ORIGINAL ARTICLE: GASTROENTEROLOGY

Antibiotic-associated Bloody Diarrhea in Infants: Clinical,

Endoscopic, and Histopathologic Profiles

Maha Barakat, yZeinab El-Kady, zMohamed Mostafa, yNaglaa Ibrahim, and yHamdy Ghazaly

ABSTRACT
starts primarily with history taking and should be suspected in any
Objective: Antibiotic-associated diarrhea constitutes 1 of the most frequent
patient who develops diarrhea during antibiotic therapy or within 6
side effects of antimicrobial therapy with widely varying clinical presenta-
to 8 weeks of treatment (3). Interestingly, this iatrogenic problem
tions; however, little is known about its antibiotic-associated bloody diar-
can be induced by almost all of the antibiotics, even after a single
rhea (AABD) form, particularly in very young children. The aim of this
dose (4).
study was to describe the clinical, endoscopic, and histopathologic profiles
Clinically, AAD may manifest through a spectrum extending
of community-acquired AABD in infants.
from mild to fulminant life-threatening colitis, with patterns varying
Patients and Methods: The study included 23 infants referred with bloody
from watery to bloody diarrhea and hemorrhagic colitis (5). Patho-
diarrhea that developed a few days after receiving antibiotics on an
genetically, various mechanisms have been proposed to explain the
outpatient basis for watery diarrhea (18), respiratory tract infections (4),
occurrence of AAD. Following an antibiotic-induced disturbance of
or urinary tract infection (1). Detailed clinical assessment,
the normal gut flora profile, Clostridium difficile contributes to
videosigmoidoscopy, and histopathologic examination of endoscopic
about 20%, whereas several other organisms including Clostridium
biopsies were performed for all.
perfringens, Staphylcoccus aureus, Candida albicans, and Kleb-
Results: Clinically, on presentation, bloody diarrhea was acute in all except
siella oxytoca can be collectively responsible for about 2% to 3% of
1 patient with a prolonged course (for 25 days) and stopped in all 2 to 6 days
AAD cases. Also, a direct antibiotic effect on the intestinal mucosa
after discontinuation of antibiotics. Fever and/or leukocytosis were present
shares as another mechanism in a minority of cases. Otherwise,
only in 8 (34.8%). Sigmoidoscopy revealed varying types of erythema
about 75% of AAD cases have been described as ‘‘nonspecific’’
(patchy, ring, diffuse) and ulcers (aphthoid, diffuse) in 18 and
with no defined mechanism. Of all of the mechanisms, C difficile
pseudomembranes in 5. Histopathologically, only 3 showed the
infection has received much attention mainly as a nosocomial
characteristic mushroom-like pseudomembranes, whereas all of the other
infection for which advanced age and hospitalization are the major
infants had nonspecific colitis.
risk factors (6,7).
Conclusions: Community-acquired AABD is not uncommon in infants
Few data are available regarding the occurrence of AAD in
presenting with acute or chronic forms even without fever or
the infancy period in a nonhospital ambulatory setting, particularly
leukocytosis. When suspected, discontinuation of antibiotics is a good
when presented as antibiotic-associated bloody diarrhea (AABD),
policy if facilities for bacterial culture with cytotoxin assays are limited.
the form that generally seems to be underdiagnosed. Although
The characteristic endoscopic or histopathologic pseudomembranes are
diarrheal illnesses in infancy constitute a common clinical problem,
encountered only in a small percentage (26%). Rational use of antibiotics
especially in developing countries (8), bloody diarrhea in particular
should be adhered to particularly in cases of watery diarrhea that is mostly of
represents an alarming event to the physician and causes much
viral origin.
anxiety and fright in the child’s parents.
Key Words: antibiotic-associated diarrhea, bloody diarrhea, infants, The aim of this study was to provide a detailed description of
pediatric endoscopy the clinical, endoscopic, and histopathologic profiles of AABD in
infants in a community-acquired non-nosocomial setting.
(JPGN 2011;52: 60–64)
PATIENTS AND METHODS
This study included 23 infants admitted to the Gastroenter-

