recommendations for CAPD Patients
Ampicillin–sulbactam 2 g every 12 hours 1,000 100
Ceftazidime 1,000–1,500 mg 500 125
Daptomycin 40 mg every 4 hours 100 20
Fluconazole 200 mg every 24–28 hours
Imipenem–cilastatin 1 g twice daily 250 50
Levofloxacin 500 mg PO every 48 hours
Polymixin B 150,000 units (IV) every 12 hours
Quinupristin–dalfopristin 25 mg/L in alternate bags
Vancomycin 15–30 mg/kg every 5–7 days 1,000 25
dGiven in conjunction with 500 mg IV twice daily.
An example of an appropriate regimen for H.M. may include vancomycin plus
cefepime or an aminoglycoside given intraperitoneally. The clinician should monitor
culture and sensitivity results to adjust therapy based on guidelines, local sensitivity
patterns, and therapeutic response.
FUNGAL CAPD-ASSOCIATED PERITONITIS
Fungal peritonitis is a rare complication of CAPD that is associated with
significant morbidity and mortality. The rate of mortality in fungal peritonitis is
35 Considering the high rate of failure of therapy, CAPD patients
with fungal peritonitis should have their catheters removed.
received prolonged or multiple courses of antibiotics, are on immunosuppressant
therapy for a malignancy, transplant, or inflammatory disease, or have a
postoperative or recurrent intra-abdominal infection are at increased risk for fungal
peritonitis and should be treated with antibiotics.
Candida species, most commonly C. albicans; however, an increase in infection
attributable to non-albicans species has emerged in many areas.
therapy should be broad and include most Candida species; echinocandins such as
caspofungin, micafungin, or anidulafungin are the empiric drugs of choice.
Amphotericin B may be administered intravenously (IV) or IP, but when given IP,
conventional amphotericin B is very irritating to the peritoneum.
antifungal agents can be administered orally, IV, or IP. Fluconazole is active against
C. albicans, but it has dose-dependent activity against certain types of non-albicans
species, such as Candida glabrata. In general,
fluconazole is the drug of choice for C. albicans; however, other options, such as a
polyene or echinocandin, may be needed for azole-resistant Candida species.
Therapy should continue for a minimum of 2 weeks after catheter removal, and the
total duration may be based on severity and clinical response.
H.M.’s treatment should include temporary catheter removal and administration of
antifungal agents. Antifungal therapy with oral fluconazole 400 mg daily should be
continued for at least 14 days.
Secondary peritonitis usually occurs after fecal or urinary contamination of the
peritoneal cavity or its surrounding structures.
2 The process leading to an infection
commonly includes an acute perforation associated with appendicitis, diverticulitis,
the uterus, neoplasm, and inflammatory bowel disease (IBD). Secondary peritonitis
can also result from postoperative or posttraumatic perforation of the GI or
genitourinary tract related to blunt trauma or ingestion of foreign material.
Localization of infection without eradication of bacteria results in intraperitoneal
or visceral abscesses. Intraperitoneal abscesses occur most often in the right lower
quadrant in association with appendicitis or a perforated peptic ulcer. Other causes
can include diverticulitis, pancreatitis, IBD, trauma, and abdominal surgery. Visceral
abscesses generally are found in the pancreas but may also occur in the liver, spleen,
Mortality with secondary peritonitis can be as high as 68%.
control with surgical intervention is imperative for clinical success of infections
resulting from secondary peritonitis. Management with appropriate antimicrobial
therapy, intensive care support, and the overall health of the patient are also critical
Clinical Presentation and Diagnosis
been taking nonsteroidal anti-inflammatory drugs (NSAIDs) for joint pain over the last 2 weeks. An
/μL and BUN, 34 mg/dL. What signs and symptoms of secondary peritonitis does R.C. display?
Making the diagnosis of a localized intra-abdominal infection may be difficult,
experienced. Fevers with or without chills, tachycardia, sparse urination secondary
to fluid loss into the peritoneum, faint or absent bowel sounds, and abdominal
distention may accompany primary GI symptoms associated with peritonitis.
