Revision sobre diagnostico y tratamiento de diarrea bacteriana

1. Diagnosis and Treatment
of Bacterial Diarrhea
James V. Lawler, MD* and Mark R. Wallace, MD
Address
*Infectious Diseases Department, National Naval Medical Center, Build-
ing 5, 2nd floor, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA.
E-mail: jvlawler@bethesda.med.navy.mil
Current Gastroenterology Reports 2003, 5:287–294
Current Science Inc. ISSN 1522-8037
Copyright © 2003 by Current Science Inc.
Introduction
Diarrheal illness is one of the most common complaints
prompting patients to seek medical care. In developing
nations, diarrheal illness accounts for 4,600,000 to 6,000,000
childhood deaths per year, and it is the second leading cause
of death worldwide [1]. In the United States, an estimated 73
million physician consultations and 1.8 million hospitaliza-
tions each year result fromdiarrheal disease [2••].
The etiology of diarrhea in the United States varies with
season and region, but bacteria are the most common cause,
with Campylobacter species being the most frequently iso-
lated bacteria [3]. Other bacterial causes are listed in Table 1.
Accurate epidemiologic data are lacking because most caus-
ative organisms are not reportable and most episodes of
diarrhea are treated in the outpatient setting, frequently
without diagnosis.
Diagnosis and management of bacterial diarrhea has
become more complex due to the globalization of food pro-
duction, burgeoning numbers of immunocompromised and
institutionalized patients, increased ease of travel to develop-
ing nations, and the changing epidemiology of pathogens
[1,2••,4]. This article reviews the global and emerging prob-
lemof antimicrobial resistance among enteric pathogens and
discusses present recommendations and coming advances in
diagnosis and treatment of bacterial diarrhea.
Emerging Antimicrobial Resistance
The rapid appearance and spread of antimicrobial resis-
tance among diarrheal pathogens has been one of the most
concerning developments in diarrheal illness. Worsening
antimicrobial resistance probably has many causes, but
unrestricted use of over-the-counter antibiotics in develop-
ing countries and use of antibiotics in animal feed have
been implicated [5•,6]. Antibiotic resistance among diar-
rhea-causing bacteria was initially confined to the develop-
ing world but has become more prevalent in developed
countries in recent years.
Emerging resistance in shigellosis provides one of the
most dramatic examples of the worldwide problem. Shigella,
originally susceptible to a broad spectrum of antibiotics,
acquired resistance in the developing world first to sulfona-
mides, then to ampicillin and trimethoprim-sulfamethox-
azole (TMP-SMX), and finally to nalidixic acid as each drug
became the first-line therapy of choice [7]. Only the fluoro-
quinolones have maintained significant susceptibility in
developing countries. This is a significant problem for the
treatment of shigellosis in children, in whom quinolones
may have toxic effects on cartilage [6].
Previous studies in the United States have yielded rela-
tively low levels of resistance among Shigella isolates (espe-
cially to TMP-SMX,) but dependable susceptibility may be
rapidly waning [8]. Replogle et al. [9] recently investigated
Shigella isolates in Oregon and found resistance to tetracy-
cline, ampicillin, and TMP-SMZ in 85%, 63%, and 59% of
isolates respectively. No isolates were resistant to ciproflox-
acin. Studies from Canada and Europe have shown simi-
larly high rates of resistance [9].
Antimicrobial resistance among Salmonella typhi (the
cause of typhoid fever) is a growing worldwide problem [10].
Althoughtyphoid fever is a distinct entity outside the realmof
this review, nontyphoidal Salmonella organisms are a com-
mon cause of diarrheal illness, and resistance to ampicillin,
TMP-SMX, and chloramphenicol has been increasingly
reported [11]. S. enterica serotype Typhimurium definitive
phage type 104 (DT104) is one particular nontyphoidal strain
that carries inherent resistance to ampicillin, chlorampheni-
col, streptomycin, sulfonamides, and tetracycline. It has made
a dramatic appearance in Europe and is now infiltrating the
United States [12].
