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Clinical manifestations and diagnosis of Shigella infection in children
Rabia Agha, Marcia B Goldberg, MD
Up to date on line 16.1 This topic last updated: Fevereiro, 2006
http://www.uptodate.com/online/content/ acessado em 04 de junho de 2008.
Modificado por Jefferson P Piva (Julho 2008)
— Shigella species are a common
Frequency of stools typically is 8 to 10 per day but may
cause of bacterial diarrhea worldwide, especially in
increase to up to 100 per day. The stools are of small
developing countries. The organism is less susceptible
volume, so significant fluid loss typically does not occur
to acid than many other bacterial pathogens; thus, as
(average approximately 30 mL/kg per day) . These
few as 10 to 100 organisms can cause disease, in part
findings are characteristic of diarrhea caused by
because the organisms can survive transit through the
infection of the colon (the major site of infection with
stomach . Thus, ingested bacteria pass into the small
Shigella) because the colon functions as a storage
intestine where they multiply, so that several logs more
organ. This is in contrast to small bowel infections in
bacteria pass into the colon, where the organisms enter
which the diarrhea typical y is watery; of large volume;
and associated with abdominal cramping, bloating, gas,
Intermediate bacterial replication in contaminated food
or water is not required to achieve this low infectious
The spectrum of severity of disease varies according to
dose. As a result, Shigella transmission can occur
the serogroup of the infecting organism. Shigel a sonnei
through direct person-to-person spread, as well as from
commonly causes mild disease, which may be limited
contaminated food and water; the former accounts for
to watery diarrhea, although Shigella dysenteriae 1 or
most cases in the United States, whereas the latter is
symptoms (bloody diarrhea) . The course of disease
— Shigella is a
in a normal healthy host general y is self-limited, lasting
pathogen that primarily infects the lower intestinal tract.
no more than seven days when left untreated.
Patients with Shigella gastroenteritis typically present
The typical course of disease varies with age group. In
with high fever, abdominal cramps, and bloody, mucoid
a review of 318 infants and children hospitalized with
diarrhea. The approximate prevalence of these signs
shigellosis in Bangladesh, infants had fewer days with
diarrhea (four versus six) and were more likely to have
Fever (30 to 40 %); abdominal pain (70 to 93%),mucoid
watery (as opposed to bloody) stools, hyponatremia,
diarrhea (70 to 85%), bloody diarrhea (35 to 55%),
abdominal distension, and acidosis than were older
watery diarrhea (30 to 40%), vomiting (35%).
children  . Older children were more likely to have a
The incubation period ranges from one to seven days,
leukemoid reaction than were infants. The mortality rate
with an average of three days . The disease typically
for infants was twice that of older children. Infants who
begins with constitutional symptoms such as fever,
were breast fed were less frequently infected and had a
anorexia, and malaise; diarrhea initially is watery, but
milder il ness than infants who were not breast fed .
subsequently may contain blood and mucus. Tenesmus
- The severe inflammation of the
rectum and distal colon that is induced by invasion of
the organism into the colonic mucosa may lead to
diarrhea caused by S. dysenteriae 1 . General y,
hyponatremia is caused by the syndrome of
- Toxic megacolon occurs primarily
inappropriate ADH secretion, not by volume depletion
in the setting of S. dysenteriae 1 infection. The
[1,13]. Several consequences of shigel osis contribute
pathogenesis is unclear; it occurs in the setting of
to malnutrition, such as: Increased catabolism
pancolitis and seems to be related to the intensity of
secondary to fever, stool protein loss, decreased intake
inflammation rather than being mediated by Shiga toxin.
The incidence of toxic megacolon in children with
— A leukemoid reaction (defined
as a white blood cell count of 50,000/mm3 or more) has
— Severe colonic disease may
been noted in approximately 4% of patients, most
result in intestinal obstruction. The incidence in one
commonly in children between 2 and 10 years of age
series of 1211 patients with shigel osis was 2.5%.
and not at all in children younger than 1 year of age
The patients with obstruction were more likely to be
. The WBC count in these patients ranged from
infected with S. dysenteriae 1 and were more severely
50,000 to 195,000/mm3 and was accompanied by an
ill, as evidenced by a significantly higher white blood
increased number of immature forms. The mortality rate
also was increased (21 versus
7.4% in those without a
concentration than patients without evidence of
leukemoid reaction). In contrast, an earlier study
conducted in the United States found no association
— Colonic perforation is an
between disease severity and a high WBC count .