Inflammation around the intestines and peritoneal cavity results in local paralysis and
reflex rigidity of the abdominal wall muscles and the diaphragm, causing rapid and
3 These signs usually are accompanied by an elevated WBC
count with a predominance of neutrophils (left shift). The hematocrit (Hct) and BUN
may be elevated as a result of dehydration. Initially, patients are usually alkalotic
owing to emesis and hyperventilation, but in the later stages of peritonitis, acidosis
usually occurs. Untreated or partially treated peritonitis can result in generalized
sepsis and hypovolemic shock, in addition to, a gradual development of
intraperitoneal abscesses. Therefore, patients with a sudden turn in disposition after
treatment and recovery from peritonitis or abdominal surgery should be assessed for
intraperitoneal abscess formation.
R.C. is likely to have a community-acquired intra-abdominal infection suggestive
of a secondary peritonitis resulting from an acute perforated peptic ulcer after using
an NSAID for 2 weeks. His current clinical status is highlighted by complaints of
severe abdominal pain and nausea, fever with tachycardia, a significant elevation in
WBC, and signs of dehydration with a BUN of 34 mg/dL.
CASE 70-4, QUESTION 2: Given these findings, what are the most likely pathogens for R.C.’s secondary
The normal flora consistent with the perforated segment of the GI tract determines the
most likely pathogens, consisting of both aerobes and anaerobes the more distal the
In general, the stomach and small bowel consist of few microbes, such as
Candida species, lactobacilli, and oral streptococci, in the fasting state. However,
the number and variety of gastric microbiota can increase with meals, achlorhydria
(use of histamine [H2] blockers or proton pump inhibitors), obstruction, and
3 The most common facultative bacterium is E. coli, which is
found in approximately 50% of cultures. A variety of other facultative gram-negative
bacteria include Klebsiella species, P. aeruginosa, Proteus species, and Enterobacter
50–53 The presence of anaerobic bacteria in the culture is
indicative of a polymicrobial infection with a predictable group of pathogens.
E. coli, enterococci, and a predominant presence of obligate anaerobes, including
Bacteroides fragilis, P. melaninogenica, Peptococcus species, Peptostreptococcus
species, and Fusobacterium species, are found in the ileum and colon of the large
bowel. B. fragilis is the most frequently isolated obligate anaerobe after perforation
54 Anaerobic cocci (Peptostreptococcus) and facultative gram-positive
cocci, such as streptococci, are also isolated.
54 B. fragilis and E. coli are the most common pathogens
found in blood culture samples after bacteremia related to an intra-abdominal
3 Highly antibiotic-resistant strains of P. aeruginosa, Enterobacteriaceae
producing ESBLs or carbapenemases, Acinetobacter species, and Enterococcus, as
well as Candida species, are often isolated from hospitalized patients who
experience secondary peritonitis.
Bacteriology of Intra-Abdominal Infections
Facultative and aerobic gram-negatives
aMost common in community-acquired intra-abdominal infections.
Gram stain and culture do not need to be routinely obtained in community-acquired
intra-abdominal infections before the initiation of antimicrobial therapy. It may be
useful in health care–associated infections for detection of gram-positive cocci, yeast
or multidrug-resistant pathogens.
6 The presence of pleomorphic gram-negative
bacilli, a strong odor, or tissue gas is strongly suggestive of infection with anaerobes,
R.C.’s secondary peritonitis is likely because of the presence of a facultative
gram-negative bacteria, such as E. coli, Proteus, Klebsiella, or Enterobacter or
possibly an obligate anaerobe, such as B. fragilis. R.C. does not present with a
history of hospitalization or recent receipt of broad-spectrum antimicrobials;
therefore, an infection caused by more resistant health care–associated pathogens
(e.g., P. aeruginosa, ESBLs, carbapenemases) is less likely.
CASE 70-4, QUESTION 3: How should R.C. be treated? On the basis of clinical studies, what empiric
antimicrobial therapy is appropriate for R.C. at this time?