Although third-generation cephalosporins and fluoroqui-
nolones are generally effective against salmonellae, reports of
resistance are on the rise. Of particular concern is the confir-
Diarrheal illnesscausedbybacterial pathogensisaglobal health
problem and remains one of the most common complaints
prompting patients to seek medical care. Strategies to increase
the yield of stool culture and new rapid diagnostic tests can
improve diagnostic ability. Emerging antimicrobial resistance
among the commonbacterial causes of diarrhea has made
treatment morechallenging. Emerging fluoroquinolone
resistance is a particular concern. Recent studies of rifaximin, a
nonabsorbed antibiotic for the treatment of bacterial diarrhea,
have shown favorable results. Rifaximin may represent a much-
needed addition to the armamentariumagainst bacterial agents.

2. 288 Gastrointestinal Infections
mation of Typhimurium DT104 isolates with nalidixic acid (a
quinolone antibiotic) resistance in enteritis acquired from
food animals [13•]. Nalidixic acid resistance may be a har-
binger of emerging quinolone (such as ciprofloxacin) resis-
tance, a development that would have significant clinical
implications [14].
The recommended treatment of Campylobacter enteritis
is generally a quinolone or macrolide, but quinolone resis-
tance has been rising rapidly around the world [10]. Qui-
nolone-resistant strains from diarrhea cases in Thailand
increased from 0% to 84% between 1990 and 1995 [15].
The most recent data indicate that resistance in Thailand is
over 95% (Tribble D, Personal communication). Quinolone
resistance has emerged in Europe and North America as
well. Resistance rates in Minnesota rose from 1.3% to 10.2%
between 1993 and 1998, and resistance rates in isolates
from Ireland have risen from 17.4% to 23% in recent years
[5•,16]. One recent study from Barcelona found that 12.5%
of Campylobacter isolates from travelers (mostly to India,
Africa, and Latin America) were resistant to ciprofloxacin,
but a stunning 88% of isolates from Spanish nontravelers
possessed ciprofloxacin resistance [17]. The Minnesota
study also found that 20% of retail chicken products were
contaminated with ciprofloxacin-resistant Campylobacter
organisms, strengthening the link between animal food
sources and spread of resistant diarrheal pathogens [5•].
Diagnostic Approach
Diagnosis and specific therapy in diarrheal illness should
be directed at certain goals: alleviation of symptoms, pre-
vention of secondary transmission, reduction of morbid-
ity and mortality, and detection and control of outbreaks
[2••]. The diagnosis of bacterial diarrhea is relatively labor
intensive, with low yield and return of results only after 24
to 72 hours. Because most cases of diarrhea are self-lim-
iting and require no specific therapy, diagnostic effort
should be focused on patients who have symptomatic,
physical, or epidemiologic findings suggesting that spe-
cific diagnosis and treatment are warranted.
The diagnosis of infectious diarrhea begins with a thor-
ough history and physical examination, the importance of
which cannot be underestimated. Historical and physical
findings can target patients who are likely to benefit from
further laboratory investigation or empiric therapy, such as
those with inflammatory diarrhea or a history of immuno-
compromising disease. Excellent reviews of important
diagnostic clues are available in the guidelines of the Infec-
tious Diseases Society of America and the American Col-
lege of Gastroenterology [2••,18].
The need for stool culture can often be established using
simple and rapid laboratory tests. Visual identification of
gross blood or a positive test for occult blood suggests an
inflammatory diarrhea (especially enterohemorrhagic Escheri-
chia coli [EHEC]) and is an indication for culture [2••]. In one
study, gross blood increased the yield of culture from 5.6% to
20.1% [19]. Microscopic examination of fresh stool with
methylene blue staining can be used to look for polymorpho-
nuclear lymphocytes (PMNs), a relatively sensitive test for
inflammatory diarrhea [19–21]. Stool may also be examined
by commercial latex agglutination assay for lactoferrin, a
surrogate marker for PMNs. A study of this type of assay for
lactoferrin found excellent correlation with microscopic
examination for fecal leukocytes, a sensitivity of greater than
95% for confirmed Clostridium difficile or Shigella infection,
and specificity of 94%and 100%, respectively [21].
