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| Equipe de Pediatria - HMD |
| Artigos sobre tratamento da desinteria |
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| TREATMENT OF BACTERIAL ENTERITIS Pediatr Infect Dis J 1998 May;17(5):420-421 Copyright � 1998 Lippincott Williams & Wilkins All rights reserved James P. Nataro, M.D., Ph.D. University of Maryland School of Medicine, Baltimore, MD THE PEDIATRIC INFECTIOUS DISEASE JOURNAL 1998;17:420-421 DECISIONS ABOUT whether to use antimicrobials to treat patients with bacterial enteritis are complicated by the variable effectiveness of antimicrobials in enteritis caused by different organisms and by increased resistance of diarrheal pathogens to standard therapy (Table). In addition, there are only limited data in children on the use of newer antimicrobials (such as the fluoroquinolones) that appear to be effective for treatment of many enteric bacterial infections. Appropriate management of dehydration, electrolyte status, and nutrition are other important aspects of treatment of bacterial enteritis. Anti-diarrheal compounds generally are contraindicated, except, perhaps, for treatment of secretory diarrhea. Shigella: In patients with Shigella enteritis, antibiotic treatment leads to more rapid resolution of fever, abdominal cramping, bloody stools, and diarrhea and to a shorter period of fecal shedding of the organism. Trimethoprim/sulfamethoxazole (TMP/SMX) has been the therapy of choice, but the frequency of infection due to strains resistant to this combination is increasing. Ampicillin, nalidixic acid, fluoroquinolones and (possibly) azithromycin are potential alternatives. Amoxicillin is not as active as ampicillin and should not be used. In a recent study of adults hospitalized with acute shigellosis, a 5-day course of treatment with either azithromycin or ciprofloxacin was associated with clinical cure in nearly 90% of patients and with bacteriologic cure in 94-100% of patients.1 For adults with mild to moderate symptoms caused by species other than S. dysenteriae, a single 1-gram dose of ciprofloxacin usually is effective.2 First- and second-generation cephalosporins are not active against Shigella spp. and should be avoided regardless of in vitro susceptibilities. The efficacy of cefixime has been inconsistent, but ceftriaxone is effective and is especially attractive for treatment of patients with severe illness. Salmonella: In patients with uncomplicated enteritis due to non-typhoidal Salmonella, treatment with an antibiotic has no beneficial effect. Treatment often prolongs fecal excretion of the organism and results in a higher risk of both bacteriologic and symptomatic relapse.3 Some experts suggest that individuals at risk of disseminated infection (infants <3 months of age and immunocompromised patients, such as those with sickle cell disease) should be treated with antibiotics, even though efficacy in such instances is unproved. Because of the high prevalence of strains resistant to ampicillin and to TMP/SMX, treatment with cefotaxime, ceftriaxone, or a fluoroquinolone is generally preferred. Campylobacter: The role of antimicrobials in the management of patients with enteritis due to Campylobacter jejuni and other enteric species of Campylobacter is controversial. Early studies indicated that although treatment shortened the duration of excretion of the organism, clinical signs and symptoms were not affected. More recently, it was reported that in Peruvian children who had dysentery, stool cultures positive for C. jejuni, and symptoms for <4 days, stools became normal within 5 days in 15 of 16 children treated with erythromycin ethyl succinate and in only 6 of 12 children who received placebo.4 The effectiveness of erythromycin for treatment of milder disease is unknown. Recent studies in adults with Campylobacter enteritis have indicated that treatment with either ciprofloxacin or azithromycin shortens the duration of symptoms.5 Antibiotic therapy for children with Campylobacter enteritis is most likely to be beneficial in those with dysenteric illness or when there is a significant risk of spread to others (e.g., in children who attend daycare). Yersinia enterocolitica: There have been few studies of the effectiveness of antimicrobial treatment for Y. enterocolitica because it is relatively uncommon. There is little evidence to support the routine use of antibiotic therapy in children with uncomplicated enteritis caused by Y. enterocolitica.6 Escherichia coli: Enteritis