A ntibiotic-associated diarrhea (AAD) has been recognized

worldwide as 1 of the most frequent side effects of anti-
microbial therapy, with an incidence ranging from 5% to 35%
particularly in hospitalized patients (1,2). The diagnosis of AAD
Received January 9, 2010; accepted February 8, 2010.
From the Department of Tropical Medicine and Gastroenterology, the
yDepartment of Pediatrics, and the zDepartment of Pathology, Assiut
University Hospital, Assiut, Egypt.
Address correspondence and reprint requests to Maha Barakat, MD,
Department of Tropical Medicine and Gastroenterology, Assiut
University Hospital, Assiut, Egypt (e-mail: mahabarakat2001@yahoo.
com).
The authors report no conflicts of interest.
Copyright # 2010 by European Society for Pediatric Gastroenterology,
Hepatology, and Nutrition and North American Society for Pediatric
Gastroenterology, Hepatology, and Nutrition
DOI: 10.1097/MPG.0b013e3181da215b
ology and Hepatology Unit, Department of Pediatrics, Assiut
University Hospital, with a history highly suspicious of AABD
between April 2004 and November 2008. They were 14 boys and
9 girls with an age range of 2 to 11 months (mean  SD
6.6  2.6 months). All of them developed bloody diarrhea a few
days after receiving antibiotic therapy for various illnesses on an
outpatient basis through other hospitals or pediatrics clinics. Of the
23 patients, 18 were receiving antibiotics for watery diarrhea, 4 for
respiratory tract infections, and 1 for urinary tract infection. The
study protocol was approved by the Assiut Faculty of Medicine
ethics committee.
Full clinical assessment was performed for all of the infants,
including a detailed history taken from the parents about the bloody
diarrhea (eg, its onset, frequency, duration, presence of colic, fever,
convulsions, or vomiting) and all of the antibiotics given to the
infant before the occurrence of bloody diarrhea, with a thorough
clinical examination including temperature and signs of

60 JPGN  Volume 52, Number 1, January 2011

Copyright 2010 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
 JPGN  Volume 52, Number 1, January 2011 Antibiotic-associated Bloody Diarrhea in Infants

dehydration on admission. None of the infants included had any of the patients had any serious complications, for example, toxic
other serious illnesses, for example, cardiac, hepatic, renal, and megacolon, toxic shock, and perforation.
cerebral diseases or malignancies. Also, none had a history of In all, the microscopic stool analysis was negative for
hospitalization before the admission for bloody diarrhea. parasites. Microscopic red blood cells were detected in all patients
For all of them, the following routine tests were done: (>10 per high-power field), and fecal leukocytes (>5 per high-
complete blood count, stool examination for parasites, red blood power field) denoting inflammatory diarrhea were seen in 13
cells or leukocytes, and a routine bacteriologic stool culture for (56.5%) patients. Routine stool culture revealed no growth of
enteric pathogens (eg, Shigella, Salmonella). enteropathogens (eg, Shigella, Salmonella) in all.
Written informed consent was obtained from the parents to On endoscopic examination, the rectal mucosa was involved
perform a short colonoscopic examination; the procedure was in all of the children and various lesions were revealed (Fig. 1)
explained, and 1 of the parents (usually the mother) was allowed including patchy erythema in 4 patients, ring erythema in 2, diffuse
to attend. The examination was performed using a videocolono- erythema with blood ooze in 1, scattered aphthoid ulcers in 2,
scope (Pentax EC-3440F, Tokyo, Japan) with a distal diameter of diffuse ulcerations in 7, mixed lesions (erythema and ulcerations) in
11.5 mm. No prior bowel preparation was done. Intravenous light 2, and ulcerations with pseudomembranes in 5 (interestingly, only 1
sedation was applied using incremental doses of midazolam; an of them had fever, 3 had leukocytosis, and 1 had no fever or
initial dose of 0.05 mg/kg body weight was given and increased if leukocytosis).
necessary according to the child’s response after 2 minutes until an On histopathologic examination of the biopsy specimens,
adequate level of sedation was achieved. Sigmoidoscopic examin- only 3 patients (13%) had the characteristic mushroom-like mass of
ation was arranged to be simple for a duration not exceeding 3 mucus and neutrophils at the surface epithelium (Fig. 2) as a
minutes with image recording. The maximum length of tube pathognomonic feature of C difficile antibiotic-associated PMC
insertion was 8 to 15 cm. All of the examinations were performed (1 of them without endoscopic PMC). In the rest of the patients,
by the same endoscopist (M.B.). No complications were reported,
and recovery from sedation was uneventful.
Using the standard biopsy forceps, 2 biopsies were obtained
from the recorded lesions in each patient. The specimens were fixed
in vials containing 10% neutral buffered formalin solution, labeled,
and sent to the histopathology laboratory to be processed, stained by
hematoxylin and eosin (H&E), and examined by the same histo-
pathologist (M.M.).
Once admitted with a suspected diagnosis of AABD, the
following lines were applied as a management strategy with follow-
up for clinical signs of improvement particularly during the next 24
to 72 hours:
1. Line 1: stoppage of all antibiotics þ supportive and fluid
therapy (in cases of dehydration or vomiting)
2. Line 2: as in line 1 þ oral metronidazole suspension (7.5 mg/kg
3 times daily for 10 days) if at least 1 of the following criteria of
severity was present: fever, abdominal colic, leukocytosis,
endoscopic or histologic pseudomembranous colitis (PMC) (9)