Stool culture for infectious diarrhea has changed very lit-
tle in the past several decades and remains the gold standard
for diagnosis of bacterial enteritis. However, it is a relatively
expensive test with a low yield. Studies of stool culture yields
have typically resulted in positive rates below 10% and as low
as 1.5%[22,23]. The cost per positive culture fromthese stud-
Table 1. Common bacterial causes of diarrheal illness
Organism Comment
Campylobacter species Most common bacterial cause of diarrhea in United States
Salmonella (nontyphoidal) species Most common bacteria associated with foodborne outbreaks in United States
Shigella species More prevalent in daycare setting or homosexual males
Clostridium difficile Common cause of antibiotic-associated diarrhea
Escherichia coli
Enterohemorrhagic (EHEC) Common cause of infectious hemorrhagic colitis in United States, associated
with hemolytic-uremic syndrome
Enterotoxigenic (ETEC) Common causes of traveler’s diarrhea and diarrhea of developing countries
Enteropathogenic (EPEC)
Enteroinvasive (EIEC) Causes dysentery-like illness
Yersinia enterocolitica May cause mesenteric adenitis that can be confused with appendicitis
Vibrio species V. cholerae mostly in developing countries; non-cholera species associated with
seafood consumption in United States
Aeromonas Recent increased recognition as cause of diarrheal illness
Treponema pallidum Can cause colitis and proctitis in persons engaging in receptive anal intercourse
Neisseria gonorrheae
Chlamydia trachomatis

3. Diagnosis and Treatment of Bacterial Diarrhea • Lawler and Wallace 289
ies ranges from $136 to $1200. Reserving stool culture for
patients with evidence of inflammatory diarrhea or with
other special indicationscansignificantlyimprove theyieldof
the culture. In one prospective study, stool culture performed
only on patients with the presence of fecal leukocytes resulted
in an improved recovery rate of 76.7% [22]. Avoiding routine
stool culture in patients developing diarrhea more than 72
hours after hospital admission(the “3-day rule”) can improve
the yield as well. Rohner et al. [24] studied the results of
almost 14,000 stool cultures at a university hospital in Swit-
zerland and found positive cultures in 12.6% versus 1.4%
(P<0.001) before and after 3 hospital days.
Culture should be performed on fresh stool. Rectal swabs
are generally inferior. If stool cannot be plated within2 hours,
it should be refrigerated or placed in a transport medium
[20,23]. Routine stool culture in most US laboratories con-
sists of selective and differential agar plates capable of isolat-
ing Salmonella, Shigella, and, if all non–E. coli gram negatives
are routinely identified, Aeromonas and Plesiomonas. Most
laboratories also include a Campylobacter-selective medium
incubated in microaerophilic conditions to detect Campylo-
bacter species [20,23]. Other organisms require special media
for culture diagnosis. Suspicion for EHEC, Yersinia, and Vibrio
should prompt culture in sorbitol-MacConkey (SMAC),
cefsulodin-ingrasan-novobiocin (CIN), and thiosulfate-cit-
rate-bile-sucrose (TCBS) agars respectively to isolate these
organisms. Turnaround time for stool culture is at least 24
hours, and frequently 48 hours for organisms such as Campy-
lobacter species.
Advances in rapid stool diagnostics
Rapid detection methods, such as the enzyme immunoassay
(EIA), are routinely used for several bacterial pathogens, and
tests for others are in development. Commercially available
assays for C. difficile toxin have become a standard tool in
most microbiology laboratories. Most kits detect only C. diffi-
cile toxin A, but kits to test against toxins A and B are available
[25]. Although a small proportion of C. difficile organisms
produce only toxin B, significant C. difficile–associated disease
missed by assay for toxin A has been reported [26]. Measured
sensitivities andspecificities of these EIAs vary widely depend-
ing on the study and the kit. Most studies have found excel-
lent specificity but sensitivity that is somewhat less than that
of the cell culture assay [25].
