Objectives

Intra-abdominal
Infections

Describe pathogenesis & clinical characteristics

of intraintra-abdominal infections
Identify most likely etiologic organism(s)
organism(s)
Review appropriate drug therapy

Marnie Peterson, Pharm.D., Ph.D., BCPS

College of Pharmacy
[email protected]
2006 Marnie Peterson. This presentation is provided to facilitate the learning of participants within
this course. It may not be modified, reproduced and/or circulated for other means without the
permission of the author.

Intra-abdominal Infections

Intra-abdominal Infections

Infections contained within the peritoneum or

retroperitoneal space.

Duodenum
Pancreas
Kidneys

GI microflora
depends on the
anatomic site!
Upper Intestine:
Streptococci
Enterococci
Staphylococci
E. coli
Klebsiella
Bacteroides
Ileum:
Streptococci
Staphylococci
Escherichia coli
Klebsiella
Enterobacter
Bacteroides
Clostridium

Food Poisoning/Traveler
Poisoning/Travelers Diarrhea

Helicobacter pylori

Pelvic Inflammatory Disease

Viral
Parasitic

Normal GI Microflora

Stomach:

Stomach:
H. pylori
Lactobacilli
Colon:
Bacteroides
Peptostreptococci
Clostridium
Bifidobacterium
Escherichia coli
Klebsiella
Enterobacter
Enterococci
Staphylococci

(Clostridium difficile)

Anatomy of the GI Tract

Stomach
Jejunum, Ileum
Appendix
Large intestine (colon)
Liver, gallbladder and spleen

Retroperitoneal space:

Peritoneal cavity contains:

Appendicitis
Peritonitis
IntraIntra-abdominal Abscess
Diverticulitis
AntibioticAntibiotic-Associated Diarrhea

Total bacterial count 00-108 log organisms/g

Helicobacter pylori
Streptococci
Lactobacilli

Upper Small Intestine:

Total bacterial count 00-105 log organisms/g

Aerobes

Enterococci
Staphylococci
Lactobacilli
E. coli, Klebsiella

Anaerobes

Bacteroides

Ileum

Total bacterial count 103-109 log organisms/g

Aerobes:

Streptococci
Staphylococci
Escherichia coli, Klebsiella
Enterobacter

Anaerobes:

Normal GI Microflora

Bacteroides
Clostridium

Peritonitis
Inflammation of the
serous lining of the
peritoneal cavity due
to:

Total bacterial count 1010-1012 log organisms/g

Anaerobes:

Microorganisms
Chemicals
Irradiation
Foreign body injury

Large Intestine (Colon)

Bacteroides
Peptostreptococci
Clostridium
Bifidobacteria

Aerobes:

Escherichia coli, Klebsiella

Enterobacter
Enterococci
Staphylococci

Peritonitis

Peritonitis

Primary
Peritonitis

Primary
No focus of disease is evident
Bacteria transported from blood stream to
peritoneal cavity (Cirrhosis, CAPD)

Secondary
Acute perforation of the GI tract (gastric,
diverticular (diverticulitis), appendix (appendicitis),
gallbladder, tumor perforations) [66%]
PostPost-operative peritonitis [24%]
PostPost-traumatic peritonitis [10%]

S. pneumoniae (15%)
Enterococci (6(6-10%)
anaerobes (<1%)
S. aureus/MRSA (CAPD)

Treatment

Seiler CA, et al. Surgery. 2000; 127:178-184.

Clinical Symptoms

Abdominal pain
Anorexia (N/V)
Fever (100 to 102 F)
Abdominal distention and tenderness
Hypoactive or faint bowl sounds
Leukocytosis

Enterobacteriaceae
Bacteroides
Enterococci
P. aeruginosa

Microbiology Enterobacteriaceae (63%)

Secondary Peritonitis

Cefotaxime,
Cefotaxime,
pip/tazo
pip/tazo,, amp/sulb
amp/sulb,,
ceftriaxone,
ceftriaxone,
carbapenem,
carbapenem, FQ,
vanco (MRSA)

Pip/tazo
Pip/tazo,, amp/sulb
amp/sulb,,
carbapenem,
carbapenem, tigecycline,
tigecycline,
moxifloxacin,
moxifloxacin,
(amp+ cipro/levo/AG +
metronidazole)
metronidazole)

Peritonitis

Normally:
Normally: 20 to 50 mL transudate

Peritoneal membrane measures approx. 1.7 m2

WBC < 300 cells/mm3
Protein: <3 g/dL

Bacterial peritonitis:
peritonitis: 300 to 500mL inflow/hr
resulting in hypovolemia.