unusual complication of shigellosis. It occurs principally
— Seizures, the most common
in infants or severely malnourished patients and is
neurologic complication associated with Shigella
associated with infection caused by S. dysenteriae 1 or
infection, are always associated with fever (usually
greater than 39ºC), are generalized, uncomplicated,
nonrecurring, and not associated with neurologic
— Bacteremia occurs in approximately 4%
deficits  . Seizures can be seen with all serotypes of
of patients with Shigella gastroenteritis and is
Shigella infection, but are least common with S.
associated with an increase in mortality . Young,
malnourished children are at greatest risk. Bacteremia
The reported prevalence of seizures in children with
with another gram-negative organism is seen in
shigellosis has ranged from 12 to 45%  and, in
approximately 5% of patients who have a stool culture
patients of all ages hospitalized with shigellosis, is
approximately 10% . In hospitalized children, the
most common age group in which seizures occur is that
depletion is uncommon in shigellosis because the stool
between 6 months and 4 years, the same group most
volume usually is low. In a review of 412 patients with
likely to have simple febrile seizures . Analysis of
shigellosis, 36% had mild, 12% had moderate, and 2%
cerebrospinal fluid obtained by lumbar puncture
had severe dehydration . In another series,
typical y is normal, although as many as 15% of these
hyponatremia (defined as serum sodium below 120
patients may have mild lymphocytic pleocytosis with as
meq/L) was noted in 29% of patients hospitalized with
In the past, neurologic complications of Shigella
accompanied by fever. Nausea and vomiting are
infection were thought to be induced by circulating
notably absent in most patients. The presence or
Shiga toxin, which is produced by S. dysenteriae 1 .
absence of leukocytes in the stool can be determined
Shiga toxin was not detected in serum or spinal fluid
rapidly and simply by microscopic examination. The
and was present in stool at levels that were 1000-fold
constellation of the above symptoms and increased
below that of cultured S. dysenteriae 1in children with
numbers of fecal leukocytes is strongly suggestive of
seizures. However, there are no conclusive studies
infection with Shigel a, Salmonella, Campylobacter,
demonstrating relationship between Shiga toxin and
Yersinia, enteroinvasive E. coli, or Clostridium difficile,
seizures. Furthermore, the majority of patients who
or of noninfectious inflammatory bowel disease .
have seizures are infected with S. flexneri or S. sonnei,
— In a study that examined the
neither of which expresses Shiga toxin. Taken together,
usefulness of fecal leukocytes in predicting the etiology
these data suggest that other Shigella enterotoxins
of diarrhea, the presence of fecal leukocytes was
might contribute to the induction of seizures, although
associated with a bacterial cause of acute diarrhea in
this possibility has not as yet been proved  .
89% of cases  . Patients infected with Shigella had
fecal polymorphonuclear leukocytes in 70 to 100% of
headache has been noted in as many as 40 percent of
samples tested, with at least 10 to 25 cells/hpf in the
children hospitalized with Shigel a infection .
majority of patients [2,34] . In comparison, healthy
Obtundation or coma and abnormal neurologic signs,
controls and patients with cholera or viral diarrhea had
encephalopathy that were fatal, cerebral edema was
experimental y, the presence of fecal leukocytes was a
more sensitive means of diagnosing infection with S.
— Although relatively
dysenteriae 1 than was stool culture  .
uncommon, the hemolytic-uremic syndrome (HUS) can
— Confirmation of the infecting organism
occur as a complication of infection caused by Shigella
can be made only by culture of the stool. Shigel a is a
dysenteriae. Because HUS is mediated by Shiga toxin,
fastidious organism; as a result, it requires prompt
which is present in S. dysenteriae type 1, but not other
handling and optimal y should be inoculated onto agar
species of Shigella, only S. dysenteriae type 1 can
at the bedside. Culture from a stool sample may give a
cause HUS. HUS is a potential y life-threatening illness
better yield than culture from a rectal swab . If
that is characterized by a microangiopathic hemolytic
transport of the sample is required, the best medium is
anemia, thrombocytopenia, and acute renal failure.
buffered glycerol saline (BGS) . The best yield is
Enterohemorrhagic Ecsherichia coli (EHEC) infection
accounts for about 70 percent of cases in the United
: In young girls, Shigella can
cause vulvovaginitis with or without diarrhea .
— Shigel a should be suspected in any
patient with frequent, smal volume, bloody stools,
abdominal cramps, and tenesmus, particularly if
Bennish, ML. Potential y lethal complications of shigel osis. Rev Infect Dis 1991; 13 Suppl 4:S319.
Stol , BJ, Glass, RI, Huq, MI, et al. Epidemiologic and clinical features of patients infected with Shigel a who attended a diarrheal disease hospital in Bangladesh. J Infect Dis 1982; 146:177.
Barrett-Connor, E, Connor, JD. Extraintestinal manifestations of shigel osis. Am J Gastroenterol 1970; 53:234.
