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Diarrea aguda infecciosa bacteriana

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Revision sobre diagnostico y tratamiento de diarrea bacteriana

Revision sobre diagnostico y tratamiento de diarrea bacteriana

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Diarrea aguda infecciosa bacteriana Diarrea aguda infecciosa bacteriana Document Transcript

  • Diagnosis and Treatment of Bacterial Diarrhea James V. Lawler, MD* and Mark R. Wallace, MD Address Emerging Antimicrobial Resistance *Infectious Diseases Department, National Naval Medical Center, Build- The rapid appearance and spread of antimicrobial resis- ing 5, 2nd floor, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA. tance among diarrheal pathogens has been one of the most E-mail: jvlawler@bethesda.med.navy.mil concerning developments in diarrheal illness. Worsening Current Gastroenterology Reports 2003, 5:287–294 Current Science Inc. ISSN 1522-8037 antimicrobial resistance probably has many causes, but Copyright © 2003 by Current Science Inc. 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- Diarrheal illness caused by bacterial pathogens is a global health rhea-causing bacteria was initially confined to the develop- problem and remains one of the most common complaints ing world but has become more prevalent in developed prompting patients to seek medical care. Strategies to increase countries in recent years. the yield of stool culture and new rapid diagnostic tests can Emerging resistance in shigellosis provides one of the improve diagnostic ability. Emerging antimicrobial resistance most dramatic examples of the worldwide problem. Shigella, among the common bacterial causes of diarrhea has made originally susceptible to a broad spectrum of antibiotics, treatment more challenging. Emerging fluoroquinolone acquired resistance in the developing world first to sulfona- resistance is a particular concern. Recent studies of rifaximin, a mides, then to ampicillin and trimethoprim-sulfamethox- nonabsorbed antibiotic for the treatment of bacterial diarrhea, azole (TMP-SMX), and finally to nalidixic acid as each drug have shown favorable results. Rifaximin may represent a much- became the first-line therapy of choice [7]. Only the fluoro- needed addition to the armamentarium against bacterial agents. quinolones have maintained significant susceptibility in developing countries. This is a significant problem for the treatment of shigellosis in children, in whom quinolones Introduction may have toxic effects on cartilage [6]. Diarrheal illness is one of the most common complaints Previous studies in the United States have yielded rela- prompting patients to seek medical care. In developing tively low levels of resistance among Shigella isolates (espe- nations, diarrheal illness accounts for 4,600,000 to 6,000,000 cially to TMP-SMX,) but dependable susceptibility may be childhood deaths per year, and it is the second leading cause rapidly waning [8]. Replogle et al. [9] recently investigated of death worldwide [1]. In the United States, an estimated 73 Shigella isolates in Oregon and found resistance to tetracy- million physician consultations and 1.8 million hospitaliza- cline, ampicillin, and TMP-SMZ in 85%, 63%, and 59% of tions each year result from diarrheal disease [2••]. isolates respectively. No isolates were resistant to ciproflox- The etiology of diarrhea in the United States varies with acin. Studies from Canada and Europe have shown simi- season and region, but bacteria are the most common cause, larly high rates of resistance [9]. with Campylobacter species being the most frequently iso- Antimicrobial resistance among Salmonella typhi (the lated bacteria [3]. Other bacterial causes are listed in Table 1. cause of typhoid fever) is a growing worldwide problem [10]. Accurate epidemiologic data are lacking because most caus- Although typhoid fever is a distinct entity outside the realm of ative organisms are not reportable and most episodes of this review, nontyphoidal Salmonella organisms are a com- diarrhea are treated in the outpatient setting, frequently mon cause of diarrheal illness, and resistance to ampicillin, without diagnosis. TMP-SMX, and chloramphenicol has been increasingly Diagnosis and management of bacterial diarrhea has reported [11]. S. enterica serotype Typhimurium definitive become more complex due to the globalization of food pro- phage type 104 (DT104) is one particular nontyphoidal strain duction, burgeoning numbers of immunocompromised and that carries inherent resistance to ampicillin, chlorampheni- institutionalized patients, increased ease of travel to develop- col, streptomycin, sulfonamides, and tetracycline. It has made ing nations, and the changing epidemiology of pathogens a dramatic appearance in Europe and is now infiltrating the [1,2••,4]. This article reviews the global and emerging prob- United States [12]. lem of antimicrobial resistance among enteric pathogens and Although third-generation cephalosporins and fluoroqui- discusses present recommendations and coming advances in nolones are generally effective against salmonellae, reports of diagnosis and treatment of bacterial diarrhea. resistance are on the rise. Of particular concern is the confir-