Data Analysis
Most of the data were descriptive, expressed as direct
numbers, percentages, or mean  SD. Differences between groups
were compared using Student t test. Probability values (P) less than
0.05 were considered significant.

RESULTS
Clinically, on admission, the reported duration of bloody
diarrhea was less than 1 week in all of the children (range 1–4;
mean 2.5 days), except 1 who had a prolonged course with bloody
diarrhea lasting for 25 days, during which the child received
repeated and changing courses of antibiotic combinations on
repeated medical consultations.
The onset of bloody diarrhea was 2 to 5 days (mean 2.8 days)
after intake of antibiotics either as a single (in 16 patients; 69.6%) or
as combined therapy (in 7 patients; 30.4%) including cotrimoxazole
in 12, penicillin derivatives in 10, cephalosporins in 7, and ami-
noglycosides in 4. FIGURE 1. Varying colonoscopic lesions in antibiotic-associ-
Abdominal colic was reported in 4, fever in 5 (one 2-month- ated bloody diarrhea: (A) patchy erythema, (B) ring erythema,
old infant had febrile convulsions), and vomiting in 2, with signs of (C) diffuse erythema and ulcerations, (D) aphthoid ulcers,
mild dehydration on admission in 3. Leukocytosis (with a white (E) small scattered pseudomembranes, and (F) diffuse yellow-
blood cell count of more than 11,000/mm3) was reported in 6. None ish pseudomembrane with ulcerations.