WBC > 300 cells/mm3

Gram stain + for bacteria

Primary Peritonitis

?????Clinical Question?????

Relatively infrequent
25% of patients with alcoholic cirrhosis
60% of all patients on chronic ambulatory
peritoneal dialysis (CAPD) will have at least one
episode in 1st year.
Average incidence in CAPD patients is 1.3 to 1.4
episodes/yr.
Catheter connecting abdominal cavity to exterior
body is a major risk factor.

Recommend dosing for

intraperitoneal administration of an
antibiotic for a CAPD patient with
a Staphylococcus peritonitis

Peritonitis in CAPD

Antibiotics may be given intraperitoneal via the

dialysate: (exchanges every 4 to 6 hrs)

Reasonable empiric therapy

Gentamicin and tobramycin: 8mg/L

Clindamycin: 1 to 3 mg/L
Penicillin G: 50,000 units/L
Cephalosporins: 125 mg/L
Ampicillin: 50 mg/L
Vancomycin: 30 mg/L
Amphotericin B: 3 mg/L

Appendicitis Case

Gentamicin or tobramycin PLUS vancomycin

Ceftazidime PLUS vancomycin

What are the considerations in a ruptured appendix?

Microbial
Therapeutics

Duration: 2 to 3 weeks

Appendicitis Case, cont.

LF, an 18 yr female, was admitted to the hospital with

diffuse abdominal pain, diarrhea, and nausea. Her pain
was localized to the right side of the abdomen.
Cefazolin was initiated and LF was taken to surgery for
a ruptured appendix to be removed.

LF, an 18 yr female, was admitted to the hospital with

diffuse abdominal pain, diarrhea, and nausea. Her pain
was localized to the right side of the abdomen.
Cefazolin was initiated and LF was taken to surgery for
a ruptured appendix to be removed.

Appendicitis

What are the considerations in a ruptured appendix?

Microbial

Highest incidence 1010-19y/o,

male>female
Pathophysiology:
Pathophysiology: Relationship to onset of sx

Staphylococcus? NOT most important

E. coli? Yes
Anaerobes? Yes

Therapeutics

Cefazolin alone? No
Unasyn yes - why?

0-24h after sx onset: obstruction within appendix

inflammation & occlusion of vascular & lymphatic flow
bacterial overgrowth necrosis
>48h after sx onset: perforation (60%)
(60%)abscess/peritonitis

Early sx:
sx: dull, nonnon-localized RLQ pain, indigestion,
bowel irregularity, flatulence
Later sx:
sx: pain/tenderness more localized, N/V

Fever >103F, leukocytes >15000: perforation likely

Sample Exam Question:

Appendicitis

Acute, nonnon-perforated appendicitis

Perforated appendicitis

cefazolin + metronidazole

For initial treatment in a pt with a ruptured appendix

and no other contributing factors, which of the
following is an incorrect choice?

Cover enteric gram rods and anaerobes

(2nd/3rd generation ceph or FQ) + metronidazole
Cefoxitin,
Cefoxitin, piperacillin/tazobactam,
piperacillin/tazobactam, ampicillin/sulbactam,
ampicillin/sulbactam,
imipenem

Antibiotics are started before surgery, continued for 7710 days

Switch to PO based on patient status

Sample Exam Question:

For initial treatment in a pt with a ruptured appendix

and no other contributing factors, which of the
following is an incorrect choice?

Ampicillin/sulbactam (Unasyn) +/+/- Aminoglycoside

Piperacillin/tazobactam (Zosyn) +/+/- Aminoglycoside

Tigecycline (Tigecil)
Tigecil) +/+/- Aminoglycoside

Clindamycin + Ampicillin + Aminoglycoside

Clindamycin + Metronidazole

Moxifloxacin + Metronidazole

Appendicitis Case, cont.

Ampicillin/sulbactam (Unasyn) +/+/- Aminoglycoside

Piperacillin/tazobactam (Zosyn) +/+/- Aminoglycoside

Tigecycline (Tigecil)
Tigecil) +/+/- Aminoglycoside

Clindamycin + Ampicillin + Aminoglycoside

Clindamycin + Metronidazole

Moxifloxacin + Metronidazole

Appendicitis Case, cont.