Therapy for secondary peritonitis should include early administration of
antimicrobial agents directed at facultative gram-negative bacteria and obligate
anaerobes, fluid therapy, and support of vital organ function, as well as source
control measures. Antibiotics should be administered within 1 hour of presentation of
septic shock and within 8 hours after hospital admission in those with stable
6 Adequate source control involving surgical
debridement and drainage, in conjunction with appropriate antimicrobial therapy,
decreases morbidity and mortality.
In general, when an intra-abdominal infection
is present, antimicrobial agents should be started immediately after appropriate
specimens (e.g., blood, peritoneal fluid) have been obtained and before any surgical
56 The parenteral route should be used to ensure
adequate systemic and tissue concentrations, especially in patients in whom shock or
poor perfusion of the muscles or GI tract precludes the use of oral administration.
Table 70-2 outlines dosing recommendations for antibiotics commonly used in the
treatment of intra-abdominal infections.
For mild-to-moderate community-acquired infections, empiric monotherapy with
ertapenem, moxifloxacin, tigecycline, or cefoxitin is recommended. Moxifloxacin has
good coverage against gram-positive and gram-negative aerobic organisms
(excluding P. aeruginosa), in addition to anaerobic organisms, and penetrates well
into inflamed GI tissue, peritoneal exudates, and abscesses.
for resistance among Bacteroides species to moxifloxacin were reevaluated in recent
studies and found moxifloxacin to be a safe and effective monotherapy option for
mild-to-moderate community-acquired cIAI.
60 However, moxifloxacin should
be used cautiously in infections with recent fluoroquinolone use. Tigecycline offers
added in-vitro activity against resistant pathogens such as MRSA, VRE, and
penicillin-resistant S. pneumoniae; however, tigecycline lacks activity against
Proteus species and P. aeruginosa. Caution should be practiced when using
tigecycline for severe infections, including cIAI, as the US Food and Drug
antibiotic options are not available. Ertapenem is another monotherapy option for
mild-to-moderate community-acquired cIAI. In comparative trials of ertapenem
versus piperacillin–tazobactam, the two agents were shown to be similar in efficacy
61–63 Because monotherapy has been shown to be efficacious in numerous
trials, combination therapy is now rarely used. Combination therapy with either a
cephalosporin or a fluoroquinolone (ciprofloxacin or levofloxacin) plus
metronidazole is also reasonable.
6 For severe community-acquired intra-abdominal
infections, meropenem, imipenem–cilastatin, doripenem, and piperacillin–
tazobactam are empiric monotherapy options that may be used. An antipseudomonal
third- or fourth-generation cephalosporin, fluoroquinolone (ciprofloxacin or
levofloxacin), or aztreonam in combination with metronidazole represent alternative
options for severe infections.
Tertiary peritonitis is described as persistent peritonitis with systemic signs of
sepsis even after appropriate management of the infection has been initiated.
health care–associated infection, tertiary peritonitis often presents in critically ill
patients and those immunocompromised where adequate source control may be
improbable. With tertiary peritonitis, pathogens can vary from those that are less
virulent such as enterococci, including VRE, coagulase-negative Staphylococcal
species, and Candida species to the more resistant health care–associated pathogens
with little to no antibiotic options. Empiric use of meropenem, imipenem–cilastatin,
doripenem, or piperacillin–tazobactam6 should be reserved for health care–
ceftazidime/avibactam, both used with metronidazole, were recently approved for
and AmpC-producing Enterobacteriaceae and multi-drug resistant P. aeruginosa.
Ceftazidime/avibactam also has in-vitro activity against K. pneumoniae
Empiric use of ampicillin–sulbactam is no longer recommended for complicated
intra-abdominal infections because of increasing rates of E. coli resistance.