  • 288 Gastrointestinal Infections 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 mation of Typhimurium DT104 isolates with nalidixic acid (a iting and require no specific therapy, diagnostic effort quinolone antibiotic) resistance in enteritis acquired from should be focused on patients who have symptomatic, food animals [13•]. Nalidixic acid resistance may be a har- physical, or epidemiologic findings suggesting that spe- binger of emerging quinolone (such as ciprofloxacin) resis- cific diagnosis and treatment are warranted. tance, a development that would have significant clinical The diagnosis of infectious diarrhea begins with a thor- implications [14]. ough history and physical examination, the importance of The recommended treatment of Campylobacter enteritis which cannot be underestimated. Historical and physical is generally a quinolone or macrolide, but quinolone resis- findings can target patients who are likely to benefit from tance has been rising rapidly around the world [10]. Qui- further laboratory investigation or empiric therapy, such as nolone-resistant strains from diarrhea cases in Thailand those with inflammatory diarrhea or a history of immuno- increased from 0% to 84% between 1990 and 1995 [15]. compromising disease. Excellent reviews of important The most recent data indicate that resistance in Thailand is diagnostic clues are available in the guidelines of the Infec- over 95% (Tribble D, Personal communication). Quinolone tious Diseases Society of America and the American Col- resistance has emerged in Europe and North America as lege of Gastroenterology [2••,18]. well. Resistance rates in Minnesota rose from 1.3% to 10.2% The need for stool culture can often be established using between 1993 and 1998, and resistance rates in isolates simple and rapid laboratory tests. Visual identification of from Ireland have risen from 17.4% to 23% in recent years gross blood or a positive test for occult blood suggests an [5•,16]. One recent study from Barcelona found that 12.5% inflammatory diarrhea (especially enterohemorrhagic Escheri- of Campylobacter isolates from travelers (mostly to India, chia coli [EHEC]) and is an indication for culture [2••]. In one Africa, and Latin America) were resistant to ciprofloxacin, study, gross blood increased the yield of culture from 5.6% to but a stunning 88% of isolates from Spanish nontravelers 20.1% [19]. Microscopic examination of fresh stool with possessed ciprofloxacin resistance [17]. The Minnesota methylene blue staining can be used to look for polymorpho- study also found that 20% of retail chicken products were nuclear lymphocytes (PMNs), a relatively sensitive test for contaminated with ciprofloxacin-resistant Campylobacter inflammatory diarrhea [19–21]. Stool may also be examined organisms, strengthening the link between animal food by commercial latex agglutination assay for lactoferrin, a sources and spread of resistant diarrheal pathogens [5•]. 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 Diagnostic Approach 95% for confirmed Clostridium difficile or Shigella infection, Diagnosis and specific therapy in diarrheal illness should and specificity of 94% and 100%, respectively [21]. be directed at certain goals: alleviation of symptoms, pre- Stool culture for infectious diarrhea has changed very lit- vention of secondary transmission, reduction of morbid- tle in the past several decades and remains the gold standard ity and mortality, and detection and control of outbreaks for diagnosis of bacterial enteritis. However, it is a relatively [2••]. The diagnosis of bacterial diarrhea is relatively labor expensive test with a low yield. Studies of stool culture yields intensive, with low yield and return of results only after 24 have typically resulted in positive rates below 10% and as low to 72 hours. Because most cases of diarrhea are self-lim- as 1.5% [22,23]. The cost per positive culture from these stud-
  • Diagnosis and Treatment of Bacterial Diarrhea • Lawler and Wallace 289 ies ranges from $136 to $1200. Reserving stool culture for sensitive than cytotoxicity assays, EIAs are commercially patients with evidence of inflammatory diarrhea or with available for detection of shiga-like toxins produced by other special indications can significantly improve the yield of Shigella and EHEC [30,31]. Such tests can be performed the culture. In one prospective study, stool culture performed directly on stool, but sensitivity increases (to 100% in one only on patients with the presence of fecal leukocytes resulted study) if stool is incubated in broth culture overnight in an improved recovery rate of 76.7% [22]. Avoiding routine before the EIA is performed [32]. The advantage of this stool culture in patients developing diarrhea more than 72 type of test is the detection of all shiga toxin–producing E. hours after hospital admission (the “3-day rule”) can improve coli organisms, regardless of sorbitol fermentation. the yield as well. Rohner et al. [24] studied the