due to pathogenic E. coli is an emerging problem in many parts of the world.7 Enterohemorrhagic E. coli can be identified easily in the clinical microbiology laboratory, but identification of enteroinvasive, enteropathogenic, enterotoxigenic, enteroaggregative, and diffusely-adherent E. coli requires tests that are not widely available. In patients with infection caused by enterohemorrhagic E. coli (type O157: H7 and others), limited data suggest that antibiotic treatment has no effect on either the duration of diarrhea or the likelihood that hemolytic-uremic syndrome will develop. Although antibiotics often are used to treat enteritis caused by enteropathogenic E. coli, there is no definitive evidence that treatment either shortens the clinical course or limits transmission. Diarrhea due to enterotoxigenic E. coli usually is short-lived so treatment rarely is necessary, although studies in adults have demonstrated that treatment of infections caused by susceptible isolates with either TMP-SMX or ciprofloxacin may be beneficial. The effects of antibiotic treatment has not yet been studied in patients with infections caused by either enteroaggregative or diffusely-adherent E. coli. Other organisms: Antibiotic treatment diminishes both the severity and the duration of symptoms and shortens the duration of fecal shedding in patients with diarrhea due to Vibrio cholerae types O1 and (probably) O139.8 A single dose of either doxycycline or ciprofloxacin usually is effective. TMP/SMX is an alternative, but resistance to this combination is common in most parts of the world. Antibiotics are not indicated for patients with enteritis caused by Bacillus cereus, Clostridium perfringens or Staphylococcus aureus, since symptoms generally resolve spontaneously within 12-24 hours. The effectiveness of antibiotics for treatment of enteritis caused by Aeromonas spp., Plesiomonas spp. or non-cholera Vibrio is unknown. Empiric Treatment Most children with acute diarrhea in the U.S. have viral gastroenteritis, especially if stools are watery and do not contain either blood or mucus. In the patient with fever, abdominal cramps and/or bloody stools, stool culture should be obtained. Patients with all of these symptoms (i.e., the dysentery syndrome) can be treated empirically with TMP/SMX while awaiting the results of culture and antimicrobial susceptibility tests. References Khan et al. Ann Intern Med 1997;126:697-703. Bennish et al. Ann Intern Med 1992;117:727-34. Nelson et al. Pediatrics 1980;65:1125-30. Salazar-Lindo et al. J Pediatr 1986;109:355-60. Kuschner et al. Clin Infect Dis 1995;21:536-41. Pai et al. J Pediatr 1984;104:308-11. Nataro et al. Clin Microbiol Rev (In press). Kaper et al. Clin Microbiol Rev 1995;8:48-86. |
| ANTIBIOTIC THERAPY OF COLITIS: In Reply Larry K. Pickering, M.D. THE PEDIATRIC INFECTIOUS DISEASE JOURNAL 2001;20:465-466 Inflammatory enteritis, often referred to as colitis, is characterized by ileal or colonic inflammation associated with a large number of noninfectious and infectious causes, including several bacterial enteric pathogens. Although therapies for specific bacterial causes of colitis have been defined, empiric therapy of infants, children and adolescents with colitis is problematic for several reasons. Clinical and diagnostic difficulties include the following: (1) varied clinical manifestations initially and during the course of illness as well as differences in presentation and outcome in immunocompromised and immunocompetent hosts; (2) inadequate diagnostic techniques to facilitate rapid identification of bacterial enteropathogens that would enhance directed therapy; and (3) lack of implementation by some diagnostic laboratories of detection methods for E. coli 0157:H7, inability of most microbiology laboratories to detect Campylobacter strains other than Campylobacter jejuni/coli and lack of use of culture techniques to detect less common causes of colitis such as Vibrio parahaemolyticus, Yersinia enterocolitica, invasive E. coli and Clostridium difficile.2 Therapeutic problems include: (1) lack of a single effective antimicrobial agent that is beneficial for treatment of the four most common causes of bacterial enteritis in the United States (C. jejuni/coli, Salmonella, Shigella and E. coli 0157:H7); (2) lack of benefit in treating most patients with Salmonella gastroenteritis and many other less commonly identified bacterial pathogens associated with diarrhea; (3) potential harm from treating children infected with E. coli 