Diarrea aguda infecciosa bacteriana

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Revision sobre diagnostico y tratamiento de diarrea bacteriana

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Diarrea aguda infecciosa bacteriana

  1. 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. 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. 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. 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. 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. 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. 7. Diagnosis and Treatment of Bacterial Diarrhea • Lawler and Wallace 293 References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1. Guerrant RL, Bobak DA: Bacterial and protozoal gastroenteritis. N Engl J Med 1991, 325:327–340. 2.•• Guerrant RL, Van Gilder T, Steiner TS, et al.: Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001, 32:331–351. These guidelines are a consensus of experts from the Infectious Diseases Society of America. They provide an in-depth look at the evidence supporting particular management strategies and are an invaluable resource. 3. Centers for Disease Control and Prevention: Campylobacter Infections. http://www.cdc.gov/ncidod/dbmd/diseaseinfo/ campylobacter_g.htm. Accessed March 3, 2003. 4. Castelli F, Pezzoli C, Tomasoni L: Epidemiology of travelers' diarrhea. J Travel Med 2001, 8(Suppl 2): S26–S30. 5.• Smith, KE, Besesr JM, Hedberg CW, et al.: Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992-1998. N Engl J Med 1999, 340:1525–1532. This important study documented a 10-fold rise in quinolone-resistant Campylobacter species in Minnesota. The investigators also found that 14% of retail market chicken products were contaminated with quinolone-resistant Campylobacter organisms. Molecular subtyping of isolates was able to link chicken as a source of human infection. 6. Sack, RB, Raman M, et al.: Antimicrobial resistance in organisms causing diarrheal disease. Clin Infect Dis 1997, 24(Suppl 1):S102–S105. 7. Bennish ML, Salam MA, Hossain MA, et al.: Antimicrobial resistance of Shigella isolates in Bangladesh, 1983-1990: increasing frequency of strains multiply resistant to ampicillin, trimethoprim-sulfamethoxazole, and nalidixic acid. Clin Infect Dis 1992, 14:1055–1060. 8. 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