results of Methods for rapid detection of Salmonella and Shigella almost 14,000 stool cultures at a university hospital in Swit- organisms are also being developed. Many immunologically zerland and found positive cultures in 12.6% versus 1.4% based commercial kits are already used in food products, and (P<0.001) before and after 3 hospital days. some have been tested in human stool specimens. A study of Culture should be performed on fresh stool. Rectal swabs multiple kits for the detection of various Shigella and Salmo- are generally inferior. If stool cannot be plated within 2 hours, nella species in Thailand reported sensitivities and specificities it should be refrigerated or placed in a transport medium between 94% and 100% [33]. A kit available in Europe for [20,23]. Routine stool culture in most US laboratories con- detection of serum IgM against Salmonella typhi was recently sists of selective and differential agar plates capable of isolat- tested for the diagnosis of Salmonella serotype enteritidis in ing Salmonella, Shigella, and, if all non–E. coli gram negatives Polish children with diarrhea [34•]. The sensitivity and speci- are routinely identified, Aeromonas and Plesiomonas. Most ficity of this assay were 92.6% and 94.8%, respectively, with laboratories also include a Campylobacter-selective medium positive and negative predictive values of 94.7% and 92.9% incubated in microaerophilic conditions to detect Campylo- when patients were compared with control subjects. Such bacter species [20,23]. Other organisms require special media immunoassays are likely to appear in diagnostic microbio- for culture diagnosis. Suspicion for EHEC, Yersinia, and Vibrio logic laboratories in the United States in the near future. should prompt culture in sorbitol-MacConkey (SMAC), Rapid molecular diagnostic techniques such as poly- cefsulodin-ingrasan-novobiocin (CIN), and thiosulfate-cit- merase chain reaction (PCR) have made their way into sev- rate-bile-sucrose (TCBS) agars respectively to isolate these eral areas of clinical microbiology. PCR assays have been organisms. Turnaround time for stool culture is at least 24 used to detect C. difficile toxin genes, Shigella, enteroinva- hours, and frequently 48 hours for organisms such as Campy- sive E. coli (EIEC), Campylobacter, and Vibrio organisms in lobacter species. stool with impressive accuracy [35–38]. Amplified DNA detection is likely to be useful in the future. However, a sig- Advances in rapid stool diagnostics nificant amount of fine tuning may be required before it is Rapid detection methods, such as the enzyme immunoassay available for commercial use because the presence of DNA (EIA), are routinely used for several bacterial pathogens, and polymerase inhibitors in human feces often interferes with tests for others are in development. Commercially available these tests [33]. 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 Treatment [25]. Although a small proportion of C. difficile organisms Most diarrheal illness is self-limited and requires no specific produce only toxin B, significant C. difficile–associated disease intervention other than hydration [10]. Loperamide is recom- missed by assay for toxin A has been reported [26]. Measured mended for symptomatic treatment as long as the illness is sensitivities and specificities of these EIAs vary widely depend- not severe or dysenteric [18]. The appropriate use of antimi- ing on the study and the kit. Most studies have found excel- crobial agents is a challenging aspect of treatment because lent specificity but sensitivity that is somewhat less than that antibiotics have the potential for serious deleterious effects. of the cell culture assay [25]. Antibiotic therapy may prolong carriage of enteric Salmonella Rapid EIA tests can reduce the diagnostic delay with organisms, probably through alteration of normal flora [14]. Campylobacter organisms from 48 hours to less than 3 hours. Antibiotic treatment of EHEC may induce toxin production Studies with a commercially available kit found a sensitivity and exacerbate hemolytic-uremic syndrome (HUS) [31]. Anti- of 80% to 96% and specificity of 99% to 100% [27,28,29•]. biotic use is the major predisposing factor for C. difficile infec- In the proper clinical setting, this type of test results in excel- tion [25]. Finally, unnecessary use of antibiotics worsens the lent positive and negative predictive values. Some laboratories problem of rapidly emerging antibiotic resistance among bac- have replaced culture with EIA for the diagnosis of Campylo- teria that cause enteric infection [6]. bacter enteritis. Despite these drawbacks, antimicrobial therapy has a Rapid tests are also available for diagnosis of EHEC definite role in the management of diarrhea caused by certain infection. Commercial latex agglutination kits for detec- pathogens. The benefit of standard antibiotic therapy for tion of the O157 or H7 antigens are reliable, but they fail diarrhea caused by Shigella, Vibrio, C. difficile, and enterotoxic to identify shiga-like toxin production [30]. Although less E. coli (ETEC) infection is firmly established [1,2••,10,11].