Rapid EIA tests can reduce the diagnostic delay with
Campylobacter organisms from 48 hours to less than 3 hours.
Studies with a commercially available kit found a sensitivity
of 80% to 96% and specificity of 99% to 100% [27,28,29•].
In the proper clinical setting, this type of test results in excel-
lent positive and negative predictive values. Some laboratories
have replaced culture with EIA for the diagnosis of Campylo-
bacter enteritis.
Rapid tests are also available for diagnosis of EHEC
infection. Commercial latex agglutination kits for detec-
tion of the O157 or H7 antigens are reliable, but they fail
to identify shiga-like toxin production [30]. Although less
sensitive than cytotoxicity assays, EIAs are commercially
available for detection of shiga-like toxins produced by
Shigella and EHEC [30,31]. Such tests can be performed
directly on stool, but sensitivity increases (to 100% in one
study) if stool is incubated in broth culture overnight
before the EIA is performed [32]. The advantage of this
type of test is the detection of all shiga toxin–producing E.
coli organisms, regardless of sorbitol fermentation.
Methods for rapid detection of Salmonella and Shigella
organisms are also being developed. Many immunologically
based commercial kits are already used in food products, and
some have been tested in human stool specimens. A study of
multiple kits for the detection of various Shigella and Salmo-
nella species in Thailand reported sensitivities and specificities
between 94% and 100% [33]. A kit available in Europe for
detection of serum IgM against Salmonella typhi was recently
tested for the diagnosis of Salmonella serotype enteritidis in
Polish children with diarrhea [34•]. The sensitivity and speci-
ficity of this assay were 92.6% and 94.8%, respectively, with
positive and negative predictive values of 94.7% and 92.9%
when patients were compared with control subjects. Such
immunoassays are likely to appear in diagnostic microbio-
logic laboratories in the United States in the near future.
Rapid molecular diagnostic techniques such as poly-
merase chain reaction (PCR) have made their way into sev-
eral areas of clinical microbiology. PCR assays have been
used to detect C. difficile toxin genes, Shigella, enteroinva-
sive E. coli (EIEC), Campylobacter, and Vibrio organisms in
stool with impressive accuracy [35–38]. Amplified DNA
detection is likely to be useful in the future. However, a sig-
nificant amount of fine tuning may be required before it is
available for commercial use because the presence of DNA
polymerase inhibitors in human feces often interferes with
these tests [33].
Treatment
Most diarrheal illness is self-limited and requires no specific
intervention other than hydration [10]. Loperamide is recom-
mended for symptomatic treatment as long as the illness is
not severe or dysenteric [18]. The appropriate use of antimi-
crobial agents is a challenging aspect of treatment because
antibiotics have the potential for serious deleterious effects.
Antibiotic therapy may prolong carriage of enteric Salmonella
organisms, probably through alteration of normal flora [14].
Antibiotic treatment of EHEC may induce toxin production
and exacerbate hemolytic-uremic syndrome (HUS) [31]. Anti-
biotic use is the major predisposing factor for C. difficile infec-
tion [25]. Finally, unnecessary use of antibiotics worsens the
problemof rapidly emerging antibiotic resistance among bac-
teria that cause enteric infection [6].
Despite these drawbacks, antimicrobial therapy has a
definite role in the management of diarrhea caused by certain
pathogens. The benefit of standard antibiotic therapy for
diarrhea caused by Shigella, Vibrio, C. difficile, and enterotoxic
E. coli (ETEC) infection is firmly established [1,2••,10,11].

4. 290 Gastrointestinal Infections
Although ETECis not routinely diagnosed inclinical microbi-
ology laboratories, it can be suspected with history of travel to
areas of high prevalence, or it can be diagnosed in research
laboratories. Treatment of ETEC is generally TMP-SMX or
ciprofloxacin for 5 days [31]. A 3-day course of TMP-SMX also
appears to be effective, showing even better outcomes with
the addition of loperamide [39]. Although mild to moderate
Vibrio infections do not usually require antibiotic therapy,
antibiotics used in severe cases (as with V. cholerae) can reduce
duration of illness, stool frequency, and fecal shedding [10].