Echeverria, P, Sethabutr, O, Pitarangsi, C. Microbiology and diagnosis of infections with Shigel a and enteroinvasive Escherichia coli. Rev Infect Dis 1991; 13 Suppl 4:S220.
DuPont, HL, Hornick, RB, Dawkins, AT, et al. The response of man to virulent Shigel a flexneri 2a. J Infect Dis 1969; 119:296.
Maurel i, AT, Lampel, KA. Shigel a. In: Foodborne Disease Handbook, Hui, YH, Gorham, JR, Murrel , KD, Cliver, DO (Eds), Marcel Dekker, New York 1994. p.321.
Acheson, DW, Keusch, GT. Shigel a and enteroinvasive Escherichia coli. In: Infections of the Gastrointestinal Tract, Blaser, MJ, Smith, PD, Ravdin, JI, et al (Eds), Raven Press, New York 1995. p.765.
Keusch, GT, Formal, SB, Bennish, ML. Shigel osis. In: Tropical and Geographical Medicine, Warren, KS, Mahmoud, AA (Eds), McGraw-Hil , New York 1990. p.763.
Huskins, WC, Griffiths, JK, Faruque, ASG, et al. Shigel osis in neonates and young infants. J Pediatr 1994; 125:14.
10. Bennish, ML, Azad, AK, Yousefzadeh, D. Intestinal obstruction during shigel osis: Incidence, clinical features, risk factors and
outcome. Gastroenterology 1991; 101:626.
11. Azad, MA, Islam, M, Butler, T. Colonic perforation in Shigel a dysenteriae 1 infection. Pediatr Infect Dis 1986; 5:103. 12. Struelens, MJ, Patte, D, Kabir, I, et al. Shigel a septicemia: Prevalence, presentation, risk factors, and outcome. J Infect Dis 1985;
13. Keusch, GT, Bennish, ML. Shigel osis: Recent progress, persisting problems and research issues. Pediatr Infect Dis J 1989;
14. Bennish, ML, Salam, MA, Wahed, MA. Enteric protein loss during shigel osis. Am J Gastroenterol 1993; 88:53. 15. Butler, T, Islam, MR, Bardhan, PK. The leukemoid reaction in shigel osis. Am J Dis Child 1984; 138:162. 16. Ashkenazi, S, Dinari, G, Zevulunov, A, et al. Convulsions in childhood shigel osis. Am J Dis Child 1987; 141:208. 17. Ashkenazi, S, Dinari, G, Weitz, R , Nitzan, M. Convulsions in shigel osis. Evaluation of possible risk factors. Am J Dis Child 1983;
18. Keusch, GT, Donohue-Rolfe, A, Jacewicz, M. Shigel a toxin(s): description and role in diarrhea and dysentery. Pharmacol Ther
19. Ashkenazi, S, Cleary, KR, Pickering, LK, et al. The association of Shiga toxin and other cytokines with the neurologic
manifestations of shigel osis. J Infect Dis 1990; 161:961.
20. Noriega, FR, Liao, FM, Formal, SB, et al. Prevalence of Shigel a enterotoxin 1 among Shigel a clinical isotypes of diverse
21. Fasano, A, Noriega, FR, Maneval, DR, et al. Shigel a enterotoxin 1: An enterotoxin of Shigel a flexneri 2a active in rabbit smal
intestine in vivo and in vitro. J Clin Invest 1995; 95:2853.
22. Nataro, JP, Seriwatana, J, Fasano, A, et al. Identification and cloning of a novel plasmid- encoded enterotoxin of enteroinvasive
Escherichia coli and Shigel a strains. Infect Immun 1995; 63:4721.
23. Avital, A, Maayan, C, Goitein, KJ. Incidence of convulsions and encephalopathy in childhood Shigel a infections. Clin Pediatr
24. Simon, G, Kaslow, RA, Rosenbaum, J, et al. Reiter's syndrome fol owing epidemic shigel osis. J Rheumatol 1981; 8:969. 25. Stieglitz, H, Lipsky, P. Association between reactive arthritis and antecedent infection with Shigel a flexneri carrying a 2-Md
plasmid and encoding an Hla-B27 mimetic epitope. Arthritis Rheum 1993; 36:1387.
26. Granfors, K, Jalkanen, S, Toivanen, P, et al. Bacterial lipopolysaccharide in synovial fluid cel s in Shigel a triggered reactive
27. Hughes, RA, Keat, AC. Reiter's syndrome and reactive arthritis: A current view. Semin Arthritis Rheum 1994; 24:190. 28. Siegler, RL. The hemolytic uremic syndrome. Pediatr Clin North Am 1995; 42:1505. 29. Bennish, ML, Khan, WA, Begum, M, et al. Low risk of hemolytic uremic syndrome after early effective antimicrobial therapy for
Shigel a dysenteriae type 1 infection in Bangladesh. Clin Infect Dis 2006; 42:356.