  • 290 Gastrointestinal Infections Although ETEC is not routinely diagnosed in clinical microbi- ment may have been handicapped because early therapy for ology laboratories, it can be suspected with history of travel to Campylobacter infection appears to be most efficacious [50]. areas of high prevalence, or it can be diagnosed in research Quinolones and macrolides can be used to treat Campylo- laboratories. Treatment of ETEC is generally TMP-SMX or bacter infection, but emerging quinolone resistance is a grow- ciprofloxacin for 5 days [31]. A 3-day course of TMP-SMX also ing problem. In areas with high levels of endemic resistance, appears to be effective, showing even better outcomes with such as Southeast Asia, a macrolide may be more appropriate; the addition of loperamide [39]. Although mild to moderate azithromycin (500 mg/d for 3 days) has proven efficacy [51]. Vibrio infections do not usually require antibiotic therapy, Rifaximin may be very useful in such cases and is discussed antibiotics used in severe cases (as with V. cholerae) can reduce later in this review. duration of illness, stool frequency, and fecal shedding [10]. Antimicrobial therapy in uncomplicated nontyphoidal Tetracycline has long been the drug of choice for such infec- Salmonella enteritis is somewhat controversial. Trials of tions, but fluctuating geographic patterns of resistance have most antibiotics have shown no clinical benefit, and in fact been seen [6]. Furazolidone and erythromycin have been have sometimes shown prolonged fecal shedding of the used successfully in lieu of tetracycline [6,40]. More recently, offending bacteria [10]. Some studies have shown that single-dose quinolones have been shown to be at least as quinolones may shorten the duration of illness with non- effective as the more traditional regimens, and quinolone typhoidal Salmonella, although carriage is probably not resistance among Vibrio species is rare [10,41]. shortened [14]. Despite the lack of evidence of efficacy in Cessation of antibiotics and re-establishment of normal uncomplicated diarrhea, patients at risk for disseminated fecal flora remains the most effective treatment for C. difficile– disease should probably be treated, because extraintestinal associated diarrhea. This strategy leads to resolution in Salmonella infection is associated with significant morbid- approximately 20% of patients [42]. Ten-day courses of oral ity and mortality [2••]. The recommended empiric anti- vancomycin and metronidazole are equivalent when anti- biotics for Salmonella infection are quinolones or third- microbial treatment is warranted [43]. The recommended generation cephalosporins because of increased resistance dosages are vancomycin, 125 mg four times daily, and met- to other traditional agents [14]. ronidazole, 500 mg three to four times daily [42]. Many alter- native therapies have been examined, but they are generally Empiric antimicrobial therapy less effective and are beyond the scope of this review. Because rapid diagnostic capability for bacterial diarrhea is Antibiotic resistance, especially among S. dysenteriae type limited, almost all antimicrobial treatment is initially I, has made treatment of shigellosis increasingly difficult. As empiric. Suspected cases of severe C. difficile colitis may war- mentioned previously, quinolones are the only drugs with rant empiric therapy with metronidazole if a toxin assay can- proven efficacy in the developing world, and although TMP- not be performed in a timely manner, especially if fecal SMX sometimes works in developing countries, resistance leukocytes are present. In the absence of risk factors for C. rates are rapidly increasing. Concerns remain regarding the difficile infection, inflammatory diarrhea may be caused by administration of quinolones to children and pregnant organisms that respond well to treatment, such as Campylo- women because of cartilage toxicity in animal models, but bacter, Shigella, and EIEC. Bloody diarrhea in the absence of arthropathy has not been seen in clinical trials of quinolo- fever or in a child should raise a clinical suspicion of EHEC, nes in children [44]. Third-generation cephalosporins are and empiric antibiotics should not be used in these patients active against Shigella organisms in vitro, but results of clini- to avoid potentially precipitating