LF improved postpost-operatively & completed 7d course of PO

cephalexin.
cephalexin. 4d after completing antibiotics she felt diffuse pain
over the appendectomy site. Abdominal CT scan revealed a
peritoneal abscess. Abscess was drained & fluid sent to the lab.

What organism(s)
organism(s) are most likely to be responsible for the
abscess?

Likely MRSA, not covered by cephalexin

Gram negative bacteria not covered by 1st generation cephalosporins
Anaerobic bacteria not covered by cephalexin

Was the cephalexin an appropriate choice of abx for LF?

No, LF should have remained in the hospital for 77-10 days with IV tx
No, there was not appropriate coverage with a 1st generation ceph
Yes, but metronidazole should have been added for anaerobic coverage

Intra-abdominal Abscess

What organism(s)
organism(s) are most likely to be responsible for the
abscess?

Likely MRSA, not covered by cephalexin:

cephalexin: MRSA not most likely here
*Gram negative bacteria not covered by 1st generation cephalosporins:
cephalosporins:
Gram s likely involved and cephalexin has limited gram coverage
*Anaerobic bacteria not covered by cephalexin:
cephalexin: anaerobes likely involved,
cephalexin not good choice for anaerobes

Was the cephalexin an appropriate choice of abx for LF?

No, LF should have remained in the hospital for 77-10 days with IV tx:
tx: no,
outpatient tx is okay with appropriate abx choice
*No, there was not appropriate coverage with a 1st generation ceph:
ceph: not
adequate coverage of gram s and anaerobes
Yes, but metronidazole should have been added for anaerobic coverage:
an agent with anaerobe coverage should be added, but also need gram
gram coverage

Intra-abdominal Abscess

Abscess: purulent collection of fluid, necrotic debris,

bacteria, inflammatory cells that is walled
off/encapsulated by adjacent healthy cells in an attempt
to keep pus from infecting neighboring structures.

encapsulation can prevent immune cells/abx

cells/abx from attacking
contained bacteria, low O2 in capsule
capsuleanaerobes thrive
here!

Result of chronic inflammation, develop over daysdays-yrs

Located within peritoneal cavity or visceral organs
May range from a few milliliters to a liter in volume

Intra-abdominal Abscess

Ruptured abscess

Presentation: nonspecific low grade or spiking fever,

abdominal pain/discomfort +/+/- distension
Labs: leukocytosis,
leukocytosis, +/+/- positive blood cultures, +/+/hyperglycemia
Ultrasound, GI contrast study, or CT scan may be used
for evaluation

Management of
IntraIntra-Abdominal Infections

IntraIntra-abdominal Abscess

Microbiology

Combination of modalities:

usually mixed infection: aerobes & anaerobes within

the same abscess

debridement

coli
Klebsiella
Enterococci
B. fragilis
Clostridium

Resection of perforated colon, small intestine, ulcers

Repair of trauma

replacement
heart rate
Monitor urine out put (0.5 ml/kg/hr)
Monitor

Ampicillin/sulbactam (Unasyn) (enterococci)

Piperacillin/tazobactam (Zosyn) (enterococci)
enterococci)
Imipenem/cilistatin (Primaxin)
Meropenem (Merrem
(Merrem))
Ertapenem (Invanz)
Invanz)
Aminoglycoside + clindamycin or metronidazole
Tigecycline (Tygacil)
Tygacil)
Moxifloxacin (Avelox)
Avelox) (active against 83% of Bacteroides strains)

(+ metronidazole:
metronidazole: per IDSA guidelines CID 2003:37 997)

Appropriate antimicrobial therapy

Empiric Antibiotic Therapy

Empiric Antibiotic Therapy

Support of Vital functions:

Blood pressure/fluid

MUST include aerobic/anaerobic coverage

Agents with Aerobic and Anaerobic activity:

Surgical
Prompt drainage of abscess (secondary peritonitis) and/or

E.

spread of bacteria+toxins into peritoneum

peritoneumperitonitis
Spread of bacteria+toxins into systemic circulation
circulationsepsis,
sepsis,
multimulti-organ failure, death

MUST include aerobic/anaerobic coverage

(one from each of the below categories)
Anaerobic activity:

Chloramphenicol( also includes aerobic Gram +/+/-)

Clindamycin (also includes aerobic Gram +)
Metronidazole (anaerobic coverage only)

Aerobic activity:

Aminoglycosides:
gentamicin, tobramycin (Gram negatives only)
BetaBeta-lactams:
Cefotaxime (Claforan)
Ceftriaxone (Rocephin)
Aztreonam (Azactam) (Gram negative only)
Quinolones:
Ciprofloxacin (Cipro) (Mostly Gram negative)
Levofloxacin (Levaquin) (Gram +/+/- and some anaerobic coverage)
Moxifloxacin (Avelox)
Avelox) (Gram +/+/- and anaerobes)
Vancomycin/Linezolid/Synercid (Enterococci, MRSA)

Antibiotic Therapy

Factors involved in selection:

Severity of infection, suspected infecting organism(s) and

resistance patterns, efficacy, toxicity (renal dysfunction),
allergies

Increases in Candida or GramGram-negative bacteria

Proliferation of antibioticantibiotic-resistant organisms
Pseudomembranous colitis from over proliferation
of toxintoxin-producing anaerobe, Clostridium difficile.
difficile.

Improvement in 2 to 3 days
Switch to oral antibiotic therapy

Failure to improve:

Broad spectrum antibiotics can change the

normal GI flora

Evaluating response:

Antibiotics and GI flora

Resistant organisms
Recurrent surgical infections
Other infections: (urinary tract infections, pneumonia)

Pseudomembranous Colitis
Antibiotic Associated Diarrhea
Diarrhea

Antibiotic Associated Diarrhea

Antibiotic therapy (broad spectrum agents: clindamycin,
clindamycin, ampicillin,
ampicillin,
3rd generation cephalosporins are most common)
Disruption of normal colonic flora
C. difficile colonization (gram +, spore forming anaerobe)
Release of toxins A (enterotoxin
), B (cytotoxin
), & binary toxin
(enterotoxin),
(cytotoxin),
CDT (associated w/ recent outbreaks)
Damage to colonic mucosa (pseudomembranous
(pseudomembranous plaques),
inflammation, intestinal fluid secretion

Pseudomembranous
Colitis

Clostridium difficile:
difficile:
toxin mediated disease

Toxin A (major)
Overproduction

in tcdC gene.

in outbreak strains of C. difficile due to deletion

Toxin B (minor)
Binary toxin CDT
associated

with recent outbreaks (NEJM 2005; 353: 2433)

with binary toxin are often resistant to
quinolones

C. difficile strains

Toxins cause inflammation, necrosis, loss of fluid

electrolytes

Pseudomembranous colitis

Antibiotic Associated Diarrhea

Spectrum of disease

Colitis w/o pseudomembrane formation

Pseudomembranous colitis

Malaise, abdominal pain, water diarrhea, nausea, low fever

Severe abdominal pain, perfuse diarrhea, high fever

Symptom onset can occur shortly after start abx

or several weeks after tx stopped

Diagnosis: stool culture of C. diff, presence of

toxin A or B, endoscopy

C. diff risk if abx use in past 2 months

FIRST LINE:
Metronidazole (Treatment of Choice)
250mg PO QID or 500mg PO/IV TID x 1010-14 days
ALTERNATIVE: (if not responding to metronidazole or
recurrences)
Vancomycin
125mg PO QID x 1010-14 days +/+/- rifampin 600mg
PO BID

Always stop the drug responsible for causing the

infection as soon as possible!

Pseudomembranous colitis

Pseudomembranous colitis

RECURRANCES:

1st: Retreat with either metronidazole or vancomycin,

vancomycin, dosed
as above, x 1010-14d
>2nd:Vancomycin taper/pulse therapy
125mg PO QID x7d, then 125mg PO BID x7d, then
125mg PO QD x7d, then 125mg PO QOD x7d, then
125mg PO every 3 days x14d

Can add

3 week course of probiotics (Saccharomyces

boulardii 500mg PO BID) starting during final week of
taper and continued for 2 weeks after vanco taper

Metronidazole vs. vanomycin

counteract disturbances & reduce risk of colonization by

pathogenic bacteria

Similar in nonnon-severe cases with time to resolution of

diarrhea, side effects, and relapse rates
2020-25% recurrence, not related to tx choice, dose or
duration
Metronidazole:
Metronidazole: cheaper, preferred due to concern of VRE
Vancomycin:
Vancomycin: okay if pt is pregnant, <10yo, or if severe case
with sx of systemic toxicity (potential for better cure rate than
metronidazole)
metronidazole)
MUST give PO concentrations in gut aren
arent high
enough with IV

(Per IDSA treatment guidelines)

?????Clinical Question?????