www.jpgn.org 61

Copyright 2010 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
 Barakat et al
FIGURE 2. Histopathologic pseudomembranous colitis;
focal explosive mushroom-like mass (arrows) of mucus and
neutrophils attached to the mucosa (hematoxylin and eosin
stain; original magnification 40).
features of nonspecific colitis were detected in their biopsy speci-
mens.
According to the management strategy applied, the criteria
of severity indicating metronidazole therapy were fulfilled in 12
patients in various combinations as shown in Table 1. In response to
the management strategy, the bloody diarrhea stopped with improve-
ment of the general condition within 2 to 6 days (mean 2.5 days) in all
of the patients of both groups, those on line 1 (11 patients), and those
who received oral metronidazole (11 patients). Interestingly, metro-
nidazole was not given to the infant who had only histopathologic
PMC with a prolonged AABD for 25 days, because by the time the
histopathology report came up (after 4 days), the child had already
improved with stoppage of bloody diarrhea after discontinuation of
all antibiotics. None of the patients developed any complications
along the period of hospitalization until discharged.
Although patients having the severity criteria (receiving line 2
therapy) tended to be younger than the other group (receiving line 1),
the difference did not reach statistical significance (5.9  2.5 vs
7.3  2.8 months, respectively; P > 0.05). Also, there was no stat-
istically significant difference regarding the time needed for improve-
ment between both groups (2.6  1.2 vs 2.3  0.7 days, respectively;
P > 0.05).
DISCUSSION
In extension to the body of literature examining various
aspects of AAD, this study is the first to describe its endoscopic and
histopathologic profiles in infants with bloody diarrhea. The diag-
nosis of AABD has been primarily based on 3 pieces of evidence:
(1) the strong circumstantial clinical evidence of occurrence shortly
after intake of antibiotics, and resolution shortly after their discon-
tinuation in all 23 patients (3,10); (2) the solid evidence of the
presence of PMC (endoscopic or histopathologic) in 26% of cases
(6/23) as a criterion for defining C difficile AAD, which is respon-
sible for almost all of the PMC cases (11–13); and (3) exclusion of
other possible parasitic or bacterial infections on routine stool
examination and culture and other colonic lesions (eg, polyps or
other inflammatory lesions) on endoscopy and histopathology.
Through this study, varying clinical presentations of AABD
were noted. For example, fever was absent in most of them (78%),
and 1 presented by a long course of AABD extending for 25 days. It
62
Copyright 2010 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
JPGN  Volume 52, Number 1, January 2011
TABLE 1. Distribution of the severity criteria in 12 patients
with AABD
Case Fever Leukocytosis Colic PMC (E) PMC (H)
1 H H
2 H H H
3 H
4 H H H
5 H
6 H H
7 H
8 H
9 H
10 H
11 H H H H
12 H H H
Total 5 6 4 5 3
AABD ¼ antibiotic-associated bloody diarrhea; E ¼ endoscopic;
H ¼ histologic; PMC ¼ pseudomembranous colitis.