HUS [30]. Patients with cal trials have not been convincing [10]. An important recent inflammatory diarrhea who have a predisposing risk for development in the treatment of bacillary dysentery has severe or disseminated infection, including those with an been the use of short-course therapy (1–3 days). Table 2 out- immunocompromising condition, diabetes, cirrhosis, lines the results of two studies of short-course treatment in advanced age, intestinal hypomotility, or hypochlorhydria, children with cholera [44,45]. Clinical outcome was similar are candidates for empiric treatment. On a case-by-case basis, in the two studies. The microbiologic cure rate was 100% in empiric treatment may be prudent for a variety of reasons, for both groups in the ZIMBASA study, whereas the study by example in a patient who is at risk of spreading disease to oth- Vinh et al. [45] found a significant reduction in the duration ers (eg, health-care worker or food handler) or when a specific of shedding in the short-course group. Thus, a shortened pathogen is suspected (eg, raw seafood consumption or con- course of quinolones appears to be effective for treatment of tact with a known case). Finally, empiric treatment of trav- dysenteric illness from Shigella infection. eler’s diarrhea is generally appropriate because treatment in Many experts recommend antibiotic treatment for cul- this instance has been shown to reduce the duration of illness ture-proven Campylobacter enteritis [2••,18], although this from 3 to 5 days to less than 1 to 2 days [2••]. opinion is not universal. Several well-constructed studies have Quinolones have become the drug of choice for empiric shown statistically significant clinical improvement with qui- treatment of acute bacterial diarrhea in adults. They remain nolone therapy. These studies also suggest that therapy may highly active against almost all of the usual pathogens, reduce the duration of fecal shedding [46–49]. Some of the achieve high fecal concentrations, and are generally tolerated studies that did not show statistically significant improve- well [52]. A number of randomized, placebo-controlled stud-
  • Diagnosis and Treatment of Bacterial Diarrhea • Lawler and Wallace 291 ies from Europe and the United States have demonstrated Rifaximin is a semisynthetic relative of the rifamycins successful treatment of acute diarrhea with ciprofloxacin and with activity against a broad spectrum of gram-positive and norfloxacin. Pichler et al. [48,53] published two reports on gram-negative organisms. It is currently licensed in several treatment with ciprofloxacin (500 mg twice daily for 5 days) European, Latin-American, and Asian countries. Less than in 50 and 85 patients, respectively. In the first study, ciproflox- 1% of oral rifaximin is absorbed systemically, but stool acin reduced the duration of diarrhea from 2.6 to 1.4 days concentrations reach levels several hundred times the min- (P<0.01) and decreased the number of positive cultures after imal inhibitory concentration for 90% (MIC90) of most 48 hours of therapy from 24 to 25 to 0 to 24 (P<0.001). Sim- enteric pathogens [56,57]. As would be expected with a ilar results were found in the second study, and the mean nonabsorbed drug, studies to date have revealed an excel- duration of fever was also reduced in a statistically significant lent safety profile with a 1% incidence of gastrointestinal manner from 3.1 to 1.3 days. Studies by Goodman et al. [49], side effects and very rare episodes of urticaria [57]. Wistrom et al. [54], and Dryden et al. [46] found a 1- to 2.4- To date, two randomized clinical trials examining the day reduction in days with diarrhea, compared with results in use of rifaximin in traveler’s diarrhea have been published. the placebo group, along with significantly reduced daily The first trial compared rifaximin (200, 400, and 600 mg symptoms and total duration of illness. These studies repre- three times a day) to a standard dose of TMP-SMX in 72 sented varied populations. Campylobacter or Salmonella were adult US students studying abroad in Mexico [58]. Overall, the predominant organisms isolated, but a large proportion the mean duration of diarrhea after treatment in all rifaxi- of patients (49% and 71% in two of the studies) had no min groups was 43.1 hours, compared with 55.7 hours for positive