30. Murphy, TV, Nelson, JD. Shigel a vaginitis: report of 38 patients and review of the literature. Pediatrics 1979; 63:511. 31. Tobias, JD, Starke, JR, Tosi, MF. Shigel a keratitis: a report of two cases and a review of the literature. Pediatr Infect Dis J 1987;
32. Rubenstein, JS, Noah, ZL, Zales, VR, Shulman, ST. Acute myocarditis associated with Shigel a sonnei gastroenteritis. J Pediatr
33. DuPont, HL, Levine, MM, Hornick, RB, Formal, SB. Inoculum size in shigel osis and implications for expected mode of
transmission. J Infect Dis 1989; 159:1126.
34. Harris, JC, Du Pont, HL, Hornick, RB. Fecal leukocytes in diarrheal il ness. Ann Intern Med1972; 76:697. 35. Rahaman, MM, Huq, I, Dey, CR. Superiority of MacConkey's agar over Salmonel a-Shigel a agar for isolation of Shigel a
dysenteriae type 1. J Infect Dis 1975; 131:700.
36. Farmer, JJ, Wel s, JG, Griffin, PM. Enterobacteriaceae infections. In: Diagnostic Procedures for Bacterial Infections, Wentworth,
BB (Ed), American Public Health Association, Washington, DC 1987. p.274.
Treatment and prevention of Shigel a infections in children
This topic last updated: Maio 22, 2008 Modificado por Jeffferson Piva em Julho de 2008.
— The mainstay of the
of isolates are resistant to nalidixic acid [21-23].
treatment of acute gastroenteritis in children,
Resistance to nalidixic acid also been reported in
irrespective of the cause, which usually is not known at
England  and the United States  .
the time of presentation, is correction of fluid and
Antimicrobial resistance is an increasing problem in the
electrolyte losses  . Oral rehydration is preferred,
United States. Between 1999 and 2002, the fol owing
when feasible , but intravenous fluids may be
necessary. (Ver texto inserido como apêndice ao final).
All isolated Shigel a were susceptible to ceftriaxone
The use of intestinal antimotility drugs, such as
diphenoxylate (Lomotil), should be avoided in children
78% of isolates were resistant
to ampicil in, 46% to
with suspected shigellosis. These drugs may prolong
TMP-SMX, 38% to both ampicillin and TMP-SMX,
duration of fever, diarrhea, and excretion of the
Early restoration of oral intake, especial y protein, is
— The goals of antibiotic therapy for Shigel a
important, particularly in developing countries, to
include improvement in symptoms and decreased
prevent the exacerbation of malnutrition [12-14] .
Patients with severe toxemia or suspected bacteremia,
antimicrobial treatment of Shigella gastroenteritis
underlying immune deficiency, and who are unable to
reduces the duration of fever, diarrhea, and fecal
take oral medications should be hospitalized.
excretion [28-31] . It also may reduce the risk of
antimicrobial resistance of Shigella species is a major
In randomized, placebo-controlled trials during the
problem in treating shigel osis. The major route for
1960s and early 1970s (before the widespread
dissemination of multiple resistance is by horizontal
development of resistance to ampicillin), children with
transfer of plasmids carrying antibiotic resistance (R-
shigella infection who were treated with ampicil in had
plasmids). A commonly isolated plasmid carries
decreased duration of diarrhea, fever, and fecal
shedding than those who received placebo [28-31] .
The findings of the largest two studies are presented
trimethoprim  . Ampicillin resistance also is
In Children hospitalized with Shigella gastroenteritis,
High rates of antimicrobial resistance were first reported
those who received ampicillin (compared to placebo)
in Asia, Africa, and South America, but antimicrobial
had shorter duration of diarrhea (3.3 versus 6 days),
resistance has rapidly spread to developed countries
fever (1.3 versus 2.6 days), and fecal shedding
[18-20] . In India and Bangladesh, 20 percent or more
(positive stool culture for 2 versus 5 days)  .
In another randomized study of 373 children with
the possibility of favoring emergence of resistant
acute diarrhea who were treated as outpatients, 101
organisms  and potential adverse effects.
children had stool cultures positive for Shigella .