Presented with AABD for 25 days.
should be noted that there are no characteristic diagnostic features
for AABD; the pattern of diarrhea together with the accompanying
symptoms (eg, fever) is nonspecific and shared by other diseases
such as bacterial infections, inflammatory bowel disease, and
ischemic colitis (14). Furthermore, there is no relation between
the pattern of AAD and its inducing mechanism with no reported
differences between C difficile–positive and –negative children
(15). Also, AAD shows no relation to the duration of antibiotic
therapy, and symptoms may start even on the first day of intake (3).
Thus, the diagnosis of AAD rests primarily on a high suspicion
index, and empirical therapy (with cessation of antibiotics or
addition of metronidazole for C difficile when suspected) is often
started even before having the stool culture results and continued
even after receiving negative culture results (16).
In the present study, fortunately, all of the infants responded
to treatment either by discontinuation of antibiotics plus supportive
measures alone or with addition of oral metronidazole in the
presence of fever, colic, leukocytosis, or PMC; this response was
itself supportive evidence of the AABD diagnosis. Various treat-
ment regimens have been proposed in severe and recurrent cases
including vancomycin and various alternative antimicrobials, pro-
biotics, bile acid sequestrants, and intravenous immunoglobulin,
extending to colectomy for fulminant cases (17).
Endoscopically, the characteristic PMC pattern was recorded
in 21.7% (5/23) of infants in this study; however, widely varying
incidences of PMC have been reported in adults having C difficile
AAD, with figures reaching 35.5% (9), 40.6% (18), 55.2% (19), and
up to 89% (20), probably owing to differences in selection criteria
and disease severity. This means that a definite evidence of AAD
cannot be obtained endoscopically in all of those affected, which
makes endoscopy of poor sensitivity for the identification of AAD.
Apart from PMC, varying patterns of erythema and ulcers have been
demonstrated in other infants with AABD (78.3%). Varying lesions
also have been described in cases of ‘‘antibiotic-associated hemor-
rhagic colitis’’ in adults (21,22). Perhaps this variation is related to
the severity and extent of mucosal affection in AABD cases.
Similarly, the variation extends to the histopathologic pictures from
that of nonspecific colitis to the pathognomonic mushroom (also
called volcano or summit)-like pattern (3,23). Interestingly, mush-
room-like histologic PMC may be detected in the absence of an
endoscopic PMC.
www.jpgn.org
 JPGN  Volume 52, Number 1, January 2011
It should be noted that in all of the infants examined through
this study, the descending colon was involved; however, in K
oxytoca AABD, the lesions may occur predominantly in the right
colon or may be segmental with rectal sparing (24). Also, in early
cases of C difficile infection, the lesions may be restricted to the
right colon (5), and recognition of such lesions, then, requires longer
intubations of the endoscope. On the contrary, the lesions may
involve the whole colon in severe cases with fulminant colitis (25).
Concerning the possible etiologies of AABD in this study,
several infectious and noninfectious mechanisms could be respon-
sible. C difficile, the most common infectious etiology, causes
bloody diarrhea as a part of its clinical spectrum (26), possibly
through gross mucosal damage by its enterotoxin as demonstrated
experimentally (27); however, the bleeding may be occult with
erythrocytes seen only on stool examination (18,26). Also, K
oxytoca has been shown to cause AABD particularly on using
penicillin derivatives leading to cytotoxin-induced mucosal damage
and hemorrhage, resulting in ‘‘antibiotic-associated hemorrhagic
colitis,’’ which resolves spontaneously on cessation of antibiotic
therapy (24,28,29). Other organisms have been reported in AAD as
C perfringens, S aureus (30), and Candida infections even in
nonimmunocompromised patients (31). Moreover, various anti-
biotics can directly or indirectly cause microcirculatory disturb-
ances and tissue damage leading to hemorrhagic colitis with no
organisms detected on stool culture (21).
The presence of several possible incriminated organisms in
AAD increases considerably the costs on trying to exactly deter-
mine the causative pathogen with application of several culture
media and cytotoxin assays. The cost issue is of significant concern
particularly in cases of limited resources where a more practical,
less costly approach is increasingly required to be adopted. For