0157:H7 with antimicrobial agents; and (4) lack of vaccines that effectively prevent these infections. When confronted with a patient with colitis before a microorganism has been identified from stool, the issue of antimicrobial therapy is difficult because of the increased risk of HUS in children with hemorrhagic colitis caused by enterohemorrhagic E. coli (EHEC) who are treated with antimicrobial agents1 as well as the risk of prolonging symptoms and extending carriage or increasing the risk of complications among persons who have Salmonella gastroenteritis.2 The role of antimicrobial therapy in patients with hemorrhagic colitis caused by E. coli 0157:H7 or other EHEC organisms has progressed through a series of studies demonstrating that trimethoprim (TMP)-sulfamethoxazole increases intracellular and extracellular concentrations of shiga-like toxins (SLT) produced by E. coli 0157:H7 in vitro3, 4 and an increase in HUS and death in nonrandomized studies in persons with E. coli 0157:H7 infections who were treated with antimicrobial agents.5, 6 Recently, as noted by Dr. Marcy, a prospective cohort study of 71 children younger than 10 years of age who had diarrhea caused by E. coli 0157:H7 demonstrated an increased risk of HUS in the 9 children treated with antimicrobial agents compared with the 62 children who did not receive antibiotic therapy (56% vs. 8%, P < 0.002, respectively).1 Considerations regarding the approach to patients with bloody diarrhea, once fluid and electrolyte therapy has been instituted and stool cultures have been obtained, include epidemiologic and clinical clues that may help direct therapy, rapid diagnostic techniques that are available to facilitate appropriate therapy, and studies that may help in selecting an effective and safe antibiotic when indicated. Patients who are immunosuppressed and develop diarrhea and fever need prompt evaluation and are candidates for more liberal use of antimicrobial agents for infections caused by enteric as well as systemic pathogens, including Salmonella.2 In immunocompetent hosts specific factors may assist in the identification of the organism, including involvement in an outbreak (i.e. child care center, hospitalization and foodborne illness), knowledge of organisms circulating in the community, dietary history, animal exposure, history of travel, antimicrobial agent use and presence of fecal leukocytes or lactoferrin as an indicator of shigellosis or invasive Campylobacter infection.2 Diagnosis of a bacterial enteric infection is problematic because of the time, expense and diversity of organisms associated with diarrhea. Rapid identification of enteric pathogens, including EHEC, is important for patient management and for prompt epidemiologic investigation. Although rapid diagnostic tests such as those utilizing PCR, have been applied to a variety of microbial cultures, tissues and directly on clinical specimens, fecal specimens are among the most complex materials for testing by direct PCR.7 Recent studies have demonstrated that enzyme immunosorbent and multiplex PCR assays for detection of E. coli 0157:H7 and SLT-producing non-0157:H7 E. coli strains provide rapid same day results.7 Availability of rapid, simple and sensitive techniques for direct detection of EHEC organisms and SLT from stool specimens will help direct appropriate therapy as these assays become commercially available. The occurrence of HUS after antimicrobial therapy of patients with EHEC infection may depend on the number of organisms present, the environmental conditions of those organisms, and the bactericidal activity or ability to induce toxin gene expression. Toxin synthesis by EHEC appears to be coregulated through induction of the integrated bacteriophage that encodes the toxin gene. Phage production is linked to induction of the bacterial SOS response, a ubiquitous response to DNA damage. Induction of toxin gene expression occurs on exposure to SOS-inducing antimicrobial agents, particularly the fluoroquinolones, TMP and furazolidone.8 The fluoroquinolones and TMP are the most potent SOS inducers. Mitomycin C, another potent SOS inducer, increases shiga toxin concentrations in vitro9 and has been associated with HUS in humans with cancer.10 SOS induction occurs with several beta-lactams but appears to be inhibited by imipenem.8 A SOS-inducing effect was not detected with fosfomycin, gentamicin, chloramphenicol, doxycycline or erythromycin under a variety of incubation conditions.8 A study in mice demonstrated