Tetracycline has long been the drug of choice for such infec-
tions, but fluctuating geographic patterns of resistance have
been seen [6]. Furazolidone and erythromycin have been
used successfully in lieu of tetracycline [6,40]. More recently,
single-dose quinolones have been shown to be at least as
effective as the more traditional regimens, and quinolone
resistance among Vibrio species is rare [10,41].
Cessation of antibiotics and re-establishment of normal
fecal flora remains the most effective treatment for C. difficile–
associated diarrhea. This strategy leads to resolution in
approximately 20% of patients [42]. Ten-day courses of oral
vancomycin and metronidazole are equivalent when anti-
microbial treatment is warranted [43]. The recommended
dosages are vancomycin, 125 mg four times daily, and met-
ronidazole, 500 mg three to four times daily [42]. Many alter-
native therapies have been examined, but they are generally
less effective and are beyond the scope of this review.
Antibiotic resistance, especially among S. dysenteriae type
I, has made treatment of shigellosis increasingly difficult. As
mentioned previously, quinolones are the only drugs with
proven efficacy in the developing world, and although TMP-
SMX sometimes works in developing countries, resistance
rates are rapidly increasing. Concerns remain regarding the
administration of quinolones to children and pregnant
women because of cartilage toxicity in animal models, but
arthropathy has not been seen in clinical trials of quinolo-
nes in children [44]. Third-generation cephalosporins are
active against Shigella organisms in vitro, but results of clini-
cal trials have not been convincing [10]. An important recent
development in the treatment of bacillary dysentery has
been the use of short-course therapy (1–3 days). Table 2 out-
lines the results of two studies of short-course treatment in
children with cholera [44,45]. Clinical outcome was similar
in the two studies. The microbiologic cure rate was 100% in
both groups in the ZIMBASA study, whereas the study by
Vinh et al. [45] found a significant reduction in the duration
of shedding in the short-course group. Thus, a shortened
course of quinolones appears to be effective for treatment of
dysenteric illness from Shigella infection.
Many experts recommend antibiotic treatment for cul-
ture-proven Campylobacter enteritis [2••,18], although this
opinionis not universal. Several well-constructed studies have
shown statistically significant clinical improvement with qui-
nolone therapy. These studies also suggest that therapy may
reduce the duration of fecal shedding [46–49]. Some of the
studies that did not show statistically significant improve-
ment may have been handicapped because early therapy for
Campylobacter infection appears to be most efficacious [50].
Quinolones and macrolides can be used to treat Campylo-
bacter infection, but emerging quinolone resistance is a grow-
ing problem. In areas with high levels of endemic resistance,
such as Southeast Asia, a macrolide may be more appropriate;
azithromycin (500 mg/d for 3 days) has proven efficacy [51].
Rifaximin may be very useful in such cases and is discussed
later in this review.
Antimicrobial therapy in uncomplicated nontyphoidal
Salmonella enteritis is somewhat controversial. Trials of
most antibiotics have shown no clinical benefit, and in fact
have sometimes shown prolonged fecal shedding of the
offending bacteria [10]. Some studies have shown that
quinolones may shorten the duration of illness with non-
typhoidal Salmonella, although carriage is probably not
shortened [14]. Despite the lack of evidence of efficacy in
uncomplicated diarrhea, patients at risk for disseminated
disease should probably be treated, because extraintestinal
Salmonella infection is associated with significant morbid-
ity and mortality [2••]. The recommended empiric anti-
biotics for Salmonella infection are quinolones or third-
generation cephalosporins because of increased resistance
to other traditional agents [14].