— Decisions regarding initiation of
Compared with those who received placebo, fewer
antimicrobial therapy must consider the appearance of
children with Shigel a who were treated with
the patient, the presence of host factors that predispose
ampicillin had positive stool cultures after 48 hours (8
to more severe infection, and public health
versus 70 %) and fewer continued to have diarrhea
after five days (5 versus 50 percent). None of the
We recommend empiric antimicrobial therapy for
patients who were treated with ampicil in required
shigellosis in children and adolescents who present
hospital admission or treatment with another
with suspected shigel osis (bloody/mucousy diarrhea,
antibiotic after completion of therapy (compared with
high fever) and are immunocompromised or bacteremic
one and five children in the placebo group,
We recommend antimicrobial therapy for children and
The decreased duration of shedding with antimicrobial
adolescents with culture-proven Shigella who :
therapy reduces the risk of person-to-person spread of
Have bacteremia, require hospitalization, attend day
the infection. In the absence of specific antibiotic
care, live in institutions or are involved in food handling.
treatment, children with Shigel a gastroenteritis shed
Treatment of mild cases or of children who have
the organism for up to four weeks, and children with
recovered by the time the report of positive Shigel a
immune deficiency, for much longer periods, even if
culture is available is controversial. Antimicrobial
their symptoms have resolved [4,6,7,33] .
treatment of such children is unlikely to significantly
Shigella is highly contagious; ingestion of only 10 to
affect the clinical course, but will shorten fecal excretion
100 organisms can produce disease. Therefore,
and thus reduce the spread of this highly contagious
treatment of an infected child at risk to transmit the
disease to others (eg, a day-care attendee, hospitalized
Choice of regimen
— The medication spectrum and
regimen (oral versus parenteral) are determined by
The benefits of antimicrobial therapy discussed above
severity of il ness, local resistance patterns, and history
outweigh the potential risks of therapy, which include
of travel to an area of frequent resistance [3,35].
Kotloff, KL, Winickoff, JP, Ivanoff, B, et al. Global burden of Shigel a infections: implications for vaccine development and implementation of control strategies. Bul World Health Organ 1999; 77:651.
Notice to readers: Final 2004 reports of notifiable diseases. MMWR Morbidity and Mortality Weekly Report 2005; 54:770. Available at: www.cdc.gov/MMWR/preview/mmwrhtml/mm5431a4.htm (Accessed on May 22, 2008).
Ashkenazi, S, Cleary, TG. Shigel a species. In: Principles and practice of pediatric infectious diseases, 3rd ed, Long SS, Pickering, LK, Prober, CG (Eds), Churchil Livingstone 2008. p.817.
Ashkenazi, S. Shigel a infections in children: new insights. Semin Pediatr Infect Dis 2004; 15:246.
Viner, Y, Miron, D, Gottfried, E, et al. Neonatal shigel osis. Isr Med Assoc J 2001; 3:964.
Baer, JT, Vugia, DJ, Reingold, AL, et al. HIV infection as a risk factor for shigel osis. Emerg Infect Dis 1999; 5:820.
Angulo, FJ, Swerdlow, DL. Bacterial enteric infections in persons infected with human immunodeficiency virus. Clin Infect Dis 1995; 21 Suppl 1:S84.
Struelens, MJ, Patte, D, Kabir, I, et al. Shigel a septicemia: Prevalence, presentation, risk factors, and outcome. J Infect Dis 1985; 152:784.
Greenberg, D, Marcu, S, Melamed, R, Lifshitz, M. Shigel a bacteremia: a retrospective study. Clin Pediatr (Phila) 2003; 42:411.
10. European Society for Paediatric Gastroenterology, Hepatology, and Nutrition/European Society for Paediatric Infectious Diseases
evidence-based guidelines for the management of acute gastroenteritis in children in Europe. J Pediatr Gastroenterol Nutr 2008; 46 Suppl 2:S81.
11. DuPont, HL, Hornick RB. Adverse effect of lomotil therapy in shigel osis. JAMA 1973; 226:1525. 12. Kabir, I, Butler, T, Underwood, LE, Rahman, MM. Effects of a protein-rich diet during convalescence from shigel osis on catch-up
growth, serum proteins, and insulin-like growth factor-I. Pediatr Res 1992; 32:689.
13. Kabir, I, Rahman, MM, Haider, R, et al. Increased height gain of children fed a high-protein diet during convalescence from
shigel osis: a six-month fol ow-Up study. J Nutr 1998; 128:1688.
14. Mazumder, RN, Hoque, SS, Ashraf, H, et al. Early feeding of an energy dense diet during acute shigel osis enhances growth in
malnourished children. J Nutr 1997; 127:51.
15. Hossain, S, Biswas, R,Kabir, I, et al. Single dose vitamin A treatment in acute shigel osis in Bangladesh children: randomised
double blind control ed trial. BMJ 1998; 316:422.