that animals treated with fosfomycin did not increase free fecal shiga toxin and death compared with animals treated with ciprofloxacin.4 In addition ciprofloxacin but not fosfomycin caused shiga toxin-encoding bacteriophage induction and enhanced shiga toxin production from E. coli 0157:H7 in vitro. Interestingly, in 1996 in an outbreak of EHEC infection in Japan associated with white radish sprouts, fosfomycin was associated with prevention of HUS.11 These data indicate that agents with SOS- inducing activity, including fluoroquinolones, TMP, furazolidone and most beta-lactams, should not be used in patients with EHEC. The potential benefit and safety of non-SOS inducers, such as macrolides, in EHEC infection are not known. In summary, until rapid diagnostic techniques become available to assist in appropriate and specific antimicrobial therapy and additional studies are conducted to determine whether non-SOS-inducing antibiotics are safe and effective therapy for patients with EHEC, utilization of clinical acumen, epidemiologic data and available diagnostic techniques are necessary to guide therapy of patients with bloody diarrhea. Larry K. Pickering, M.D. Eastern Virginia Medical School Norfolk, VA References Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli 0157: H7 infections. N Engl J Med 2000; 342: 1930-6. Pickering LK. Approach to diagnosis and management of gastrointestinal tract infections. In: Long SS, Pickering LK, Prober CG, eds. Principles and practice of pediatric infectious diseases. New York: Churchill-Livingstone, 1997: 410-18. Walterspiel JN, Ashkenazi S, Morrow AL, Cleary TG. Effect of subinhibitory concentrations of antibiotics on the release of shiga-like toxin I. Infection 1992; 20: 25-9. Zhang X, McDaniel AD, Wolf LE, Keusch GT, Waldor MK, Acheson DW. Quinolone antibiotics induce shiga toxin-encoding bacteriophages, toxin production, and death in mice. J Infect Dis 2000; 181: 664-70. Pavia AT, Nichols CR, Green DP, et al. Hemolytic-uremic syndrome during an outbreak of Escherichia coli 0157: H7 infections in institutions for mentally retarded persons: clinical and epidemiologic observations. J Pediatr 1990; 116: 544-51. Carter AO, Borczyk AA, Carlson JAK, et al. A severe outbreak of Escherichia coli 0157: H7-associated hemorrhagic colitis in a nursing home. N Engl J Med 1987; 317: 1496-500. Holland JL, Louie L, Simor AE, Louie M. PCR detection of Escherichia coli 0157: H7 directly from stools: evaluation of commercial extraction methods for purifying fecal DNA. J Clin Microbiol 2000; 38: 4108-13. Kimmitt PT, Harwood CR, Barer MR. Toxin gene expression by shiga toxin-producing Escherichia coli: the role of antibiotics and the bacterial SOS response. Emerg Infect Dis 2000; 6: 458-65. Yee AJ, DeGrandis S, Gyles CL. Mitomycin-induced synthesis of a shiga-like toxin from enteropathogenic Escherichia coli H. I.8. Infect Immun 1993; 61: 4510-13. Lesesne JB, Rothschild N, Erickson B, et al. Cancer-associated hemolytic-uremic syndrome: analysis of 85 cases from a national registry. J Clin Oncol 1989; 115: 781-9. Ikeda K, Ida O, Kimoto K, Takatorige T, Nakanishi N, Tatara K. Effect of early fosfomycin treatment on prevention of hemolytic uremic syndrome accompanying Escherichia coli 0157: H7 infection. Clin Nephrol 1999; 52: 357-62. Accepted for publication Jan. 19, 2001. |
| ANTIBIOTIC THERAPY OF COLITIS - reply Georges Peter, M.D. S. Michael Marcy, M.D. Georges Peter, M.D. THE PEDIATRIC INFECTIOUS DISEASE JOURNAL 2001;20:465-466 The findings described in a recent article indicate that antibiotic treatment of children infected with Escherichia coli 0157:H7 put them at increased risk of the hemolytic-uremic syndrome (HUS).1 Most children present with a dysenteric illness of unknown etiology, compatible with Campylobacter, Shigella, Salmonella, Yersinia or Clostridium difficile colitis as well as enterohemorrhagic E. coli infection. In some cases toxicity or immunosuppression, with or without clinical evidence of bacteremia or sepsis syndrome, warrants prompt institution of empiric antimicrobial therapy in addition to rehydration, correction of electrolyte abnormalities and general supportive care.2 With a 17-fold greater likelihood of provoking the development of HUS by treating an unsuspected E. coli 0157 infection with antibiotics, what is the appropriate management of the child presenting with bloody diarrhea, dysentery and toxicity? S. Michael Marcy, M.D. Beverly Hills, CA |
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