Alternative/Investigational Therapies

Nitazoxanide vs. metronidazole (non(non-inferior)

Musher et al. CID 2006:43:4212006:43:421-7

Rifaximin (follow up tx after vanco in pts with

recurrent CDAD)

Anion binding resins: bind toxins

Cholestyramine and colestipol

Tolevamer

inferior to primary tx,

tx, possible adjunct to vanco for relapse
Promising results, not yet FDA approved

IVIG

Pharmacy consult is ordered for a

patient presenting with
pseudomembranous colitis after recent
therapy with oral cefuroxime -

What is the likely organism

responsible?
What other info do you need
about the patient?
What is the best antibiotic
treatment this patient?

Johnson et al. CID 2007;44:8462007;44:846-8

No sig benefit in pts with refractory disease

?????Clinical Question, cont.?????

What is the likely organism responsible?

E. coli
Clostridium difficile
Shigella

What other info do you need about the patient?

Ht and wt to calculate IBW for accurate dosing tx for C. diff

Is this the first or recurrent episode, severity of sx,
sx, pregnancy
status, allergies, ect.
ect.
Both of the above

This is the pts first episode;

episode; what is the best antibiotic
treatment?

?????Clinical Question, cont.?????

Metronidazole 500mg PO Q 8h x14d

Vancomycin 125mg PO or IV Q 6h x14d
Vancomycin pulse/taper with probiotic overlap

What is the likely organism responsible?

What other info do you need about the patient?

E. coli
*Clostridium difficile
Shigella
Ht and wt to calculate IBW for accurate dosing tx for C. diff
*Is this the first or recurrent episode, severity of sx,
sx, pregnancy status,
allergies, ect.
ect. (these factors influence your tx recommendation)
Both of the above (no, dose is not based on wt)

This is the pts first episode;

episode; what is the best antibiotic treatment?

*Metronidazole 500mg PO Q 8h x14d (yes!)

Vancomycin 125mg PO or IV Q 6h x14d (IV vanco not effective!)
Vancomycin pulse/taper with probiotic overlap (not indicated for first
episode)

References

IDSA: Guidelines for the Selection of AntiAnti-infective Agents for Complicated IntraIntra-abdominal
Infections. CID. 2003; 37(15): 997997-1005.
Goldstein EJC, Snydman DR. IntraIntra-abdominal infections: review of the bacteriology,
antimicrobial susceptibility and role of ertapenem in their therap. JAC. 2004; 53(S2):ii2953(S2):ii29-ii36.
Malangoni MA, Song J, Herrington J, Choudhri S, Pertel P. Randomized Controlled Trial of
Moxifloxacin Compared with PiperacillinPiperacillin-Tazobactam and AmoxicillinAmoxicillin-Clavulanate for the
Treatment of Complicated IntraIntra-abdominal Infections. Annals of Surgery. 2006; 244(2): 204204-211.
UpToDate
UpToDate. Treatment of antibioticantibiotic-associated diarrhea caused by Clostridium difficile.
difficile.
Accessed 3/10/2008.
UpToDate
UpToDate. Anaerobic bacterial infections. Accessed 3/10/2008.
UpToDate
UpToDate. Treatment and prophylaxis of spontaneous bacterial peritonitis.
peritonitis. Accessed
3/10/2008.
UpToDate
UpToDate. Appendicitis in adults. Accessed 3/10/2008.
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML. Pharmacotherapy: A
Pathophysiologic Approach, Sixth Ed. 2005.
Gilbert DN, Moellering RC, Eliopoulos GM, Sande MA. The Sanford Guide to Antimicrobial
Therapy, 37th Ed. 2007.
Lin WJ, L WT, Chu CC, Chu ML, Wang CC. Bacteriology and antibiotic
antibiotic susceptibility of
communitycommunity-acquired intraintra-abdominal infection in children. J Microbiol Immunol Infect. 2006; 39:
249249-254.