example, the gold standard tissue culture–stool cytotoxin assay for
C difficile (to detect the cytopathic effect on a cell culture) is
expensive especially if a small number of specimens is to be
examined, and is not routinely available in all of the hospital
laboratories even in developed countries because it necessitates a
maintained cell line (32). Stool culture alone or stool toxin detection
alone by enzyme immunoassays cannot be relied upon, particularly
in our study group, because of the normal high carriage rate of C
difficile approaching 52% of healthy children younger than the first
year of age, contrary to 0% to 3% carriage rate in healthy adults
(33), and the presence of toxin at a high frequency in infants in the
absence of clinical manifestations (34). Thus, awareness of the
AAD problem with all of its forms, particularly the bloody diarrhea
form, is critically important for avoiding the diagnostic dilemma of
performing several tests, and also avoiding the therapeutic dilemma
of adding more antibiotics or changing the currently received
antibiotics after being labeled as ‘‘noneffective’’ leading to a
vicious circle complicating and aggravating the problem.
Unfortunately, in most of the cases of AABD included in this
study, the inciting antibiotics were prescribed on inappropriate basis
for infants experiencing watery diarrhea (18/23; 78%). The latter is
almost of viral etiology because rotavirus infection represents the
most common cause of infantile diarrhea particularly in developing
countries (8,35). Even in developed countries, it has been estimated
that up to 50% of antibiotic usage is inappropriate (36). Therefore,
AAD control depends on adherence to evidence-based antibiotics
prescription, and improving decision making by junior doctors
about whether or not to start antibiotics (37), taking into consider-
ation that the AAD problem has been augmented by the recent
identification of a hypervirulent C difficile strain causing a more
serious illness and showing relative refractoriness to standard
therapy (38).
Most of the studies on AAD have been conducted on
hospitalized patients, and C difficile infection has been regarded
www.jpgn.org
Copyright 2010 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
Antibiotic-associated Bloody Diarrhea in Infants
primarily as a nosocomial infection (6). The present study points to
the community-acquired AABD in infants who are receiving
antibiotics on an outpatient basis. The occurrence of the bloody
diarrhea form of AAD may be related to the vulnerability of the
colonic mucosa, to bacterial toxins, or directly to antibiotics, in this
very young age group of patients. Only a few data are available
about the incidence of community-acquired AAD, with figures
reaching 6.2% in children receiving antibiotics on an ambulatory
basis (39).
CONCLUSIONS
AABD is not uncommon in infants presenting as acute or
chronic forms even without fever or leukocytosis. When suspected,
discontinuation of antibiotics is a good policy, particularly if
facilities for bacterial culture with cytotoxic assays are limited.
The characteristic endoscopic or histopathologic pseudomembranes
are encountered only in a small percentage (26%). Rational use of
antibiotics should be adhered to particularly in cases of watery
diarrhea that is mostly of viral origin.
REFERENCES
1. Kim J, Smathers SA, Prasad P, et al. Epidemiological features of
Clostridium difficile-associated disease among inpatients at children’s
hospital in the United States, 2001–2006. Pediatrics 2008;122:1266–
70.
2. McFarland LV. Antibiotic-associated diarrhea: epidemiology, trends and
treatment. Future Microbiol 2008;3:563–78.
3. Mylonakis E, Ryan ET, Calderwood SB. Clostridium difficile-asso-
ciated diarrhea. Arch Intern Med 2001;161:525–33.
4. Wiström J, Norrby SR, Myhre EB, et al. Frequency of antibiotic-
associated diarrhea in 2462 antibiotic-treated hospitalized patients: a
prospective study. J Antimicrob Chemother 2001;47:43–50.
5. Finegold SM. Clinical considerations in the diagnosis of antimicrobial
agent-associated gastroenteritis. Diag Microbiol Infect Dis 1986;4
(Suppl 3):87S–91S.
6. Hurley BW, Nguyen CC. The spectrum of pseudomembranous enter-
ocolitis and antibiotic-associated diarrhea. Arch Intern Med 2002;
162:2177–84.
7. Beaugerie L, Petit JC. Microbial-gut interactions in health and disease.
Antibiotic-associated diarrhea. Best Pract Res Clin Gastroenterol
2004;18:337–52.
8. O’Ryan M, Prado V, Pickering LK. A millennium update on pediatric
diarrheal illness in the developing world. Semin Pediatr Infect Dis
2005;16:125–36.
9. Barbut F, Gariazzo B, Bonné L, et al. Clinical features of Clostridium