16. Roy, SK, Raqib, R, Khatun, W, et al. Zinc supplementation in the management of shigel osis in malnourished children in
17. Rowe, B, Threlfal , EJ. Drug resistance in gram negative aerobic bacil i. Br Med Bul 1984; 40:68. 18. Kruse, H, Kariuki, S, Soli, N, et al. Multiresistant Shigel a species from African AIDS patients: Antibacterial resistance patterns and
application of the E-test for determination of minimum inhibitory concentration. Scand J Infect Dis 1992; 24:733.
19. Ashkenazi, S, Levy, I, Kazaronovski, V, Samra, Z. Growing antimicrobial resistance of Shigel a isolates. J Antimicrob Chemother
20. Sivapalasingam, S, Nelson, JM, Joyce, K, et al. High prevalence of antimicrobial resistance among Shigel a isolates in the United
States tested by the National Antimicrobial Resistance Monitoring System from 1999 to 2002. Antimicrob Agents Chemother 2006; 50:49.
21. Bennish, ML, Salam, MA, Hossain, MA, et al. Antimicrobial resistance of Shigel a isolates in Bangladesh, 1983-1990: Increasing
frequency of strains multiply resistant to ampicil in, trimethoprim-sulfamethoxazole, and nalidixic acid. Clin Infect Dis 1992; 14:1055.
22. Munshi, MH, Sack, DA, Haider, K, et al. Plasmid-mediated resistance to nalidixic acid in Shigel a dysenteriae type 1. Lancet 1987;
23. Salam, MA, Bennish, ML. Antimicrobial therapy for shigel osis. Rev Infect Dis 1991; 13(Suppl 4):S332. 24. Cheasty, T, Day, M, Threlfal , EJ. Increasing incidence of resistance to nalidixic acid in shigel as from humans in England and
Wales: implications for therapy. Clin Microbiol Infect 2004; 10:1033.
25. Outbreaks of multidrug-resistant Shigel a sonnei gastroenteritis associated with day care centers--Kansas, Kentucky, and
Missouri, 2005. MMWR Morb Mortal Wkly Rep 2006; 55:1068.
26. Rahman, M, Shoma, S, Rashid, H, et al. Increasing spectrum of antimicrobial resistance of Shigel a isolates in Bangladesh:
resistance to azithromycin and ceftriaxone and decreased susceptibility to ciprofloxacin. J Health Popul Nutr 2007; 25:158.
27. Kuo, CY, Su, LH, Perera, J, et al. Antimicrobial susceptibility of Shigel a isolates in eight Asian countries, 2001-2004. J Microbiol
28. Haltalin, KC, Nelson, JD, Ring, R, et al. Double-blind treatment study of shigel osis comparing ampicil in, sulfadiazine, and
29. Haltalin, KC, Kusmiesz, HT, Hinton, LV, Nelson, JD. Treatment of acute diarrhea in outpatients. Double-blind study comparing
ampicil in and placebo. Am J Dis Child 1972; 124:554.
30. Garcia de, Olarte D, Trujil o, H, Agudelo, N, et al. Treatment of diarrhea in malnourished infants and children. A double-blind study
comparing ampicil in and placebo. Am J Dis Child 1974; 127:379.
31. Nelson, JD, Haltalin, KC. Broad-spectrum penicil ins in enteric infections of children. Ann N Y Acad Sci 1967; 145:414. 32. Ashkenazi, S. Shigel a species. In: Antimicrobial therapy and vaccines, 2nd ed, Yu, VL, Weer, R, Raoult, D (Eds), Apple Tree
33. American Academy of Pediatrics. Shigel a infections. In: Red Book: 2006 Report of the Committee on Infectious Diseases, 27th
ed, Pickering, LK (Ed), American Academy of Pediatrics, Elk Grove Vil age, IL 2006. p. 589.
34. Bennish, ML, Khan, WA, Begum, M, et al. Low risk of hemolytic uremic syndrome after early effective antimicrobial therapy for
Shigel a dysenteriae type 1 infection in Bangladesh. Clin Infect Dis 2006; 42:356.
35. Tauxe, RV, Puhr, ND, Wel s, JG, et al. Antimicrobial resistance of Shigel a isolates in the USA: The importance of international
36. Eidlitz-Marcus, T, Cohen, YH, Nussinovitch, M, et al. Comparative efficacy of two- and five-day courses of ceftriaxone for
treatment of severe shigel osis in children. J Pediatr 1993; 123:822.
37. Varsano, I, Eldlitz-Marcus, T, Nussinovitch, M, et al. Comparative efficacy of ceftriaxone and ampicil in for treatment of severe
shigel osis in children. J Pediatr 1991; 118:627.