Clindamycin and cefotetan are not recommended for community-acquired cIAI
because of rising resistance rates from B. fragilis. The association of clindamycin
with Clostridium difficile–associated diarrhea has also resulted in the use of other
61–63,69,70 With the risk of toxicity when using aminoglycosides, safer
agents are now considered first-line treatment options. Fluoroquinolone-resistant E.
coli has become more common in the community. Caution should be taken when using
fluorquinolones empirically, particularly if hospital antibiograms indicate <90%
6 Susceptibility patterns within the community and
institutional antibiograms may assist with selection of optimal empiric antimicrobials
when managing community-acquired cIAIs.
hours would be an appropriate treatment for R.C.’s mild-to-moderate cIAI.
CASE 70-4, QUESTION 4: How long should R.C. receive antimicrobial therapy?
DURATION OF ANTIMICROBIAL THERAPY
Recommendations for the duration of therapy for intra-abdominal infection vary from
4 to 7 days and depend primarily on the patient’s clinical response to therapy and
In general, antimicrobial therapy should be continued
until resolution of signs of infection takes place, including return of WBC count to
normal and elimination of fever.
abdominal pain. Laboratory values include a WBC count of 18.4 × 10
/μL and creatinine of 1.1 mg/dL. B.B.’s
Should she receive additional antimicrobial therapy active against Enterococcus?
Although Enterococcus is commonly cultured in patients with secondary
peritonitis, its pathogenicity has been questioned. Enterococcus can cause serious
infections (e.g., endocarditis, urinary tract infections), but it is less virulent in the
setting of polymicrobial infections such as intra-abdominal infections.
An important issue is whether empiric treatment should include antibiotics with
activity against Enterococcus. Some investigators believe that Enterococcus species
are commensal organisms that need not be treated in most clinical settings. They
point to clinical studies in which antibiotic regimens lacking in-vitro activity against
Enterococcus have been successful. The pathogenicity of Enterococcus lies in its
ability to enhance the formation of abscesses.
3 The presence of enterococci suggests
active disease; however, use of anti-enterococcal antibiotics has not shown to
In general, coverage is warranted if Enterococcus is present in blood cultures or is
6 Anti-enteroccocal therapy is recommended in patients
with nosocomial or health care–associated infections,
received antibiotics selecting for Enterococcus spp. (e.g., cephalosporins), are
immunocompromised, have postoperative infection, or have valvular heart disease or
prosthetic intravascular materials.
If susceptible, Enterococcus species should be
treated with ampicillin or piperacillin/tazobactam. Vancomycin should be reserved
for ampicillin-resistant enterococcus, whereas VRE can be treated with linezolid or
daptomycin. Because B.B.’s blood cultures are negative and ascitic culture has
demonstrated mixed pathogens, Enterooccus coverage, specifically VRE, may not be
necessary. B.B. should be treated with an antimicrobial regimen that has activity
against gram-negative pathogens, anaerobes and susceptible enterococci for a
ANTIFUNGAL THERAPY: TREATMENT OF CANDIDA
The need to treat Candida species as a solitary isolate or as part of a polymicrobial
infection is controversial. Certainly, Candida has the potential to cause peritonitis, IP
abscesses, and subsequent candidemia. Mortality resulting from Candida peritonitis
72 Risk factors for Candida peritonitis have included
recurrent abdominal surgery, GI tract perforation, particularly in those untreated
within the first 24 hours, surgical drains, intravenous and urinary catheters, severe
sepsis, and colonization by Candida species.
73 Significance for intra-abdominal
candidiasis worthy of treatment rises when Candida species are isolated surgically
or directly from an intra-abdominal collection (e.g., within 24 hours of drain
placement) in patients with severe community-acquired or health care–associated
74 This may include patients who recently received immunosuppressive
therapy for neoplasm, has a perforated gastric ulcer while on acid suppression, has
malignancy, transplantation or inflammatory disease, or a postoperative or recurrent
Echinocandins and azoles are initial options for fungal peritonitis.
about the toxicity of conventional amphotericin B have limited the use of this agent.
To date, no clinical trials have assessed the efficacy and safety of lipid-based
amphotericin B, azoles, or echinocandins in the treatment of intra-abdominal fungal
infections. Fluconazole is considered an appropriate drug of choice for C. albicans.