Empiric antimicrobial therapy
Because rapid diagnostic capability for bacterial diarrhea is
limited, almost all antimicrobial treatment is initially
empiric. Suspected cases of severe C. difficile colitis may war-
rant empiric therapy with metronidazole if a toxin assay can-
not be performed in a timely manner, especially if fecal
leukocytes are present. In the absence of risk factors for C.
difficile infection, inflammatory diarrhea may be caused by
organisms that respond well to treatment, such as Campylo-
bacter, Shigella, and EIEC. Bloody diarrhea in the absence of
fever or in a child should raise a clinical suspicion of EHEC,
and empiric antibiotics should not be used in these patients
to avoid potentially precipitating HUS [30]. Patients with
inflammatory diarrhea who have a predisposing risk for
severe or disseminated infection, including those with an
immunocompromising condition, diabetes, cirrhosis,
advanced age, intestinal hypomotility, or hypochlorhydria,
are candidates for empiric treatment. On a case-by-case basis,
empiric treatment may be prudent for a variety of reasons, for
example ina patient whois at risk of spreading disease to oth-
ers (eg, health-care worker or food handler) or whena specific
pathogen is suspected (eg, raw seafood consumption or con-
tact with a known case). Finally, empiric treatment of trav-
eler’s diarrhea is generally appropriate because treatment in
this instance has been shown to reduce the duration of illness
from3 to 5 days to less than 1 to 2 days [2••].
Quinolones have become the drug of choice for empiric
treatment of acute bacterial diarrhea in adults. They remain
highly active against almost all of the usual pathogens,
achieve high fecal concentrations, and are generally tolerated
well [52]. A number of randomized, placebo-controlled stud-

5. Diagnosis and Treatment of Bacterial Diarrhea • Lawler and Wallace 291
ies from Europe and the United States have demonstrated
successful treatment of acute diarrhea with ciprofloxacin and
norfloxacin. Pichler et al. [48,53] published two reports on
treatment with ciprofloxacin (500 mg twice daily for 5 days)
in 50 and 85 patients, respectively. In the first study, ciproflox-
acin reduced the duration of diarrhea from 2.6 to 1.4 days
(P<0.01) and decreased the number of positive cultures after
48 hours of therapy from 24 to 25 to 0 to 24 (P<0.001). Sim-
ilar results were found in the second study, and the mean
duration of fever was also reduced in a statistically significant
manner from 3.1 to 1.3 days. Studies by Goodman et al. [49],
Wistrom et al. [54], and Dryden et al. [46] found a 1- to 2.4-
day reduction in days with diarrhea, compared with results in
the placebo group, along with significantly reduced daily
symptoms and total duration of illness. These studies repre-
sented varied populations. Campylobacter or Salmonella were
the predominant organisms isolated, but a large proportion
of patients (49% and 71% in two of the studies) had no
positive culture, perhaps reflecting a high incidence of patho-
genic E. coli. Three of these studies mention travel history in
patients, with incidence rates of 1%, 25%, and 70% [46,49,
54]. Studies that specifically examined quinolones for the
treatment of traveler’s diarrhea have demonstrated similar
reductions in days of diarrhea and illness [52]. These findings
appear to be independent of the predominant organisms
isolated; the same effect is present with a predominance of
pathogenic E. coli, Salmonella, or Campylobacter [47,55].
Alternatives to quinolones for empiric treatment may be
appropriate for children and patients with sensitivity to
quinolones or in areas where quinolone-resistant organisms
are prevalent. TMP-SMX is a reasonable alternative that is
commonly used in children with traveler’s diarrhea [2••].
Among travelers in Thailand, where quinolone-resistant
Campylobacter predominates, azithromycin or another mac-
rolide is an appropriate choice for empiric therapy [51].
Finally, local epidemiology of diarrheal illness and resis-
tance patterns should always be considered in choosing an
empiric antibiotic, and a thorough knowledge of these data
may prevent future complications.