38. Kabir, I, Butler, T, Khanam, A. Comparative efficacies of single intravenous doses of ceftriaxone and ampicil in for Shigel osis in a
placebo-control ed trial. Antimicrob Agents Chemother 1986; 29:645.
39. Lolekha, S, Vibulbandhitkit, S, Poonyarit, P. Response to antimicrobial therapy for shigel osis in Thailand. Rev Infect Dis 1991; 13
40. Salam, MA, Dhar, U, Khan, WA, Bennish, ML. Randomised comparison of ciprofloxacin suspension and pivmecil inam for
childhood shigel osis. Lancet 1998; 352:522.
41. Khan, WA, Seas, C, Dhar, U, et al. Treatment of shigel osis: V. Comparison of azithromycin and ciprofloxacin. A double-blind,
randomized, control ed trial. Ann Intern Med 1997; 126:697.
42. Basualdo, W, Arbo, A. Randomized comparison of azithromycin versus cefixime for treatment of shigel osis in children. Pediatr
43. Miron, D, Torem, M, Merom, R, Colodner, R. Azithromycin as an alternative to nalidixic acid in the therapy of childhood
shigel osis. Pediatr Infect Dis J 2004; 23:367.
44. American Academy of Pediatrics. Antimicrobial agents and related therapy. In: Red Book: 2006 Report of the Committee on
Infectious Diseases, 27th ed, Pickering, LK (Ed), American Academy of Pediatrics, Elk Grove Vil age, IL 2006. p. 735.
45. The use of systemic fluoroquinolones. Pediatrics 2006; 118:1287. 46. Burkhardt, JE, Walterspiel. JN. Schaad. UB. Quinolone arthropathy in animals versus children. Clin Infect Dis 1997; 25:1196. 47. Leibovitz, E, Janco, J, Piglansky, L, et al. Oral ciprofloxacin vs. intramuscular ceftriaxone as empiric treatment of acute invasive
diarrhea in children. Pediatr Infect Dis J 2000; 19:1060.
48. Bhattacharya, K, Bhattacharya, MK, Dutta, D, et al. Double-blind, randomized clinical trial for safety and efficacy of norfloxacin for
shigel osis in children. Acta Paediatr 1997; 86:319.
49. Rogerie, F, Ott, D, Vandepitte, J, et al. Comparison of norfloxacin and nalidixic acid for treatment of dysentery caused by Shigel a
dysenteriae type 1 in adults. Antimicrob Agents Chemother 1986; 29:883.
50. Vinh, H, Wain, J, Chinh, MT, et al. Treatment of bacil ary dysentery in Vietnamese children: two doses of ofloxacin versus 5-days
nalidixic acid. Trans R Soc Trop Med Hyg 2000; 94:323.
51. Ashkenazi, S, Amir, J, Waisman, Y, et al. A randomized, double-blind study comparing cefixime and trimethoprim-
sulfamethoxazole in the treatment of childhood shigel osis. J Pediatr 1993; 123:819.
52. Helvaci, M, Bektaslar, D, Ozkaya, B, et al. Comparative efficacy of cefixime and ampicil in-sulbactam in shigel osis in children.
53. Prado, D, Lopez, E, Liu, H, et al. Ceftibuten and trimethoprim-sulfamethoxazole for treatment of Shigel a and enteroinvasive
Escherichia coli disease. Pediatr Infect Dis J 1992; 11:644.
54. Martin, JM, Pitetti, R, Maffei, F, et al. Treatment of shigel osis with cefixime: Two days vs. five days. Pediatr Infect Dis J 2000;
55. Salam, MA, Seas, C, Khan, WA, et al. Treatment of Shigel osis: cefixime is ineffective in shigel osis in adults. Ann Intern Med
56. Islam, MR, Alam, AN, Hussain, MS, Mahalanabis, D. Effect of antimicrobial (nalidixic acid) therapy in shigel osis and predictive
values of outcome variables in patients susceptible or resistant to it. J Trop Med Hyg 1995; 98:121.
57. Kagalwal a, AF, Khan, SN, Kagalwal a, YA, et al. Childhood shigel osis in Saudi Arabia. Pediatr Infect Dis J 1992; 11:215. 58. Bennish, M, Salam, MA, Wahed, MA. Enteric protein loss during shigel osis. Am J Gastroenterol 1993; 88:53. 59. Curtis, V, Cairncross, S. Effect of washing hands with soap on diarrhoea risk in the community: a systematic review. Lancet Infect
60. Gangaros, EJ. Annotation: a community-focused strategy for the control of day-care center shigel osis. Am J Public Health 1995;
61. Hoffman, RE, Shil am, PJ. The use of hygiene, cohorting, and antimicrobial therapy to control an outbreak of shigel osis. Am J Dis
(texto extraído e modificado de: Bruno F et al. Distúrbios Hidroeletrolíticos na criança. IN: Piva J, Garcia PC (Eds).