For C. glabrata or other fluconazole-resistant species, an echinocandin (caspofungin,
micafungin, or anidulafungin) or an amphotericin product is an appropriate option.
critically ill, initial therapy with an echinocandin is recommended.
Therapy with an antifungal agent such as fluconazole 400mg daily is acceptable for
B.B and the C. albicans isolated.
CASE 70-5, QUESTION 3: The surgical resident initiated piperacillin–tazobactam for the treatment of
With the introduction of broad-spectrum antimicrobial agents with in-vitro activity
against B. fragilis and a significant problem of increasing resistance, the choice of a
specific antianaerobic agent has become more complex. Multiple mechanisms of
resistance are encountered, and resistance rates differ among various geographic
areas of the United States. Although Bacteroides resistance to metronidazole is
resistance to clindamycin has increased substantially.
carbapenems and the β-lactamase inhibitor combinations are exquisitely active
against Bacteroides, occasional resistance has been reported.
The Clinical and Laboratory Standards Institute has suggested that susceptibility
testing be performed only to determine patterns of anaerobic susceptibility to new
antimicrobial agents and to monitor susceptibility patterns periodically on a
Because most anaerobes are cultured in the setting of mixed flora, isolation of
individual components of a complex mixture can be time-consuming. In addition,
most anaerobes are very slow growing, and it may take days to weeks for a definitive
culture and sensitivity report. If specimens are not collected and transported in
optimal media or in a timely manner, inaccurate or misleading results may be
reported. The methods for susceptibility testing of anaerobic bacteria are not well
standardized, and many hospital laboratories do not have resources to perform
extensive culture and sensitivity testing. Routine cultures rarely impact the choice of
antibiotic regimen, and thus the empiric choice of therapy usually determines the
77 Routine susceptibility testing for patient-specific cases is not
recommended because of the prolonged time needed to achieve results, but it may be
useful when resistant organisms are suspected or high-risk patients have been
Abscesses are collections of necrotic tissue, bacteria, and WBCs that form during
a period of days to years. They generally result from chronic inflammation and the
body’s attempt to localize organisms and toxic substances by formation of an
avascular fibrous wall. This process isolates bacteria and the liquid core from
opsonins and antimicrobial agents.
Pathogens encountered in intra-abdominal abscesses often include facultative aerobic
gram negatives (e.g., E. coli) and obligate anaerobes (e.g., B. fragilis).
infections involving E. coli or enterococci with B. fragilis have been associated with
a synergistic mechanism responsible for late intraperitoneal abscess
Abscesses pose a therapeutic challenge because they typically contain large bacterial
inocula that are likely to include subpopulations of resistant bacteria.
or surgical debridement of R.K.’s abscess is crucial, adjunctive therapy with
antimicrobial agents is warranted. The optimal antimicrobial agent should penetrate
into the abscess in adequate concentrations and have an adequate spectrum of
55 R.K. should be placed on an antimicrobial regimen, such as
piperacillin–tazobactam 3.375 g IV every 6 hours, that covers gram-negative bacteria
INFECTIONS AFTER ABDOMINAL TRAUMA AND
Risk factors for infection after penetrating abdominal trauma include the number,
type, and location of injuries; the presence of hypotension; large transfusion
requirements; prolonged operation; advanced age; and the mechanism of injury.
Most investigators stress the importance of instituting antimicrobial therapy as
close to the time of trauma as possible. Bozorgzadeh et al.
significant reduction in the incidence of postoperative infections when antibiotics
were administered before surgical repair of the penetrating abdominal trauma.
QUESTION 1: T.I., a 19-year-old man, is admitted to the emergency department within 1 hour after
sustaining a gunshot wound to the stomach and colon. He is to undergo emergency laparotomy. What
antimicrobial therapy is appropriate at this time?
As with other types of intra-abdominal infections, antibiotics active against both
aerobic and anaerobic pathogens should be used.