Rifaximin
Increasing antimicrobial resistance, combined with the
side effects and potential toxicity of absorbed antibiotics,
have renewed interest in nonabsorbed antibiotics for the
treatment of diarrhea. Prior studies with oral aztreonam
and bicozamycin have proven the efficacy of this approach,
although neither of these drugs was pursued for marketing
[56]. Studies of rifaximin, a nonabsorbed rifamycin deriva-
tive, in the treatment of traveler’s diarrhea are a new and
exciting development.
Rifaximin is a semisynthetic relative of the rifamycins
with activity against a broad spectrum of gram-positive and
gram-negative organisms. It is currently licensed in several
European, Latin-American, and Asian countries. Less than
1% of oral rifaximin is absorbed systemically, but stool
concentrations reach levels several hundred times the min-
imal inhibitory concentration for 90% (MIC90) of most
enteric pathogens [56,57]. As would be expected with a
nonabsorbed drug, studies to date have revealed an excel-
lent safety profile with a 1% incidence of gastrointestinal
side effects and very rare episodes of urticaria [57].
To date, two randomized clinical trials examining the
use of rifaximin in traveler’s diarrhea have been published.
The first trial compared rifaximin (200, 400, and 600 mg
three times a day) to a standard dose of TMP-SMX in 72
adult US students studying abroad in Mexico [58]. Overall,
the mean duration of diarrhea after treatment in all rifaxi-
min groups was 43.1 hours, compared with 55.7 hours for
TMP-SMX (a nonsignificant difference). These results were a
statistically significant improvement over historical placebo
controls from a similar population. Although sample size
prevented statistical significance, the 200-mg dose of rifaxi-
min appeared to be as effective as the higher doses. In fact,
all of the microbiologic failures (four of 20 isolated patho-
gens from the combined rifaximin groups) occurred in the
400- and 600-mg groups (Table 3). The second study com-
pared rifamixin (400 mg twice a day) with ciprofloxacin in a
similar population in Mexico (n=163) and in tourists in
Jamaica (n=24) [59••]. Results in the two groups were simi-
lar, with a time to last unformed stool of 25.7 versus 25.0
hours in the rifaximin and ciprofloxacin groups, respec-
tively. These results were similar for patients with and with-
out specific microbiologic diagnosis. Differences in side
effects appear to be clinically insignificant. A third random-
ized, controlled study comparing rifaximin with placebo
was presented at a recent scientific meeting [56]. In this
study rifaximin (200 and 400 mg three times a day) cut the
time to last unformed stool in half, compared with placebo.
Conclusions
Diarrheal illness from bacterial pathogens continues to be
a disease of global significance. Rapidly evolving organ-
isms and rapid emergence of antimicrobial resistance are
expanding threats to the treatment advances of the past few
decades. To counter these threats, new tools have recently
been added to the diagnostic and therapeutic armamentar-
ium, and promising additions are on the horizon. The next
decade should bring interesting changes in the manage-
ment of this important disease.

6. 292 Gastrointestinal Infections
Table2.Studiesofshort-coursetherapyforshigellosisinchildren
RegimenTreatmentsuccess,%
StudyLocationPatients,nShortcourseControl
Short
courseControlP-value
Vinhetal.[45]Vietnam66Ofloxacin,7.5mg/kg
every12hoursfor2doses
Nalidixicacid,13.8mg/kg
4timesadayfor5days
9075Notsignificant
ZIMBASAgroup[44]Zimbabwe,Bangladesh,
SouthAfrica
128Ciprofloxacin,15mg/kg
every12hoursfor3days
Ciprofloxacin(samedose)
for5days
6569Notsignificant
Table3.Microbiologiccureintraveler'sdiarrheawithidentifiedorganism
Microbiologiccure,n(%)*
StudyLocationPatients,nControldrugRifaximinControl
DuPontetal.[58]Mexico72TMP-SMX16of20(80)7of7(100)
DuPontetal.[59••]MexicoandJamaica187Ciprofloxacin29of30(74)38of43(88)
*Differencesarenotstatisticallysignificant.
TMP-SMX—trimethoprim-sulfamethoxazole.

7. Diagnosis and Treatment of Bacterial Diarrhea • Lawler and Wallace 293
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