Medicina Intensiva em Pediatria. Rio de janeiro: Revinter. 2005. p317-333.
O tratamento da desidratação inicia pela análise da
osmolaridade séricos, além de creatinúria, glicosúria,
história clínica, da diurese (se possível), da perda de
cetonúria, pH urinário, osmolaridade e dosagem de
peso e estimativas de perdas e aporte de líquidos. O
exame físico deve ser acurado, procurando detectar
Na desidratação leve e em alguns casos
sinais de comprometimento do intravascular. Os
moderada, a reidratação deve ser realizada por via
exames complementares devem incluir sódio, potássio,
oral, pois, não há comprometimento dos espaços
cálcio, hemograma, uréia, creatinina, glicose, pH,
intravascular e intracelular. Nestes casos administra-se
bicarbonato, podendo ainda ser indicados em casos
25-30 ml/kg/hora de solução de hidratação oral. A
selecionados a dosagem sérica de albumina e
solução de hidratação oral recomendada pela OMS foi
modificada em 2002. O conteúdo de Na foi reduzido de
(melhora do pulso, diminuição da taquicardia, retorno
90 para 75 mEq/L, o K foi mantido em 20 mEq/L e o
bicarbonato mantido em 30 mEq/L, enquanto que a
A fase de recuperação
da reidratação por via
glicose foi reduzida de 2 para 1,3%. Com estas
endovenosa deve ser o mais breve possível, para que
modificações a osmolaridade foi reduzida de 310 para
utilize preferentemente a via oral. Entretanto, em um
grande contingente de pacientes de UTI e de salas de
Nos pacientes com desidratação de III grau e naqueles
emergência, em razão de situações associadas (sepse,
de II grau com menos de 3 meses, com alteração de
pós-operatório, alterações do sensório, etc), esta fase
estado de consciência, vômitos intratáveis, distensão
de recuperação é mantida por via endovenosa e pode
perdurar por cerca de 20 horas. Após a restauração da
recomendado é a hidratação endovenosa (5,6
volemia, o objetivo é administrar a manutenção
Existem vários esquemas de reidratação, que levam
hidroeletrolítica adicionada das possíveis perdas e das
em consideração a quantidade de líquido perdido, as
deficiências eletrolíticas ainda existentes. A estimativa
possíveis perdas posteriores e a quantidade de líquidos
do volume a ser administrado depende da causa da
de manutenção para cada indivíduo. Na prática, a
desidratação, da resposta à infusão inicial e do próprio
reidratação endovenosa deve ser um procedimento
grau de desidratação. Utilizamos infundir a manutenção
simples, eficaz e com controle clínico contínuo. De
hídrica diária (~100 ml/kg/dia emlactentes) sob a forma
forma que ao compensar o comprometimento
de solução fisiológica (150 mEq/L de sódio) com 5% de
intravascular retorna-se a hidratação pela via oral.
glicose ou uma proporção de 50% de cada uma destas
A reidratação endovenosa é constituída por duas
soluções. Nesta etapa deve ser adicionado potássio na
etapas: a fase de reposição ou de expansão
proporção de 20 a 40 mEq/ para cada litro de solução.
volumétrica e a fase de recuperação ou de
No caso de haver perdas volumosas durante este
período (vômitos, drenagem volumos pela sonda
A fase de expansão
é rápida e agressiva, visando a
gástrica, gastroenterites, etc), optamos por fazer novas
restauração do volume intravascular nas primeiras
expansões com Solução fisiológica (20 ml/kg em 20
horas (em média de 2 horas). Assim, quanto maior for
a depleção de volume, mais agressiva e rápida deve
Após as primeiras 24 horas de tratamento, a
grande maioria dos pacientes apresenta reversão do
Em crianças desidratadas de II e III grau, preconizamos
quadro com melhora clínica e compensação fisiológica
expansões com solução fisiológica (NaCl 0,9%) de 20
dos distúrbios hidroeletrolíticos e ácido-básicos. Nesta
ml/kg a cada 20 minutos ou 30 minuto (40 a 60
fase de equilíbrio, a hidratação venosa pode ser
ml/kg/hora) que podem ser repetidas tantas vezes
reduzida, incentivando-se a administração por via oral.
quanto necessárias para reverter a depleção
volumétrica. É importante ressaltar que ao redor de
25% desta solução permanece dentro do espaço
intravascular, sendo que os restantes 75% se
distribuem no espaço intersticial. Repete-se estas
expansões até que ocorra resposta hemodinâmica
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