difficile-associated infections and molecular characterization of strains:
results of a retrospective study, 2002–2004. Infect Control Hosp
Epidemiol 2007;28:131–9.
10. Chassany O, Michaux A, Bergmann JF. Drug-induced diarrhea. Drug
Saf 2000;22:53–72.
11. Gerding DN, Johnson S, Peterson LR, et al. Clostridium difficile-
associated diarrhoea and colitis. Infect Control Hosp Epidemiol
1995;16:459–77.
12. Hull MW, Beck BL. Clostridium difficile-associated colitis. Can Fam
Physician 2004;50:1536–40.
13. Brook I. Pseudomembranous colitis in children. J Gastroenterol
Hepatol 2005;20:182–6.
14. Abreu MT, Harpaz N. Diagnosis of colitis: making the initial diagnosis.
Clin Gastroenterol Hepatol 2007;5:295–301.
15. Ahmad SH, Kumar P, Fakhir S, et al. Antibiotic associated colitis.
Indian J Pediatr 1993;60:591–4.
16. El-Gammal A, Scotto V, Malik S, et al. Evaluation of the clinical
usefulness of C. difficile toxin testing in hospitalized patients with
diarrhea. Diagn Microbiol Infect Dis 2000;36:169–73.
17. Leffler DA, Lamont JT. Treatment of Clostridium difficile-associated
disease. Gastroenterology 2009;136:1899–912.
18. Gebhard RL, Gerding DN, Olson MM, et al. Clinical and endoscopic
findings in patients early in the course of Clostridium difficile-associated
pseudomembranous colitis. Am J Med 1985;78:45–8.
63
 Barakat et al
19. Bergstein JM, Kramer A, Wittman DH, et al. Pseudomembranous
colitis: how useful is endoscopy? Surg Endosc 1990;4:217–9.
20. Johal SS, Hammond J, Solomon K, et al. Clostridium difficile associated
diarrhea in hospitalized patients: onset in the community and hospital
and role of flexible sigmoidoscopy. Gut 2004;53:673–7.
21. Yonei Y, Yoshizaki Y, Tsukada N, et al. Microvascular disturbances in
the colonic mucosa in antibiotic-associated hemorrhagic colitis: invol-
vement of platelet aggregation. Gastroenterol Hepatol 1996;11:681–5.
22. Kishida T, Sato J, Fujimori S, et al. An endoscopic study of antibiotic-
associated hemorrhagic colitis. Nippon Ika Dalgaku Zasshi 1992;
59:450–6.
23. Rosai J. Pseudomembranous colitis. In: Rosai and Ackerman’s Surgical
Pathology. St Louis: Mosby; 2004: p. 792.
24. Högenauer C, Langner C, Beubler E, et al. Klebsiella oxytoca as a
causative organism of antibiotic-associated hemorrhagic colitis. N Engl
J Med 2006;355:2418–26.
25. Adams SD, Mercer DW. Fulminant Clostridium difficile colitis. Curr
Opin Crit Care 2007;13:450–5.
26. Manabe YC, Vinetz JM, Moore RD, et al. Clostridium difficile colitis: an
efficient clinical approach to diagnosis. Ann Intern Med 1995;123:835–
40.
27. Aronsson B, Mollby R, Nord CE. Clostridium difficile and antibiotic
associated diarrhea in Sweden. Scand J Infect Dis Suppl 1982;35:53–8.
28. Philbrick AM, Ernst ME. Amoxicillin-associated hemorrhagic colitis in
the presence of Klebsiella oxytoca. Pharmacotherapy 2007;27:1603–7.
29. Zollner-Schwetz I, Hogenauer C, Joainig M, et al. Role of Klebsiella
oxytoca in antibiotic-associated diarrhea. Clin Infect Dis 2008;
47:e74–8.
64
Copyright 2010 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
JPGN  Volume 52, Number 1, January 2011
30. Asha NJ, Tompkins D, Wilcox MH. Comparative analysis of preva-
lence, risk factors, and molecular epidemiology of antibiotic-associated
diarrhea due to Clostridium difficile, Clostridium perfringens, and
Staphylococcus aureus. J Clin Microbiol 2006;44:2785–91.
31. Vaishnavi C, Kaur S, Prakash S. Speciation of fecal Candida isolates in
antibiotic-associated diarrhea in non-HIV patients. Jpn J Infect Dis
2008;61:1–4.
32. Delmée M. Laboratory diagnosis of Clostridium difficile disease. Clin
Microbiol Infect 2001;7:411–6.
33. Jumaa P, Wren B, Tabaqchali S. Epidemiology and typing of Clostri-
dium difficile. Eur J Gastroenterol Hepatol 1996;8:1035–40.
34. Bartlett JG. Management of Clostridium difficile infection and other
antibiotic-associated diarrheas. Eur J Gastroenterol Hepatol 1996;
8:1054–61.
35. Ford-Jones EL, Wang E, Petric M, et al. Hospitalization for community-
acquired Rotavirus-associated diarrhea. Arch Pediatr Adolesc Med
2000;154:578–85.
36. Davey P, Brown E, Fenelon L, et al. Interventions to improve antibiotic
prescribing practices for hospital inpatients. Cochrane Database Syst
Rev 2005;4:CD003543.
37. Davey P. The potential role of computerized decision support systems to
improve empirical antibiotic prescribing. J Antimicrobial Chemother
2006;58:1105–6.
38. Bartlett J. Clostridium difficile: old and new observations. J Clin
Gastroenterol 2007;41(Suppl 1):S24–9.
39. Damrongmanee A, Ukarapol N. Incidence of antibiotic-associated
diarrhea in a pediatric ambulatory care setting. J Med Assoc Thai
2007;90:513–7.
www.jpgn.org