Anti-infective therapy has been studied in patients who have sustained penetrating
trauma to the abdomen (usually from knife or gunshot wounds). In several
comparative trials, single-drug therapy with cefoxitin was as effective as the
combination of clindamycin or metronidazole plus an aminoglycoside.
these studies, however, it is important to note that most patients did not sustain
injuries to the colon, where the risk of infection is highest. Although the age of this
patient suggests he would tolerate aminoglycoside therapy, monotherapy with
cefoxitin or one of the β-lactamase inhibitor combinations would be appropriate.
Consensus guidelines regarding the duration of therapy were published by the
Eastern Association for the Surgery of Trauma (EAST) Practice Management Group.
These investigators reviewed all literature from 1976 to 1997 regarding the duration
of antimicrobial use after penetrating abdominal trauma. They concluded that
antimicrobial use should not exceed 24 hours in this patient population.
CASE 70-7, QUESTION 2: How long should antibiotic therapy be administered to T.I.?
The shortest duration of antimicrobial therapy that has been shown to be effective
has been 12 hours with the possibility that a short course (<48 hours) is as
efficacious as 5-to 7-day course if antimicrobial therapy is promptly instituted.
Several other trials have confirmed no additional benefit exists in providing a longer
Because antimicrobial therapy carries a risk of adverse reactions, development of
resistance, and unnecessary costs, short-term therapy seems warranted as long as it is
instituted soon after the injury.
If the initial dose of antibiotic is administered
more than 3 to 4 hours after injury, therapy should be continued for 3 to 7 days
because the incidence of infection in this circumstance is high.
Antimicrobial therapy was instituted soon after T.I. sustained the colonic injury;
therefore, a short course of antimicrobial therapy is appropriate. Therapy should be
how long should it be continued?
Clinical manifestations commonly encountered with acute appendicitis include
right lower quadrant abdominal pain, rebound tenderness, and low-grade fever
complicated by nausea, vomiting, and anorexia.
A variety of antimicrobial agents are effective in the treatment of acute
88–92 Antimicrobial therapy selection for uncomplicated appendicitis can
follow those recommended for community-acquired intra-abdominal infection where
therapy for less than 24 hours is sufficient.
6 Patients with gangrenous or perforated
β-lactams, and β-lactamase inhibitor combinations has been found to be as effective
as the combination of clindamycin or metronidazole plus an aminoglycoside.
Patients with gangrenous or perforated appendices who were afebrile for 48 hours
have been treated for durations ranging from a single dose
S.R. should receive a preoperative dose of β-lactam antimicrobials with activity
against facultative gram-negative and anaerobic bacteria, such as cefoxitin alone or
cefazolin plus metronidazole (Table 70-2). Cost, potential side effects, and ease of
administration guide selection of a specific agent. If a gangrenous or perforated
appendix is found during surgery, antimicrobial therapy should
be continued for a minimum of 3 to 5 days or until S.R. has been afebrile for 48
A full list of references for this chapter can be found at
http://thepoint.lww.com/AT11e. Below are the key references and websites for this
chapter, with the corresponding reference number in this chapter found in parentheses
hemorrhage, ascites, and spontaneous bacterial peritonitis. Gastroenterology. 2001;120:726. (22)
(SMART). Antimicrob Agents Chemother. 2010;54:3031. (16)
the EAST Practice Management Guidelines Work Group. J Trauma. 2000;48: 508. (82)
Philadelphia, PA: Elsevier Saunders; 2015:960–968. (5)
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Carpenter HA. Bacterial and parasitic cholangitis. Mayo Clin Proc. 1998;73:473.
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Podnos YD et al. Intra-abdominalsepsis in elderly persons. Clin Infect Dis. 2002;35:62.
(SMART). Antimicrob Agents Chemother. 2010;54:3031.
Ginès P et al. Management of cirrhosis and ascites. N EnglJ Med. 2004;350:1646.
hemorrhage, ascites, and spontaneous bacterial peritonitis. Gastroenterology. 2001;120:726.
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