culture, perhaps reflecting a high incidence of patho- TMP-SMX (a nonsignificant difference). These results were a genic E. coli. Three of these studies mention travel history in statistically significant improvement over historical placebo patients, with incidence rates of 1%, 25%, and 70% [46,49, controls from a similar population. Although sample size 54]. Studies that specifically examined quinolones for the prevented statistical significance, the 200-mg dose of rifaxi- treatment of traveler’s diarrhea have demonstrated similar min appeared to be as effective as the higher doses. In fact, reductions in days of diarrhea and illness [52]. These findings all of the microbiologic failures (four of 20 isolated patho- appear to be independent of the predominant organisms gens from the combined rifaximin groups) occurred in the isolated; the same effect is present with a predominance of 400- and 600-mg groups (Table 3). The second study com- pathogenic E. coli, Salmonella, or Campylobacter [47,55]. pared rifamixin (400 mg twice a day) with ciprofloxacin in a Alternatives to quinolones for empiric treatment may be similar population in Mexico (n=163) and in tourists in appropriate for children and patients with sensitivity to Jamaica (n=24) [59••]. Results in the two groups were simi- quinolones or in areas where quinolone-resistant organisms lar, with a time to last unformed stool of 25.7 versus 25.0 are prevalent. TMP-SMX is a reasonable alternative that is hours in the rifaximin and ciprofloxacin groups, respec- commonly used in children with traveler’s diarrhea [2••]. tively. These results were similar for patients with and with- Among travelers in Thailand, where quinolone-resistant out specific microbiologic diagnosis. Differences in side Campylobacter predominates, azithromycin or another mac- effects appear to be clinically insignificant. A third random- rolide is an appropriate choice for empiric therapy [51]. ized, controlled study comparing rifaximin with placebo Finally, local epidemiology of diarrheal illness and resis- was presented at a recent scientific meeting [56]. In this tance patterns should always be considered in choosing an study rifaximin (200 and 400 mg three times a day) cut the empiric antibiotic, and a thorough knowledge of these data time to last unformed stool in half, compared with placebo. may prevent future complications. Rifaximin Conclusions Increasing antimicrobial resistance, combined with the Diarrheal illness from bacterial pathogens continues to be side effects and potential toxicity of absorbed antibiotics, a disease of global significance. Rapidly evolving organ- have renewed interest in nonabsorbed antibiotics for the isms and rapid emergence of antimicrobial resistance are treatment of diarrhea. Prior studies with oral aztreonam expanding threats to the treatment advances of the past few and bicozamycin have proven the efficacy of this approach, decades. To counter these threats, new tools have recently although neither of these drugs was pursued for marketing been added to the diagnostic and therapeutic armamentar- [56]. Studies of rifaximin, a nonabsorbed rifamycin deriva- ium, and promising additions are on the horizon. The next tive, in the treatment of traveler’s diarrhea are a new and decade should bring interesting changes in the manage- exciting development. ment of this important disease.
  • Table 2. Studies of short-course therapy for shigellosis in children 292 Regimen Treatment success, % Short Study Location Patients, n Short course Control course Control P-value Vinh et al. [45] Vietnam 66 Ofloxacin, 7.5 mg/kg Nalidixic acid, 13.8 mg/kg 90 75 Not significant every 12 hours for 2 doses 4 times a day for 5 days ZIMBASA group [44] Zimbabwe, Bangladesh, 128 Ciprofloxacin, 15 mg/kg Ciprofloxacin (same dose) 65 69 Not significant South Africa every 12 hours for 3 days for 5 days Table 3. Microbiologic cure in traveler's diarrhea with identified organism Gastrointestinal Infections Microbiologic cure, n (%)* Study Location Patients, n Control drug Rifaximin Control DuPont et al. [58] Mexico 72 TMP-SMX 16 of 20 (80) 7 of 7 (100) DuPont et al. [59••] Mexico and Jamaica 187 Ciprofloxacin 29 of 30 (74) 38 of 43 (88) *Differences are not statistically significant. TMP-SMX—trimethoprim-sulfamethoxazole.
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